RESUMEN
The relationship of energy intake, growth rate and serum concentration of somatomedin-A was evaluated in eighteen children with chronic renal insufficiency. Serum concentrations of somatomedin-A were found to be 0.84 micro/ml in normal children and were elevated to 3.06 micro/ml in children with chronic renal insufficiency prior to dialysis (p less than 0.01). Somatomedin-A concentrations increased during chronic hemodialysis to 5.81 micro/ml and decreased to 1.59 micro/ml following successful renal transplantation (p less than 0.01). Serum concentrations of somatomedin-A correlated with residual glomerular filtration rates (r = -0.5), serum creatinine concentration (r = 0.59), and blood urea nitrogen (r = 0.6). Growth rates correlated with energy intake (r = 0.58) and somatomedin-A concentrations (r = 0.4) in the children with chronic renal insufficiency. Both energy intake and somatomedin-A increased significantly after one year of nutritional supplementation. Our findings are consistent with the hypothesis that somatomedin, like other polypeptide hormones, is elevated in uremia and that increased energy intake may affect the growth of children with chronic renal insufficiency by increasing somatomedin levels.
Asunto(s)
Metabolismo Energético , Crecimiento , Fallo Renal Crónico/fisiopatología , Somatomedinas/sangre , Adolescente , Niño , Preescolar , HumanosRESUMEN
In children with chronic renal insufficiency serum levels of somatomedin measured by radioreceptor assay were found to be strikingly elevated and were in the same range as in acromegaly in spite of decreased growth. The serum somatomedin level was inversely correlated with renal function and children on haemodialysis had the highest values. The elevated somatomedin was most likely due to progressive destruction of the kidney, the primary catabolic site for somatomedin and other polypeptides. After successful transplantation the somatomedin values fell to slightly above normal even though growth was still impaired. Using a bioassay based on the mitogenic property of somatomedin, a lower than normal rather than an increased level was found in chronic renal insufficiency suggesting that in uraemia an inhibitor to somatomedin bioactivity was present. It is concluded that the cause of the growth failure in chronic renal insufficiency and after transplantation is not due to a lack of somatomedin, but an inhibitor to its action could be a factor. It would appear that a normal somatomedin may be necessary for normal growth, but it is not sufficient.
Asunto(s)
Trastornos del Crecimiento/etiología , Fallo Renal Crónico/complicaciones , Somatomedinas/sangre , Adolescente , Bioensayo , Niño , Preescolar , Humanos , Lactante , Fallo Renal Crónico/sangre , Pruebas de Función Renal , Trasplante de Riñón , Ensayo de Unión Radioligante , Diálisis Renal , Trasplante HomólogoRESUMEN
Somatomedin (SM) activity was measured by a placental membrane receptor assay using 125I-labeled somatomedin A, as radioligand in serum samples obtained from 33 ovine fetuses, 14 neonatal lambs, 8 pregnant, and 3 postpartum ewes. The mean serum concentration of SM activity in eight adult rams was 2.06 +/- 0.12 U/ml. In fetal sheep, SM activity was detected at 66 days gestation (term 147 days), in the youngest fetus studied. Before 100 days of gestation, SM was lower (P less than 0.001) in fetal sheep (1.08 +/- 0.18 U/ml) than in adult rams. In fetuses between 101 and 125 days, SM rose (P less than 0.001) to 2.64 +/- 0.32 U/ml. In late gestation fetal serum SM fell but during the neonatal period it rose to 3.38 +/- 0.3 U/ml, higher (P less than 0.01) than that in adult rams. Serum SM activity in the pregnant ewe prior to 100 days was 1.01 +/- 0.11 U/ml, increased (P less than 0.05) to 1.75 +/- 0.21 U/ml between 125 days and term, and rose further to 2.56 +/- 0.32 U/ml in the postpartum period. Maternal concentrations of serum SM in late gestation were significantly less than in the fetus. Gel chromatography of fetal, maternal, and neonatal sera indicated that over 90% of SM activity circulated in high-molecular weight form. The rise in SM activity in fetal serum between 100 and 125 days parallels the rise in fetal growth hormone and prolactin concentrations; however, in maternal serum the increase in SM activity is associated with rising maternal chorionic somatomammotropin concentrations.
Asunto(s)
Animales Recién Nacidos/sangre , Sangre Fetal/análisis , Somatomedinas/sangre , Animales , Femenino , Hormona del Crecimiento/sangre , Lactógeno Placentario/sangre , Embarazo , Prolactina/sangre , OvinosRESUMEN
A particulate membrane fraction from human placental membrane was shown to be rich in binding sites not only for insulin but also for somatomedin A. The binding of the 125I-labelled peptide was time and temperature dependent. Degrading activity present in the membrane fraction was negligible at +4 degrees C. The Scatchard plot for insulin binding revealed two types of binding sites with an apparent high affinity constant of 3.8 times 108 M(-1) and with 5.4 times 10(-9) moles of binding sites per mg of membrane protein. The Scatchard analysis of somatomedin A revealed two classes of binding sites with an apparent high affinity constant of 2.7 times 107 M(-1) and with 1.9 times 10(-8) moles of binding sites per mg of membrane protein. In high concentrations insulin interfered with the specific binding sites for somatomedin A and vice versa. In comparison with insulin the somatomedin A preparation was one million times more potent in displacing labelled somatomedin A than in displacing labelled insulin from their respective binding sites. A radioreceptor assay utilizing particulate placental membrane and labelled somatomedin A purified on the membrane enabled the determination of somatomedin in unextracted serum. The mean values of somatomedin A in sera from patients with pituitary dwarfism and acromegaly were 0.57 and 3.2 U/ml, respectively by radioreceptor assay and 0.41 and 1.61 U/ml, respectively by bioassay. Various causes of this discrepancy between the methods are discussed.
Asunto(s)
Insulina/metabolismo , Placenta/metabolismo , Somatomedinas/metabolismo , Acromegalia/sangre , Sitios de Unión , Sangre , Enanismo Hipofisario/sangre , Femenino , Humanos , Métodos , Unión Proteica , Ensayo de Unión Radioligante , Somatomedinas/sangre , Temperatura , Factores de TiempoAsunto(s)
Somatomedinas/análisis , Bioensayo , Células Cultivadas , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Glicosaminoglicanos/biosíntesis , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Somatomedinas/aislamiento & purificación , Somatomedinas/farmacología , Sulfatos/metabolismoAsunto(s)
Somatomedinas , Aminoácidos/análisis , Animales , Bioensayo , Cartílago/efectos de los fármacos , Cartílago/metabolismo , Línea Celular , Pollos , Cromatografía en Gel , Embrión de Mamíferos , Embrión no Mamífero , Femenino , Fibroblastos/efectos de los fármacos , Humanos , Pulmón/efectos de los fármacos , Embarazo , Somatomedinas/aislamiento & purificación , Somatomedinas/farmacologíaAsunto(s)
Somatomedinas/farmacología , Ácidos Aminoisobutíricos/metabolismo , Animales , Transporte Biológico Activo , Peso Corporal , Cartílago/efectos de los fármacos , Cartílago/metabolismo , Pollos , Diafragma/efectos de los fármacos , Diafragma/metabolismo , Femenino , Hormona del Crecimiento/farmacología , Hipofisectomía , Insulina/farmacología , Anticuerpos Insulínicos , Leucina/metabolismo , Metilglucósidos/metabolismo , Proteínas Musculares/biosíntesis , Puromicina/farmacología , Ratas , Sulfatos/metabolismo , Teofilina/farmacología , Tibia/anatomía & histología , Tibia/efectos de los fármacosAsunto(s)
Línea Celular/metabolismo , Péptidos , Somatomedinas , Aminoácidos/análisis , Transporte Biológico , Medios de Cultivo , Disulfuros/análisis , Humanos , Pulmón/embriología , Peso Molecular , Péptidos/sangre , Péptidos/aislamiento & purificación , Somatomedinas/sangre , Somatomedinas/farmacología , Timidina/metabolismoAsunto(s)
Somatomedinas , Somatomedinas/aislamiento & purificación , Aminoácidos/análisis , Animales , Bioensayo , Huesos/efectos de los fármacos , Cartílago/efectos de los fármacos , Cartílago/metabolismo , Embrión de Pollo , Pollos , Humanos , Metionina/metabolismo , Ratas , Somatomedinas/farmacologíaAsunto(s)
Membranas/metabolismo , Proteínas Musculares/biosíntesis , Músculos/metabolismo , Somatomedinas/farmacología , Ácidos Aminoisobutíricos/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Radioisótopos de Carbono , Embrión de Pollo , Cromatografía en Gel , Diafragma/metabolismo , Femenino , Cobayas/inmunología , Humanos , Hipofisectomía , Insulina/inmunología , Insulina/farmacología , Anticuerpos Insulínicos , Leucina/metabolismo , Metilglucósidos/metabolismo , Puromicina/farmacología , Ratas , Somatomedinas/aislamiento & purificación , Sulfatos/metabolismo , Radioisótopos de Azufre , Teofilina/farmacología , TritioRESUMEN
1. A simple method is described for the determination of small amounts of [(35)S]sulphated polysaccharide with 95-100% recovery in the range from 0.3 to 150mug of polysaccharide. 2. The method is based on precipitation with cetylpyridinium chloride of polysaccharide samples applied to filter paper. It is not significantly disturbed by the presence in the sample of a large excess of inorganic (35)SO(4) (2-). 3. Sulphated glucosamino- and galactosaminoglycans may be determined separately by treatment of the sample with chondroitinase ABC. 4. The method is applicable to the assay of [(35)S]sulphated polysaccharide biosynthesis in cell cultures. A stimulation of sulphate incorporation obeying a linear dose-response curve, was demonstrated in somatomedin-incubated fibroblast and glia cell cultures. 5. The described system provides a new assay method for somatomedin. 6. The stimulatory effect of somatomedin on the synthesis of [(35)S]sulphated polysaccharide appeared to be general, rather than specific, for a particular type of polysaccharide.