Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

Autores
Stefanolo, Juan Pablo; Segura, Verónica; Grizzuti, Martina; Heredia, Abel; Comino, Isabel; Costa, Ana Florencia; Puebla, Roberto; Temprano, María Paz; Niveloni, Sonia Isabel; de Diego, Gabriel Alejandro; Oregui, María E.; Smecuol, Edgardo Gustavo; de Marzi, Mauricio Cesar; Verdú, Elena F.; Sousa, Carolina; Bai, Julio César
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background/Aim: The gluten-free diet has limitations, and there is intense research in the development of adjuvant therapies. Our aim was to examine the effects of orally administered Aspergillus niger endopeptidase (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult patients with celiac disease (CeD) following their usual gluten-free diet (GFD).Methods: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled patients with CeD on a long-term GFD. After a four-week run-in period, patients were randomized to 4 weeks of 2 AN-PEP capsules (GliadinX. AVI Research LLC; USA) at each of 3 meals/day or placebo. Outcome endpoints were: 1- the average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments, and between AN-PEP and placebo; 2) the Celiac Symptom Index (CSI); 3- CeD-specific serology; and 4- the quality of life. Stool samples were collected for GIP by ELISA every Tuesday and Friday during run-ins and treatments.Results: 40 patients were randomized to the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (<0.08 µg/g) in 65.6% of samples, and no differences between arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (>0.32µg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP >0.08 µg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run-in period, the proportion of symptomatic patients (CSI >38) in the AN-PEP arm was significantly lower (p<0.03). AN-PEP did not result in changes in specific serologies.Conclusions: This exploratory study, conducted in a real-life setting, revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce overall GIP stool concentration. However, given the observation of a significantly lower prevalence of severe symptoms in the AN-PEP arm in patients following their usual GFD, further clinical research is warranted.
Fil: Stefanolo, Juan Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Segura, Verónica. Universidad de Sevilla. Facultad de Farmacia.; España
Fil: Grizzuti, Martina. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Heredia, Abel. Universidad de Sevilla. Facultad de Farmacia.; España
Fil: Comino, Isabel. Universidad de Sevilla. Facultad de Farmacia.; España
Fil: Costa, Ana Florencia. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Puebla, Roberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Temprano, María Paz. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Niveloni, Sonia Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: de Diego, Gabriel Alejandro. Universidad Nacional de Luján. Instituto de Ecología y Desarrollo Sustentable. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ecología y Desarrollo Sustentable; Argentina
Fil: Oregui, María E.. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Smecuol, Edgardo Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: de Marzi, Mauricio Cesar. Universidad Nacional de Luján. Instituto de Ecología y Desarrollo Sustentable. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ecología y Desarrollo Sustentable; Argentina
Fil: Verdú, Elena F.. Mc Master University; Canadá
Fil: Sousa, Carolina. Universidad de Sevilla. Facultad de Farmacia.; España
Fil: Bai, Julio César. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Materia
Celiac disease
Gluten immunogenic peptides
AN-PEP
Real-life trial
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266979
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/266979
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free dietStefanolo, Juan PabloSegura, VerónicaGrizzuti, MartinaHeredia, AbelComino, IsabelCosta, Ana FlorenciaPuebla, RobertoTemprano, María PazNiveloni, Sonia Isabelde Diego, Gabriel AlejandroOregui, María E.Smecuol, Edgardo Gustavode Marzi, Mauricio CesarVerdú, Elena F.Sousa, CarolinaBai, Julio CésarCeliac diseaseGluten immunogenic peptidesAN-PEPReal-life trialhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background/Aim: The gluten-free diet has limitations, and there is intense research in the development of adjuvant therapies. Our aim was to examine the effects of orally administered Aspergillus niger endopeptidase (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult patients with celiac disease (CeD) following their usual gluten-free diet (GFD).Methods: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled patients with CeD on a long-term GFD. After a four-week run-in period, patients were randomized to 4 weeks of 2 AN-PEP capsules (GliadinX. AVI Research LLC; USA) at each of 3 meals/day or placebo. Outcome endpoints were: 1- the average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments, and between AN-PEP and placebo; 2) the Celiac Symptom Index (CSI); 3- CeD-specific serology; and 4- the quality of life. Stool samples were collected for GIP by ELISA every Tuesday and Friday during run-ins and treatments.Results: 40 patients were randomized to the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (<0.08 µg/g) in 65.6% of samples, and no differences between arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (>0.32µg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP >0.08 µg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run-in period, the proportion of symptomatic patients (CSI >38) in the AN-PEP arm was significantly lower (p<0.03). AN-PEP did not result in changes in specific serologies.Conclusions: This exploratory study, conducted in a real-life setting, revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce overall GIP stool concentration. However, given the observation of a significantly lower prevalence of severe symptoms in the AN-PEP arm in patients following their usual GFD, further clinical research is warranted.Fil: Stefanolo, Juan Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Segura, Verónica. Universidad de Sevilla. Facultad de Farmacia.; EspañaFil: Grizzuti, Martina. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Heredia, Abel. Universidad de Sevilla. Facultad de Farmacia.; EspañaFil: Comino, Isabel. Universidad de Sevilla. Facultad de Farmacia.; EspañaFil: Costa, Ana Florencia. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Puebla, Roberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Temprano, María Paz. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Niveloni, Sonia Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: de Diego, Gabriel Alejandro. Universidad Nacional de Luján. Instituto de Ecología y Desarrollo Sustentable. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ecología y Desarrollo Sustentable; ArgentinaFil: Oregui, María E.. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Smecuol, Edgardo Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: de Marzi, Mauricio Cesar. Universidad Nacional de Luján. Instituto de Ecología y Desarrollo Sustentable. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ecología y Desarrollo Sustentable; ArgentinaFil: Verdú, Elena F.. Mc Master University; CanadáFil: Sousa, Carolina. Universidad de Sevilla. Facultad de Farmacia.; EspañaFil: Bai, Julio César. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaW J G Press2024-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266979Stefanolo, Juan Pablo; Segura, Verónica; Grizzuti, Martina; Heredia, Abel; Comino, Isabel; et al.; Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet; W J G Press; World Journal of Gastroenterology; 30; 11; 3-2024; 1545-15551007-93272219-2840CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3748/wjg.v30.i11.1545info:eu-repo/semantics/altIdentifier/url/https://www.wjgnet.com/1007-9327/full/v30/i11/1545.htminfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:14:11Zoai:ri.conicet.gov.ar:11336/266979instacron: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:34982025-10-22 11:14:11.625CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet
title Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet
spellingShingle Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet
Stefanolo, Juan Pablo
Celiac disease
Gluten immunogenic peptides
AN-PEP
Real-life trial
title_short Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet
title_full Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet
title_fullStr Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet
title_full_unstemmed Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet
title_sort Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet
dc.creator.none.fl_str_mv Stefanolo, Juan Pablo
Segura, Verónica
Grizzuti, Martina
Heredia, Abel
Comino, Isabel
Costa, Ana Florencia
Puebla, Roberto
Temprano, María Paz
Niveloni, Sonia Isabel
de Diego, Gabriel Alejandro
Oregui, María E.
Smecuol, Edgardo Gustavo
de Marzi, Mauricio Cesar
Verdú, Elena F.
Sousa, Carolina
Bai, Julio César
author Stefanolo, Juan Pablo
author_facet Stefanolo, Juan Pablo
Segura, Verónica
Grizzuti, Martina
Heredia, Abel
Comino, Isabel
Costa, Ana Florencia
Puebla, Roberto
Temprano, María Paz
Niveloni, Sonia Isabel
de Diego, Gabriel Alejandro
Oregui, María E.
Smecuol, Edgardo Gustavo
de Marzi, Mauricio Cesar
Verdú, Elena F.
Sousa, Carolina
Bai, Julio César
author_role author
author2 Segura, Verónica
Grizzuti, Martina
Heredia, Abel
Comino, Isabel
Costa, Ana Florencia
Puebla, Roberto
Temprano, María Paz
Niveloni, Sonia Isabel
de Diego, Gabriel Alejandro
Oregui, María E.
Smecuol, Edgardo Gustavo
de Marzi, Mauricio Cesar
Verdú, Elena F.
Sousa, Carolina
Bai, Julio César
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Celiac disease
Gluten immunogenic peptides
AN-PEP
Real-life trial
topic Celiac disease
Gluten immunogenic peptides
AN-PEP
Real-life trial
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background/Aim: The gluten-free diet has limitations, and there is intense research in the development of adjuvant therapies. Our aim was to examine the effects of orally administered Aspergillus niger endopeptidase (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult patients with celiac disease (CeD) following their usual gluten-free diet (GFD).Methods: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled patients with CeD on a long-term GFD. After a four-week run-in period, patients were randomized to 4 weeks of 2 AN-PEP capsules (GliadinX. AVI Research LLC; USA) at each of 3 meals/day or placebo. Outcome endpoints were: 1- the average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments, and between AN-PEP and placebo; 2) the Celiac Symptom Index (CSI); 3- CeD-specific serology; and 4- the quality of life. Stool samples were collected for GIP by ELISA every Tuesday and Friday during run-ins and treatments.Results: 40 patients were randomized to the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (<0.08 µg/g) in 65.6% of samples, and no differences between arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (>0.32µg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP >0.08 µg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run-in period, the proportion of symptomatic patients (CSI >38) in the AN-PEP arm was significantly lower (p<0.03). AN-PEP did not result in changes in specific serologies.Conclusions: This exploratory study, conducted in a real-life setting, revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce overall GIP stool concentration. However, given the observation of a significantly lower prevalence of severe symptoms in the AN-PEP arm in patients following their usual GFD, further clinical research is warranted.
Fil: Stefanolo, Juan Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Segura, Verónica. Universidad de Sevilla. Facultad de Farmacia.; España
Fil: Grizzuti, Martina. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Heredia, Abel. Universidad de Sevilla. Facultad de Farmacia.; España
Fil: Comino, Isabel. Universidad de Sevilla. Facultad de Farmacia.; España
Fil: Costa, Ana Florencia. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Puebla, Roberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Temprano, María Paz. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Niveloni, Sonia Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: de Diego, Gabriel Alejandro. Universidad Nacional de Luján. Instituto de Ecología y Desarrollo Sustentable. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ecología y Desarrollo Sustentable; Argentina
Fil: Oregui, María E.. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Smecuol, Edgardo Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: de Marzi, Mauricio Cesar. Universidad Nacional de Luján. Instituto de Ecología y Desarrollo Sustentable. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ecología y Desarrollo Sustentable; Argentina
Fil: Verdú, Elena F.. Mc Master University; Canadá
Fil: Sousa, Carolina. Universidad de Sevilla. Facultad de Farmacia.; España
Fil: Bai, Julio César. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
description Background/Aim: The gluten-free diet has limitations, and there is intense research in the development of adjuvant therapies. Our aim was to examine the effects of orally administered Aspergillus niger endopeptidase (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult patients with celiac disease (CeD) following their usual gluten-free diet (GFD).Methods: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled patients with CeD on a long-term GFD. After a four-week run-in period, patients were randomized to 4 weeks of 2 AN-PEP capsules (GliadinX. AVI Research LLC; USA) at each of 3 meals/day or placebo. Outcome endpoints were: 1- the average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments, and between AN-PEP and placebo; 2) the Celiac Symptom Index (CSI); 3- CeD-specific serology; and 4- the quality of life. Stool samples were collected for GIP by ELISA every Tuesday and Friday during run-ins and treatments.Results: 40 patients were randomized to the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (<0.08 µg/g) in 65.6% of samples, and no differences between arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (>0.32µg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP >0.08 µg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run-in period, the proportion of symptomatic patients (CSI >38) in the AN-PEP arm was significantly lower (p<0.03). AN-PEP did not result in changes in specific serologies.Conclusions: This exploratory study, conducted in a real-life setting, revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce overall GIP stool concentration. However, given the observation of a significantly lower prevalence of severe symptoms in the AN-PEP arm in patients following their usual GFD, further clinical research is warranted.
publishDate 2024
dc.date.none.fl_str_mv 2024-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/266979
Stefanolo, Juan Pablo; Segura, Verónica; Grizzuti, Martina; Heredia, Abel; Comino, Isabel; et al.; Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet; W J G Press; World Journal of Gastroenterology; 30; 11; 3-2024; 1545-1555
1007-9327
2219-2840
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266979
identifier_str_mv Stefanolo, Juan Pablo; Segura, Verónica; Grizzuti, Martina; Heredia, Abel; Comino, Isabel; et al.; Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet; W J G Press; World Journal of Gastroenterology; 30; 11; 3-2024; 1545-1555
1007-9327
2219-2840
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3748/wjg.v30.i11.1545
info:eu-repo/semantics/altIdentifier/url/https://www.wjgnet.com/1007-9327/full/v30/i11/1545.htm
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv W J G Press
publisher.none.fl_str_mv W J G Press
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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