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81.
Norito Takamura Toru Maruyama Etsuo Chosa Keiichi Kawai Yasuhiro Tsutsumi Yukie Uryu Keishi Yamasaki Tsuneo Deguchi Masaki Otagiri 《Drug metabolism and disposition》2005,33(4):596-602
To determine whether bucolome (5-n-butyl-1-cyclohexyl-2,4,6-trioxoperhydropyrimidine), a nonsteroidal anti-inflammatory agent, can reverse diuretic resistance of furosemide in patients with nephrotic syndrome, we examined the inhibitory effect of bucolome on the protein binding of furosemide in serum and urine. Bucolome significantly inhibited the protein binding of furosemide not only in serum but also in urine of preparation albumin (UPA), which mimics urinary albumin concentration in patients with nephrotic syndrome by ultrafiltration method. The binding percentage of furosemide to albumin was approximately 70% in UPA. With coadministration of bucolome to healthy volunteers, renal clearance of furosemide was increased, reflecting the increase of the free fraction of furosemide in serum. Furthermore, coadministration of bucolome caused a significant increase of urine volume and sodium concentration in urine. Even at higher urine levels of furosemide, the inhibitory effect of bucolome on the protein binding of furosemide in UPA remains constant, and changes in pH at weakly acidic pH levels (pH 5.5-6.5) did not alter the inhibitory effect of bucolome. Interestingly, coadministration of bucolome with furosemide in doxorubicin (Adriamycin)-induced nephrotic syndrome model rats alleviated the diuretic resistance. These results suggest that bucolome has a potent inhibitory effect on the protein binding of furosemide in the urine and can partially restore the diuretic response of furosemide in patients with nephrotic syndrome by increasing the free fraction of furosemide at the site of action. 相似文献
82.
Kamei H Yoshida S Yamasaki K Tajiri T Ozaki K Shirouzu K 《The Journal of surgical research》2000,89(1):20-25
BACKGROUND: The greater nitrogen loss that occurs with increasing severity of trauma is believed to occur because activation of the hypothalamus-pituitary axis is greater with severe injury. Cytokines in the brain stimulate the hypothalamus-pituitary-adrenal axis. This study was carried out to investigate whether the brain would recognize severity of trauma via TNF-alpha mRNA synthesis in the brain. METHODS: Male C57BL/6 mice (n = 70, BW: 20-28 g) were randomly assigned into four groups, (1) control (no anesthesia or incision), (2) anesthesia alone, (3) anesthesia plus laparotomy by short incision (short), and (4) anesthesia plus laparotomy by long incision (long). A laparotomy was carried out in the short and long groups by a 1.2-cm vertical incision and by a horizontal plus a vertical incision (2.4 x 2.4 cm), respectively. Exactly either 3 or 24 h after surgery, the animals were decapitated. TNF-alpha mRNA levels in the tissues were determined by semi-quantitative PCR. RESULTS: Nitrogen and catecholamine excretion were increased in the long wound group compared with the short wound group. Expression of TNF-alpha mRNA in the brain was greater in the long group after surgery than in the control, anesthesia, and short groups (brain, long: 0.150 +/- 0.005; P < 0.01 vs control, anesthesia alone, and short groups), but TNF-alpha levels in the plasma were the same in the short and long groups after surgery. CONCLUSION: Levels of TNF-alpha mRNA in the brain were enhanced according to the length of the wound probably because of greater neural stimuli from the wound site, and this elevation was involved in the greater nitrogen loss. 相似文献
83.
84.
Yamasaki N Matsumoto K Ohta Y Nishida T Adachi A Nakagawa K Kawakami K 《Kyobu geka. The Japanese journal of thoracic surgery》2000,53(9):791-794
We have experienced thoracoscopic surgery for benign solitary fibrous tumor of the parietal pleura. A 46-year-old woman was admitted to our hospital because of chest abnormal shadow. Under thoracoscopy the tumor that was connected to the parietal pleura with a wide pedicle was completely resected with combined parietal resection of the pleura. Pathological diagnosis was a benign solitary fibrous tumor developed from the connective tissues under the parietal pleura. Thoracoscopic surgery is well indicated for a solitary fibrous tumor and wide excision of the tumor with combined resection of the pleura is important to prevent a local recurrence. 相似文献
85.
Toshiaki Tanaka Agnès Duflot-Dancer Michèle Tiraby Colette Piccoli Gérard Tiraby Hiroshi Yamasaki Marc Mesnil 《Cancer letters》2009
Among gene therapy strategies elaborated to kill cancer cells, one uses the CodA gene, coding for cytosine deaminase (CD) that converts 5-fluorocytosine (5-FC) into toxic 5-fluorouracil (5-FU). To enhance 5-FC metabolic activation, we prepared a vector carrying CodA and upp (uracil phosphoribosyl transferase) genes which rendered HeLa cells sensitive to 5-FC and enhanced a bystander effect not mediated by gap junctions. However, 1% CD+–UPP+ cells were able to kill 40% of the cell population if the cells were communicating. This suggests that, at very low percentages of CD+–UPP+ cells, CodA and upp induce a bystander effect through gap junction-dependent mechanisms. 相似文献
86.
Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor
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Daisuke Honma Osamu Kanno Jun Watanabe Junzo Kinoshita Makoto Hirasawa Emi Nosaka Machiko Shiroishi Takeshi Takizawa Isao Yasumatsu Takao Horiuchi Akira Nakao Keisuke Suzuki Tomonori Yamasaki Katsuyoshi Nakajima Miho Hayakawa Takanori Yamazaki Ajay Singh Yadav Nobuaki Adachi 《Cancer science》2017,108(10):2069-2078
Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 functions as a catalytic subunit of PRC2, so there are two PRC2 complexes containing either EZH2 or EZH1. Tumorigenic functions of EZH2 and its synthetic lethality with some subunits of SWItch/Sucrose Non‐Fermentable (SWI/SNF) chromatin remodeling complexes have been observed. However, little is known about the function of EZH1 in tumorigenesis. Herein, we developed novel, orally bioavailable EZH1/2 dual inhibitors that strongly and selectively inhibited methyltransferase activity of both EZH2 and EZH1. EZH1/2 dual inhibitors suppressed trimethylation of histone H3 lysine 27 in cells more than EZH2 selective inhibitors. They also showed greater antitumor efficacy than EZH2 selective inhibitor in vitro and in vivo against diffuse large B‐cell lymphoma cells harboring gain‐of‐function mutation in EZH2. A hematological cancer panel assay indicated that EZH1/2 dual inhibitor has efficacy against some lymphomas, multiple myeloma, and leukemia with fusion genes such as MLL‐AF9, MLL‐AF4, and AML1‐ETO. A solid cancer panel assay demonstrated that some cancer cell lines are sensitive to EZH1/2 dual inhibitor in vitro and in vivo. No clear correlation was detected between sensitivity to EZH1/2 dual inhibitor and SWI/SNF mutations, with a few exceptions. Severe toxicity was not seen in rats treated with EZH1/2 dual inhibitor for 14 days at drug levels higher than those used in the antitumor study. Our results indicate the possibility of EZH1/2 dual inhibitors for clinical applications. 相似文献
87.
88.
Katsuhiro Yamasaki Takaomi Tagami Masami Kawaguchi Masahiro Okihashi Satoshi Takatori Yoshikazu Sakagami Setsuko Sekita Motoyoshi Satake 《Journal of natural medicines》2009,63(4):451-458
Simple and rapid analysis of aristolochic acid (AA) in crude drugs and Kampo extracts using a solid-phase extraction method
and HPLC-PDA analysis was investigated. Extraction of AA from samples was accomplished by adding methanol containing 1% ammonia.
The addition of ammonia ionized the AA of acidic substances so that they adhered to an acrylamide copolymer of a strong anion
exchange resin (Sep-Pak QMA) coupled to diol silica easily. Furthermore, a mixture of acetonitrile–water–phosphoric acid (75:25:2,
v/v) was effective in isolating AA from its carrier. Since almost all interfering peaks originating from contaminants in crude
drugs and Kampo extract formulations could be removed, a satisfactory HPLC chromatogram of AA was obtained. A good result
was also obtained when Aristolochiaceae and crude drugs containing AA were tested. Particularly in the case of the medicinal
parts of Asarum, several interfering peaks and a ghost peak detected near the AA peak were eliminated. The AA contents of two Kampo extract
formulations, tokishigyakukagoshuyushokyoto and ryutanshakanto, were calculated by HPLC analysis. The AA content (the sum
of AA-I and AA-II) was 1.25–6.13 mg per daily dose. From an additional recovery experiment for Kampo formulations, high recovery
rates of AA were obtained. Neither LC/MS nor special instrumentation was necessary. Our results suggest that this simple,
quick, and sensitive analytical method to detect AA in crude drugs and Kampo extract formulations would be valuable in safety
inspections of AA in crude drugs and their products. 相似文献
89.
Hiroki Ueno Narumi Ohno Takafumi Abe Kazuki Kimoto Chika Matsuoka Mayumi Giga Hiroyuki Naito Tomoyuki Kono Miyuki Takasu Naoya Kidani Rie Yamasaki Koichi Ichimura Eiichi Nomura 《Internal medicine (Tokyo, Japan)》2022,61(24):3733
Central nervous system methotrexate-associated lymphoproliferative disorder (CNS-MTX-LPD) is rare, but its spontaneous regression has been observed in some patients after withdrawal of agents. We herein report three cases of primary CNS-MTX-LPD that received oral MTX for rheumatoid arthritis. Epstein-Barr virus and oligoclonal bands (OCBs) were positive, while proton magnetic resonance spectroscopy (1H-MRS) showed an elevated lipid peak and slightly elevated choline/N-acetylaspartate ratio in common. After MTX withdrawal, brain lesions showed spontaneous regression in all cases. Our patient''s 1H-MRS findings and OCBs may reflect a non-monoclonal lymphoproliferative histology as benign-type lesions in CNS-MTX-LPD. 相似文献
90.