ABSTRACT
A varfarina é um anticoagulante utilizado na prevenção e no tratamento de doenças tromboembólicas, com janela terapêutica estreita e, elevado risco de hemorragias. Nos idosos, a principal indicação para tratamento anticoagulante oral é fibrilação atrial, cuja prevalência aumenta com a idade, atingindo 8% após os 80 anos. O exame utilizado para controle da anticoagulação oral é o tempo de protrombina, através do cálculo da razão normalizada internacional (RNI), visando o ajuste de dose e manutenção da faixa terapêutica (RNI= 2 a 3). Os idosos requerem um monitoramento efetivo devido a fatores inerentes da idade. Embora seja conhecido que os fatores genéticos influenciam na resposta terapêutica à varfarina, na rotina da maioria dos hospitais a farmacogenética ainda não é considerada no ajuste de dose. Visando estabelecer uma conduta terapêutica personalizada, o presente estudo tem como objetivo avaliar a associação entre o polimorfismo rs9934438 do gene VKORC1, que codifica a enzima vitamina K epóxido redutase, e a dose semanal de varfarina necessária para atingir o RNI adequado. Até o momento, foram incluídos 52 pacientes com idade superior a 70 anos, de ambos os sexos e em uso de varfarina. A análise do polimorfismofoi realizada através da PCR em tempo real utilizando os reagentes TaqMan™ Sample-to-SNP™ e o sistema de detecção TaqMan® SNP Genotyping Assay. As análises estatísticas foram realizadas utilizando o pacote SPSS v. 16.0 e nível de significância adotado foi de 5%. Dos 52 pacientes incluídos até o momento, 37 (71%) permaneceram na faixa terapêutica (Time in Therapeutic Range, TTR) em pelo menos 50% do tempo de anticoagulação e, para eles a dose semanal de varfarina variou de 15mg a 62,5mg. Apesar de ser um estudo piloto, a distribuição dos genótipos está em equilíbrio gênico, segundo Hardy-Weinberg (AA=19,2%, AG=34,6%, GG= 46,2%, χ2= 3,34 e p=0,067). Para os idosos com TTR ≥50%, a frequência do alelo A foi significantemente maior entre os pacientes que utilizaram doses menores de varfarina (Exato de Fisher, p=0,005). Adicionalmente, os portadores do genótipo AA necessitaram, em média, de aproximadamente metade da dose para atingir a faixa terapêutica quando comparados aos portadores do genótipo GG, 20,5 versus 36,5 mg/semana, respectivamente (ANOVA, p=0,006/ Pós-teste Bonferroni, p=0,039). Os resultados permitem concluir que portadores de alelo A são mais responsivos ao tratamento com varfarina, sugerindo que o perfil genotípico pode ser de grande valor para o direcionamento da dose terapêutica em idosos. (AU)
Subject(s)
Humans , Warfarin , AgedABSTRACT
The preparation of impregnated active carbons was optimized, in order to use them as catalysts for the deep oxidation of volatile organic compounds on atmospheric emissions. When impregnation is performed on the raw material or after activation, the influence of raw material on the texture and on the catalyst dispersion is already well studied. This paper aims to analyze the influence of raw material when the impregnation step is performed after the carbonization of different carbon precursors, as yet knowledge is very scarce. Olive stones, pinewood sawdust, nut shells, and almond shells were used as raw materials. In order to evaluate the influence of impregnation methodology of CoO, Co(3)O(4), and CrO(3) on the catalyst dispersion in the porous carbon texture, the impregnation step was made after activation and between carbonization and activation. On the first sequence, for all the raw materials, the impregnated oxides must be deposited on the internal surface, blocking part of the initial porous texture. When the impregnation step is conducted after carbonization, metal species act as catalysts during the activation step. The textures developed strongly depend either on the raw material or on the chemical state and distribution of the catalyst in the carbonized material. Olive stones and sawdust carbons stay with a microporous texture with very narrow pores where catalysts are not deposited. In nut shell and almond shell carbons, metal species are dispersed in the largest micropores and in a well-developed mesoporous texture.
ABSTRACT
Impregnated active carbons were prepared to be used as catalysts for complete oxidation, aiming at the reduction of atmospheric emission of volatile organic compounds. Good dispersion of the catalyst is required, as it regulates the conversion efficiency in the pores where pollutants can access to be converted. When impregnation is performed on the raw material or after activation, the influence of impregnated species on the structure and on the catalyst dispersion is already well studied. This paper aims to analyze the influence of impregnated species on the structure and on the catalyst dispersion when the impregnation step is performed after carbonization, as this knowledge is yet very scarce. Olive stones were used as raw material. In order to evaluate the influence of the methodology of impregnation with CoO, Co(3)O(4), and CrO(3), the impregnation step was completed after activation and between carbonization and activation. In the first sequence, the impregnated oxides must be deposited on the internal surface, blocking part of the initial microporous structure. When impregnation is conducted after carbonization, metal species act as catalysts during the activation step. The structure developed strongly depends either on the chemical state of the catalyst or on its distribution in the carbonized material. A well-developed pore structure can appear just where metal species can access, remaining a micropore structure with pores of very small sizes. The better efficiency of Co(3)O(4) as a catalyst of the activation step is conditioned by a worse distribution of the carbonized material, related to the bigger size of its crystals. CrO(3) is the least efficient catalyst for the activation step.
