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991.
Purpose: To investigate whether liposome encapsulated total alkaloid of Harmaline (TAH) as a therapeutic agent is beneficial to prevention of posterior capsular opacifi-cation (PCO).Methods: Liposome-encapsulated TAH was prepared by modified freeze-thawing method. 0. 1ml of liposome-encapsulated TAH (0. 2mg/ml) was injected into the capsular bag during extracapsular lens extraction (ECLE) of each eye in total 10 rabbit eyes. Blank liposome or balance salt solution (BSS) was used as control. Slit-lamp examination and histopathological examination was used to evaluated capsule opacifica-tion. Intraocular pressure (IOP) , density and morphology of corneal endothelia cells, the amplitude and latency of b wave of ERG were measured.Results: The inflammatory response was mild both in TAH treated and the control group. PCO formation occurred in the control group 2 weeks postoperatively, but the posterior capsule was clear in TAH treated eyes. 4 weeks and 8 weeks after operation, PCO occurred both in TAH treated 相似文献
992.
Penta-O-galloyl-beta-D-glucose is structurally related to (-)-epigallocatechin gallate and is isolated from hydrolyzed tannin. Penta-O-galloyl-beta-D-glucose can inhibit tumor promotion by teleocidin. We investigated the effects of penta-O-galloyl-beta-D-glucose and various tea polyphenols on cell viability in human leukemia HL-60 cells. In this study, we demonstrated that penta-O-galloyl-beta-D-glucose was able to induce apoptosis in a concentration- and time-dependent manner; however, other polyphenols were less effective. We further investigated the molecular mechanisms of penta-O-galloyl-beta-D-glucose-induced apoptosis. Treatment with penta-O-galloyl-beta-D-glucose caused induction of caspase-3/CPP32 activity in dose- and time-dependent manner, but not caspase-1 activity, and induced the degradation of poly-(ADP-ribose) polymerase. Pretreatment with acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO) and Z-Val-Ala-Asp-fluoromethyl-ketone (Z-VAD-FMK) inhibited penta-O-galloyl-beta-D-glucose-induced DNA fragmentation. Furthermore, treatment with penta-O-galloyl-beta-D-glucose (50 microM) caused a rapid loss of mitochondrial transmembrane potential, release of mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 processing. Our results indicate that penta-O-galloyl-beta-D-glucose allows caspase-activated deoxyribonuclease to enter the nucleus and degrade chromosomal DNA, and induces DFF-45 (DNA fragmentation factor) degradation. These results lead to a working hypothesis that penta-O-galloyl-beta-D-glucose-induced apoptosis is triggered by the release of cytochrome c into the cytosol, procaspase-9 processing, activation of caspase-3, degradation of poly-(ADP-ribose) polymerase, and DNA fragmentation caused by the caspase-activated deoxyribonuclease through the digestion of DFF-45. The induction of apoptosis by penta-O-galloyl-beta-D-glucose may provide a pivotal mechanism for its cancer chemopreventive action. 相似文献
993.
G Phillips D D Davey K A Eagen S K Koovakkat A Liang H P Ng M Pinkerton L Trinh M Whitlow A M Beatty M M Morrissey 《Journal of medicinal chemistry》1999,42(10):1749-1756
A novel series of 2,6-diphenoxypyridines has been designed to inhibit factor Xa, a serine protease strategically located in the coagulation cascade. The evolution from the photochemically unstable bisamidine (Z,Z)-BABCH to potent bisamidine compounds with a pyridine heterocycle as the core scaffold has been achieved. The most potent compound in the series, 6h, has a Ki for human factor Xa of 12 nM. The selectivity of 6h against bovine trypsin and human thrombin was greater than 90- and 1000-fold, respectively. Two proposed modes of binding of 6h to factor Xa are made based on the crystal structures of 6h by itself and of 6h bound to bovine trypsin. 相似文献
994.
Ng HP May K Bauman JG Ghannam A Islam I Liang M Horuk R Hesselgesser J Snider RM Perez HD Morrissey MM 《Journal of medicinal chemistry》1999,42(22):4680-4694
Ligands for the CCR1 receptor (MIP-1alpha and RANTES) have been implicated in a number of chronic inflammatory diseases, most notably multiple sclerosis and rheumatoid arthritis. Because these ligands share a common receptor, CCR1, we sought to discover antagonists for this receptor as an approach to treating these disorders. A novel series of 4-hydroxypiperidines has been discovered by high throughput screening (HTS) which potently inhibits the binding of MIP-1alpha and RANTES to the recombinant human CCR1 chemokine receptor. The structure-activity relationships of various segments of this template are described as the initial HTS lead 1 was optimized synthetically to the highly potent receptor antagonist 6s. This compound has been shown to have at least 200-fold selectivity for inhibition of CCR1 over other human 7-TM receptors, including other chemokine receptors. In addition, data obtained from in vitro functional assays demonstrate the functional antagonism of compound 6s and structurally related analogues against the CCR1 receptor in a concentration dependent manner. The discovery and optimization of potent and selective CCR1 receptor antagonists represented by compound 6s potentially represent a novel approach to the treatment of chronic inflammatory diseases. 相似文献
995.
Sun L Tran N Liang C Tang F Rice A Schreck R Waltz K Shawver LK McMahon G Tang C 《Journal of medicinal chemistry》1999,42(25):5120-5130
Receptor tyrosine kinases (RTKs) have been implicated as therapeutic targets for the treatment of human diseases including cancers, inflammatory diseases, cardiovascular diseases including arterial restenosis, and fibrotic diseases of the lung, liver, and kidney. Three classes of 3-substituted indolin-2-ones containing propionic acid functionality attached to the pyrrole ring at the C-3 position of the core have been identified as catalytic inhibitors of the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) RTKs. Some of the compounds were found to inhibit the tyrosine kinase activity associated with isolated vascular endothelial growth factor receptor 2 (VEGF-R2) [fetal liver tyrosine kinase 1 (Flk-1)/kinase insert domain-containing receptor (KDR)], fibroblast growth factor receptor (FGF-R), and platelet-derived growth factor receptor (PDGF-R) tyrosine kinase with IC(50) values at nanomolar level. Thus, compound 1 showed inhibition against VEGF-R2 (Flk-1/KDR) and FGF-R1 tyrosine kinase activity with IC(50) values of 20 and 30 nM, respectively, while compound 16f inhibited the PDGF-R tyrosine kinase activity with IC(50) value of 10 nM. Structural models and structure-activity relationship analysis of these compounds for the target receptors are discussed. The cellular activities of these compounds were profiled using cellular proliferation assays as measured by bromodeoxyuridine (BrdU) incorporation. Specific and potent inhibition of cell growth was observed for some of these compounds. These data provide evidence that these compounds can be used to inhibit the function of these target receptors. 相似文献
996.
Curcumin, the yellow pigment in turmeric and curry, has antioxidative and anticarcinogenic activities. In this study, we investigated the pharmacokinetic properties of curcumin in mice. After i.p. administration of curcumin (0.1 g/kg) to mice, about 2.25 microg/ml of curcumin appeared in the plasma in the first 15 min. One hour after administration, the levels of curcumin in the intestines, spleen, liver, and kidneys were 177.04, 26.06, 26.90, and 7.51 microg/g, respectively. Only traces (0.41 microg/g) were observed in the brain at 1 h. To clarify the nature of the metabolites of curcumin, the plasma was analyzed by reversed-phase HPLC, and two putative conjugates were observed. Treatment of the plasma with beta-glucuronidase resulted in a decrease in the concentrations of these two putative conjugates and the concomitant appearance of tetrahydrocurcumin (THC) and curcumin, respectively. To investigate the nature of these glucuronide conjugates in vivo, the plasma was analyzed by electrospray. The chemical structures of these metabolites, determined by mass spectrometry/mass spectrometry analysis, suggested that curcumin was first biotransformed to dihydrocurcumin and THC and that these compounds subsequently were converted to monoglucuronide conjugates. Because THC is one of the major metabolites of curcumin, we studied its stability at different pH values. THC was very stable in 0.1 M phosphate buffers of various pH values. Moreover, THC was more stable than curcumin in 0.1 M phosphate buffer, pH 7.2 (37 degrees C). These results, together with previous findings, suggest that curcumin-glucuronoside, dihydrocurcumin-glucuronoside, THC-glucuronoside, and THC are major metabolites of curcumin in vivo. 相似文献
997.
褪黑激素对大鼠大脑皮层脑片在缺氧后羟自由基及乳酸脱氢酶生 … 总被引:2,自引:0,他引:2
目的 研究褪黑激素对大鼠大脑皮层脑片在缺氧后羟自由基及乳酸脱氢酶生成的影响。方法 通过水杨酸捕获法一观察缺氧再给氧中自由基含量的变化,脑片通以91.6%,N2+8.4%O2造成缺氧。LDH用细胞毒检测盒测定。结果:DHBA水平在缺氧及再给氧后显著升高,缺氧时给予褪黑激素可以浓度依赖性地降低再给氧15min时DHBA的含量,但对缺氧30min时DHBA的含量没有显著作用,LDH的含量在缺氧后1h内持 相似文献
998.
RP—HPLC法对不同产地蝙蝠葛几种主要生物碱的测定 总被引:13,自引:0,他引:13
目的:研究不同产地蝙蝠葛几种主要生物碱在质与量上的区别。方法:采用有机溶剂提取生药,应用RP-HPLC方法在东北产和咸宁产蝙蝠葛根茎中几种主要脂溶性生物碱定性定量测定。结果:东北生一最高的生物碱前3位依次是蝙蝠葛苏林碱、蝙蝠碱和guattegaunerine;而咸宁药材则为蝙蝠葛碱、蝙蝠葛诺林碱及蝙蝠葛新诺林碱,不含蝙蝠葛苏林碱。结论:不同产地蝙蝠葛药材所含生物碱在质和量两方面均有显著差异。 相似文献
999.
Wang TK Ho SI Tsai JL Pan TM 《Zhonghua Minguo wei sheng wu ji mian yi xue za zhi = Chinese journal of microbiology and immunology》1996,29(4):210-224
From 1983 through 1993, 786 strains of Vibrio parahaemolyticus were collected from food-borne disease outbreaks and sporadic cases of diarrheal illness in northern Taiwan, involving 42 K-serotypes. Five top leading serotypes were K8 (36.8%), K15 (10.8%), K12 (8.7%), K56 (7.9%) and K63 (4.7%). However, a variation of K-serotypes was found during this study period. From 112 food-borne outbreaks associated with this microorganism, only 54 (48.2%) outbreaks were caused by a single serotype, while 58 (51.8%) were caused by multiple K-serotypes. Numbers of outbreaks caused by two, three and more than three K-serotypes were 29 (26%), 16 (14.2%), and 13 (11.6%), respectively. In a special outbreak, eight K-serotypes was found. Outbreaks caused by party caterers were most frequently associated with multiple K-serotypes. 相似文献
1000.
Dam rats were given lead (0, 0.58, 1.76, and 5.27 mmol/l) containing water ad lib from day 16 of gestation to weaning of the offspring on day 21 postpartum. The pups continued drinking the same lead containing water until the postnatal day 30. At the 30th day postpartum, the pups in each lead treated group were divided into four groups. The first group contains six male pups (PN30M). The second, third, and fourth groups contain six female pups (PN30F, PN60a, PN60b), respectively. The six female pups from control group formed the fifth group (PN60c). PN60a continued drinking the same lead-containing water until the postnatal day 60. PN60b were dosed with distilled water instead of lead-containing water from the 30th day to the 60th day postpartum. PN60c began to expose to 5.27 mmol Pb/l from the 30th day to the 60th day postpartum. The rats in PN30M and PN30F were decapitated on the 30th day postartum, whereas PN60a, PN60b, and PN60c were decapitated on the 60th day postpartum. The contents of metabolites of monoamine neurotransmitters: homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyin-doleacetic acid (5-HIAA) in striatum were determined using high performance liquid chromatography with electrochemical detection (HPLC-ECD). There were significant increases in the concentrations of HVA (1.58 ± 0.30 vs. 1.17 ± 0.12 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30M, p < 0.01; and 1.44 ± 0.08 vs. 1.17 ± 0.10 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN60a, p < 0.05) and DOPAC (2.39 ± 0.25, 2.47 ± 0.28, 2.39 ± 0.44 vs. 1.82 ± 0.24 ng/mg wet tissue in three lead treated groups of PN60a, p < 0.05). The significant decreases in the concentration of MHPG (37.33 ± 5.53, 32.02 ± 6.87, 33.31 ± 2.41 vs. 43.85 ± 4.93 ng/mg wet tissue in the 0.58 mmol Pb/l group of PN60a, p < 0.05; in the 1.76 and the 5.27 mmol Pb/l group of PN60a, p < 0.01) and 5-HIAA (0.23 ± 0.04 vs. 0.38 ± 0.05 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30M, p < 0.05; 0.26 ± 0.09 vs. 0.45 ± 0.09 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30F, p < 0.05; 0.31 ± 0.08 vs. 0.44 ± 0.08 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN60a, p < 0.05) were observed. No significant changes in the concentration of monoamine metabolites were observed either in rats of PN60b or PN60c. The results demonstrated the disturbances of monoamine metabolism in the striatum of developmental lead exposed rats. 相似文献