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1.
Charlotte Schou Erik R. Ottosen Hans Jørgen Petersen Fredrik Björkling Scilla Latini Pernille V. Hjarnaa Erik Bramm Lise Binderup 《Bioorganic & medicinal chemistry letters》1997,7(24):616-3100
4-Pyridyl cyanoguanidines with hydrophobic aromatic side chains showed potent antiproliferative activity in the human breast and lung cancer cell lines MCF-7, NYH and H460. In vivo, treatment with N-(6-chlorophenoxyhexyl)-N′-cyano-N″-4-pyridylguanidine (18, 20 mg/kg/day po.), gave a complete remission of tumours in a model of NYH inoculated nude mice. 相似文献
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Raquel Bridi Alexandra Latini César A. Braum Giovanni K. Zorzi Moacir Wajner Eduardo Lissi 《Free radical research》2013,47(1):71-79
Maple syrup urine disease (MSUD) is a metabolic disorder caused by the deficiency of the activity of the mitochondrial enzyme complex branched-chain l-2-keto acid dehydrogenase. The metabolic block results in tissue and body fluid accumulation of the branched-chain amino acids leucine (Leu), isoleucine and valine, as well as of their respective α-keto acids. Neurological sequelae are usually present in MSUD, but the pathophysiologic mechanisms of neurotoxicity are still poorly known. It was previously demonstrated that Leu elicits oxidative stress in rat brain. In the present study we investigated the possible mechanisms involved in Leu-induced oxidative damage. We observed a significant attenuation of Leu-elicited increase of thiobarbituric acid-reactive substances (TBA-RS) measurement when cortical homogenates were incubated in the presence of the free radical scavengers ascorbic acid plus trolox, dithiothreitol, glutathione, and superoxide dismutase, suggesting a probable involvement of superoxide and hydroxyl radicals in this effect. In contrast, the use of Nω-nitro-l-arginine methyl ester or catalase (CAT) did not affect TBA-RS values. We also demonstrated an inhibitory effect of Leu on the activities of the antioxidant enzymes CAT and gluthathione peroxidase, as well as a significant reduction in the membrane-protein thiol content from mitochondrial enriched preparations. Furthermore, dichlorofluorescein levels were increased although not significantly by Leu. Taken together, our present data indicate that an unbalance between free radical formation and inhibition of critical enzyme activities may explain the mechanisms involved in the Leu-induced oxidative damage. 相似文献
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Laura Brunelli Giuseppe Ristagno Renzo Bagnati Francesca Fumagalli Roberto Latini Roberto Fanelli Roberta Pastorelli 《Metabolomics : Official journal of the Metabolomic Society》2013,9(4):839-852
The mechanisms responsible for post-resuscitation myocardial and cerebral dysfunction are not well understood, especially in the early post-resuscitation phases. In this investigation, we first adopted unbiased mass spectrometry-based metabolomic profiling to identify perturbations in circulating metabolites in a rat model of cardiac arrest and cardiopulmonary resuscitation. Our findings strongly indicated early alterations in a major route of the tryptophan catabolism, namely the kynurenines pathway, after resuscitation. Specific metabolites involved in the tryptophan catabolism were quantified absolutely using liquid chromatography-multiple reaction monitoring-mass spectrometry. Tryptophan plasma concentration fell significantly very early in the post-resuscitation phase, while its metabolites, l-kynurenine, kynurenic acid, 3-hydroxyanthranilic acid and 5-hydroxyindoleacetic acid, rose significantly. Changes in their concentration reflected changes in rat post-resuscitation myocardial dysfunction. Elevated plasma level of kynurenic acid, 3-hydroxyanthranilic acid were associated with significant decrease in ejection fraction and stroke volume. It is well known that kynurenines pathway is involved in the pathogenesis of numerous central nervous system disorders. By implication, altered levels of tryptophan metabolites in the early post resuscitation phase might contribute to the degree of cognitive recovery. Our results suggest that kynurenine pathway is activated early following resuscitation from cardiac arrest and might account for the severity of post-resuscitation syndrome. Our explorative investigation indicate that metabolomics can help to clarify unexplored biochemical pathways in cardiopulmonary resuscitation. 相似文献
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Bridi R Latini A Braum CA Zorzi GK Moacir W Lissi E Dutra-Filho CS 《Free radical research》2005,39(1):71-79
Maple syrup urine disease (MSUD) is a metabolic disorder caused by the deficiency of the activity of the mitochondrial enzyme complex branched-chain L-2-keto acid dehydrogenase. The metabolic block results in tissue and body fluid accumulation of the branched-chain amino acids leucine (Leu), isoleucine and valine, as well as of their respective alpha-keto acids. Neurological sequelae are usually present in MSUD, but the pathophysiologic mechanisms of neurotoxicity are still poorly known. It was previously demonstrated that Leu elicits oxidative stress in rat brain. In the present study we investigated the possible mechanisms involved in Leu-induced oxidative damage. We observed a significant attenuation of Leu-elicited increase of thiobarbituric acid-reactive substances (TBA-RS) measurement when cortical homogenates were incubated in the presence of the free radical scavengers ascorbic acid plus trolox, dithiothreitol, glutathione, and superoxide dismutase, suggesting a probable involvement of superoxide and hydroxyl radicals in this effect. In contrast, the use of Nomega-nitro-L-arginine methyl ester or catalase (CAT) did not affect TBA-RS values. We also demonstrated an inhibitory effect of Leu on the activities of the antioxidant enzymes CAT and gluthathione peroxidase, as well as a significant reduction in the membrane-protein thiol content from mitochondrial enriched preparations. Furthermore, dichlorofluorescein levels were increased although not significantly by Leu. Taken together, our present data indicate that an unbalance between free radical formation and inhibition of critical enzyme activities may explain the mechanisms involved in the Leu-induced oxidative damage. 相似文献
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Binderup E Björkling F Hjarnaa PV Latini S Baltzer B Carlsen M Binderup L 《Bioorganic & medicinal chemistry letters》2005,15(10):2491-2494
To overcome pharmacokinetic and solubility problems observed in early clinical trials with the potent anticancer compound CHS828, we synthesised a series of prodrugs with improved properties. The best compound obtained was EB1627, with a tetraethyleneglycol moiety attached to the parent drug via a carbonate linkage. This compound was found soluble enough to be given i.v. and the drug was rapidly released in vivo exerting a very potent inhibitory activity alone and in combination with known cytostatics (etoposide) in animal models in vivo. 相似文献
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Rotenone calibration of fish density and biomass in a tropical stream sampled by two removal methods
A catch-depletion method was applied using two sampling gears in three sites of a small tributary of the Corumba River (Goiás State, Brazil) in two seasons. The gears were: a double stick net (DSN) in one site and electric fishing (EF) in two sites. The calibration of both gears was performed using rotenone. EF was almost sufficient to establish a complete local species list, but DSN was not. Underestimation of calculated density (N) and biomass (B) values for DSN and EF amounted to 62 and 29%, respectively. The results of N and B obtained by EF were too imprecise to calculate secondary fish production to be applied in a field bioenergetics model. We could not conclusively prove that mean body weight of sampled populations was significantly lower for fish caught by EF, although all of these means were higher for fish collected by rotenone, at each site and on two sampling occasions. 相似文献
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Igor de Paiva Affonso Luiz Carlos Gomes Angelo Antonio Agostinho Hugo José Message João Dirço Latini Emili García-Berthou 《Reviews in Fish Biology and Fisheries》2016,26(1):71-81
Understanding the variation of fish assemblages in reservoirs is crucial for precise interpretations of ecological processes. However, representative samples in such environments are subjected both to spatial zonation (longitudinal and transversal gradients) and limitations of fishing gears. We used a large zoned reservoir (Itaipu, Brazil) to perform a quasi-experiment that assessed the relative role of spatial gradients and fishing methods on fish diversity and composition. Active (cast nets, electrofishing and seines) and passive (gillnets and longlines) fishing gears were employed in lotic, transitional and lentic habitats of the reservoir and three large tributaries. In total 6281 individuals of 101 species were captured. Sampling methods and spatial gradients had an influence on species composition, with significant interactions between these factors. In addition, results produced by a variation partitioning analysis suggested that 21 % of the species richness was explained by the sampling methods and 7 % by the longitudinal gradient; whereas for species composition, 12 and 3 % corresponded to sampling methods and transversal gradients, respectively. Overall, our results suggest that variations among fishing gears is greater than across strong spatial gradients, emphasizing the importance of using multiple and complementary fishing methods in reservoirs for characterization of fish assemblages. The interactions between spatial gradients and sampling methods were higher with transversal than with longitudinal gradients, suggesting that substantial differences in species richness and composition among sampling gears depend to some extent on habitat. The approach used here would be applicable to any large zoned inland waterscape. 相似文献