{"id":18827,"date":"2002-05-09T00:00:00","date_gmt":"2002-05-09T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/estudio-de-los-mecanismos-de-toxicidad-hepatica-inducida-por-el-tratamiento-con-un-adenovirus-portador-del-gen-de-la-timida%c2%adn-kinasa-del-virus-herpes-simple-y-ganciclovir\/"},"modified":"2002-05-09T00:00:00","modified_gmt":"2002-05-09T00:00:00","slug":"estudio-de-los-mecanismos-de-toxicidad-hepatica-inducida-por-el-tratamiento-con-un-adenovirus-portador-del-gen-de-la-timida%c2%adn-kinasa-del-virus-herpes-simple-y-ganciclovir","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/ciencias-de-la-vida\/estudio-de-los-mecanismos-de-toxicidad-hepatica-inducida-por-el-tratamiento-con-un-adenovirus-portador-del-gen-de-la-timida%c2%adn-kinasa-del-virus-herpes-simple-y-ganciclovir\/","title":{"rendered":"Estudio de los mecanismos de toxicidad hep\u00e1tica inducida por el tratamiento con un adenovirus portador del gen de la timid\u00edn kinasa del virus herpes simple y ganciclovir"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Maite Herra\u00edz Bayod <\/strong><\/h2>\n<p>Una de las estrategias antitumorales basadas en terapia g\u00e9nica desarrollada recientemente, es la que utiliza la timid\u00edn-kinasa del virus herpes-simple (hsv-tk) para convertir el prof\u00e1rmaco ganciclovir en un metabolito t\u00f3xico que resulta letal para la c\u00e9lula. El ganciclovir produce la muerte celular debido a su capacidad para ser incorporado a la mol\u00e9cula de dna e interrumpir su s\u00edntesis en c\u00e9lulas en divisi\u00f3n. En virtude de este mecanismo de acci\u00f3n, no deber\u00eda resultar t\u00f3xico para c\u00e9lulas quiescentes, sin embargo se ha demostrado que el ganciclovir produce da\u00f1o en el h\u00edgado sano.  el objetivo de este trabajo ha sido investigar la repercusi\u00f3n del tratamiento con hsv-tk y ganciclovir en las mitocondr\u00edas del h\u00edgado, estudiando en particular si el tratamiento produce disfunci\u00f3n mitocondrial y da\u00f1o en el dna miticondrial.  se ha podido comprobar que la administraci\u00f3n de ganciclovir a ratas sanas, que previamente hab\u00edan recibido un adenovirus que codifica para hsv-tk, induce da\u00f1o hepatocelular caracterizado por la presencia de metamorfosis grasa microgotular, balonizaci\u00f3n de hepatocitos y cuerpos apopt\u00f3ticos. ultraestructuralmente se confirma la alteraci\u00f3n en la forma y tama\u00f1o de las mitocondrias que presentan crestas aberrantes y una matriz hipodensa. tambi\u00e9n se ha posido demostrar un descenso en la actividad de la enzima citocromo c oxidasa que forma parte de la cadena respiratoria mitocondrial. a esta alteraci\u00f3n podr\u00eda contribuir la disminuci\u00f3n detectada en la expresi\u00f3n de una de las subunidades prot\u00e9ticas codificada por el adn mitocondrial como es la subunidad ii. El an\u00e1lisis de southern blot revel\u00f3 una reducci\u00f3n substancial del contenido total de dna mitocondrial en el h\u00edgado. Utilizando ganciclovir marcado radiactivamente se pudo demostrar la incorporaci\u00f3n de este compuesto tanto en el dna nuclear como mitocondrial de una l\u00ednea celular hep\u00e1tica de rata que hab\u00eda sido transducida previamente con hsv<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Estudio de los mecanismos de toxicidad hep\u00e1tica inducida por el tratamiento con un adenovirus portador del gen de la timid\u00edn kinasa del virus herpes simple y ganciclovir<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Estudio de los mecanismos de toxicidad hep\u00e1tica inducida por el tratamiento con un adenovirus portador del gen de la timid\u00edn kinasa del virus herpes simple y ganciclovir <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Maite Herra\u00edz Bayod <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 05\/09\/2002<\/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>acebo Sangro G\u00f3mez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Jes\u00fas m. Prieto valtue\u00f1a <\/li>\n<li>julio Montoya villarroya (vocal)<\/li>\n<li>Francisco Javier Pardo mind\u00e1n (vocal)<\/li>\n<li>cristina Fillat (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Maite Herra\u00edz Bayod Una de las estrategias antitumorales basadas en terapia g\u00e9nica desarrollada recientemente, es la que [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[212,35,962,2820,17749],"tags":[51612,46347,2940,15059,28639,58180],"class_list":["post-18827","post","type-post","status-publish","format-standard","hentry","category-biologia-humana","category-ciencias-de-la-vida","category-genetica","category-genetica-humana","category-navarra","tag-acebo-sangro-gomez","tag-cristina-fillat","tag-francisco-javier-pardo-mindan","tag-jesus-m-prieto-valtuena","tag-julio-montoya-villarroya","tag-maite-herraiz-bayod"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/18827","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=18827"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/18827\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=18827"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=18827"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=18827"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}