RESUMO
The as/agu rat is a spontaneously occurring mutation which exhibits locomotor abnormalities, reduced tyrosine hydroxylase levels in the substantia nigra and lower extracellular levels of dopamine. The animal could represent a model of some human locomotor disorders. High-potassium medium evoked a 460% rise of dopamine levels in control rats but double this in mutants. Amphetamine increased extracellular dopamine by 710% in controls and 1480% in mutants. Clorgyline produced a small increase of dopamine levels in controls but an 1170% increase in mutants. The uptake inhibitor nomifensine increased dopamine levels by 910% in controls but only 270% in mutants. After treatment with benserazide plus L-DOPA, an acute injection of L-DOPA evoked a release of dopamine which was twice as large in the as/agu rats compared with controls. The results show reduced extracellular dopamine in as/agu rats when the locomotor disorder is apparent, but there has been little loss of tyrosine hydroxylase. The responses to drugs are qualitatively different from those obtained using 6-hydroxydopamine.Overall, the effects of compounds affecting aminergic neurons suggest that one possible mechanism for the neuronal abnormality in as/agu rats is a defective regulation of dopamine release from striatal terminals.
Assuntos
Corpo Estriado/metabolismo , Dopamina/metabolismo , Espaço Extracelular/metabolismo , Transtornos dos Movimentos/genética , Transtornos dos Movimentos/metabolismo , Anfetamina/farmacologia , Animais , Clorgilina/farmacologia , Corpo Estriado/efeitos dos fármacos , Dopaminérgicos/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Levodopa/farmacologia , Masculino , Camundongos , Camundongos Mutantes/genética , Inibidores da Monoaminoxidase/farmacologia , Nomifensina/farmacologia , Potássio/farmacologia , Valores de ReferênciaRESUMO
The AS/AGU rat provides an alternative to experimentally produced laboratory models of basal ganglia disorders. This mutant is characterised by disturbances of movement including clumsy gait, whole body tremor, rigidity and difficulty in initiating movement. From an early age, there is a profound depletion of extracellular dopamine in the dorsal caudate-putamen as measured via in vivo microdialysis; levels are only 10-20% of those found in the parent Albino Swiss (AS) strain. Subsequently a depletion of whole tissue dopamine levels occurs and, later still, loss of dopaminergic cells in the substantia nigra pars compacta. The dysfunction in movement and the nigrostriatal dopaminergic system are clearly linked, since movement can be ameliorated by L-DOPA administration. Furthermore, there are depletions in glucose utilisation in several regions of the basal ganglia circuitry, including the substantia nigra pars compacta, the subthalamic nucleus and the ventrolateral thalamus. The AS/AGU rat represents a unique opportunity to investigate the intrinsic factors controlling the integrity of dopaminergic systems and the recent successful positional cloning of the agu gene will allow the molecular mechanisms underlying this interesting phenotype to be analysed.
Assuntos
Doenças dos Gânglios da Base/genética , Modelos Animais de Doenças , Ratos Mutantes , Animais , Doenças dos Gânglios da Base/tratamento farmacológico , Doenças dos Gânglios da Base/metabolismo , Dopamina/metabolismo , Genes Recessivos , Levodopa/uso terapêutico , RatosAssuntos
Antiparkinsonianos/farmacologia , Transplante de Tecido Encefálico/fisiologia , Transplante de Tecido Fetal/fisiologia , Levodopa/farmacologia , Locomoção/fisiologia , Mesencéfalo/transplante , Transtornos dos Movimentos/genética , Fatores Etários , Animais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiopatologia , Locomoção/efeitos dos fármacos , Transtornos dos Movimentos/fisiopatologia , Ratos , Ratos MutantesRESUMO
The AS/AGU rat is a mutant derived from the Albino Swiss (AS) strain. It is characterized by an ungainly, staggering gait, hind limb rigidity, whole body tremor and, in older animals, difficulty in initiating movement. As and AS/AGU males aged three, six and nine months (n=6 per group) were used to estimate the levels of dopamine and its metabolites in the extracellular fluid of the caudate-putamen. The results indicate a profound loss of dopamine in the extracellular fluid at all age points examined, together with an increase in the concentration of the metabolite 3,4-dihydroxyphenylacetic acid. It is suggested that these changes reflect a defect of dopaminergic neuron function which may underlie the motor disorder seen in these animals.
Assuntos
Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Corpo Estriado/química , Dopamina/metabolismo , Espaço Extracelular/metabolismo , Microdiálise , Animais , Dopamina/deficiência , Masculino , Modelos Neurológicos , Transtornos dos Movimentos/genética , Transtornos dos Movimentos/metabolismo , Mutação , Ratos , Ratos MutantesRESUMO
In this article, the authors discuss case management automation and the preparation that an organization should be making to install such a system successfully. They begin with a discussion of the goals of case management automation, and then review the steps that all facilities with case management programs can undertake to standardize their process, structure their organization, and strategically plan for case management automation. The current status of case management automation efforts also is discussed. The authors conclude by describing the efforts of one organization to develop an integrated case management documentation system.
