RESUMO
On the basis of pharmacokinetic modeling, this study provides some insights into predicting in vivo plasma progesterone concentrations when using bovine intravaginal inserts for systemic progesterone delivery. More significantly, this contribution is the first attempt to build a simple pharmacokinetic model that links plasma progesterone concentrations with the hormone released from bovine intravaginal inserts. After evaluating three rival pharmacokinetic models and considering some phenomena involved in the intravaginal administration of progesterone, a primary pharmacokinetic model having a good data fitting capability with only two adjustable parameters is proposed to the above mentioned task. Kinetic parameters are given for lactating Holstein dairy cows with two levels of daily milk yields; and non-pregnant, non-lactating Holstein-Friesian cattle. Model predictions indicate the occurrence of a preferential distribution of the intravaginally administered progesterone dose through a first uterine pass effect.
Assuntos
Bovinos/sangue , Sincronização do Estro/métodos , Progesterona/sangue , Progesterona/farmacocinética , Administração Intravaginal , Animais , Indústria de Laticínios , Preparações de Ação Retardada , Feminino , Meia-Vida , Lactação , Modelos Biológicos , Gravidez , Progesterona/administração & dosagemRESUMO
Progesterone pharmacokinetics were analyzed for plasma hormone concentrations ranging from linear to saturated metabolism in lactating Holstein cows with differing daily milk yields. The adequacy of 2-coupled first-order (bi-exponential equation), hyperbolic (Michaelis-Menten equation), and sigmoidal (Hill equation) kinetic models to describe the experimental progesterone pharmacokinetic profiles was examined on a statistical basis. After nonlinear regression and statistical analysis of the data-fitting capability, a simple one-compartment model based on Hill equation proved to be most adequate. This model indicates an enzyme-catalyzed metabolism of progesterone involving cooperative substrate-binding sites, resulting from allosteric effects that yield a sigmoidal saturation rate curve. Kinetic parameters were estimated for 2 groups of lactating Holstein cows with different daily milk yields. We found, for the first time, a remarkable quantitative agreement of the Hill coefficient value with that reported in pharmacokinetic studies involving cytochrome P450, family 3, subfamily A (CYP3A)-mediated reactions in other mammals, humans included. It seems that positive cooperativity makes enzymes much more sensitive to plasma progesterone concentration, and their activities can undergo significant changes in a narrow range of concentration as characteristic of sigmoidal behavior. Therefore, the values of classical pharmacokinetic parameters, such as the elimination constant, half-life, and clearance rate, were found to be highly dependent on the plasma progesterone concentration.
Assuntos
Bovinos/metabolismo , Lactação/fisiologia , Progesterona/farmacocinética , Progestinas/farmacocinética , Animais , Indústria de Laticínios , Feminino , Meia-Vida , Taxa de Depuração Metabólica , Leite/metabolismo , Modelos Biológicos , Progesterona/sangue , Análise de RegressãoRESUMO
Detection of genetic variability in Cercospora kikuchii isolates from a single soybean field. Current knowledge about epidemiology and population structure of Cercospora kikuchii is little developed and no studies regarding this subject have been reported in Argentina. The aim of this work was to select primers to study genetic variability in C. kikuchii isolated from the same soybean field using RAPD (Random Amplified Polymorphism DNA). RAPD was applied to the DNA of 5 C. kikuchii, isolated from diseased tissue of the soybean in the same field, another isolate, from a strain collection. Out of seven primers, five of them proved to be useful to study the population of C. kikuchii isolates.
Assuntos
Ascomicetos/genética , Variação Genética , Glycine max/microbiologia , Ascomicetos/isolamento & purificaçãoRESUMO
El conocimiento de la epidemiología y la estructura poblacional de Cercospora kikuchii está poco desarrollado y no se han comunicado estudios al respecto en la Argentina. El objetivo de este trabajo fue seleccionar oligonucleótidos que permitan detectar variabilidad genética en aislamientos de C. kikuchii obtenidos a partir de soja proveniente de un mismo sembradío, mediante la aplicación de RAPD. Se trabajó con 6 aislamientos de C. kikuchii, 5 de ellos se obtuvieron a partir de trozos de tejido enfermo y el restante provenía de una colección de cultivos. De los 7 oligonucleótidos empleados, 5 resultaron útiles para el estudio poblacional de los aislamientos de C. kikuchii.
Current knowledge about epidemiology and population structure of Cercospora kikuchii is little developed and no studies regarding this subject have been reported in Argentina. The aim of this work was to select primers to study genetic variability in C. kikuchii isolated from the same soybean field using RAPD (Random Amplified Polymorphism DNA). RAPD was applied to the DNA of 5 C. kikuchii, isolated from diseased tissue of the soybean in the same field, another isolate, from a strain collection. Out of seven primers, five of them proved to be useful to study the population of C. kikuchii isolates.