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Busca de inibidores da catepsina K em plantas medicinais utilizadas no tratamento de doenças osteoarticulares
(Universidade Federal de São Carlos, 2011-09-26) Silva, James Almada da; Vieira, Paulo Cezar; https://lattes.cnpq.br/8923844563320377; https://lattes.cnpq.br/9465211204304702
Ten herbs used in traditional medicine supported by literature for its effectiveness to osteoarticular diseases were selected to conduct a screening of inhibition activity against the cathepsin K, an important enzyme responsible for cleavage of collagen, the main constituent of extracellular matrix of cartilage and bone. Out of the ten herbs selected (ginger, saffron, camellia, cat s claw, mentrasto , moringa , babaçu , devil s claw, urtica e pequi ), one, gengibre (Z. officinale), should be highlighted by a high inhibitory activity of its extracts and fractions against cathepsin K and due to its ancient use as a therapeutic agent. From the dichloromethane fraction obtained of the crude extract of the rhizome of Z. officinale were isolated and identified 18 compounds (4-gingerol, 6-gingerol, 8-gingerol, 6-shogaol, 8-shogaol, 10-shogaol, 6- paradol, 6-gingerdiol, methyl 6-gingerol, methyl 6-shogaol, diacetoxy-6-gingerdiol, methyl diacetoxy-6-gingerdiol, zingerone, gingerenone A, galanolactone, 3-acetoxy- 5-hydroxy-1,7-bis(4 -hydroxy-3 -methoxyphenyl)-heptane and hexahydrocurcumin). From the hexane fraction and essential oil were identified two monoterpenes and four sesquiterpenes. The most active compounds against cathepsin K were gingerols and shogaols with longer alkyl chain. Optimization of the separation of major compounds (6, 8 and 10-gingerol) and an overload study of C18 column was performed using HPLC, obtained as result dozens to hundreds of milligrams of each gingerol with high purity. Structural modifications of 6-gingerol were carried out and of the seven derivatives obtained 4 presented significant increase in inhibition of cathepsin K. Of all the compounds, three, SSi6, 10-gingerol, 6-shogaol, were selected for later tests: determinating of the mode the inhibition against cathepsin K, inhibition against cathepsin K and inhibition of nitric oxide (NO) production, in cellular culture. The inhibitions determined were: partially noncompetitive, partially uncompetitive and complete uncompetitive for the SSi6, 10-gingerol and 6-shogaol, respectively. Excellent inhibition activity against the cathepsin K, in cellular culture, can be observed for SSi6 and 6-shogaol. In the inhibition assay of NO production, the 6- shogaol was the only compound that appeared as effective.
Método de avaliação ambiental de conceitos de produtos baseado nas estratégias do DFE e no AHP
(Universidade Federal de São Carlos, 2011-09-26) Ruy, Marcelo; Alliprandini, Dário Henrique; https://lattes.cnpq.br/0656240596485093
The objective of the present thesis is to propose and structure a method for environmental evaluation of products concepts based on DfE Strategies and AHP. The focus is on physical products, mainly consumer durable goods and capital goods. The justification for this choice is that sustainability is a big issue today, and in particular: the urgency of approaching environmental problems; its strong relationship with product development; and the need of methods and tools for addressing environmental issues at the initial phases of product design, more specifically methods for environmental evaluation of product concepts, due to its scarcity in the literature. This objective was reached in two stages. Initially, the method was structured in phases, stages and activities arranged in an orderly manner. The method was built from DfE strategies related to the product physical dimensions and expressed by the use and consumption of material resources. DfE Strategies was condensed in evaluation criteria. These criteria was subsequently related to a products environmental typology and further grouped by degree of similarity, forming a hierarchy of environmental criteria to be used with AHP. Thus, we sought to create a method applicable to a wide range of physical products and whose aim is to guide the user, step by step, in the evaluation of the concept that better fulfills DfE criteria, taking the whole life cycle of the product into account. In the second stage, the practical utility potential of the method was assessed by means of interviews and questionnaires with product development practitioners from three companies and with one DfE consultant. As a result, it was concluded that the proposed method constitutes in a contribution to the development of environmental responsible products.