RESUMEN
The aim was to investigate if functional balance performance in patients with Parkinson's disease (PD) was affected by long-term (3 years) treatment with bilateral subthalamic nucleus (STN) high-frequency stimulation. Thirty-five patients were consecutively included, and 28 patients completed the study (mean age 62 years, SD 6.5). The Berg Balance Scale (BBS) was assessed preoperatively and 1 and 3 years postoperatively (with and without anti-PD medication and with the STN stimulation turned OFF or ON). Although the balance performance of patients with PD decreased over time, the functional balance performance was still positively affected by STN stimulation alone 3 years after surgery.
Asunto(s)
Terapia por Estimulación Eléctrica/métodos , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapia , Equilibrio Postural , Desempeño Psicomotor/fisiología , Núcleo Subtalámico/fisiología , Anciano , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Desempeño Psicomotor/efectos de la radiación , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del TratamientoRESUMEN
In vitro studies have been performed to demonstrate and characterize specific binding sites for synthetic GH secretagogues (sGHS) on membranes from pituitary gland and different human brain regions. A binding assay for sGHS was established using a peptidyl sGHS (Tyr-Ala-hexarelin) which had been radioiodinated to high specific activity at the Tyr residue. Specific binding sites for 125I-labelled Tyr-Ala-hexarelin were detected mainly in membranes isolated from pituitary gland and hypothalamus, but they were also present in other brain areas such as choroid plexus, cerebral cortex, hippocampus and medulla oblongata with no sex-related differences. In contrast, negligible binding was found in the thalamus, striatum, substantia nigra, cerebellum and corpus callosum. The binding of 125I-labelled Tyr-Ala-hexarelin to membrane-binding sites is a saturable and reversible process, depending on incubation time and pH of the buffer. Scatchard analysis of the binding revealed a finite number of binding sites in the hypothalamus and pituitary gland with a dissociation constant (Kd) of (1.5 +/- 0.3) x 10(-9) and (2.1 +/- 0.4) x 10(-9) mol/l respectively. Receptor activity is sensitive to trypsin and phospholipase C digestion, suggesting that protein and phospholipids are essential for the binding of 125I-labelled Tyr-Ala-hexarelin. The binding of 125I-labelled Tyr-Ala-hexarelin to pituitary and hypothalamic membranes was displaced in a dose-dependent manner by different unlabelled synthetic peptidyl (Tyr-Ala-hexarelin, GHRP2, hexarelin, GHRP6) and non-peptidyl (MK 0677) sGHS. An inhibition of the specific binding was also observed when binding was performed in the presence of [D-Arg1-D-Phe5-D-Trp7,9-Leu11]-substance P, a substance P antagonist that has been found to inhibit GH release in response to sGHS. In contrast, no competition was observed in the presence of other neuropeptides (GHRH, somatostatin, galanin or Met-enkephalin) which have a known influence on GH release. In conclusion, the present data demonstrate that sGHS have specific receptors in human brain and pituitary gland and reinforce the hypothesis that these compounds could be the synthetic counterpart of an endogenous GH secretagogue involved in the neuroendocrine control of GH secretion and possibly in other central activities.