Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12104/67540
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dc.contributor.authorGalvez-Gastelum, F.J.
dc.contributor.authorGarcia-Bauelos, J.J.
dc.contributor.authorBeas-Zárate, Carlos
dc.contributor.authorSegura-Flores, A.
dc.contributor.authorGonzalez, H.
dc.contributor.authorChaparro-Huerta, V.
dc.contributor.authorSalazar-Montes, A.
dc.contributor.authorSandoval-Rodriguez, A.S.
dc.contributor.authorBueno-Topete, M.
dc.contributor.authorLucano-Landeros, S.
dc.contributor.authorMedina-Preciado, D.
dc.contributor.authorGonzalez-Garcia, I.
dc.contributor.authorArmendariz-Borunda, J.
dc.date.accessioned2015-11-19T18:52:16Z-
dc.date.available2015-11-19T18:52:16Z-
dc.date.issued2011
dc.identifier.urihttp://hdl.handle.net/20.500.12104/67540-
dc.description.abstractCapillarization of the sinusoid impedes the clearance of neurotoxic substances in liver fibrosis. These events may result in hepatic encephalopathy. Neurological and hepatic features of rats after bile duct ligation (BDL) supplemented with Manganese (BDLMn 2+) were examined. The 4-week-old BDL rats had elevated levels of ammonia and were concomitantly fed with 1 mg ml -1 of MnCl -2 in drinking water (BDL/Mn 2+). Five out of fifteen rats were killed and the serum, liver and brain tissue (striatum and substantia nigra) were recovered. Of the remaining BDL/Mn 2+-cirrhotic animals (n10), five were injected with a combination of Adenovirus-human plasminogen activator (Ad-huPA) and Adenovirus-matrix metalloproteinase-8 (Ad-MMP-8) (3 × 10 11+1.5 × 10 11 vector particles per kg), and five with 4.5 × 10 11 vector particles per kg of Adenovirus-Β-galactosidase (Ad-Β-Gal). This treatment was carried on for 10 days. The BDL/Mn 2+ rats displayed tremor, rigidity and gait abnormalities, which improved notably with combinatorial gene therapy, as well as motor coordination. Liver fibrosis was evidently less after treatment with Ad-huPAAd-MMP-8 (25%). In the brain (striatum), Ad-huPAAd-MMP-8 treatment rendered higher concentrations of dopamine compared with Ad-Β-Gal-treated encephalopathic rats (210 and 162 ng g -1 of tissue, respectively). The BDL/Mn 2+ animals and controls treated with Ad-Β-Gal showed abnormal morphology in astrocytes (gliosis) in striatum and substantia nigra, in which expressions of green fibrillar acidic protein and tyrosine hydroxylase were altered. These abnormalities decreased with Ad-huPAAd-MMP-8 treatment. Importantly, the latter animals showed an increment in sprouting of nervous fibers in substantia nigra. Combinatorial gene therapy improves neuroanatomical and neurochemical characteristics similar to human hepatic encephalopathy. © 2011 Macmillan Publishers Limited All rights reserved.
dc.titleCombinatorial gene therapy induces regression of hepatic encephalopathy
dc.typeArticle
dc.identifier.doi10.1038/gt.2010.107
dc.relation.ispartofjournalGene Therapy
dc.relation.ispartofvolume18
dc.relation.ispartofissue1
dc.relation.ispartofpage88
dc.relation.ispartofpage94
dc.subject.keywordfibrosis; metalloprotease; plasminogen
dc.contributor.affiliationGálvez-Gastélum, F.J., Institute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Jalisco, Mexico; Garcia-Bãuelos, J.J., Institute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Jalisco, Mexico; Beas-Zárate, C., Laboratory of Molecular and Cell Neurobiology, CIBO, University of Guadalajara, Mexico; Segura-Flores, A., Institute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Jalisco, Mexico; González, H., Research and Pharmaceutical Development Laboratory, Pharmacology Department, University of Guadalajara, Mexico; Chaparro-Huerta, V., Laboratory of Molecular and Cell Neurobiology, CIBO, University of Guadalajara, Mexico; Salazar-Montes, A., Institute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Jalisco, Mexico; Sandoval-Rodriguez, A.S., Institute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Jalisco, Mexico; Bueno-Topete, M., Institute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Jalisco, Mexico; Lucano-Landeros, S., Institute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Jalisco, Mexico; Medina-Preciado, D., OPD Civil Hospital, Guadalajara, Mexico; Gonzalez-Garcia, I., OPD Civil Hospital, Guadalajara, Mexico; Armendariz-Borunda, J., Institute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Jalisco, Mexico, OPD Civil Hospital, Guadalajara, Mexico
dc.contributor.affiliationBeas-Zárate, Carlos., Universidad de Guadalajara. Centro Universitario de Ciencias de la Salud
dc.subject.headingIndex Medicus;Adenoviridae/ge [Genetics];Adenoviridae/me [Metabolism];Animals;Bile Ducts/me [Metabolism];Genetic Therapy/mt [Methods];Hepatic Encephalopathy/pa [Pathology];Hepatic Encephalopathy/th [Therapy];Humans;Liver/me [Metabolism];Liver/pa [Pathology];Liver Cirrhosis/me [Metabolism];Liver Cirrhosis/th [Therapy];Matrix Metalloproteinase 8/ad [Administration & Dosage];Matrix Metalloproteinase 8/ge [Genetics];Matrix Metalloproteinase 8/me [Metabolism];Plasminogen Activators/ad [Administration & Dosage];Plasminogen Activators/ge [Genetics];Plasminogen Activators/me [Metabolism];Rats;Rats, Inbred Strains;beta-Galactosidase/ge [Genetics];beta-Galactosidase/me [Metabolism]
dc.relation.isReferencedByScopus
dc.relation.isReferencedByWOS
dc.relation.isReferencedByMEDLINE
dc.identifier.urlhttp://www.scopus.com/inward/record.url?eid=2-s2.0-78650970733&partnerID=40&md5=b7b6da470818d8fb7a9606a8bf35cbeb
dc.identifier.urlhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=20703313
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