RESUMO
This is the first demonstration of process scale-up of a membrane gradostat reactor for continuous enzyme production using Phanerochaete chrysosporium ME446. The fungus was immobilised by reverse filtration on to externally unskinned, ultrafiltration capillary membranes and then nutrient gradients were induced across the biofilm. A 10-fold scale-up from a single capillary bioreactor to a 2.4 l multi-capillary unit resulted in a 7-fold increase in enzyme productivity with a peak at 209 U l(-1) d(-1). Subsequent scale effects on the spore distribution, continuous manganese peroxidase production profile and biofilm development are discussed.
Assuntos
Reatores Biológicos , Filtração/instrumentação , Peroxidases/biossíntese , Phanerochaete/fisiologia , Phanerochaete/ultraestrutura , Biofilmes/crescimento & desenvolvimento , Técnicas de Cultura de Células/métodos , Células Imobilizadas/enzimologia , Células Imobilizadas/fisiologia , Células Imobilizadas/ultraestrutura , Desenho de Equipamento , Filtração/métodos , Membranas Artificiais , Phanerochaete/enzimologia , Projetos PilotoRESUMO
The relationship between chlorpromazine, six of its metabolites and therapeutic response in chronic schizophrenic patients was investigated in this study. Logistic regression revealed no correlation between therapeutic response and four metabolites viz. Nor1 chlorpromazine, Nor2 chlorpromazine, chlorpromazine-N-oxide and Nor2 chlorpromazine sulfoxide. A good correlation was seen between CPZ (P = 0.036), 7-hydroxychlorpromazine (P = 0.004), chlorpromazine sulfoxide (P = 0.002) and therapeutic response. Good therapeutic response was correlated to high levels of chlorpromazine and its 7-hydroxy metabolite while high levels of the sulfoxide metabolite appeared to have a negative effect on therapeutic response. Poor responders who had high levels of chlorpromazine also had high levels of the sulfoxide metabolite. This suggests that the difference in response may lie in the difference in the metabolism of the drug.