RESUMEN
Aging is associated with an impairment in the GH response to GHRH and to several other stimuli of GH secretion. We evaluated the effect of pyridostigmine (PD) or placebo pretreatment (Protocol A: placebo or 120 mg PD orally at 8 a.m.; Protocol B: placebo or 60 mg PD twice orally at 9 p.m. and 7 a.m.) on GH responsiveness to GHRH (1 micrograms/kg BW bolus i.v. at 9 a.m.) in 15 normal elderly males (65-92 years) and in 14 normal young adults (20-37 years). GH response to GHRH was significantly reduced in elderly subjects compared to young adults (p < 0.05). PD (Protocol A) increased GH release in both elderly and young subjects. In elderly men, PD enhanced GH response to GHRH. The phenomenon was more evident when PD was administered according to Protocol B (p < 0.01). The area under the curve of GH was significantly greater after PD plus GHRH than it was after placebo plus GHRH (p < 0.01). In young adults, PD induced an increase in GH responsiveness to GHRH when administered according to Protocol A (p < 0.05) but not Protocol B. Both GH peak and AUC of GH after PD plus GHRH (Protocols A and B) in elderly subjects were not significantly different from the same parameters found in young subjects after placebo plus GHRH. Our data confirm that pituitary somatotrophin responsiveness to GHRH in man changes with aging. PD restores GH responsiveness to GHRH in elderly subjects. The effect of PD on GH secretion suggests that cholinergic mechanisms may be involved in GH control in normal aging.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Envejecimiento/fisiología , Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona del Crecimiento/metabolismo , Sistema Nervioso Parasimpático/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Bromuro de Piridostigmina/farmacologíaRESUMEN
Recent studies in adults have shown that cholinergic enhancement by pyridostigmine (PD) has a stimulatory effect on growth hormone (GH) response to GH-releasing hormone (GHRH). PD probably reduces somatostatin release from the hypothalamus by increasing the central cholinergic tone. The aim of this study was to evaluate the effect of PD (120 mg orally) or placebo pretreatment on GH responsiveness to GHRH (1 micrograms/kg b.w. i.v.) or placebo in 10 normal elderly males (68-92 years). PD induced a significant increase in GH secretion (GH peak 7.3 +/- 1.8 micrograms/L, mean +/- SEM) over the basal value (0.9 +/- 0.2 micrograms/L; P less than 0.01) and enhanced GH response to GHRH (peak after GHRH: 17.0 +/- 3.8 micrograms/L; after PD plus GHRH: 42.6 +/- 12.2 micrograms/L; P less than 0.05). There was a significant difference in the secretory areas of GH among tests (P less than 0.05). The secretory area was greater after PD plus GHRH (2722 +/- 801 micrograms/L/120 min) than after GHRH (1185 +/- 206 micrograms/L 120 min; P less than 0.01). The effect of PD on GH secretion suggests that cholinergic mechanisms may be involved in GH control in normal aging. During the life-span cholinergic neurons and/or the somatostatin pathways could exert a differential effect on GH control.
Asunto(s)
Envejecimiento/fisiología , Hormona del Crecimiento/metabolismo , Adenohipófisis/metabolismo , Bromuro de Piridostigmina/farmacología , Anciano , Anciano de 80 o más Años , Fibras Colinérgicas/fisiología , Hormona Liberadora de Hormona del Crecimiento/farmacología , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/fisiología , Masculino , Adenohipófisis/efectos de los fármacos , Tasa de Secreción/efectos de los fármacos , Estimulación QuímicaRESUMEN
Sodium vanadate activates "in vitro" insulin receptor autophosphorylation and protein tyrosine kinase in a dose-dependent manner. Insulin receptor protein tyrosine kinase is directly activated also by the anti-insulin receptor beta subunit monoclonal antibody 18-44. We previously demonstrated that the anti-insulin receptor monoclonal antibody MA-10 decreases insulin-stimulated receptor protein tyrosine kinase activity "in vitro", without inhibiting insulin receptor binding. In this report we show that insulin receptor protein tyrosine kinase, activated by sodium vanadate or by monoclonal antibody 18-44, is inhibited by MA-10 antibody. These data suggest that insulin receptor protein tyrosine kinase activity can be either activated and inhibited through mechanisms different from insulin binding.
Asunto(s)
Anticuerpos Monoclonales , Proteínas Tirosina Quinasas/metabolismo , Receptor de Insulina/inmunología , Vanadatos/farmacología , Animales , Activación Enzimática , Humanos , Insulina/metabolismo , Ratones , FosforilaciónRESUMEN
Personal experience with arrythmia in 57 out of 132 cases of myocardial infarct treated over a period of one yr. in a coronary unit. The ECG and biohumoral enzyme pictures gave clear indications of infarct in all 132 cases. The various types of primary stimulus formation or conduction arrhythmia observed in these 57 patients are examined in relation to the site and extent of infarct. The treatment modalities are described. Mortality was less than 10 per cent in the entire series, with 3 per cent deaths due to serious rhythm disturbances. It is concluded that the introduction of coronary units has primarily contributed to the reduction of infarct deaths by their effective treatment of arrhythmia. Earlier admission to such units would lead to further reductions in mortality.