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Minami-rinkan, Japan

Tsuji Y.,University of Toyama | Hashimoto W.,Nagasaki University | Taniguchi S.,Sasebo Chuo Hospital | Hiraki Y.,National Hospital Organization Kumamoto Medical Center | And 3 more authors.
International Journal of Infectious Diseases | Year: 2013

The purpose of this study was to investigate the penetration of linezolid into the mediastinum and pleural space by comparing its concentration in the serum, mediastinum, and pleural space. The linezolid area under the concentration-versus-time curve from zero to 12h (AUC)mediastinum fluid/serum and AUCpleural fluid/serum ratio were 1.32 and 1.64, respectively. The results suggest that the linezolid concentration in the mediastinum varies as in the serum, and that the concentration in the mediastinum is the same as or greater than that in the serum. © 2013 International Society for Infectious Diseases.


Shimizu R.,Hiroshima International University | Yamaguchi M.,Hiroshima International University | Uramaru N.,Nihon Pharmaceutical University | Kuroki H.,Daiichi University of Pharmacy | And 3 more authors.
Toxicology | Year: 2013

The aim of this study was to investigate the possible influence of halogenated compounds on thyroid hormone metabolism via inhibition of iodotyrosine deiodinase (IYD) activity. The structure-activity relationships of 44 halogenated compounds for IYD-inhibitory activity were examined in vitro using microsomes of HEK-293 T cells expressing recombinant human IYD. The compounds examined were 17 polychlorinated biphenyls (PCBs), 15 polybrominated diphenyl ethers (PBDEs), two agrichemicals, five antiparasitics, two pharmaceuticals and three food colorants. Among them, 25 halogenated phenolic compounds inhibited IYD activity at the concentration of 1×10-4M or 6×10-4M. Rose bengal was the most potent inhibitor, followed by erythrosine B, phloxine B, benzbromarone, 4'-hydroxy-2,2',4-tribromodiphenyl ether, 4-hydroxy-2,3',3,4'-tetrabromodiphenyl ether, 4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl, 4'-hydroxy-2,2',4,5'-tetrabromodiphenyl ether, triclosan, and 4-hydroxy-2,2',3,4',5-pentabromodiphenyl ether. However, among PCBs and PBDEs without a hydroxyl group, including their methoxylated metabolites, none inhibited IYD activity. These results suggest that halogenated compounds may disturb thyroid hormone homeostasis via inhibition of IYD, and that the structural requirements for IYD-inhibitory activity include halogen atom and hydroxyl group substitution on a phenyl ring. © 2013 Elsevier Ireland Ltd.


Ishii Y.,Kyushu University | Takeda S.,Kyushu University | Takeda S.,Daiichi University of Pharmacy | Yamada H.,Kyushu University
Drug Metabolism Reviews | Year: 2010

Drug oxidation and conjugation mediated by cytochrome P450 (P450) and UDP-glucuronosyltransferase (UGT) have long been considered to take place separately. However, our recent studies have suggested that CYP3A4 specifically associates with UGT2B7 and alters the regioselectivity of morphine glucuronidation. This observation strongly supports the view that there is functional cooperation between P450 and UGT to facilitate multistep drug metabolism. In recent years, accumulating evidence has suggested an interaction between UGT isoforms or between P450 and UGTs and a change in UGT function by protein-protein association. In this review, we summarize these interactions and discuss their relevance to UGT function. © 2010 Informa UK Ltd.


Eto H.,Kyushu University | Hyodo F.,Kyushu University | Kosem N.,Kyushu University | Kobayashi R.,Kyushu University | And 5 more authors.
Free Radical Biology and Medicine | Year: 2015

Disorders of skeletal muscle are often associated with inflammation and alterations in redox status. A non-invasive technique that could localize and evaluate the severity of skeletal muscle inflammation based on its redox environment would be useful for disease identification and monitoring, and for the development of treatments; however, no such technique currently exists. We describe a method for redox imaging of skeletal muscle using dynamic nuclear polarization magnetic resonance imaging (DNP-MRI), and apply this method to an animal model of local inflammation. Female C57/BL6 mice received injections of 0.5% bupivacaine into their gastrocnemius muscles. Plasma biomarkers, myeloperoxidase activity, and histological sections were assessed at 4 and 24 h after bupivacaine injection to measure the inflammatory response. In vivo DNP-MRI was performed with the nitroxyl radicals carbamoyl-PROXYL (cell permeable) and carboxy-PROXYL (cell impermeable) as molecular imaging probes at 4 and 24 h after bupivacaine administration. The images obtained after carbamoyl-PROXYL administration were confirmed with the results of L-band EPR spectroscopy. The plasma biomarkers, myeloperoxidase activity, and histological findings indicated that bupivacaine injection caused acute muscle damage and inflammation. DNP-MRI images of mice treated with carbamoyl-PROXYL or carboxy-PROXYL at 4 and 24 h after bupivacaine injection showed similar increases in image intensity and decay rate was significantly increased at 24 h. In addition, reduction rates in individual mice at 4 h and 24 h showed faster trends with bupivacaine injection than in their contralateral sides by image-based analysis. These findings indicate that in vivo DNP-MRI with nitroxyl radicals can non-invasively detect changes in the focal redox status of muscle resulting from locally-induced inflammation. © 2015 Elsevier Inc.


Tsuji Y.,Sasebo Chuo Hospital | Hiraki Y.,Kumamoto Medical Center | Matsumoto K.,Doshisha Womens College of Liberal Arts | Mizoguchi A.,Sasebo Chuo Hospital | And 6 more authors.
Scandinavian Journal of Infectious Diseases | Year: 2012

We evaluated the pharmacokinetics of linezolid in the case of an obese Japanese patient (body weight 116 kg; body mass index 37 kg/m2). Linezolid was administered at a dose of 600 mg by intravenous drip infusion for 6090 min at 12-h intervals. The results showed increased clearance of linezolid and a reduced serum concentration compared to population pharmacokinetic parameters, with trough levels below the 90% minimum inhibitory concentration. However, linezolid was effective for improving lung infection and inflammation in our patient, which may be due to its particularly effective transfer into lung tissues. Linezolid undergoes slow non-enzymatic oxidation in vivo that may be increased in obese patients, and this may account for the greater clearance. Our findings are useful for the planning of linezolid therapy in obese patients. © 2012 Informa Healthcare.

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