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1.
Nature ; 599(7885): 436-441, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34732894

RESUMEN

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.


Asunto(s)
Desarrollo Infantil/fisiología , Estado Nutricional/fisiología , Pubertad/fisiología , Receptor de Melanocortina Tipo 3/metabolismo , Maduración Sexual/fisiología , Adolescente , Anciano de 80 o más Años , Animales , Niño , Ciclo Estral/genética , Ciclo Estral/fisiología , Femenino , Homocigoto , Humanos , Hipotálamo/citología , Hipotálamo/fisiología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Melanocortinas/metabolismo , Menarquia/genética , Menarquia/fisiología , Ratones , Fenotipo , Pubertad/genética , Receptor de Melanocortina Tipo 3/deficiencia , Receptor de Melanocortina Tipo 3/genética , Maduración Sexual/genética , Factores de Tiempo , Aumento de Peso
2.
Br J Audiol ; 35(4): 259-64, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11694100

RESUMEN

It is not always possible to undertake extensive real-ear measurements, especially in infants and young children. An alternative approach is to estimate the real-ear SPL by use of an acoustic transform function such as the real-ear-to-coupler difference (RECD). This may be used to estimate the real-ear sound pressure level (SPL) obtained from an insert transducer or a hearing instrument. The aim of the present study was to investigate the effects of tympanic membrane perforation on the RECD transform function. Subjects in the study comprised two groups of 12 individuals aged between nine and 65 years. One group of subjects had a tympanic membrane perforation and was recruited to the study before admission for myringoplasty. There was no evidence of middle ear pathology in the remaining subjects who comprised the control group. An RECD transform function for an insert transducer was measured on each subject using the standard clinical protocol on the Audioscan RM500 real-ear measurement system. There was a statistically significant difference between the two groups; mean RECD transform value of the perforation group was 9-12 dB lower than the corresponding value in the control group at audiometric frequencies below 1.5 kHz. This difference is probably due to the perforation acting as a vent and allowing low-frequency acoustic energy to escape into the middle ear cavity. Use of an average RECD transform function to estimate real-ear SPL in subjects with a perforation will overestimate the SPL reaching the tympanic membrane. As a result, the derived real-ear SPL obtained by use of either an insert transducer or a hearing instrument will be overestimated. This has implications for the selection and verification of a hearing instrument. The difference in the mean RECD transform function between the control group and subjects with a tympanic membrane perforation supports the use of individually measured RECD values wherever possible.


Asunto(s)
Trastornos de la Audición/diagnóstico , Trastornos de la Audición/etiología , Perforación de la Membrana Timpánica/complicaciones , Pruebas de Impedancia Acústica/métodos , Estimulación Acústica/instrumentación , Adolescente , Adulto , Anciano , Conducción Ósea/fisiología , Niño , Diseño de Equipo , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Miringoplastia , Perforación de la Membrana Timpánica/cirugía
3.
Med J Aust ; 160(6): 347-51, 1994 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-8133819

RESUMEN

OBJECTIVE: To report a case of hypocalcaemic tetany occurring in a child secondary to two phosphate enemas administered for faecal retention, and review the literature of phosphate enema toxicity in children. CLINICAL FEATURES: A 23-month-old child with a repaired anorectal malformation and associated unilateral renal hypodysplasia presented with hypocalcaemic tetany (minimum serum calcium level, 1.11 mmol/L), hyperphosphataemia (maximum serum phosphate level, 6.06 mmol/L), hypokalaemia (minimum serum potassium level, 1.9 mmol/L) and dehydration 10 hours after the administration of two phosphate enemas for acute on chronic faecal retention. MANAGEMENT AND OUTCOME: Management consisted of parenteral rehydration, potassium supplementation, calcium gluconate, an enterally administered phosphate binder and saline bowel washouts to evacuate the remaining enema. She was discharged on day eight, with normal biochemical parameters and no neurological sequelae. CONCLUSION: The use of phosphate enemas in children under five years of age is associated with significant morbidity due to hyperphosphataemia, hypocalcaemia, hypokalaemia and dehydration. They should not be used in children under two years of age, and should be used only with extreme caution in children aged two to five years, especially in those with underlying bowel or renal dysfunction.


Asunto(s)
Enema/efectos adversos , Hipocalcemia/inducido químicamente , Fosfatos/envenenamiento , Niño , Preescolar , Femenino , Humanos , Soluciones Hipertónicas , Hipocalcemia/complicaciones , Lactante , Tetania/etiología
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