RESUMEN
BACKGROUND: High levels of cytokines in juvenile idiopathic arthritis (JIA) can alter target cell sensitivity to growth hormone (GH) leading to short stature in adulthood. We hypothesized that the down-regulation of GH receptor (GHR) gene expression could be involved in growth failure of children with JIA. METHODS: In 18 (12 F and 6 M) prepubertal JIA patients and 13 age- and sex-matched healthy children, we evaluated serum growth-promoting factors and inflammatory indexes. We also measured GHR gene expression, by real-time PCR, in lymphocytes of patients and controls. All parameters were evaluated in patients before and after treatment of JIA. RESULTS: The most interesting (p = 0.007) result was the increase in GHR mRNA expression in all JIA patients. Moreover, we observed a significant (p = 0.0156) decrease in IL-6 levels in JIA patients after 2 years of therapy (19.37 ± 41.01) with respect to basal values (90.84 ± 124.71). On the contrary, IGF-I significantly (p = 0.0005) increased to a mean SDS value of 0 (range -1.69 to +1.70 SDS) with respect to values at disease onset (-0.64 SDS). CONCLUSIONS: Our preliminary data suggest that the restoration of both GHR gene expression and IGF-I secretion correlate with inactive disease in JIA children.
Asunto(s)
Artritis Juvenil/metabolismo , Receptores de Somatotropina/metabolismo , Antropometría , Artritis Juvenil/terapia , Estudios de Casos y Controles , Niño , Femenino , Expresión Génica , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Linfocitos/metabolismo , Masculino , Receptores de Somatotropina/sangre , Receptores de Somatotropina/genéticaRESUMEN
Adipose tissue seems to be a pivotal organ in the aging process. We investigated whether healthy aging could have its roots in a sound metabolic condition from the first year of life by evaluating leptin and adiponectin levels in neonates [33 adequate for gestational age (AGA) and 29 small for gestational age (SGA)], 48 centenarians, and 50 healthy elderly subjects. At birth, SGA neonates showed lower leptin levels (SGA 0.88 +/- 0.28; AGA 2.22 +/- 0.91 ng/mL; p < 0.05) and comparable adiponectin levels with respect to AGA. At 1 year, SGA showed increased leptin (SGA 1.74 +/- 0.28; AGA 1.31 +/- 0.19 ng/mL) and slightly reduced adiponectin concentrations (SGA 35.51 +/- 2.53; AGA 38.56 +/- 3.18 microg/mL) than AGA. Centenarians showed lower leptin (centenarians 18.71 +/- 3.78; elderly 34.81 +/- 7.27 ng/mL; p < 0.05) and higher adiponectin levels (centenarians 55.63 +/- 7.7; elderly 33.51 +/- 4.1 microg/mL; p < 0.05) than elderly subjects. Centenarians, like AGA infants during the first year of life, show a favorable adipokine profile, suggesting that the metabolic condition at early age could affect the longevity of an individual.
Asunto(s)
Tejido Adiposo/metabolismo , Anciano de 80 o más Años/fisiología , Envejecimiento/metabolismo , Recién Nacido Pequeño para la Edad Gestacional/metabolismo , Leptina/sangre , Adiponectina/sangre , Anciano , Peso al Nacer/fisiología , Metabolismo Energético/fisiología , Femenino , Humanos , Recién Nacido de Bajo Peso/fisiología , Recién Nacido , MasculinoRESUMEN
We analyzed the ability of the BaF3 cell line bioassay to select patients with biologically inactive GH. We first evaluated the biological response of the Ba/F3-hGHR cells to rhGH additional doses from 10 to 5000 pg/ml. The concentration points corresponding to the linear part of the curve were selected. We then analyzed a group of sera, diluted like the standard, including the entire range of GH concentrations that can be analyzed by bioassay. The serum/standard area below the curve ratio was calculated. Serum GH immunoactivity determined by IMMULITE/GH bioactivity ratios was calculated. Our experimental data showed that GH-bioactivity/GH-immunoactivity ratios below 0.303 are indicative of a bioinactive GH molecule. This bioassay would recognize only extreme cases of GH bioinactivity, and it would not be a useful tool in the search for patients with altered forms of GH.
Asunto(s)
Bioensayo/métodos , Trastornos del Crecimiento/sangre , Hormona de Crecimiento Humana/sangre , Adolescente , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Niño , Preescolar , Femenino , Trastornos del Crecimiento/diagnóstico , Hormona de Crecimiento Humana/inmunología , Hormona de Crecimiento Humana/farmacología , Humanos , Masculino , Ratones , Valor Predictivo de las Pruebas , Proteínas Recombinantes , Valores de Referencia , Reproducibilidad de los ResultadosRESUMEN
Several reports suggest a role of growth hormone (GH) in the regulation of the haematopoietic system, as regards the normal differentiation and function of blood cells. The aim of this study was to evaluate the influence of rhGH therapy on erythropoietin (Epo) and granulocyte-colony stimulating factor (G-CSF) levels in 18 prepubertal short children with idiopathic GH deficiency (GHD) (n = 8) or without GHD (n = 10), during the first year of treatment. In non-GHD children Epo levels significantly decreased and G-CSF levels increased from basal to 12 months of therapy, whereas in GHD children they did not change significantly. Circulating levels of G-CSF are significantly lower in GHD than in non-GHD children. In non-GHD children the number of red blood cells, haemoglobin and haematocrit values significantly increased after 1 year of rhGH treatment. rhGH therapy influences Epo and G-CSF levels in short non-GHD children, while it shows no effects in GHD children.
Asunto(s)
Estatura/efectos de los fármacos , Eritropoyetina/sangre , Factor Estimulante de Colonias de Granulocitos/sangre , Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/uso terapéutico , Adolescente , Desarrollo del Adolescente/efectos de los fármacos , Determinación de la Edad por el Esqueleto , Niño , Desarrollo Infantil/efectos de los fármacos , Eritropoyetina/análisis , Femenino , Trastornos del Crecimiento/sangre , Terapia de Reemplazo de Hormonas , Hormona de Crecimiento Humana/administración & dosificación , Hormona de Crecimiento Humana/farmacología , Humanos , Masculino , Proyectos Piloto , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéuticoRESUMEN
Coeliac disease (CD) is a genetically determined gluten-sensitive enteropathy resulting in nutrient malabsorption, with an increasing incidence world-wide. Clinical presentation in early childhood may include classic malabsorption symptoms, whereas older CD children often present extra-intestinal symptoms including short stature and pubertal delay. A gluten-free diet (GFD) generally leads to a rapid catch-up in growth and to normalization of the pituitary function. The pathogenesis of CD-associated short stature is still unclear. Besides the involvement of the growth hormone (GH)/insulin-like growth factor-I axis, a role for ghrelin was recently proposed. Furthermore, some CD patients do not show catch-up growth during GFD, despite reversion to seronegativity for CD markers including antiendomysial and anti-tissue transglutaminase antibodies. These subjects show GH deficiency and could potentially benefit from recombinant human GH therapy. This review deals with the management of short stature and the evaluation of growth axis function in CD children.