Diabetes hipofisaria en perros sin suprarrenales

La acción diabetógena de la pars distalis de la hipófisis ha sido comprobada en el sapo hipofisoprivo-pancreatoprivo en ausencia de las suprarrenales (Houssay y Biasotti, 1933-36; Houssay y Leloir, 1935). Ha sido obtenida por Houssay y Biasotti (1938) en perros privados primero de la suprarrenal derecha, luego del páncreas dejando sólo 4 g y por fin de la suprarrenal izquierda; en esas condiciones se les mantuvo con extracto corticosuprarrenal, a dosis no diabetógenas, y luego se les inyectó extracto ánterohipofisario pofisario que provocó la hiperglucemia diabética en 3 sobre 4 perros. Para descartar la posible acción sinérgica del extracto córticoadrenal se realizaron los experimentos descritos en este trabajo, los que han permitido demostrar que el extracto ánterohipofisario produce la acción diabetógena en perros sin suprarrenales, ya sea inyectados con desoxicorticosterona, que no es hiperglucemiante, o bien mantenidos en vida con sólo cloruro de sodio. Estos experimentos fueron realizados en 1940-41-42 y no fueron publicados en detalle, aunque han sido mencionadas sus conclusiones (Houssay, 1942).Fil: Houssay, Bernardo A.. Fundación de Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Foglia, Virgilio G.. Fundación de Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Dosne Pasqualini, Christiane. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Fundación de Instituto de Biología y Medicina Experimental; ArgentinaPresentado a la Sociedad Argentina de Biología el 6 de junio de 1946.papelKofax Power v.3.1Fujitsu ScanSnap SV600Trabajos IBYMEUnidad documental simpleBiblioteca Bernardo A. Houssay-0

Understanding the drug exposure-response relationship of bedaquiline to predict efficacy for novel dosing regimens in the treatment of multidrug-resistant tuberculosis

Aims: To externally validate an earlier characterized relationship between bedaquiline exposure and decline in bacterial load in a more difficult-to-treat patient population, and to explore the performances of alternative dosing regimens through simulations. Methods: The bedaquiline exposure-response relationship was validated using time-to-positivity data from 233 newly diagnosed or treatment-experienced patients with drug-resistant tuberculosis from the C209 open-label study. The significance of the exposure-response relationship on the bacterial clearance was compared to a constant drug effect model. Tuberculosis resistance type and the presence and duration of antituberculosis pre-treatment were evaluated as additional covariates. Alternative dosing regimens were simulated for tuberculosis patients with different types of drug resistance. Results: High bedaquiline concentrations were confirmed to be associated with faster bacterial load decline in patients, given that the exposure-effect relationship provided a significantly better fit than the constant drug effect (relative likelihood = 0.0003). The half-life of bacterial clearance was identified to be 22% longer in patients with pre-extensively drug-resistant (pre-XDR) tuberculosis (TB) and 86% longer in patients with extensively drug-resistant (XDR) TB, compared to patients with multidrug-resistant (MDR) TB. Achievement of the same treatment response for (pre-)XDR TB patients as for MDR TB patients would be possible by adjusting the dose and dosing frequency. Furthermore, daily bedaquiline administration as in the ZeNix regimen, was predicted to be as effective as the approved regimen. Conclusion: The confirmed bedaquiline exposure-response relationship offers the possibility to predict efficacy under alternative dosing regimens, and provides a useful tool for potential treatment optimization

Configural perception of 6-odorant mixtures in newborn rabbits and human adults

International audienc