69 resultados para Multifunctional inhibitors


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Urease inhibitor (UI) and nitrification inhibitor (NI) have the potential to improve N-use efficiency of applied urea and minimize N losses via gaseous emissions of ammonia (NH 3) to the atmosphere and nitrate (NO3-) leaching into surface and ground water bodies. There is a growing interest in the formulations of coating chemical fertilizers with both UI and NI. However, limited information is available on the combined use of UI and NI applied with urea fertilizer. Therefore the aim of this study was to investigate the effects of treating urea with both UI and NI to minimize NH 3 volatilization. Two experiments were set up in volatilization chambers under controlled conditions to examine this process. In the first experiment, UR was treated with the urease inhibitor NBPT [N-(n-butyl) thiophosphoric acid triamide] at a rate of 1060 mg kg -1 urea and/or with the nitrification inhibitor DCD (dicyandiamide) at rates equivalent to 5 or 10% of the urea N. A randomized experimental design with five treatments and five replicates was used: 1) UR, 2) UR + NBPT, 3) UR + DCD 10%, 4) UR + NBPT + DCD 5%, and 5) UR + NBPT + DCD 10%. The fertilizer treatments were applied to the surface of an acidic Red Latosol soil moistened to 60% of the maximum water retention and placed inside volatilization chambers. Controls chambers were added to allow for NH 3 volatilized from unfertilized soil or contained in the air that swept over the soil surface. The second experiment had an additional treatment with surface-applied DCD. The chambers were glass vessels (1.5 L) fit with air inlet and outlet tubings to allow air to pass over the soil. Ammonia volatilized was swept and carried to a flask containing a boric acid solution to trap the gas and then measured daily by titration with a standardized H 2SO 4 solution. Continuous measurements were recorded for 19 and 23 days for the first and second experiment, respectively. The soil samples were then analyzed for UR-, NH4+-, and NO3--N. Losses of NH 3 by volatilization with unamended UR ranged from 28 to 37% of the applied N, with peak of losses observed the third day after fertilization. NBPT delayed the peak of NH 3 losses due to urease inhibition and reduced NH 3 volatilization between 54 and 78% when compared with untreated UR. Up to 10 days after the fertilizer application, NH 3 losses had not been affected by DCD in the UR or the UR + NBPT treatments; thereafter, NH 3 volatilization tended to decrease, but not when DCD was present. As a consequence, the addition of DCD caused a 5-16% increase in NH 3 volatilization losses of the fertilizer N applied as UR from both the UR and the UR + NBPT treatments. Because the effectiveness of NBPT to inhibit soil urease activity was strong only in the first week, it could be concluded that DCD did not affect the action of NBPT but rather, enhanced volatilization losses by maintaining higher soil NH4+ concentration and pH for a longer time. Depending on the combination of factors influencing NH 3 volatilization, DCD could even offset the beneficial effect of NBPT in reducing NH 3 volatilization losses. © 2012 Elsevier Ltd.

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The cysteine proteinase inhibitor cystatin C inhibited RANKL-stimulated osteoclast formation in mouse bone marrow macrophage cultures, an effect associated with decreased mRNA expression of Acp5, Calcr, Ctsk, Mmp9, Itgb3, and Atp6i, without effect on proliferation or apoptosis. The effects were concentration dependent with half-maximal inhibition at 0.3 μM. Cystatin C also inhibited osteoclast formation when RANKL-stimulated osteoclasts were cultured on bone, leading to decreased formation of resorption pits. RANKL-stimulated cells retained characteristics of phagocytotic macrophages when cotreated with cystatin C. Three other cysteine proteinase inhibitors, cystatin D, Z-RLVG-CHN2 (IC50 0.1 μM), and E-64 (IC 50 3 μM), also inhibited osteoclast formation in RANKL-stimulated macrophages. In addition, cystatin C, Z-RLVG-CHN2, and E-64 inhibited osteoclastic differentiation of RANKL-stimulated CD14+ human monocytes. The effect by cystatin C on differentiation of bone marrow macrophages was exerted at an early stage after RANKL stimulation and was associated with early (4 h) inhibition of c-Fos expression and decreased protein and nuclear translocation of c-Fos. Subsequently, p52, p65, IκBα, and Nfatc1 mRNA were decreased. Cystatin C was internalized in osteoclast progenitors, a process requiring RANKL stimulation. These data show that cystatin C inhibits osteoclast differentiation and formation by interfering intracellularly with signaling pathways downstream RANK. © FASEB.

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Despite the improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has changed very little over the past 30 years. In the present study we tested and compared the in vitro antitumor activities of four different inhibitors of Polo-like kinase 1 (PLK1) (BI 2536, BI 6727, GW843682X, and GSK461364), against 3 bladder carcinoma cell lines RT4, 5637 and T24. The impact on radiosensitivity and drug interactions in simultaneous treatments with cisplatin, methotrexate, and doxorubicin were also investigated. Our results showed that PLK1 inhibition prevented cell proliferation and clonogenicity, causing significant inhibition of invasion of tumor cells, though modest differences were observed between drugs. Moreover, all PLK1 inhibitors induced G2/M arrest, with the subsequent induction of death in all 3 cell lines. Drug interactions studies showed auspicious results for all PLK1 inhibitors when combined with the commonly used cisplatin and methotrexate, though combinations with doxorubicin showed mostly antagonistic effects. Comparably, the four PLK1 inhibitors efficiently sensitized cells to ionizing radiation. Our findings demonstrate that irrespective of the inhibitor used, the pharmacological inhibition of PLK1 constrains bladder cancer growth and dissemination, providing new opportunities for future therapeutic intervention. However, further laboratorial and preclinical tests are still needed to corroborate the usefulness of using them in combination with other commonly used chemotherapeutic drugs. © 2013 Landes Bioscience.

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The filamentous fungus Aspergillus terreus secretes both invertase and beta-glucosidase when grown under submerged fermentation containing rye flour as the carbon source. The aim of this study was to characterize the co-purified fraction, especially the invertase activity. An invertase and a beta-glucosidase were co-purified by two chromatographic steps, and the isolated enzymatic fraction was 139-fold enriched in invertase activity. SDS-PAGE analysis of the co-purified enzymes suggests that the protein fraction with invertase activity was heterodimeric, with subunits of 47 and 27 kDa. Maximal invertase activity, which was determined by response surface methodology, occurred in pH and temperature ranges of 4.0-6.0 and 55-65 A degrees C, respectively. The invertase in co-purified enzymes was stable for 1 h at pH 3.0-10.0 and maintained full activity for up to 1 h at 55 A degrees C when diluted in water. Invertase activity was stimulated by 1 mM concentrations of Mn2+ (161 %), Co2+ (68 %) and Mg2+ (61 %) and was inhibited by Al3+, Ag+, Fe2+ and Fe3+. In addition to sucrose, the co-purified enzymes hydrolyzed cellobiose, inulin and raffinose, and the apparent affinities for sucrose and cellobiose were quite similar (K-M = 22 mM). However, in the presence of Mn2+, the apparent affinity and V-max for sucrose hydrolysis increased approximately 2- and 2.9-fold, respectively, while for cellobiose, a 2.6-fold increase in V-max was observed, but the apparent affinity decreased 5.5-fold. Thus, it is possible to propose an application of this multifunctional extract containing both invertase and beta-glucosidase to degrade plant biomass, thus increasing the concentration of monosaccharides obtained from sucrose and cellobiose.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)