RESUMO
The microencapsulation of recombinant cells is a novel and potentially cost-effective method of heterologous protein delivery. A 'universal' cell line, genetically modified to secrete any desired protein, is immunologically protected from tissue rejection by enclosure in microcapsules. The microcapsule can then be implanted in different recipients to deliver recombinant proteins in vivo.
Assuntos
Transplante de Células/métodos , Portadores de Fármacos , Proteínas Recombinantes/administração & dosagem , Animais , Materiais Biocompatíveis , Encéfalo/efeitos dos fármacos , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Nanismo/terapia , Previsões , Humanos , Falência Hepática/terapia , Doenças por Armazenamento dos Lisossomos/terapia , Insuficiência Renal/terapiaRESUMO
Two techniques are commonly used to measure antipsychotic induced dopamine D(2) occupancy in animals: competition with a reversible radioligand (3H-raclopride) or with an irreversible receptor inactivator (EEDQ). While both of these techniques have been used in the past, there is no direct and systematic comparison. In the first direct comparison of these two methods we find that the dose of haloperidol required for blocking 50% of the dopamine D(2) receptors was 0.02 mg/kg/sc (95% CI 0.018-0.022 mg/kg) as measured using 3H-raclopride method; but was significantly higher with the EEDQ method 0.14 mg/kg/s.c. (95% CI 0.048-0.224 mg/kg). The 3H-raclopride method showed significantly lesser variance (p = 0.02) despite the higher sensitivity. This seven-fold difference in the sensitivity of the two techniques to measure antipsychotic-induced D(2) occupancy explains discrepancies in the previous studies which have used these two methods and also suggest that for future studies the 3H-raclopride method is a more sensitive and, likely, a more valid reflector of true receptor occupancy.
Assuntos
Antagonistas de Dopamina/farmacologia , Haloperidol/farmacologia , Quinolinas/farmacologia , Racloprida/farmacologia , Receptores de Dopamina D2/efeitos dos fármacos , Animais , Cinética , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
1. Canine models of human neurodegenerative disorders are uncommon. However, the similarity between canines and humans in body sizes and physiology provides an exceptional opportunity to use these models to study human diseases. 2. The authors will present a review on the neurological deficits that have been observed in canine models of genetic neurodegenerative diseases, and summarize the current gene therapy treatments being developed for some of these conditions.