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131.
Katsumi Kadekawa Kimio Sugaya Saori Nishijima Katsuhiro Ashitomi Minoru Miyazato Tomoyuki Ueda Hideyuki Yamamoto 《Life sciences》2013,92(20-21):1024-1028
AimsAlpha1D-adrenoceptors (α1D-ARs) located in the spinal cord are involved in the control of lower urinary tract function. In order to clarify the effect of α1D-ARs on storage function in the spinal cord, we examined the effect of oral administration and intrathecal injection of the α1D/A-AR antagonist, naftopidil, on bladder activity, as well as the effect of naftopidil on bladder wall histology, in female rats with spinal cord injury (SCI).Main methodsAdult female Sprague–Dawley rats with Th9–10 spinal cord transection were used. In SCI rats with or without 5 mg/day of naftopidil for 4 weeks, bladder activity was examined via continuous cystometry. In other SCI rats, bladder activity was examined before and after intrathecal injection of naftopidil. In addition, bladder wall histology was compared between SCI rats with or without oral administration of naftopidil for 4 weeks.Key findingsOral administration of naftopidil decreased the number of non-voiding contractions (NVCs). Intrathecal injection of naftopidil prolonged the interval between voiding contractions, decreased the maximum voiding contraction pressure and the number of NVCs, and increased bladder capacity without affecting the residual urine volume. Oral administration of naftopidil also decreased bladder wall fibrosis.SignificanceThe α1D/A-AR antagonist naftopidil might act on the bladder and spinal cord to improve detrusor hyperreflexia in the storage state in SCI female rats. Naftopidil also suppressed bladder wall fibrosis, suggesting that it may be effective for the treatment of neurogenic lower urinary tract dysfunction after SCI. 相似文献
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134.
Shinya Harusawa Koichi Sawada Takuji Magata Hiroki Yoneyama Lisa Araki Yoshihide Usami Kouta Hatano Kouichi Yamamoto Daisuke Yamamoto Atsushi Yamatodani 《Bioorganic & medicinal chemistry letters》2013,23(23):6415-6420
S-Alkyl-N-alkylisothiourea compounds containing various cyclic amines were synthesized in the search for novel nonimidazole histamine H3 receptor (H3R) antagonists. Among them, four N-alkyl S-[3-(piperidin-1-yl)propyl]isothioureas 18, 19, 22, and 23 were found to exhibit potent and selective H3R antagonistic activities against in vitro human H3R, but were inactive against in vitro human H4R. Furthermore, three alkyl homologs 18–20 showed inactivity for histamine release in in vivo rat brain microdialysis, suggesting differences in antagonist affinities between species. In addition, in silico docking studies of N-[4-(4-chlorophenyl)butyl]-S-[3-piperidin-1-yl)propyl]isothiourea 19 and a shorter homolog 17 with human/rat H3Rs revealed that structural differences between the antagonist-docking cavities of rat and human H3Rs were likely caused by the Ala122/Val122 mutation. 相似文献
135.
Ryuji Asano Amon Nagami Yuki Fukumoto Futoshi Yazama Hideyuki Ito Isao Sakata Akihiro Tai 《Bioorganic & medicinal chemistry》2013,21(8):2298-2304
Three new water-soluble chlorin derivatives 3, 5 and 8 for potential use as photosensitizers in photodynamic therapy (PDT) for cancer were synthesized from photoprotoporphyrin IX dimethyl ester (1). The in vivo biodistribution and clearance of chlorin derivatives 3, 5 and 8 were investigated in tumor-bearing mice. Iminodiacetic acid derivative 8 showed the greatest tumor-selective accumulation among the new chlorin derivatives with maximum accumulation in tumor tissue at 3 h after intravenous injection and rapid clearance from normal tissues within 24 h after injection. The in vivo therapeutic efficacy of PDT using 8 was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 3 h after injection of 8. Tumor growth was significantly inhibited by PDT using 8. These results indicate that iminodiacetic acid derivative 8 is useful as a new photosensitizer to overcome the disadvantages of photosensitizers that are currently in clinical use. 相似文献
136.
Shigemitsu Matsumoto Naoki Miyamoto Takaharu Hirayama Hideyuki Oki Kengo Okada Michiko Tawada Hidehisa Iwata Kazuhide Nakamura Seiji Yamasaki Hiroshi Miki Akira Hori Shinichi Imamura 《Bioorganic & medicinal chemistry》2013,21(24):7686-7698
To identify compounds with potent antitumor efficacy for various human cancers, we aimed to synthesize compounds that could inhibit c-mesenchymal epithelial transition factor (c-Met) and vascular endothelial growth factor receptor 2 (VEGFR2) kinases. We designed para-substituted inhibitors by using co-crystal structural information from c-Met and VEGFR2 in complex with known inhibitors. This led to the identification of compounds 3a and 3b, which were capable of suppressing both c-Met and VEGFR2 kinase activities. Further optimization resulted in pyrazolone and pyridone derivatives, which could form intramolecular hydrogen bonds to enforce a rigid conformation, thereby producing potent inhibition. One compound of particular note was the imidazo[1,2-a]pyridine derivative (26) bearing a 6-methylpyridone ring, which strongly inhibited both c-Met and VEGFR2 enzyme activities (IC50 = 1.9, 2.2 nM), as well as proliferation of c-Met-addicted MKN45 cells and VEGF-stimulated human umbilical vein endothelial cells (IC50 = 5.0, 1.8 nM). Compound 26 exhibited dose-dependent antitumor efficacy in vivo in MKN45 (treated/control ratio [T/C] = 4%, po, 5 mg/kg, once-daily) and COLO205 (T/C = 13%, po, 15 mg/kg, once-daily) mouse xenograft models. 相似文献
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138.
Tooru Iwamoto Megumu Inaoka Hideyuki Naka 《Bioscience, biotechnology, and biochemistry》2013,77(8):1913-1915
Formation of transfer products from soybean arabinogalactan and glycerol by endo-1,4-β-d-galactanase from Penicillium citrinum was described. The amount of transfer products depended on the glycerol concentration. About 50% of the galactose residues which could be liberated from the polysaccharide by the enzyme were transferred to glycerol at an acceptor concentration of 2.5% (w/v). Transfer products with various polymerization degrees were accumulated at the beginning of the reaction and then those with higher polymerization degrees were degraded gradually. At a final stage of the reaction, two transfer products in addition to two hydrolysis products (galactose and galactobiose) were mainly accumulated. The two transfer products were isolated and their structures were examined. They were 2-O-β-d-galactosyl glycerol and O-β-d-galactosyl-(1 → 4)-O-β-d-galactosyl-(1 → 2)glycerol. 相似文献
139.
Lee Jae-Sung Yoshihiko Iijima Hideyuki Kobayashi Sonoe O. Yanagi 《Bioscience, biotechnology, and biochemistry》2013,77(7):1877-1878
Both enantiomers of aliphatic and aromatic cyanohydrins were hydrolyzed with the aid of Rhodococcus butanica ATCC 21197 to afford optically active α-hydroxy acids. The usefulness of this reaction is demonstrated by the synthesis of optically pure (R)-4-dodecanolide, a defensive secretion of rove beetles, starting from (R)-2-hydroxydecanenitrile. 相似文献
140.
Yukio Satomura Susumu Oi Akira Sawada 《Bioscience, biotechnology, and biochemistry》2013,77(3):194-200
Intracellular lipase of the fungus Sclerotina Libertiana Fcl. could be formed powerfully by washed mycelium during shaking in a plain buffer solution, just as well as in the case of shaking culture. Experiments showed revealed it to be favourable to set the mycelium in the experiment harvested at the end of its stationary phase of growth, and that the addition of various respiratory carbon sources had inhibiting effects, while several surface active agents and some enzyme preparations accelerating effects on the lipase formation. Also, the quality and the quantity of consumed cell-materials in the shaking experiment were investigated in relation to lipase formation. 相似文献