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991.
Ito K Satoh T Watanabe Y Ikarashi N Asano T Morita T Sugiyama K 《Biological & pharmaceutical bulletin》2008,31(5):893-896
The Kampo medicines are more and more often used in recent years, usually together with the Western drugs. The need for the investigation of drug interactions between Kampo medicines and Western drugs are, therefore, widely recognized. In the present study, the effects of 3 Kampo medicines (Rikkunshito, Yokukansan and Boiogito) on the activity of cytochrome P450 (CYP), a superfamily of drug-metabolizing enzymes, were investigated in an in vitro study using human CYP recombinants. Their effects on the P-glycoprotein (P-gp), one of the major drug transporters, were also evaluated by the ATPase assay using human P-gp membranes and verapamil as a substrate. The inhibition rate of Rikkunshito, Yokukansan and Boiogito on human CYP3A4, 2C9, 2C19, 2D6 and 2E1 was less than 50% at the concentrations below 0.1 mg/ml except for the inhibition of CYP2D6 by Boiogito. Furthermore, none of the Kampo medicines affected the ATPase activity at the concentrations lower than 0.1 mg/ml, either in the absence or presence of verapamil, indicating their low inhibitory potency against P-gp. These findings indicate that Rikkunshito, Yokukansan and Boiogito are unlikely to cause clinically relevant drug interactions involving the inhibition of major CYP isozymes and P-gp. 相似文献
992.
Matzno S Yamaguchi Y Akiyoshi T Nakabayashi T Matsuyama K 《Biological & pharmaceutical bulletin》2008,31(6):1270-1273
The possibility of vitamin K3 (VK3) as an anticancer agent was assessed. VK3 dose-dependently diminished the cell viability (measured as esterase activity) with IC50 of 13.7 microM and Hill coefficient of 3.1 in Hep G2 cells. It also decreased the population of S phase and arrested cell cycle in the G2/M phase in a dose-dependent manner. G2/M arrest was regulated by the increment of cyclin A/cdk1 and cyclin A/cdk2 complex, and contrasting cyclin B/cdk1 complex decrease. Finally, combined application demonstrated that VK3 significantly enhanced the cytotoxicity of etoposide, a G2 phase-dependent anticancer agent, whereas it reduced the cytotoxic activity of irinotecan, a S phase-dependent agent. These findings suggest that VK3 induces G2/M arrest by inhibition of cyclin B/cdk1 complex formation, and is thus useful as an enhancer of G2 phase-dependent drugs in hepatic cancer chemotherapy. 相似文献
993.
994.
Kawasaki T Sasaki Y Dan A Bekku R Hashimoto T Tamaki M Yamagishi F 《Kekkaku : [Tuberculosis]》2008,83(7):519-524
A 26-year-old man was admitted to a hospital complaing of continuous high fever and abdominal swelling. As his sputum and ascites culture was positive for acid-fast bacilli and PCR-TB, he was diagnosed as miliary tuberculosis, tuberculous with pleuritis and peritonitis, and transferrd to our hospital. After initiation of treatment with isoniazid, rifampicin (RFP), ethambutol, and pyrazinamide, RFP was suspended because of direct-reacting hyperbilirubinemia. As the liver function recovered after discontinuation of RFP, low dose of RFP was re-administrated and renal dysfunction was observed. The renal dysfunction continued after discontinuation of suspicious drugs including RFP. As renal biopsy revealed interstitial nephritis, prednisolon 20 mg/day was started and renal function recovered quickly. From the clinical course and examination, we considered interstitial nephritis was due to re-administration of RFP and steroid therapy was effective. 相似文献
995.
ASP8497 is a novel selective and competitive dipeptidyl peptidase-IV inhibitor with antihyperglycemic activity 总被引:1,自引:0,他引:1
Matsuyama-Yokono A Tahara A Nakano R Someya Y Nagase I Hayakawa M Shibasaki M 《Biochemical pharmacology》2008,76(1):98-107
Dipeptidyl peptidase (DPP)-IV inhibitors are expected to become a useful new class of antidiabetic agent. The aim of the present study is to characterize the in vitro and in vivo profile of ASP8497, (2S,4S)-4-fluoro-1-({[4-methyl-1-(methylsulfonyl)piperidin-4-yl]amino}acetyl)pyrrolidine-2-carbonitrile monofumarate, which is a novel DPP-IV inhibitor. ASP8497 inhibited DPP-IV in plasma from mice, rats, dogs and humans with IC(50) values of 3.86, 2.36, 5.53 and 5.30 nM, respectively. In contrast, ASP8497 did not potently inhibit DPP8 or DPP9 activity (IC(50)>200 nM). Kinetic analysis indicated that ASP8497 inhibits DPP-IV activity in a competitive manner. In streptozotocin-nicotinamide-induced diabetic mice, ASP8497 (3 mg/kg) significantly reduced glucose excursion during the oral glucose tolerance test conducted 0.5 and 8.5 h after administration, with increases in plasma insulin and active glucagon-like peptide-1 (GLP-1) levels. In contrast, ASP8497 (3 and 30 mg/kg) did not cause hypoglycemia in fasted normal mice. Furthermore, administration of exogenous GLP-1 induced significant inhibition of gastric emptying and small intestinal transit rates, but ASP8497 (30 mg/kg) had no significant effects in normal mice. These present preclinical studies indicate that ASP8497 is a novel selective DPP-IV inhibitor with long-acting antidiabetic effect that might be a potential agent for type 2 diabetes. 相似文献
996.
Shimizu M Matsumoto Y Kurosawa T Azuma C Enomoto M Nakamura H Hirabayashi T Kaneko M Okuma Y Murayama T 《Biochemical pharmacology》2008,75(6):1358-1369
Stimulation of L929 cells with tumor necrosis factor-alpha (TNFalpha) caused cell death accompanied by a release of arachidonic acid (AA). Although the inhibition of caspases has been shown to cause necrosis in TNFalpha-treated L929 cells, its role in the TNFalpha-induced release of AA has not been elucidated. The release of AA is tightly regulated by phospholipase A(2) (PLA(2)). To find out the mechanisms underlying the TNFalpha-induced release of AA, we investigated the relationship between TNFalpha stimulation and PLA(2) regulation with and without zVAD, an inhibitor of caspases. In the present study, we found that treatment with TNFalpha and zVAD stimulated release of AA and cell death in C12 cells (a variant of L929 cells lacking alpha type of cytosolic PLA(2) (cPLA(2)alpha)). Stimulation with TNFalpha/zVAD also caused the release of AA from L929-cPLA(2)alpha-siRNA cells. Treatment with pyrrophenone (a selective inhibitor of cPLA(2)alpha) completely inhibited the TNFalpha-induced release of AA, but only partially inhibited the TNFalpha/zVAD-induced response in L929 cells. The TNFalpha/zVAD-induced release of AA from C12 and L929-cPLA(2)alpha-siRNA cells was pyrrophenone-insensitive, but inhibited by treatment with butylated hydroxyanisole (BHA, an antioxidant). Treatment with dithiothreitol, which inactivates secretory PLA(2) activity, decreased the amount of AA released by TNFalpha/zVAD. TNFalpha/zVAD appears to stimulate release of AA from C12 cells in a cPLA(2)alpha-independent, BHA-sensitive manner. The possible roles of secretory PLA(2) and reactive oxygen species from different pools in the release of AA and cell death were discussed. 相似文献
997.
Yasui T Uemura H Tomita J Miyatani Y Yamada M Kuwahara A Matsuzaki T Maegawa M Miura M Irahara M 《Maturitas》2007,56(3):288-296
Objective
We investigated changes in serum undercarboxylated osteocalcin (ucOC) concentrations, bone turnover markers and spine bone mineral density (BMD) in women who had undergone bilateral oophorectomy during the premenopausal period.Methods
The study population comprised 141 bilaterally oophorectomized and 32 premenopausal women for a cross-sectional study. The longitudinal study consisted of 21 bilaterally oophorectomized women. Serum ucOC concentration, serum concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) as bone formation markers, urine N-telopeptide (NTx) concentration as a bone resorption marker and serum parathyroid hormone (PTH) concentration were measured.Results
Serum concentration of ucOC in women at 1 month after bilateral oophorectomy was significantly (p < 0.05) higher than that in premenopausal women and the high level was sustained after surgical menopause. On the other hand, serum OC concentration at 1 month after surgical menopause was not different from that in premenopausal women. In the longitudinal study, serum ucOC concentration at 1 month after surgical menopause was significantly (p < 0.05) increased compared to that before bilateral oophorectomy, while serum OC concentrations before and at 1 month after surgical menopause were not significantly different.Conclusion
The results of this study showed that serum ucOC concentration rapidly increases in women after bilateral oophorectomy and that change in serum ucOC concentration after surgical menopause is different from change in serum OC concentration. 相似文献998.
Takekawa Y Kimura M Sakakibara M Yoshii R Yamashita Y 《Rinsho byori. The Japanese journal of clinical pathology》2007,55(6):535-539
Gastrointestinal stromal tumor (GIST) usually occurs in the gastrointestinal tract, mainly in the stomach. Recently, GIST arising in extragastrointestinal organs was been reported. This case was a 49-year-old female who was diagnosed as having uterine leiomyoma and pelvic tumor in the rectovaginal septum. The pelvic tumor showed no connection with the uterus and rectum. Grossly, the pelvic tumor was light brown and solid. Cytologically, the tumor cells of the pelvic tumor showed vague interlacing fascicles with spindle/fibrous cytoplasm and elongated nuclei. No necrosis or mitosis was present. Histological findings of the pelvic tumor revealed an interlacing bundle fashioned with one to two mitotic figures per 50 HPE No necrosis was found in the tumor. The tumor cells were positive for CD117 (c-kit protein), CD34, and vimentin by immunohistochemistry, but negative for actin, desmin, and S-100. The tumor was diagnosed as GIST in the pelvic cavity. GIST rarely presents in extragastrointestinal regions such as this case. It is difficult to make a differential diagnosis between GIST and other mesenchymal spindle cell tumors only from a cytologic specimen. A positive reaction for CD117 is useful for the diagnosis of GIST. 相似文献
999.
Hirota-Kawadobora M Ishikawa S Fujihara N Wakabayashi S Kamijo Y Yamauchi K Terasawa F Okumura N Katsuyama T 《Rinsho byori. The Japanese journal of clinical pathology》2007,55(11):989-995
We analyzed the clinical factors resulting in hypofibrinogenemia, which is defined as less than 100mg/dl of plasma fibrinogen values determined by a procedure based on the Thrombin-time method. Within a 12-month period, we assayed 5,746 patients (19,309 plasmas) and found 113 patients (1.97%) with hypofibrinogenemia. We categorized these patients as having decreased synthesis of fibrinogen (less than 3.0g/dl of albumin, 140 IU/l of Cholinesterase, and/or 50% on Hepaplastin Test), increased consumption of fibrinogen (more than 10 microg/ml of FDP D-dimer), known side effect of L-asparaginase administration, or other causes. Details are follows: 1) decreased synthesis: 26 patients, suspected of decreased synthesis (albumin: 3.1-3.4 g/dl): 4 patients, 2) increased consumption: 15 patients, suspected of increased consumption (FDP D-dimer: 5.0-9.9 g/dl): 1 case, 3) decreased synthesis combined with increased consumption: 24 patients, suspected of decreased synthesis and/or suspected of increased consumption: 14 patients, 4) side-effect of L-asparaginase administration: 24 patients, 5) heterozygous dysfibrinogenemia: 1 patient, 6) heterozygous fibrinogen deficiency: 1 patient, suspected of heterozygous fibrinogen deficiency: 1 patient, 7) unidentified: 2 patients with West syndrome treated with a combination of ACTH and valproic acid. Three patients with dysfibrinogenemia or fibrinogen deficiency showed normal or slightly prolonged PT values and normal APTT values. These data and our previous reports suggest that heterozygous patients with dysfibrinogenemia or fibrinogen deficiency do not demonstrate markedly prolonged PT and APTT values, differing from patients with afibrinogenemia. 相似文献
1000.
Hiromi Watanabe Eiki Ichihara Hiroe Kayatani Go Makimoto Kiichiro Ninomiya Kazuya Nishii Hisao Higo Chihiro Ando Sachi Okawa Takamasa Nakasuka Hirohisa Kano Naofumi Hara Atsuko Hirabae Yuka Kato Takashi Ninomiya Toshio Kubo Kammei Rai Kadoaki Ohashi Katsuyuki Hotta Masahiro Tabata Yoshinobu Maeda Katsuyuki Kiura 《Cancer science》2021,112(5):1853-1864
Molecular agents targeting the epidermal growth factor receptor (EGFR)-, anaplastic lymphoma kinase (ALK)- or c-ros oncogene 1 (ROS1) alterations have revolutionized the treatment of oncogene-driven non-small-cell lung cancer (NSCLC). However, the emergence of acquired resistance remains a significant challenge, limiting the wider clinical success of these molecular targeted therapies. In this study, we investigated the efficacy of various molecular targeted agents, including erlotinib, alectinib, and crizotinib, combined with anti-vascular endothelial growth factor receptor (VEGFR) 2 therapy. The combination of VEGFR2 blockade with molecular targeted agents enhanced the anti-tumor effects of these agents in xenograft mouse models of EGFR-, ALK-, or ROS1-altered NSCLC. The numbers of CD31-positive blood vessels were significantly lower in the tumors of mice treated with an anti-VEGFR2 antibody combined with molecular targeted agents compared with in those of mice treated with molecular targeted agents alone, implying the antiangiogenic effects of VEGFR2 blockade. Additionally, the combination therapies exerted more potent antiproliferative effects in vitro in EGFR-, ALK-, or ROS1-altered NSCLC cells, implying that VEGFR2 inhibition also has direct anti-tumor effects on cancer cells. Furthermore, VEGFR2 expression was induced following exposure to molecular targeted agents, implying the importance of VEGFR2 signaling in NSCLC patients undergoing molecular targeted therapy. In conclusion, VEGFR2 inhibition enhanced the anti-tumor effects of molecular targeted agents in various oncogene-driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. Hence, combination therapy with anti-VEGFR2 antibodies and molecular targeted agents could serve as a promising treatment strategy for oncogene-driven NSCLC. 相似文献