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1.
Int J Biol Macromol ; 166: 1149-1161, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-33161078

ABSTRACT

Platelet activity is essential in cardiovascular diseases. Therefore our objective was to evaluate the main effects of activating RAGE in platelets which are still unknown. A search for RAGE expression in different databases showed poor or a nonexistent presence in platelets. We confirmed the expression in platelets and secreted variable of RAGE (sRAGE). Platelets from elderly adults expressed in resting showed 3.2 fold more RAGE from young individuals (p < 0.01) and 3.3 fold with TRAP-6 (p < 0.001). These results could indicate that the expression of RAGE is more inducible in older adults. Then we found that activating RAGE with AGE-BSA-derived from methylglyoxal and subthreshold TRAP-6, showed a considerable increase with respect to the control in platelet aggregation and expression of P-selectin (respectively, p < 0.01). This effect was almost completely blocked by using a specific RAGE inhibitor (FSP-ZM1), confirming that RAGE is important for the function and activation platelet. Finally, we predict the region stimulated by AGE-BSA is located in region V of RAGE and 13 amino acids are critical for its binding. In conclusion, the activation of RAGE affects platelet activation and 13 amino acids are critical for its stimulation, this information is crucial for future possible treatments for CVD.


Subject(s)
Glycation End Products, Advanced/metabolism , Platelet Activation , Receptor for Advanced Glycation End Products/metabolism , Signal Transduction , Adult , Aged , Blood Platelets/metabolism , Computer Simulation , Humans , Serum Albumin, Bovine/metabolism
2.
Bol. Hosp. Viña del Mar ; 72(4): 140-143, 2016.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1397381

ABSTRACT

La hiperplasia suprarrenal congénita (HSC) es un grupo de trastornos genéticos del metabolismo del cortisol. Su forma clásica y más frecuente, incluye una forma perdedora de sal que evoluciona de forma grave con shock hipovolémico en periodo neonatal; y una forma virilizante simple, que en neonatos de sexo femenino puede generar trastornos del desarrollo sexual, antes llamados, genitales ambiguos. En el sexo masculino puede manifestarse sólo como macrogenitosomía, lo que muchas veces retrasa el diagnóstico. Éste se confirma objetivando la elevación de niveles plasmáticos de 17 Hidroxiprogesterona, asociado a niveles elevados de andrógenos adrenales; una vez hecho el diagnóstico, es necesario iniciar terapia de reemplazo esteroidal con hidrocortisona, y si existe déficit de mineralocorticoides, fludrocortisona. Presentamos un paciente preescolar de sexo masculino, con diagnóstico tardío de HSC, correspondiente a la forma virilizante simple y sus consecuencias sobre su estatura.


Congenital adrenal hyperplasia (CAH) includes a wide group of genetic cortisol metabolism disorders. The most frequent form, the classic one, may present as a severe salt wasting syndrome, with hypovolemic shock during the neonatal period; or as a simple virilizing form. In girls, this may produce a disorder of sexual development, formerly called, ambigous genitalia. In boys, clinical manifestations can be subtle, with penile enlargement and small testes, which can delay the diagnosis. The elevated serum levels of 17-OH Progesterone, along with elevated adrenal androgens, allow to confirm the diagnosis. Once confirmed, it is imperative to initiate steroid treatment, with Hydrocortisone, and mineralocorticoid if needed. We present a case of simple virilizing CAH in a preeschool male, who had a late diagnosis que comprometió su estatura.

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