RESUMEN
Certain dog breeds, especially Collies, are observed to exhibit neurotoxicity to avermectin drugs, which are P-glycoprotein (P-gp) substrates. This neurotoxicity is due to an ABCB1 gene mutation (ABCB1-1Δ) that results in non-functional P-gp expression. A developed Abcb1a knock-in/Abcb1b knock-out mouse model expressing the ABCB1-1Δ canine gene was previously reported and mice exhibited sensitivity upon ivermectin administration. Here, model and wild-type mice were administered P-gp substrates doramectin, moxidectin, and digoxin. While knock-in/knock-out mice exhibited ataxia, lethargy and tremor, wild-type mice remained unaffected. In addition, no neurotoxic clinical signs were observed in either mouse type administered domperidone, a P-gp substrate with no reported neurotoxicity in ABCB1-1Δ Collies. Overall, neurotoxic signs displayed by model mice closely paralleled those observed in ivermectin-sensitive Collies. This model can be used to identify toxic P-gp substrates with altered safety in dog populations and may reduce dog use in safety studies that are part of the drug approval process.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/efectos de los fármacos , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Antiinfecciosos/toxicidad , Encéfalo/efectos de los fármacos , Digoxina/toxicidad , Ivermectina/análogos & derivados , Macrólidos/toxicidad , Subfamilia B de Transportador de Casetes de Unión a ATP/fisiología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Animales , Modelos Animales de Enfermedad , Enfermedades de los Perros/inducido químicamente , Enfermedades de los Perros/tratamiento farmacológico , Perros , Domperidona/toxicidad , Femenino , Ivermectina/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutagénesis Insercional/genética , Mutagénesis Insercional/métodosRESUMEN
Plants were obtained from protoplasts of shoot cultures of potato (Solarium tuberosum L. cv. 'Maris Bard') and from in situ calluses upon plants of cv. 'Majestic'. None of the protoplast-derived plants resembled each other in all of ten morphological characteristics scored and only one resembled the parental 'Maris Bard' type. As there were a number of plants regenerated from each of ten protoplast-derived calluses it is concluded that variation arose after protoplast isolation during the cell culture phase. Plants regenerated from in situ calluses of cv. 'Majestic' were quite uniform. Reported cases of variation and uniformity from cultured potato tissues are discussed. It is concluded that the variation is not a consequence of using protoplasts and that the expression or induction of variation is controllable.
RESUMEN
Ten volatile compounds derived from the cephalic glands of the fire beeTrigona (Oxytrigona)mellicolor were bioassayed for possible allomonal activities facilitating nest plundering. Two diketones, (E)-3-heptene-2,5-dione and (E)-3-nonene-2,5-dione, caused the honeybeeApis mellifera to display avoidance behavior and reduced defensive behavior. These diketones are produced in relatively large quantities in fire-bee cephalic glands.