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151.
Marisa Cabeza Armando Zambrano Ivonne Heuze Erick Carrizales Anay Palacios Tania Segura Norma Valencia Eugene Bratoeff 《Steroids》2009,74(10-11):793-802
The present study is addressed to ascertain the inhibitory effect of several progesterone derivatives having a chlorine substituent at C-6 (12a–12d), 15 with a bromine substituent at C-6 and 14a–14d, without any halogen atom at C-6 all having an ester side chain at C-17 (benzoate ester bearing a Cl, F and a Br atom at C-4 position of the phenyl ring) on the 5α-reductase enzyme activity present in human prostate. In addition, it was also of interest to investigate the pharmacological effect on hamster flank organs diameter size.In order to study the structure–activity relationships of steroids 12a–12d, 14a–14d and 15 we determined the concentration of these steroids that inhibited 50% of the activity of human prostate 5α-reductase enzyme (IC50), as well as the in vivo effect of these compounds in the hamster flank organs diameter size. We also ascertained, the capacity of these steroids to bind to the androgen receptors present in the rat prostate cytosol using labeled mibolerone (MIB) for monitoring the binding to the androgen receptor.The results from this study indicated that compounds 12a–12d (having a chlorine substituent at C-6), 14a–14d (lacking a halogen atom at C-6), 13 and 15 (having a bromine atom at C-6) showed an increased antiandrogenic effect (lower value for the diameter of the flank organs) as compared to the flank organs from testosterone-treated hamsters. On the other hand, the series of compounds containing a chlorine substituent at C-6 compounds (12a–12d) showed a higher antiandrogenic activity as compared to the compounds lacking a halogen atom at C-6 (14a, 14b and 14d). Although compounds 13 and 15 decreased the flank organs diameter size, however, this increase was not statistically significant as compared to that of the commercially available product finasteride. The steroidal derivatives 13, 14a–14d (lacking the chlorine substituent at C-6) and 15 (having a bromine atom at C-6) exhibited a higher 5α-reductase inhibitory activity (lower IC50 values) as compared to the series of compounds 12a–12d having the halogen substituent at C-6.Finasteride reduced the diameter size of the flank organs. The effect of this steroid and compounds 12a–12d, 13, 14a–14d and 15 on hamster flank organs can be explained by the fact that these steroids did not bind to the androgens receptor, which indicates that its mechanism of action is an inhibiting for the 5α-reductase activity. This enzyme is present in the hamster flank organs and was inhibited by the novel steroids in the human prostate homogenates. 相似文献
152.
Concetta Ambrosino Roberta Tarallo Angela Bamundo Danila Cuomo Gianluigi Franci Giovanni Nassa Ornella Paris Maria Ravo Alfonso Giovane Nicola Zambrano Tatiana Lepikhova Olli A. J?nne Marc Baumann Tuula A. Nyman Luigi Cicatiello Alessandro Weisz 《Molecular & cellular proteomics : MCP》2010,9(6):1352-1367
153.
Interactions of Photobleaching and Inorganic Nutrients in Determining Bacterial Growth on Colored Dissolved Organic Carbon 总被引:8,自引:0,他引:8
Abstract Bacteria are key organisms in the processing of dissolved organic carbon (DOC) in aquatic ecosystems. Their growth depends on both organic substrates and inorganic nutrients. The importance of allochthonous DOC, usually highly colored, as bacterial substrate can be modified by photobleaching. In this study, we examined how colored DOC (CDOC) photobleaching, and phosphorus (P) and nitrogen (N) availability, affect bacterial growth. Five experiments were conducted, manipulating nutrients (P and N) and sunlight exposure. In almost every case, nutrient additions had a significant, positive effect on bacterial abundance, production, and growth efficiency. Sunlight exposure (CDOC photobleaching) had a significant, positive effect on bacterial abundance and growth efficiency. We also found a significant, positive interaction between these two factors. Thus, bacterial use of CDOC was accelerated under sunlight exposure and enhanced P and N concentrations. In addition, the accumulation of cells in sunlight treatments was dependent on nutrient availability. More photobleached substrate was converted into bacterial cells in P- and N-enriched treatments. These results suggest nutrient availability may affect the biologically-mediated fate (new biomass vs respiration) of CDOC. 相似文献
154.
Alexander Zambrano 《Bioethics》2016,30(9):689-697
Some philosophers and physicians have argued that alcoholic patients, who are responsible for their liver failure by virtue of alcoholism, ought to be given lower priority for a transplant when donated livers are being allocated to patients in need of a liver transplant. The primary argument for this proposal, known as the Responsibility Argument, is based on the more general idea that patients who require scarce medical resources should be given lower priority for those resources when they are responsible for needing them and when they are competing with patients who need the same resources through no fault of their own. Since alcoholic patients are responsible for needing a new liver and are in direct competition with other patients who need a new liver through no fault of their own, it follows that alcoholic patients ought to be given lower priority for a transplant. In this article, I argue against the Responsibility Argument by suggesting that in order for it to avoid the force of plausible counter examples, it must be revised to say that patients who are responsible for needing a scarce medical resource due to engaging in behavior that is not socially valuable ought to be given lower priority. I'll then argue that allocating organs according to social value is inconsistent or in tension with liberal neutrality on the good life. Thus, if one is committed to liberal neutrality, one ought to reject the Responsibility Argument. 相似文献
155.
156.
Zambrano CA Egaña JT Núñez MT Maccioni RB González-Billault C 《Free radical biology & medicine》2004,36(11):1393-1402
Oxidative stress has been demonstrated to produce modifications in several intracellular proteins that lead to alterations in their activities. Alzheimer's disease is related to an increase of oxidative stress markers, which may be an early event in the progression of the disease and neurofibrillary tangles formation. Abnormal phosphorylation of tau has been implicated in the etiopathogenesis of Alzheimer's disease. By using phospho-specific antibodies, we analyzed the changes in tau phosphorylation patterns after treatment of rat hippocampal and SHSY5Y human neuroblastoma cells with H2O2. We found that tau isoforms were hypophosphorylated at the Tau1 epitope after 2 h in the presence of H2O2. The decrease in the phosphorylation levels of tau protein were prevented by pretreatment with N-acetyl-L-cysteine. These changes were shown to depend on the activity of the cdk5/p35 complex, since a 3-fold increase in substrate phosphorylation and a 2-fold increase for the complex association were observed. Also, a decrease in the amount of inhibitor-2 bound to phosphatase PP1 was found in SHSY5Y cells under oxidative stress conditions. This decrease of inhibitor-2 bound to PP1 is due to an increased phosphorylation of the inhibitor-2 protein, thus leading to increased PP1 activity. Therefore, we propose that oxidative stress-induced activation of cdk5 leads to inhibitor-2 phosphorylation, relieving its inhibitory effect on PP1. 相似文献
157.
158.
Porras JC Zambrano C Echeverri D Fontanilla MR 《Biomédica : revista del Instituto Nacional de Salud》2003,23(4):476-485
Evidence has accumulatd to support the hypothesis that atherosclerosis involves lipid imbalance as well as inflammatory responses mediated by macrophage and foam cells. These findings have been based on animal models. To rationalize animal use and to propose an alternative biological model, a technique was standardized for macrophage-foam cell isolation and culture. The cultures were characterized by non-denaturing polyacrylamide gel electrophoresis (PAGE) of nonspecific esterases and histochemical staining. This method has not been applied previously for the characterization of the non specific esterases from leucocytes. The biological model presented here can be used to study macrophage-foam cell responses related to atherosclerosis. 相似文献
159.
Lamberti A Longo O Del Vecchio P Zambrano N Barone G Russo T Arcari P 《Bioscience, biotechnology, and biochemistry》2005,69(12):2395-2400
Rat brain Fe65 and its truncated forms corresponding to the combined PTB1 and PTB2 domains, as well as to the isolated PTB2 domain, were expressed in Escherichia coli and purified from inclusion bodies by affinity chromatography. The recombinant proteins were refolded and judged functionally active by their ability to interact with native APP. Limited proteolysis of recombinant Fe65 and PTB1-2 with trypsin, chymotrypsin and V8 proteases showed that the most sensitive proteoltytic sites were positioned at the level of the interdomain regions comprised between WW/PTB1 and PTB1/PTB2. Secondary structure of the recombinant proteins, evaluated by CD spectroscopy, showed a different degree of unordered structures, the PTB2 domain being the higher organised region. In addition, intrinsic fluorescence measurements of PTB2, indicated that a conformational transition of the protein can be induced by denaturating agents such as GuHCl. These data provide first evidences on the secondary structural levels of Fe65. 相似文献
160.
Microorganisms growing on surfaces can form biofilms under certain conditions. In this issue of Cell, Ojha et al. (2005) investigate biofilm formation in mycobacteria. They identify new cell-wall components that are required for the formation of architecturally complex mature biofilms in these bacteria and the surprising involvement of a chaperone protein in this process. 相似文献