RESUMEN
To evaluate reports of abnormal levels of free amino acids (AA) in patients with amyotrophic lateral sclerosis (ALS), we studied serum, cerebrospinal fluid, and urine AA in 12 patients with ALS and 12 controls matched for age, sex, and severity of disability. ALS patients had statistically significant elevations in serum levels of tyrosine, total aromatic AA, and total basic AA. ALS patients also had statistically significant elevations in cerebrospinal fluid of total basic AA, lysine, essential AA, and leucine. The severity of ALS correlated inversely with acidic AA (glutamate and aspartate) and O-phosphoserine in cerebrospinal fluid. Activity of ALS correlated directly with serum aspartate and cerebrospinal fluid alanine. We conclude that subtle abnormalities of AA levels are present in ALS and that these are not due to age, sex, or disability. The pattern of distribution of AA levels differs from that in hepatic or renal disease and suggests defective membrane transport or poor cellular utilization of basic and essential AA in the central nervous system.
Asunto(s)
Aminoácidos/metabolismo , Esclerosis Amiotrófica Lateral/metabolismo , Adulto , Anciano , Aminoácidos/sangre , Aminoácidos/líquido cefalorraquídeo , Aminoácidos/orina , Esclerosis Amiotrófica Lateral/sangre , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Esclerosis Amiotrófica Lateral/orina , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Infusions of epinephrine or levarterenol bitartrate into a rabbit nerve-muscle preparation decreased the force of the evoked twitch of anterior tibial and gastrocnemius-soleus muscles. The adverse effect of the catecholamines was not directly on skeletal muscle. The alpha-receptor blocking drug phenoxybenzamine hydrochloride prevented the adverse effect of the catecholamines if it was given prior to catecholamine infusions and unmasked a weak augmentation of twitch tension. Taken with the finding of abnormal accumulation of catecholamine in human dystrophic muscles, the production of an experimental myopathy resembling human dystrophy by the monoamine oxidase inhibitor pargyline hydrochloride, and the finding of excessive levels of catecholamines in the tissues and urine of dystrophic animals, these experiments support the hypothesis that catecholamines could play a pathogenetic role in some dystrophic diseases of muscle.
Asunto(s)
Catecolaminas/farmacología , Unión Neuromuscular/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Bungarotoxinas/farmacología , Interacciones Farmacológicas , Estimulación Eléctrica , Epinefrina/farmacología , Miembro Posterior , Masculino , Contracción Muscular/efectos de los fármacos , Unión Neuromuscular/fisiología , Norepinefrina/análogos & derivados , Norepinefrina/farmacología , Fenoxibenzamina/farmacología , Propranolol/farmacología , Conejos , Nervio Ciático/efectos de los fármacos , Nervio Ciático/fisiología , Factores de TiempoRESUMEN
To identify antecedent events contributing to the development of amyotrophic lateral sclerosis, we studied 25 amyotrophic lateral sclerosis patients in whom we tabulated the incidence of factors previously associated with motor neuron disease and compared the incidences with those found in 25 hospitalized patients and 25 normal people. More amyotrophic lateral sclerosis patients reported exposure to lead and mercury, participation in athletics, and consumption of large quantities of milk. Exposure to lead and mercury, athletic participation, and milk ingestion are possible risk factors that may predispose to the development of amyotrophic lateral sclerosis.
