Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2

Autores
Girón Reyes, Claudio Daniel; Gomez, Fernando Daniel; Amaral, María Marta; Chiappetta, Diego Andrés; Moretton, Marcela Analía; Ibarra, Cristina Adriana; Sacerdoti, Flavia
Año de publicación
2021
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Shiga toxin type 2 (Stx2) is the main virulence factor of Shiga toxinproducing Escherichia coli and is responsible for triggering HemolyticUremic Syndrome (HUS). We aimed to develop and characterizepolymeric nanomicelles (PN) with the amphiphilic polymerSoluplus® coupled to anti-Stx2 IgG in order to introduce innovativeproposals for the detection of Stx2 and treatment of HUS. PN ofSoluplus® were formulated in PBS and coupled with IgG anti Stx2from hyperimmune (PN-IgG-Stx2) or control bovine colostrum (PNIgG-Ctrl). The hydrodynamic size of PN, PN-IgG-Stx2 and PN-IgGCtrlwas evaluated by Dynamic Light Scattering. Morphology of PNor PN-IgG-Stx2 was analyzed by Transmission Electron Microscopy(TEM). The PN toxicity was evaluated on both Vero and Human GlomerularEndothelial cells (HGEC) and cell viability was determinedby neutral red uptake. After coupling PN with IgG, Stx2 neutralizationcapacity of PN-IgG-Stx2 or PN-IgG-Ctrl was evaluated on Vero andHGEC cells and the percentage of cell viability was analyzed. Thehydrodynamic size of the PN of Soluplus® and IgG-Stx2 showed anaverage diameter of 70.2 ± 1.5 nm and 40.9 ± 2 nm, respectively.When both components were coupled, a single peak with a similarhydrodynamic size of the PN was observed (70.4 ± 0.2 nm). TEManalysis revealed circular particles with a diameter corresponding to100 nm either in PN and PN-IgG-Stx2 particles. PN-IgG-Stx2 wereable to neutralize Stx2 on Vero and HGEC cells in a dose dependentmanner. When comparing the neutralization capacity of Stx2 by IgGStx2vs PN-IgG-Stx2 a significant improvement in the cell viabilityof Vero and HGEC was observed with the PN-IgG-Stx2 (p<0.001).The association between anti-Stx2 IgG from bovine colostrum andSoluplus® PN was optimized and characterized. Encouraging resultsof antibody functionality coupled with PN were registered.These results may open the perspective of the design of new nanoplatformsfor neutralization and/or detection of Stx2.
Fil: Girón Reyes, Claudio Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Gomez, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Amaral, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Chiappetta, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Moretton, Marcela Analía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Nanomedicinas
Materia
SHIGA TOXIN
NANOPARTICLES
NEUTRALIZATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/193200
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2Girón Reyes, Claudio DanielGomez, Fernando DanielAmaral, María MartaChiappetta, Diego AndrésMoretton, Marcela AnalíaIbarra, Cristina AdrianaSacerdoti, FlaviaSHIGA TOXINNANOPARTICLESNEUTRALIZATIONhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Shiga toxin type 2 (Stx2) is the main virulence factor of Shiga toxinproducing Escherichia coli and is responsible for triggering HemolyticUremic Syndrome (HUS). We aimed to develop and characterizepolymeric nanomicelles (PN) with the amphiphilic polymerSoluplus® coupled to anti-Stx2 IgG in order to introduce innovativeproposals for the detection of Stx2 and treatment of HUS. PN ofSoluplus® were formulated in PBS and coupled with IgG anti Stx2from hyperimmune (PN-IgG-Stx2) or control bovine colostrum (PNIgG-Ctrl). The hydrodynamic size of PN, PN-IgG-Stx2 and PN-IgGCtrlwas evaluated by Dynamic Light Scattering. Morphology of PNor PN-IgG-Stx2 was analyzed by Transmission Electron Microscopy(TEM). The PN toxicity was evaluated on both Vero and Human GlomerularEndothelial cells (HGEC) and cell viability was determinedby neutral red uptake. After coupling PN with IgG, Stx2 neutralizationcapacity of PN-IgG-Stx2 or PN-IgG-Ctrl was evaluated on Vero andHGEC cells and the percentage of cell viability was analyzed. Thehydrodynamic size of the PN of Soluplus® and IgG-Stx2 showed anaverage diameter of 70.2 ± 1.5 nm and 40.9 ± 2 nm, respectively.When both components were coupled, a single peak with a similarhydrodynamic size of the PN was observed (70.4 ± 0.2 nm). TEManalysis revealed circular particles with a diameter corresponding to100 nm either in PN and PN-IgG-Stx2 particles. PN-IgG-Stx2 wereable to neutralize Stx2 on Vero and HGEC cells in a dose dependentmanner. When comparing the neutralization capacity of Stx2 by IgGStx2vs PN-IgG-Stx2 a significant improvement in the cell viabilityof Vero and HGEC was observed with the PN-IgG-Stx2 (p<0.001).The association between anti-Stx2 IgG from bovine colostrum andSoluplus® PN was optimized and characterized. Encouraging resultsof antibody functionality coupled with PN were registered.These results may open the perspective of the design of new nanoplatformsfor neutralization and/or detection of Stx2.Fil: Girón Reyes, Claudio Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Gomez, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Amaral, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Chiappetta, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Moretton, Marcela Analía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaLXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de NanomedicinasArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de NanomedicinasFundación Revista Medicina2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/193200Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas; Argentina; 2021; 179-179CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://inmunologia.org.ar/reunion-conjunta-2021/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:43Zoai:ri.conicet.gov.ar:11336/193200instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:57:43.509CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2
title Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2
spellingShingle Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2
Girón Reyes, Claudio Daniel
SHIGA TOXIN
NANOPARTICLES
NEUTRALIZATION
title_short Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2
title_full Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2
title_fullStr Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2
title_full_unstemmed Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2
title_sort Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2
dc.creator.none.fl_str_mv Girón Reyes, Claudio Daniel
Gomez, Fernando Daniel
Amaral, María Marta
Chiappetta, Diego Andrés
Moretton, Marcela Analía
Ibarra, Cristina Adriana
Sacerdoti, Flavia
author Girón Reyes, Claudio Daniel
author_facet Girón Reyes, Claudio Daniel
Gomez, Fernando Daniel
Amaral, María Marta
Chiappetta, Diego Andrés
Moretton, Marcela Analía
Ibarra, Cristina Adriana
Sacerdoti, Flavia
author_role author
author2 Gomez, Fernando Daniel
Amaral, María Marta
Chiappetta, Diego Andrés
Moretton, Marcela Analía
Ibarra, Cristina Adriana
Sacerdoti, Flavia
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv SHIGA TOXIN
NANOPARTICLES
NEUTRALIZATION
topic SHIGA TOXIN
NANOPARTICLES
NEUTRALIZATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Shiga toxin type 2 (Stx2) is the main virulence factor of Shiga toxinproducing Escherichia coli and is responsible for triggering HemolyticUremic Syndrome (HUS). We aimed to develop and characterizepolymeric nanomicelles (PN) with the amphiphilic polymerSoluplus® coupled to anti-Stx2 IgG in order to introduce innovativeproposals for the detection of Stx2 and treatment of HUS. PN ofSoluplus® were formulated in PBS and coupled with IgG anti Stx2from hyperimmune (PN-IgG-Stx2) or control bovine colostrum (PNIgG-Ctrl). The hydrodynamic size of PN, PN-IgG-Stx2 and PN-IgGCtrlwas evaluated by Dynamic Light Scattering. Morphology of PNor PN-IgG-Stx2 was analyzed by Transmission Electron Microscopy(TEM). The PN toxicity was evaluated on both Vero and Human GlomerularEndothelial cells (HGEC) and cell viability was determinedby neutral red uptake. After coupling PN with IgG, Stx2 neutralizationcapacity of PN-IgG-Stx2 or PN-IgG-Ctrl was evaluated on Vero andHGEC cells and the percentage of cell viability was analyzed. Thehydrodynamic size of the PN of Soluplus® and IgG-Stx2 showed anaverage diameter of 70.2 ± 1.5 nm and 40.9 ± 2 nm, respectively.When both components were coupled, a single peak with a similarhydrodynamic size of the PN was observed (70.4 ± 0.2 nm). TEManalysis revealed circular particles with a diameter corresponding to100 nm either in PN and PN-IgG-Stx2 particles. PN-IgG-Stx2 wereable to neutralize Stx2 on Vero and HGEC cells in a dose dependentmanner. When comparing the neutralization capacity of Stx2 by IgGStx2vs PN-IgG-Stx2 a significant improvement in the cell viabilityof Vero and HGEC was observed with the PN-IgG-Stx2 (p<0.001).The association between anti-Stx2 IgG from bovine colostrum andSoluplus® PN was optimized and characterized. Encouraging resultsof antibody functionality coupled with PN were registered.These results may open the perspective of the design of new nanoplatformsfor neutralization and/or detection of Stx2.
Fil: Girón Reyes, Claudio Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Gomez, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Amaral, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Chiappetta, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Moretton, Marcela Analía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Nanomedicinas
description Shiga toxin type 2 (Stx2) is the main virulence factor of Shiga toxinproducing Escherichia coli and is responsible for triggering HemolyticUremic Syndrome (HUS). We aimed to develop and characterizepolymeric nanomicelles (PN) with the amphiphilic polymerSoluplus® coupled to anti-Stx2 IgG in order to introduce innovativeproposals for the detection of Stx2 and treatment of HUS. PN ofSoluplus® were formulated in PBS and coupled with IgG anti Stx2from hyperimmune (PN-IgG-Stx2) or control bovine colostrum (PNIgG-Ctrl). The hydrodynamic size of PN, PN-IgG-Stx2 and PN-IgGCtrlwas evaluated by Dynamic Light Scattering. Morphology of PNor PN-IgG-Stx2 was analyzed by Transmission Electron Microscopy(TEM). The PN toxicity was evaluated on both Vero and Human GlomerularEndothelial cells (HGEC) and cell viability was determinedby neutral red uptake. After coupling PN with IgG, Stx2 neutralizationcapacity of PN-IgG-Stx2 or PN-IgG-Ctrl was evaluated on Vero andHGEC cells and the percentage of cell viability was analyzed. Thehydrodynamic size of the PN of Soluplus® and IgG-Stx2 showed anaverage diameter of 70.2 ± 1.5 nm and 40.9 ± 2 nm, respectively.When both components were coupled, a single peak with a similarhydrodynamic size of the PN was observed (70.4 ± 0.2 nm). TEManalysis revealed circular particles with a diameter corresponding to100 nm either in PN and PN-IgG-Stx2 particles. PN-IgG-Stx2 wereable to neutralize Stx2 on Vero and HGEC cells in a dose dependentmanner. When comparing the neutralization capacity of Stx2 by IgGStx2vs PN-IgG-Stx2 a significant improvement in the cell viabilityof Vero and HGEC was observed with the PN-IgG-Stx2 (p<0.001).The association between anti-Stx2 IgG from bovine colostrum andSoluplus® PN was optimized and characterized. Encouraging resultsof antibody functionality coupled with PN were registered.These results may open the perspective of the design of new nanoplatformsfor neutralization and/or detection of Stx2.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/193200
Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas; Argentina; 2021; 179-179
CONICET Digital
CONICET
url http://hdl.handle.net/11336/193200
identifier_str_mv Development and characterization of soluplus® nanomicelles associated to specific igg as an innovative strategy for the detection and neutralization of shiga toxin type 2; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de Nanomedicinas; Argentina; 2021; 179-179
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://inmunologia.org.ar/reunion-conjunta-2021/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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