ABSTRACT
Noonan syndrome (NS) is a relatively common genetic condition characterised by short stature, congenital heart defects, and distinctive facial features. NS and other clinically overlapping conditions such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, or Costello syndrome, are caused by mutations in genes encoding proteins of the RAS-MAPKinases pathway. Because of this shared mechanism, these conditions have been collectively termed «RASopathies¼. Despite the recent advances in molecular genetics, nearly 20% of patients still lack a genetic cause, and diagnosis is still made mainly on clinical grounds. NS is a clinically and genetically heterogeneous condition, with variable expressivity and a changing phenotype with age, and affects multiple organs and systems. Therefore, it is essential that physicians involved in the care of these patients are familiarised with their manifestations and the management recommendations, including management of growth and development. Data on growth hormone treatment efficacy are sparse, and show a modest response in height gains, similar to that observed in Turner syndrome. The role of RAS/MAPK hyper-activation in the pathophysiology of this group of disorders offers a unique opportunity for the development of targeted approaches.
Subject(s)
Noonan Syndrome , Diagnosis, Differential , Genetic Markers , Genotype , Humans , Mitogen-Activated Protein Kinases/genetics , Mutation , Noonan Syndrome/diagnosis , Noonan Syndrome/genetics , Noonan Syndrome/physiopathology , Noonan Syndrome/therapy , Phenotype , Proto-Oncogene Proteins p21(ras)/geneticsABSTRACT
El síndrome de Turner (ST) afecta a uno de cada 2000-2500 recién nacidos vivos y tiene una prevalencia de 50 por cada 100 000 mujeres. Las manifestaciones clínicas son variables, dependiendo del tipo de alteración cromosómica y de la edad de presentación. Una de las características más prevalentes y sobresalientes del síndrome es su estatura extremadamente baja. La hormona de crecimiento humana recombinante (rh-GH) se ha usado para aumentar el crecimiento y la estatura final en las niñas que tienen el síndrome de Turner. Para valorar los efectos de la hormona de crecimiento recombinante en las niñas y adolescentes con ST, hemos tomado en cuenta el efecto de la hGH, considerando la velocidad en la talla de crecimiento como un punto importante del estudio observacional retrospectivo. Resultados principales: El uso de rh-GH tiene una relación estadísticamente significativa (p0.049 <0.05), que se asocia con un factor de influencia positiva en relación con la velocidad de crecimiento, como variable principal. Al comparar a las pacientes que recibieron la hormona de crecimiento con las que no la recibieron, en las primeras existe la tendencia a acercarse a la curva del percentil 10 en comparación con la de aquellas que no recibieron la rh-GH, que estuvieron más lejos de la curva.
Turner syndrome (TS) affects about one in 1500 to 2500 live-born females. One of the most prevalent and salient features of the syndrome is extremely short stature. Recombinant human growth hormone (rh-GH) has been used to increase growth and final height in girls who have Turner syndrome. To assess the effects of recombinant growth hormone in children and adolescents with TS we have evaluated the effect of HGH considering growth rate as an important point through a retrospective observational study. Main results: The use of rh-GH has a statistically significant relationship (p0.049 <0.05) that is associated with an influencing factor in favor of the use of rh-GH in relation to the variable growth rate. When comparing the patients who received growth hormone with those who did not receive, there is the tendency to arrive closer to the 10th percentile curve compared to the curve of the patients who did not receive rh-GH, which is further away.
Subject(s)
Humans , Female , Child , Adolescent , Turner Syndrome , Growth Hormone , Growth , Women , Body Height , ChromosomesABSTRACT
La baja talla en la infancia es una causa frecuente de derivación al endocrinólogo infantil, y corresponde la mayoría de las veces a variantes normales del crecimiento. Inicialmente la terapéutica con hormona de crecimiento humana estaba circunscripta a los niños que presentaban deficiencia de dicha hormona. A partir de la producción de la hormona recombinante humana por ingeniería genética se pudo ampliar su uso a otras patologías.
Short stature in children is a common cause for referral to pediatric endocrinologists, corresponding most times to normal variants of growth. Initially growth hormone therapy was circumscribed to children presenting growth hormone deficiency. Since the production of recombinant human hormone its use had spread to other pathologies.
Subject(s)
Humans , Child , Human Growth Hormone/therapeutic use , Growth Disorders/drug therapy , Turner Syndrome/complications , Turner Syndrome/drug therapy , Practice Guidelines as Topic , Growth Disorders/etiology , Hypopituitarism/complications , Hypopituitarism/drug therapyABSTRACT
Se estudió el efecto del uso de una proteína de alto valor nutricional y su interacción con la hormona de crecimiento recombinante (rbST) sobre la respuesta superovulatoria y la viabilidad embrionaria en ovejas de pelo. Se utilizaron doce ovejas adultas de raza Pelibuey, distribuidas completamente al azar en dos tratamientos. TA : Control. TB : 100 mg de Somatotropina Bovina recombinante (rbST). La sincronización del estro en ambos grupos duró 14 días, utilizando esponjas vaginales impregnadas con 40 mg de FGA, con cambio a los 7 días. La superovulación se realizó con FSH ovina (oFSH) a intervalos de 12 h en dosis decrecientes, iniciando 72 h antes de la retirada de las esponjas. En la primera aplicación se les administró adicionalmente 2 mL de prostaglandina PGF2a las ovejas. La inyección de rbST en el TB se hizo junto con la octava aplicación de oFSH. Todas las ovejas se inseminaron vía intrauterina a las 56 ±1 h de la retirada de las esponjas, con semen refrigerado (10 a la 8 espermatozoides/pajuela). Los embriones se colectaron 5 días después de la inseminación y la viabilidad embrionaria se midió utilizando criterios morfológicos. Se observó un incremento en todas las variables de respuesta evaluadas por efecto de la aplicación de rbST: cuerpos lúteos (89 vs 119), cuerpos lúteos considerados (77 vs 117), embriones recuperados (64 vs 78), embriones viables (35 vs 64) y embriones viables por oveja (5,8 vs 10,6) siendo significativa la tasa de ovulación (86,52 por ciento vs 96,64 por ciento) y la tasa de viabilidad embrionaria (54,69 por ciento vs 82,05 por ciento) (P<0,01), esto probablemente se atribuye a que la rbST altera los componentes del sistema de factores de crecimiento insulínico estimulando la esteroidogénesis folicular. La hormona de crecimiento aplicada antes de la ovulación estimula la maduración de mayor cantidad de folículos e incrementa la cantidad recuperada de embriones y la viabilidadembrionaria.
The objective of this study was measure the effect of using nutritional high quality protein and its interaction with recombinant growth hormone over the ovulatory response and embryo viability in hair ewes. Twelve adult multiparous Pelibuey ewes were used and randomly submitted to two different treatments. In treatment A (TA, Control group), the ewes received a superovulation treatment without the application of recombinant growth hormone (rbST) in treatment B (TB), the ewes received the same superovulation treatment with the addition of 100 mg of recombinant bovine somatotropin (rbST). The induction and synchronization of the estrous cycle was realized by the insertion of vaginal sponges impregnated with 40 mg of FGA during 14 days, with sponge change at the seventh day. To induce the superovulation follicle stimulating ovine hormone (oFSH) was used in decreasing doses levels (every 12 h) starting 72 h before the sponges withdrawal. In the first application 2 mL of prostaglandin PGF2a were additionally applied. The application of 100 mg of rbST was done during the eighth administration of oFSH. The ewes were inseminated 56 ± 1 h after the sponge withdrawal with refrigerated semen (108 sperm/ straw). The embryos were collected 5 days after the insemination and the embryo viability was measured by morphological evaluation. An increase was observed in all the variables evaluated in the rbST group: corporea lutea (89 vs 119), corporea lutea considered (77 vs 117), embryos recovered (64 vs 78), viable embryos (35 vs 64), and viable embryos by ewe (5.8 vs 10.6), with statistical significance, considered ovulation rate (86.52% vs 96.64%) and embryo viability rate (54.69% vs 82.05%) (P<0.01), this is probably due to the effect of rbST over the growing insuline factors that control the follicular esteroidogenesis. The rbST application before the ovulation influence the maturation of higher amount of follicles and increase the quantity and viability of the embryos obtained.
