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According to FDA regulations, a combination drug is not efficacious unless each component contributes to the claimed effects. For a univariate endpoint, this implies that the combination at specific doses must be superior to each of its components at the same doses. More demanding is the property of synergy, in which the effect of the combination must be superior to the effect expected based on those of its components. If it is equal to those effects, it is additive, and if it is inferior, it is antagonistic. We give regions in the combination dose plane where these concepts are well defined. If the effect of the combination is greater than the greatest effect achievable by any of its components it is therapeutically synergistic. A combination can be antagonistic, yet its components can still contribute to the claimed effects. If it is additive, synergistic or therapeutically synergistic, its components must contribute to the claimed effects. We relate these concepts and provide designs and sequential procedures for determining whether a combination is therapeutically synergistic, synergistic, additive, antagonistic and contributing or antagonistic and non-contributing. 相似文献
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Aneta Kaczor Nikoletta Szemerédi Dr. Katarzyna Kucwaj-Brysz Dr. Monika Dąbrowska Dr. Małgorzata Starek Dr. Gniewomir Latacz Dr. Gabriella Spengler Prof. Jadwiga Handzlik 《ChemMedChem》2021,16(15):2386-2401
ABCB1 modulation is an interesting strategy in the search for new anticancer agents that can overcome multidrug resistance (MDR). Hence, 17 new 5-arylideneimidazolones containing an amine moiety, as potential ABCB1 inhibitors, were designed, synthesized, and investigated. The series was tested in both parental (PAR) and multidrug-resistant (MDR) ABCB1-overexpressing T-lymphoma cancer cells using cytotoxicity assays. The ABCB1-modulating activity was examined in rhodamine 123 accumulation tests, followed by Pgp-Glo™ Assay to determine the influence of the most active compounds on ATPase activity. Lipophilic properties were assessed both, in silico and experimentally (RP-TLC). Pharmacophore-based molecular modelling toward ABCB1 modulation was performed. The studies allowed the identification of anticancer agents (p-fluorobenzylidene derivatives) more potent than doxorubicin, with highly selective action on MDR T-lymphoma cells (selectivity index >40). Most of the investigated compounds showed ABCB1-modulating action; in particular, two 5-benzyloxybenzylidene derivatives displayed activity nearly as strong as that of tariquidar. 相似文献
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Jadwiga Wieckowska 《Fuel》1978,57(12):781-784
These studies concern residues of the vacuum petroleum distillation of crude oil, used as binders for briquetting comminuted materials. The residues have been separated into the group components asphaltenes, resins, and oils. Chemical analyses of these components and calculations of some structural parameters by means of the Hazelwood and van Krevelen methods have been carried out on all these materials in order to indicate differences between the residues. The chemical constitutions of the binders examined do not differ basically but there are differences between some physical and rheological properties (viscosity, ductility), electrical properties (specific resistance, dielectric loss factor) and in molar refraction and in the carbon aromaticity (from volatile matter). 相似文献
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Jadwiga Wieckowska 《Fuel》1984,63(2):202-204
These studies concern the carbonization process of residues from vacuum distillation of crude oil. Some explanation aspects of the hypothetic reaction mechanism controlling the carbonization of high molecular weight components of crude oil are developed. On the basis of numerous experimental investigations, the thermal decomposition process can be divided into two stages, the first, from 670 to 790 K, in which the decomposition reactions take place and low and medium weight molecular compounds are emitted and the second stage, from above 790 K to 1000 K, in which cyclization, condensation and aromatization processes take place, and the degree of structural ordering in the solid products increases. 相似文献
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Jadwiga Bucheska 《应用聚合物科学杂志》2001,80(11):1914-1919
Graft copolymerization of acrylic acid onto PA6 yarn was examined in this study. Prior to the grafting process, the fibers were activated with a benzene solution of benzoyl peroxide. Next, the fibers were put into a bath containing acrylic acid, a dispersing agent, and the activator of reaction. The effects of the main process parameters and auxiliary additives on the degree of grafting, quantity of the homopolymer formed during grafting, effectiveness of grafting, extent of conversion, and grafting ratio were determined. Using calculation factors such as the reaction efficiency, the extent of reaction, and the ratio of grafting, the conditions of grafting were found that made possible the reduction or elimination of the by‐product. Also determined were the influence of the degree of grafting on the moisture sorption and the swelling of modified fibers. In addition, the value of apparent activation energy was calculated (49.123 kJ/mol). © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 1914–1919, 2001 相似文献
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Krzysztof Marycz Monika Marędziak Jakub Grzesiak Ryszard Fryczkowski Jadwiga Laska 《Polymer-Plastics Technology and Engineering》2016,55(18):1897-1907
Articular cartilage dysfunctions are major cause of pain and disability and lead to serious health complications. Cell-based therapies are proposed as treatment methods for cartilage regeneration. In this study, we proposed polyurethane/poly(L-lactide-co-D, L-lactide)-based electrospun nonwovens as carriers for the delivery of human adipose-derived stromal stem cells. We found that 6:4 and 8:2 polyurethane/poly(L-lactide-co-D, L-lactide) initially enhance proliferative rate of human adipose-derived stromal stem cells, shorten their population doubling time, promote creation of functional chondrogenic nodules during chondrogenic differentiation, improve the collagen-2-to-collagen-1 protein ratio, and upregulate the expression of collagen-2 and aggrecan genes. 相似文献
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Jadwiga Bucheska 《应用聚合物科学杂志》1996,60(4):519-529
Nuclear magnetic resonance spectroscopy was used to investigate the position of active centers in polyamide fibers subjected to graft copolymerization with poly(acrylic acid), poly(itaconic acid), and poly(2-vinylpyridine) initiated by thermal oxidation in air. As a result, structural changes in polyamide fibers brought about by oxidation and subsequent grafting of the above mentioned polymers were observed. It was estimated that the generation of active centers that initiate the copolymerization take place at the nitrogen atoms of the amide groups in the polyamide chain. This was confirmed by the broadening of the absorption band for the methylone group adjacent to the nitrogen as well as by the absence of a new absorption band for the methine groups, assuming that the generation of active centers and grafting would take place at the carbon atom of the methylene group in position α to the amide group. © 1996 John Wiley & Sons, Inc. 相似文献