RESUMEN
OBJECTIVE: To determine pharmacokinetics of marbofloxacin in water buffalo calves (Bubalus bubalis) after multiple SC administrations and to assess differences in regimen efficacy. ANIMALS: 18 healthy buffalo calves. PROCEDURES: Calves (n = 6 calves/group) were assigned to receive marbofloxacin SC in the neck at 1 of 3 dosages (2 mg/kg, q 24 h for 6 days [regimen 1]; 4 mg/kg, q 48 h for 6 days [regimen 2]; and 4 mg/kg, q 24 h for 3 days [regimen 3]). Serum marbofloxacin concentrations were analyzed. Efficacy predictors were estimated on the basis of minimum inhibitory concentration and mutant prevention concentration reported for Pasteurella multocida and Mannheimia haemolytica. RESULTS: Mean ± SD area under the concentration-time curve was 5.92 ± 0.40 µgâ¢h/mL for regimen 1, which differed significantly from that for regimens 2 (14.26 ± 0.92 µgâ¢h/mL) and 3 (14.17 ± 0.51 µgâ¢h/mL). Mean residence time and mean elimination half-life for regimen 2 (9.93 ± 0.20 hours and 8.77 ± 0.71 hours) both differed significantly from those for regimens 1 (721 ± 0.11 hours and 5.71 ± 0.38 hours) and 3 (759 ± 0.13 hours and 737 ± 1.19 hours). Values obtained from indices for P multocida and M haemolytica had an excessively wide range because of the various degrees of antimicrobial susceptibility (low, medium, and high) of the strains. CONCLUSIONS AND CLINICAL RELEVANCE: Regimen 3 had the most favorable indices, and it would be conducive for owner compliance and require less handling of animals.
Asunto(s)
Antibacterianos/farmacocinética , Búfalos/sangre , Fluoroquinolonas/farmacocinética , Animales , Antibacterianos/administración & dosificación , Antibacterianos/sangre , Área Bajo la Curva , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/sangre , Semivida , Pruebas de Sensibilidad MicrobianaRESUMEN
Clathrin-mediated endocytosis plays an important role in the maintenance of neuronal integrity in the synaptic terminals. Here we studied the effect of anomalous polyglutamine expansion in huntingtin on the interaction of coat proteins with membranes, in areas of mouse brain or in cultured striatal cells. We observed that this anomaly induces a redistribution of AP-2, but not other coat proteins, from the membrane to the cytosol in the striatum, and in the cultured striatal cells. It was also noted that huntingtin associates with AP-2, and that this association decreases due to the mutation in huntingtin. This decreased receptor-mediated endocytosis, measured by the internalization of transferrin in the mutated cells. It was also confirmed that huntingtin mutation made the cells more vulnerable to the action of quinolinic acid, with an increasing degradation of the AP-2 alpha subunits. On the basis of these results, we conclude that abnormal polyglutamine expansion in huntingtin affects clathrin-mediated endocytosis, and may be one of the pathogenic mechanisms of neurodegeneration.
Asunto(s)
Cuerpo Estriado/citología , Endocitosis/genética , Mutación/genética , Proteínas del Tejido Nervioso/genética , Neuronas/fisiología , Proteínas Nucleares/genética , Factor de Transcripción AP-2/metabolismo , Animales , Adhesión Celular/efectos de los fármacos , Adhesión Celular/genética , Membrana Celular/efectos de los fármacos , Membrana Celular/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Células Cultivadas , Clatrina/farmacología , Citosol/efectos de los fármacos , Citosol/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Humanos , Proteína Huntingtina , Inmunoprecipitación , Ratones , Ratones Transgénicos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neuronas/citología , Neuronas/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Unión Proteica/genética , Ácido Quinolínico/farmacología , Estadísticas no Paramétricas , Factores de Tiempo , Transferrina/farmacologíaAsunto(s)
Antibacterianos/farmacocinética , Fluoroquinolonas/farmacocinética , Animales , Animales Recién Nacidos , Antibacterianos/administración & dosificación , Antibacterianos/sangre , Búfalos/sangre , Búfalos/metabolismo , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/sangre , Inyecciones Intramusculares/veterinaria , Inyecciones Intravenosas/veterinaria , Inyecciones Subcutáneas/veterinariaRESUMEN
The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose subcutaneous (SC) administration of 2mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography and the data obtained were subjected to non-compartmental kinetic analysis. Marbofloxacin peak plasma concentration (C(max)=1.77+/-0.24microg/mL) was reached 1.25+/-0.50h (T(max)) after SC administration. The elimination half-life (t(1/2beta)) and area under curve (AUC) were 5.74+/-1.21h and 8.15 vs 2.33microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, it was concluded that a SC dose of 2mg/kg/24h of marbofloxacin could be adequate to treat infections caused by high susceptible bacteria like Escherichia coli or Salmonella spp.