RESUMEN
Deletion of glucose transporter gene Slc2a3 (GLUT3) has previously been reported to result in embryonic lethality. Here, we define the exact time point of growth arrest and subsequent death of the embryo. Slc2a3(-/-) morulae and blastocysts developed normally, implanted in vivo, and formed egg-cylinder-stage embryos that appeared normal until day 6.0. At day 6.5, apoptosis was detected in the ectodermal cells of Slc2a3(-/-) embryos resulting in severe disorganization and growth retardation at day 7.5 and complete loss of embryos at day 12.5. GLUT3 was detected in placental cone, in the visceral ectoderm and in the mesoderm of 7.5-day-old wild-type embryos. Our data indicate that GLUT3 is essential for the development of early post-implanted embryos.
Asunto(s)
Implantación del Embrión , Desarrollo Embrionario , Transportador de Glucosa de Tipo 3/metabolismo , Animales , Blastocisto/metabolismo , Embrión de Mamíferos , Femenino , Transportador de Glucosa de Tipo 3/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones NoqueadosAsunto(s)
Trastorno Bipolar/genética , Cromosomas Humanos Par 12/genética , Haplotipos/genética , Polimorfismo de Nucleótido Simple/genética , Triptófano Hidroxilasa/genética , Encéfalo/enzimología , Estudios de Casos y Controles , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Isoenzimas/genéticaRESUMEN
Serotonin (5-HT) is a monoaminergic neurotransmitter involved in various processes in the mammalian nervous system with tryptophan hydroxylase (TPH) as the rate-limiting enzyme in its biosynthesis. Interestingly, there is accumulating evidence that neurotransmitters including 5-HT are directly involved in cleavage divisions and morphogenetic movements during early embryogenesis, even before neurons appear. Clonal cell models will be indispensable for investigating these pre-neuronal actions of neurotransmitter systems. Totipotent embryonic stem (ES) cells represent early embryonic stages, are amenable to genetic manipulations and can be easily induced to differentiate into cells with neuronal and glial properties enabling the recapacitation of neurulation. In this study, we used high-pressure liquid chromatography with fluorometric detection (HPLC-FD) to demonstrate the presence of 5-HT in ES cells. In addition, RNase protection assays and immunohistochemical methods detected TPH mRNA and protein, respectively, confirming the endogeneous production of 5-HT in these cells. Furthermore, TPH protein was detected in mouse zygotes after fertilization. These results indicate that ES cells may be useful for the investigation of neurotransmitters in pre-nervous embryos and their actions during ontogeny.
Asunto(s)
Embrión de Mamíferos/metabolismo , Serotonina/biosíntesis , Células Madre/metabolismo , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Embrión de Mamíferos/citología , Inmunohistoquímica , Ratones , Oocitos/metabolismo , ARN Mensajero/biosíntesis , Transmisión Sináptica/fisiología , Triptófano Hidroxilasa/genéticaRESUMEN
In a randomized, double-blind crossover study, 29 patients with painful diabetic neuropathy received 6 weeks of amitriptyline and 6 weeks of an "active" placebo that mimicked amitriptyline side effects. Amitriptyline was superior to placebo in relieving pain in weeks 3 through 6. Both steady, burning pain and lancinating pains were relieved. Patients able to tolerate higher amitriptyline doses reported greater relief, through the maximum dose of 150 mg nightly. Amitriptyline analgesia was similar in depressed and nondepressed subgroups and was not associated with mood improvement. We conclude that amitriptyline relieves pain in diabetic neuropathy; this effect is independent of mood elevation.
Asunto(s)
Amitriptilina/uso terapéutico , Neuropatías Diabéticas/tratamiento farmacológico , Cuidados Paliativos , Adulto , Anciano , Amitriptilina/efectos adversos , Depresión/tratamiento farmacológico , Neuropatías Diabéticas/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distribución AleatoriaRESUMEN
Six classes of students attending private parochial high schools were matched according to geographic and grade level variables and were randomly assigned as intact groups to view either a film concerning wife abuse or a neutral control film. The experimental film had no significant impact on attitude ratings given for the two most common student-generated situations of abuse: the intoxicated husband and the unfaithful wife. Correlational assessments between demographic variables and attitude ratings revealed that greater suspicion of abuse was associated with higher justifiability ratings for the intoxicated husband situation. Estimations of higher frequencies of spouse abuse were associated with higher justifiability ratings for the unfaithful wife situation. Results are discussed in light of current wife abuse education programs and prevention strategies.