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161.
Johnson L Kim HK Tanabe M Gorcsan J Schwartzman D Shroff SG Pinsky MR 《American journal of physiology. Heart and circulatory physiology》2007,293(5):H3046-H3055
The goal of the present study was to assess the effects of left ventricular (LV) pacing sites (apex vs. free wall) on radial synchrony and global LV performance in a canine model of contraction dyssynchrony. Ultrasound tissue Doppler imaging and hemodynamic (LV pressure-volume) data were collected in seven anesthetized, opened-chest dogs. Right atrial (RA) pacing served as the control, and contraction dyssynchrony was created by simultaneous RA and right ventricular (RV) pacing to induce a left bundle-branch block-like contraction pattern. Cardiac resynchronization therapy (CRT) was implemented by adding simultaneous LV pacing to the RV pacing mode at either the LV apex (CRTa) or free wall (CRTf). A new index of synchrony was developed via pair-wise cross-correlation analysis of tissue Doppler radial strain from six midmyocardial cross-sectional regions, with a value of 15 indicating perfect synchrony. Compared with RA pacing, RV pacing significantly decreased radial synchrony (11.1 +/- 0.8 vs. 4.8 +/- 1.2, P < 0.01) and global LV performance (cardiac output: 2.0 +/- 0.3 vs. 1.4 +/- 0.1 l/min and stroke work: 137 +/- 22 vs. 60 +/- 14 mJ, P < 0.05). Although both CRTa and CRTf significantly improved radial synchrony, only CRTa markedly improved global function (cardiac output: 2.1 +/- 0.2 l/min and stroke work: 113 +/- 13 mJ, P < 0.01 vs. RV pacing). Furthermore, CRTa decreased LV end-systolic volume compared with RV pacing without any change in LV end-systolic pressure, indicating an augmented global LV contractile state. Thus, LV apical pacing appears to be a superior pacing site in the context of CRT. The dissociation between changes in synchrony and global LV performance with CRTf suggests that regional analysis from a single plane may not be sufficient to adequately characterize contraction synchrony. 相似文献
162.
Kawai M Ando K Matsumoto Y Sakurada I Hirota M Nakamura H Ohta A Sudo M Hattori K Takashima T Hizue M Watanabe S Fujita I Mizutani M Kawamura M 《Bioorganic & medicinal chemistry letters》2007,17(20):5558-5562
(-)-6-[2-[4-(3-Fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone was identified as an orally active NR2B-subunit selective N-methyl-d-aspartate (NMDA) receptor antagonist. It has very high selectivity for NR2B subunits containing NMDA receptors versus the HERG-channel inhibition (therapeutic index=4200 vs NR2B binding IC(50)). This compound has improved pharmacokinetic properties compared to the prototype CP-101,606. 相似文献
163.
Structure-activity relationship and biological property of cortistatins, anti-angiogenic spongean steroidal alkaloids 总被引:1,自引:0,他引:1
Aoki S Watanabe Y Tanabe D Arai M Suna H Miyamoto K Tsujibo H Tsujikawa K Yamamoto H Kobayashi M 《Bioorganic & medicinal chemistry》2007,15(21):6758-6762
Previously, bioassay-guided separation led us to isolate eleven novel steroidal alkaloids named cortistatins from the marine sponge Corticium simplex. These cortistatins were classified into three types based on the chemical structure of the side chain part, that is, isoquinoline, N-methyl piperidine or 3-methylpyridine units. From the structure-activity relationship study, the isoquinoline unit in the side chain was found to be crucial for the anti-angiogenic activity of cortistatins. Cortistatin A (1) showed cytostatic growth-inhibitory activity against human umbilical vein endothelial cells (HUVECs). Cortistatin A (1) also inhibited VEGF-induced migration of HUVECs and bFGF-induced tubular formation. Although cortistatin A (1) showed no effect on VEGF-induced phosphorylation of ERK1/2 and p38, which are one of the signaling pathways for migration and tubular formation, the phosphorylation of the unidentified 110kDa protein in HUVECs was inhibited by the treatment with cortistatin A. 相似文献
164.
Tanabe G Yoshikai K Hatanaka T Yamamoto M Shao Y Minematsu T Muraoka O Wang T Matsuda H Yoshikawa M 《Bioorganic & medicinal chemistry》2007,15(11):3926-3937
De-O-sulfonated analogs (10a, Y(-)=CH(3)OSO(3) and 10b, Y(-)=Cl) of salacinol, a naturally occurring glycosidase inhibitor, and its diastereomer (12a, Y(-)=CH(3)OSO(3)) with L-thiosugar moiety (1,4-dideoxy-1,4-epithio-L-arabinitol) were prepared. Their inhibitory activities against intestinal maltase and sucrase were examined and compared with those of the parent alpha-glycosidase inhibitor, salacinol (1a). Compounds 10a and 10b showed a potent inhibitory activity equal to that of 1a against both enzymes, although 12a was a weak inhibitor against sucrase and maltase. These results indicated that the O-sulfonate anion moiety of 1a is not essential for the inhibitory activity. 相似文献
165.
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168.
Tanabe H Ito H Sugiyama K Kiriyama S Morita T 《Bioscience, biotechnology, and biochemistry》2007,71(2):575-578
Changes in the small intestinal mucin contents in rats were evaluated by two methods, viz., a newly established ELISA and a method based on the measurement of O-linked oligosaccharide chains (OSC) as a mucin marker. Significant correlation was observed between the values of ELISA-derived mucins and OSC. The results confirm the usefulness of measurement of OSC as an alternative method for mucin determination. 相似文献
169.
Effects of dietary soybean peptides on hepatic production of ketone bodies and secretion of triglyceride by perfused rat liver 总被引:2,自引:0,他引:2
Tamaru S Kurayama T Sakono M Fukuda N Nakamori T Furuta H Tanaka K Sugano M 《Bioscience, biotechnology, and biochemistry》2007,71(10):2451-2457
Soybean protein isolate (SPI) was digested with protease to produce a peptides containing the low-molecular fraction (LD3) or a mixture of high- and low-molecular fractions (HD1). Rats were fed a diets containing SPI, LD3, or HD1 at a protein level equivalent to the 20% casein diet for 4 weeks. The serum triglyceride concentration was lower in rats fed SPI, LD3, and HD1 diets than in rats fed the casein diet, and the differences were significant for the cholesterol-enriched diet. The value for the LD3 group was the lowest among all groups for both the cholesterol-free and -enriched diets. The level of triglyceride in the post-perfused liver was significantly lower in the LD3 and HD1 groups and the SPI group than in the casein group irrespective of the presence of cholesterol in the diet. In the cholesterol-free diet, LD3 feeding as compared to casein feeding caused a reduction in triglyceride secretion from the liver to perfusate and an increment of hepatic ketone body production. The addition of cholesterol to the diets somewhat attenuated these effects of LD3. These results suggest that the low-molecular fraction in soybean peptides causes triglyceride-lowering activity through a reduction in triglyceride secretion from the liver to the blood circulation and the stimulation of fatty acid oxidation in the liver. There is a possibility that soybean peptides modulate triglyceride metabolism by changes in the hepatic contribution. 相似文献
170.
Tanabe S Kinuta Y Yasumatsu H Takayanagi M Kobayashi S Takido N Sugiyama M 《Bioscience, biotechnology, and biochemistry》2007,71(11):2852-2855
We evaluated the effects of a 50% methanol extract of Citrus unshiu powder (MEC) on cytokines in peripheral blood mononuclear cells (PBMCs) obtained from patients with seasonal allergic rhinitis to cedar pollen. The levels of cytokines, such as TNF-alpha, IFN-gamma, IL-2, IL-4, IL-5, IL-10, IL-12 (p70), IL-13, and GM-CSF, produced by pollen-stimulated PBMC were measured. We found that MEC suppressed pollen-induced TNF-alpha release and increased IFN-gamma release from PBMCs. The results suggest that Citrus unshiu powder has an immunomodulatory effect in vitro and that its use could improve seasonal allergic rhinitis symptoms. 相似文献