Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial
Background. Diabetic foot ulcers are one disabling complication of diabetes mellitus. Pirfenidone (PFD) is a potent modulator of extracellular matrix. Modified diallyl disulfide oxide (M-DDO) is an antimicrobial and antiseptic agent. Aim. To evaluate efficacy of topical PFD + M-DDO in a randomized,...
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Wiley
2017-01-01
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Series: | Journal of Diabetes Research |
Online Access: | http://dx.doi.org/10.1155/2017/3159798 |
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author | Luz E. Gasca-Lozano Silvia Lucano-Landeros Héctor Ruiz-Mercado Adriana Salazar-Montes Ana Sandoval-Rodríguez Jesus Garcia-Bañuelos Arturo Santos-Garcia Judith R. Davila-Rodriguez José Navarro-Partida Hiram Bojórquez-Sepúlveda Juan Castañeda-Gomez José Domínguez-Rosales Myriam A. Ruiz-Arcos María Guadalupe Sánchez-Parada Juan Armendariz-Borunda |
author_facet | Luz E. Gasca-Lozano Silvia Lucano-Landeros Héctor Ruiz-Mercado Adriana Salazar-Montes Ana Sandoval-Rodríguez Jesus Garcia-Bañuelos Arturo Santos-Garcia Judith R. Davila-Rodriguez José Navarro-Partida Hiram Bojórquez-Sepúlveda Juan Castañeda-Gomez José Domínguez-Rosales Myriam A. Ruiz-Arcos María Guadalupe Sánchez-Parada Juan Armendariz-Borunda |
author_sort | Luz E. Gasca-Lozano |
collection | DOAJ |
description | Background. Diabetic foot ulcers are one disabling complication of diabetes mellitus. Pirfenidone (PFD) is a potent modulator of extracellular matrix. Modified diallyl disulfide oxide (M-DDO) is an antimicrobial and antiseptic agent. Aim. To evaluate efficacy of topical PFD + M-DDO in a randomized, double-blind trial versus ketanserin in the treatment of noninfected chronic DFU. Methods. Patients received PFD + M-DDO or ketanserin for 6 months. Relative ulcer volume (RUV) was measured every month; biopsies were taken at baseline and months 1 and 2 for histopathology and gene expression analysis for COL-1α, COL-4, KGF, VEGF, ACTA2 (α-SMA), elastin, fibronectin, TGF-β1, TGF-β3, HIF-1α, and HIF-1β. Results. Reduction of median RUV in the PFD + M-DDO group was 62%, 89.8%, and 99.7% at months 1–3 and 100% from months 4 to 6. Ketanserin reduced RUV in 38.4%, 56%, 60.8%, 94%, 94.8%, and 100% from the first to the sixth month, respectively. Healing score improved 4.5 points with PFD + M-DDO and 1.5 points with ketanserin compared to basal value. Histology analysis revealed few inflammatory cells and organized/ordered collagen fiber bundles in PFD + M-DDO. Expression of most genes was increased with PFD + M-DDO; 43.8% of ulcers were resolved using PFD + M-DDO and 23.5% with ketanserin. Conclusion. PFD + M-DDO was more effective than ketanserin in RUV reduction. |
format | Article |
id | doaj-art-52f4e94276d44b019a934d87e7e40784 |
institution | Kabale University |
issn | 2314-6745 2314-6753 |
language | English |
publishDate | 2017-01-01 |
publisher | Wiley |
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series | Journal of Diabetes Research |
spelling | doaj-art-52f4e94276d44b019a934d87e7e407842025-02-03T01:30:56ZengWileyJournal of Diabetes Research2314-67452314-67532017-01-01201710.1155/2017/31597983159798Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled TrialLuz E. Gasca-Lozano0Silvia Lucano-Landeros1Héctor Ruiz-Mercado2Adriana Salazar-Montes3Ana Sandoval-Rodríguez4Jesus Garcia-Bañuelos5Arturo Santos-Garcia6Judith R. Davila-Rodriguez7José Navarro-Partida8Hiram Bojórquez-Sepúlveda9Juan Castañeda-Gomez10José Domínguez-Rosales11Myriam A. Ruiz-Arcos12María Guadalupe Sánchez-Parada13Juan Armendariz-Borunda14Institute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoRegional Hospital Dr. Valentín Gómez Farías ISSSTE, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoTecnologico de Monterrey, Campus Guadalajara, Jalisco, MexicoHospital Civil de Guadalajara, Guadalajara, JAL, MexicoTecnologico de Monterrey, Campus Guadalajara, Jalisco, MexicoHospital Civil de Guadalajara, Guadalajara, JAL, MexicoHospital Civil de Guadalajara, Guadalajara, JAL, MexicoInstitute of Chronic-Degenerative Diseases, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoBackground. Diabetic foot ulcers are one disabling complication of diabetes mellitus. Pirfenidone (PFD) is a potent modulator of extracellular matrix. Modified diallyl disulfide oxide (M-DDO) is an antimicrobial and antiseptic agent. Aim. To evaluate efficacy of topical PFD + M-DDO in a randomized, double-blind trial versus ketanserin in the treatment of noninfected chronic DFU. Methods. Patients received PFD + M-DDO or ketanserin for 6 months. Relative ulcer volume (RUV) was measured every month; biopsies were taken at baseline and months 1 and 2 for histopathology and gene expression analysis for COL-1α, COL-4, KGF, VEGF, ACTA2 (α-SMA), elastin, fibronectin, TGF-β1, TGF-β3, HIF-1α, and HIF-1β. Results. Reduction of median RUV in the PFD + M-DDO group was 62%, 89.8%, and 99.7% at months 1–3 and 100% from months 4 to 6. Ketanserin reduced RUV in 38.4%, 56%, 60.8%, 94%, 94.8%, and 100% from the first to the sixth month, respectively. Healing score improved 4.5 points with PFD + M-DDO and 1.5 points with ketanserin compared to basal value. Histology analysis revealed few inflammatory cells and organized/ordered collagen fiber bundles in PFD + M-DDO. Expression of most genes was increased with PFD + M-DDO; 43.8% of ulcers were resolved using PFD + M-DDO and 23.5% with ketanserin. Conclusion. PFD + M-DDO was more effective than ketanserin in RUV reduction.http://dx.doi.org/10.1155/2017/3159798 |
spellingShingle | Luz E. Gasca-Lozano Silvia Lucano-Landeros Héctor Ruiz-Mercado Adriana Salazar-Montes Ana Sandoval-Rodríguez Jesus Garcia-Bañuelos Arturo Santos-Garcia Judith R. Davila-Rodriguez José Navarro-Partida Hiram Bojórquez-Sepúlveda Juan Castañeda-Gomez José Domínguez-Rosales Myriam A. Ruiz-Arcos María Guadalupe Sánchez-Parada Juan Armendariz-Borunda Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial Journal of Diabetes Research |
title | Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial |
title_full | Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial |
title_fullStr | Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial |
title_full_unstemmed | Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial |
title_short | Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial |
title_sort | pirfenidone accelerates wound healing in chronic diabetic foot ulcers a randomized double blind controlled trial |
url | http://dx.doi.org/10.1155/2017/3159798 |
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