RESUMEN
Both conventional and genetic engineering techniques can significantly improve the performance of animal cell cultures for the large-scale production of pharmaceutical products. In this paper, the effect of such techniques on cell yield and antibody production of two NS0 cell lines is presented. On the one hand, the effect of fed-batch cultivation using dialysis is compared to cultivation without dialysis. Maximum cell density could be increased by a factor of approximately 5-7 by dialysis fed-batch cultivation. On the other hand, suppression of apoptosis in the NS0 cell line 6A1 bcl-2 resulted in a prolonged growth phase and a higher viability and maximum cell density in fed-batch cultivation in contrast to the control cell line 6A1 (100)3. These factors resulted in more product formation (by a factor of approximately 2). Finally, the adaptive model-based OLFO controller, developed as a general tool for cell culture fed-batch processes, was able to control the fed-batch and dialysis fed-batch cultivations of both cell lines.
Asunto(s)
Algoritmos , Reactores Biológicos , Técnicas de Cultivo de Célula/métodos , Diálisis/métodos , Retroalimentación , Modelos Biológicos , Mieloma Múltiple/fisiopatología , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Adaptación Fisiológica , Animales , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/inmunología , Apoptosis , División Celular , Línea Celular Tumoral , Supervivencia Celular , Simulación por Computador , Humanos , Inmunoglobulina G/inmunología , Ratones , Mieloma Múltiple/patología , Ingeniería de Proteínas/métodos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Control de Calidad , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
After i.v. injection of 0.33 mg nicotine/kg the elimination of unchanged nicotine as well as nicotine-N-oxide, cotinine, nornicotine and norcotinine was determined in the urine of pigs dependent on time. In female pigs 16.3% and in male pigs 25.9% of the applied nicotine were recovered in form of the mentioned compounds within 31h. Nicotine elimination essentially stopped in the collecting period 3-8 h. The main decomposition products nicotine-N-oxide and cotinine were eliminated to a significant extent also 8-23 h after application.