{"id":68481,"date":"2008-05-12T00:00:00","date_gmt":"2008-05-12T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/compuestos-gamma-hidroxibutenolidos-como-moduladores-de-la-respuesta-inflamatoria-a-traves-de-la-expresion-de-mpges-1\/"},"modified":"2008-05-12T00:00:00","modified_gmt":"2008-05-12T00:00:00","slug":"compuestos-gamma-hidroxibutenolidos-como-moduladores-de-la-respuesta-inflamatoria-a-traves-de-la-expresion-de-mpges-1","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/quimica\/compuestos-gamma-hidroxibutenolidos-como-moduladores-de-la-respuesta-inflamatoria-a-traves-de-la-expresion-de-mpges-1\/","title":{"rendered":"Compuestos gamma-hidroxibuten\u00f3lidos como moduladores de la respuesta inflamatoria a trav\u00e9s de la expresi\u00f3n de mpges-1"},"content":{"rendered":"<h2>Tesis doctoral de <strong> M\u00aa Dolores Guerrero Masi\u00e1 <\/strong><\/h2>\n<p>La presente tesis recoge el estudio in vitro de la actividad de 21 nuevos derivados de petrosaspongiolida m con estructura gamma-hidroxibuten\u00f3lida en tres dianas del proceso inflamatorio: actividad pla2, producci\u00f3n de pge2, y expresi\u00f3n de cox-2 y mpges-1. Fruto de este estudio se ha seleccionado el an\u00e1logo 4e como el m\u00e1s interesante en virtud de su estrecha ci50:1,8 (0,5-3,8) micromolar y su inhibici\u00f3n selectiva hacia mpges-1 frente a cox-2.  en la segunda parte del estudio se prueba la actividad del derivado 4e en un modelo de analgesia en rat\u00f3n (estiramientos por ac\u00e9tico) y en modelos agudos (bolsa de aire en rat\u00f3n) y cr\u00f3nicos de inflamaci\u00f3n (artritis inducida por col\u00e1geno).   como resultado de estos experimentos se demuestra en t\u00e9rminos generales la selectividad de este an\u00e1logo inhibiendo la expresi\u00f3n de mpges-1, su capacidad analg\u00e9sica y de reducci\u00f3n de la severidad e incidencia de la artritis experimental  inducida. Estudios inmunohistoqu\u00edmicos confirman la inhibici\u00f3n de la expresi\u00f3n de mpges-1 (sin afectar a cox-2) lograda por 4e as\u00ed como una reversi\u00f3n de la degradaci\u00f3n articular, p\u00e9rdida de proteoglicano e infiltraci\u00f3n leucocitaria.  la selectividad de este an\u00e1logo frente a mpges-1, le concede una ventaja terap\u00e9utica potencial, en cuanto a un control de los efectos adversos asociados a los tradicionales inhibidores de cox. Esta hip\u00f3tesis requiere sin embargo ser confirmada con mayor n\u00famero de estudios mecan\u00edsticos y en cultivos primarios a fin de resolver la utilidad real del an\u00e1logo 4e como herramienta farmacol\u00f3gica.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Compuestos gamma-hidroxibuten\u00f3lidos como moduladores de la respuesta inflamatoria a trav\u00e9s de la expresi\u00f3n de mpges-1<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Compuestos gamma-hidroxibuten\u00f3lidos como moduladores de la respuesta inflamatoria a trav\u00e9s de la expresi\u00f3n de mpges-1 <\/li>\n<li><strong>Autor:<\/strong>\u00a0 M\u00aa Dolores Guerrero Masi\u00e1 <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Universitat de val\u00e9ncia (estudi general)<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 05\/12\/2008<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Miguel Pay\u00e1 Peris<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Juan Sastre belloch <\/li>\n<li>beatriz De las heras polo (vocal)<\/li>\n<li>inmaculada Posadas mayo (vocal)<\/li>\n<li>rut Lucas dominguez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de M\u00aa Dolores Guerrero Masi\u00e1 La presente tesis recoge el estudio in vitro de la actividad de 21 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