Authors: Piccioni, Flavia Valeria; Fiore, Esteban Juan; Bayo Fina, Juan Miguel; Atorrasagasti, María Catalina; Peixoto, Estanislao; Mazzolini Rizzo, Guillermo Daniel; Malvicini, Mariana; Tirado González, Irene; García, Mariana Gabriela; Alaniz, Laura Daniela; Mazzolini Rizzo, Guillermo Daniel
Publication Date: 2015.
Language: English.
Abstract:
Cirrhosis is characterized by an excessive accumulation of extracellular matrix components including hyaluronic acid (HA) and is widely considered a pre-neoplastic condition for hepatocellular carcinoma (HCC). 4-methylumbelliferone (4MU) is an inhibitor of HA synthesis and has anti-cancer activity in an orthotopic HCC model with underlying fibrosis. Our aim was to explore the effects of HA inhibition by 4MU orally administered on tumour microenvironment. Hepa129 tumour cells were inoculated orthotopically in C3H/HeJ male mice with fibrosis induced by thioacetamide. Mice were orally treated with 4MU. The effects of 4MU on angiogenesis were evaluated by immunostaining of CD31 and quantification of proangiogenic factors (VEGF, IL-6, CXCL12). IL-6 was also quantified in Hepa129 cells in vitro after treatment with 4MU. Migration of endothelial cells and tube formation were also analyzed. As a result, 4MU treatment decreases tumour growth and increased animal survival. Systemic levels of VEGF were significantly inhibited in 4MU-treated mice. Expression of CD31 was reduced after 4MU therapy in liver parenchyma in comparison with control group. In addition, mRNA expression and protein levels of IL-6 and VEGF were inhibited both in tumour tissue and in non-tumoral liver parenchyma. Interestingly, IL-6 production was dramatically reduced in Kupffer cells isolated from 4MU-treated mice, and in Hepa129 cells in vitro. Besides, 4MU was able to inhibit endothelial cell migration and tube formation. In conclusion, 4MU has antitumour activity in vivo and its mechanisms of action involve an inhibition of angiogenesis and IL-6 production. 4MU is an orally available molecule with potential for HCC treatment.
Author affiliation: Piccioni, Flavia Valeria. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina
Author affiliation: Fiore, Esteban Juan. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Bayo Fina, Juan Miguel. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Atorrasagasti, María Catalina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Peixoto, Estanislao. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Malvicini, Mariana. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Tirado González, Irene. Universität zu Berlin; Alemania
Author affiliation: García, Mariana Gabriela. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina
Author affiliation: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Rios, Glenda Laura; Buschiazzo, Jorgelina; Mucci, Nicolas Crescencio; Kaiser, German Gustavo; Cesari, Andreina; Alberio, Ricardo
Publication Date: 2015.
Language: English.
Abstract:
The conditions for in vitro oocyte maturation impact on cytoplasmic and nuclear processes in the oocyte. These events are differentially influenced by the nature of the maturation inducer and the presence of intact cumulus in cumulus–oocyte complexes. Epidermal growth factor is the main growth factor promoting oocyte maturation. Also, hyaluronic acid (HA) produced by cumulus cells is known to be responsible for the correct structural and functional organization of the cumulus during oocyte maturation. Therefore, we evaluated the developmental competence of bovine oocytes matured in vitro in a maturation medium supplemented with both EGF and HA, compared to FSH and fetal bovine serum (FBS). In addition, the impact of IVM conditions on the proteomic profile of metaphase II bovine oocytes was analyzed by two-dimensional electrophoresis. Cumulus–oocyte complexes were matured in two media: (1) 10 ng/mL EGF, 15 μg/mL HA, and 100-μM cysteamine and (2) 0.01 UI/mL rh-FSH and 10% FBS. The percentages of first polar body and embryo production and the kinetics of embryo development and oocyte proteomic profiles were analyzed. Oocytes matured in the presence of EGF-HA showed an increase (6%, P < 0.05) in the percentage of polar body extrusion. The blastocyst rate was 3% (P < 0.05) higher in the FSH-FBS group, but no differences were found in the rate of expanded blastocyst neither in total embryo production between IVM conditions. Cleavage rate of oocytes matured with FSH-FBS was 5% higher (P < 0.05) with respect to EGF-HA–matured oocytes when evaluated 30 hours after fertilization. However, at Day 7, those inseminated oocytes that underwent division at a correct timing showed that although there are still early blastocysts in the FSH-FBS condition, EGF-HA embryos have developed completely into blastocysts. Still, the production rate of those embryos that achieved expansion was similar between both maturation conditions. On the other hand, noncleaved presumptive zygotes at Day 7 developed into the different stages with similar rates (∼4%) independently of the medium condition. Modifications of IVM medium composition markedly affected protein profile of bovine oocytes in a differential manner. The proteomic approach revealed the presence of 68 spots in both treatments, 41 exclusively found in the FSH-FBS group and 64 exclusive for the EGF-HA group. Taken together, these results indicate that combined EGF-HA supplementation of in vitro maturation medium could be used to improve oocyte meiotic competence and ensure a better timing to develop into the blastocyst stage.
EEA Balcarce
Author affiliation: Rios, Glenda Laura. INTA. Estación Experimental Agropecuaria Balcarce. Departamento de Producción Animal. Biotecnología de la Reproducción; Argentina
Author affiliation: Buschiazzo, Jorgelina. INTA. Estación Experimental Agropecuaria Balcarce. Departamento de Producción Animal. Biotecnología de la Reproducción; Argentina. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca; Argentina
Author affiliation: Mucci, Nicolas Crescencio. INTA. Estación Experimental Agropecuaria Balcarce. Departamento de Producción Animal. Biotecnología de la Reproducción; Argentina
Author affiliation: Kaiser, German Gustavo. INTA. Estación Experimental Agropecuaria Balcarce. Departamento de Producción Animal. Biotecnología de la Reproducción; Argentina
Author affiliation: Cesari, Andreina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina
Author affiliation: Alberio, Ricardo. INTA. Estación Experimental Agropecuaria Balcarce. Departamento de Producción Animal. Biotecnología de la Reproducción; Argentina
Repository: INTA Digital (INTA). Instituto Nacional de Tecnología Agropecuaria
Authors: Luquita, A.; Urli, L.; Svetaz, M. J.; Gennaro, Ana Maria; Giorgietti, M.; Pistone, G.; Volpintesta, R.; Palatnik, S.; Rasia, M.
Publication Date: 2010.
Language: English.
Abstract:
Background: Hyaluronic acid (HA) is present in many tissues; its presence in serum may be related to certaininflammatory conditions, tissue damage, sepsis, liver malfunction and some malignancies. In the present work, ourgoal was to investigate the significance of hyaluronic acid effect on erythrocyte flow properties. Therefore weperformed in vitro experiments incubating red blood cells (RBCs) with several HA concentrations. Afterwards, in orderto corroborate the pathophysiological significance of the results obtained, we replicated the in vitro experiment with exvivo RBCs from diagnosed rheumatoid arthritis (RA) patients, a serum HA-increasing pathology.Methods: Erythrocyte deformability (by filtration through nucleopore membranes) and erythrocyte aggregability (EA)were tested on blood from healthy donors additioned with purified HA. EA was measured by transmitted light andanalyzed with a mathematical model yielding two parameters, the aggregation rate and the size of the aggregates.Conformational changes of cytoskeleton proteins were estimated by electron paramagnetic resonance spectroscopy(EPR).Results: In vitro, erythrocytes treated with HA showed increased rigidity index (RI) and reduced aggregability, situationstrongly related to the rigidization of the membrane cytoskeleton triggered by HA, as shown by EPR results. Also, asignificant correlation (r: 0.77, p Conclusions: Our results lead us to postulate the hypothesis that HA interacts with the erythrocyte surface leading tomodifications in erythrocyte rheological and flow properties, both ex vivo and in vitro.
Author affiliation: Luquita, A.. Universidad Nacional de Rosario; Argentina
Author affiliation: Urli, L.. Universidad Nacional de Rosario; Argentina
Author affiliation: Svetaz, M. J.. Universidad Nacional de Rosario; Argentina
Author affiliation: Gennaro, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina. Universidad Nacional del Litoral; Argentina
Author affiliation: Giorgietti, M.. Universidad Nacional de Rosario; Argentina
Author affiliation: Pistone, G.. Universidad Nacional de Rosario; Argentina
Author affiliation: Volpintesta, R.. Universidad Nacional de Rosario; Argentina
Author affiliation: Palatnik, S.. Universidad Nacional de Rosario; Argentina
Author affiliation: Rasia, M.. Universidad Nacional de Rosario; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Ernst, Glenda; Jancic, Carolina Cristina; Auteri, Santiago; Rodriguez Moncalvo, Juan; Galíndez, Fernando; Grynblat, Pedro; Hajos, Silvia Elvira
Publication Date: 2014.
Language: English.
Abstract:
Purpose: Interstitial Lung Diseases (ILD) are characterized by inflammation and fibrosis. It described the role of hyaluronic acid (HA) as an immune-regulator. It is not known if HA contributes to the recruitment of inflammatory cells associated with ILD. If this hypothesis was correct, then concentrations of HA in bronchoalveolar lavage (BAL) should correlate with the severity of ILD. Methods: We collected BAL from 22 ILD patients and 15 control subjects. We determined HA and cytokine levels by ELISA. In vitro chemotaxis assays were performed by using a transwell system. Results: We found that ILD patients showed a significant increase in HA, IL-6 levels and the amount of cells in BAL compared to control subjects. We detected a significant positive correlation between HA and IL-6 levels (r = 0.53 and p < 0.001) and an inverse relationship between HA levels and diffusion capacity (r = -0.59, p < 0.01). In vitro, HA induced migration of macrophages and monocytes through a CD44-dependent process. BAL from patients with ILD stimulated macro-phage migration and this was abrogated by hyaluronidase. Conclusions: Our results support the hypothesis that HA contributes to the recruitment of monocytes towards the alveolar space, leading to exacerbation of lung inflammation in ILD patients.
Author affiliation: Ernst, Glenda. Ciudad Autónoma de Buenos Aires. Hospital María Ferrer; Argentina
Author affiliation: Jancic, Carolina Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Auteri, Santiago. Ciudad Autónoma de Buenos Aires. Hospital María Ferrer; Argentina
Author affiliation: Rodriguez Moncalvo, Juan. Ciudad Autónoma de Buenos Aires. Hospital María Ferrer; Argentina
Author affiliation: Galíndez, Fernando. Ciudad Autónoma de Buenos Aires. Hospital María Ferrer; Argentina
Author affiliation: Grynblat, Pedro. Ciudad Autónoma de Buenos Aires. Hospital María Ferrer; Argentina
Author affiliation: Hajos, Silvia Elvira. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Olivares, Carla Noemi; Alaniz, Laura Daniela; Menger, Michael D.; Barañao, Rosa Ines; Laschke, Matthias W.; Meresman, Gabriela Fabiana
Publication Date: 2016.
Language: English.
Abstract:
Background: The development and long-term survival of endometriotic lesions is crucially dependent on an adequate vascularization. Hyaluronic acid (HA) through its receptor CD44 has been described to be involved in the process of angiogenesis. Objective: To study the effect of HA synthesis inhibition using non-toxic doses of 4-methylumbelliferone (4-MU) on endometriosis-related angiogenesis. Materials and Methods: The cytotoxicity of different in vitro doses of 4-MU on endothelial cells was firstly tested by means of a lactate dehydrogenase assay. The anti-angiogenic action of non-cytotoxic doses of 4-MU was then assessed by a rat aortic ring assay. In addition, endometriotic lesions were induced in dorsal skinfold chambers of female BALB/c mice, which were daily treated with an intraperitoneal injection of 0.9% NaCl (vehicle group; n = 6), 20mg/kg 4-MU (n = 8) or 80mg/kg 4-MU (n = 7) throughout an observation period of 14 days. The effect of 4-MU on their vascularization, survival and growth were studied by intravital fluorescence microscopy, histology and immunohistochemistry. Main Results: Non-cytotoxic doses of 4-MU effectively inhibited vascular sprout formation in the rat aortic ring assay. Endometriotic lesions in dorsal skinfold chambers of 4-MU-treated mice dosedependently exhibited a significantly smaller vascularized area and lower functional microvessel density when compared to vehicle-treated controls. Histological analyses revealed a downregulation of HA expression in 4-MU-treated lesions. This was associated with a reduced density of CD31-positive microvessels within the lesions. In contrast, numbers of PCNA-positive proliferating and cleaved caspase-3-positive apoptotic cells did not differ between 4-MU-treated and control lesions. Conclusions: The present study demonstrates for the first time that targeting the synthesis of HA suppresses angiogenesis in developing endometriotic lesions. Further studies have to clarify now whether in the future this anti-angiogenic effect can be used beneficially for the treatment of endometriosis.
Author affiliation: Olivares, Carla Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Author affiliation: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina
Author affiliation: Menger, Michael D.. Universitat Saarland; Alemania
Author affiliation: Barañao, Rosa Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Author affiliation: Laschke, Matthias W.. Universitat Saarland; Alemania
Author affiliation: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Minaberry, Yanina Susana; Chiappetta, Diego Andrés; Sosnik, Alejandro Dario; Jobbagy, Matias
Publication Date: 2013.
Language: English.
Abstract:
Hyaluronic acid (HA) hydrogels were structured in the form of porous monoliths by means of the ice-segregation-induced self-assembly (ISISA) method coupled with freeze-drying. Physical and chemical parameters were explored in order to fine-tune the microstructure and the incidence on both swelling and dissolution behavior in aqueous media. Gentamicin-loaded HA matrices with tuned drug release properties were also prepared; their inherent properties and behavior in solution are discussed in the framework of thermal analysis and scanning electron microscopy inspection.
Author affiliation: Minaberry, Yanina Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina
Author affiliation: 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
Author affiliation: Sosnik, Alejandro Dario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Author affiliation: Jobbagy, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina. Centro Interdisciplinario de Nanociencia y Nanotecnología; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Minaberry, Yanina Susana; Chiappetta, Diego Andrés; Sosnik, Alejandro Dario; Jobbagy, Matias
Publication Date: 2013.
Language: English.
Abstract:
Hyaluronic acid (HA) hydrogels were structured in the form of porous monoliths by means of the ice-segregation-induced self-assembly (ISISA) method coupled with freeze-drying. Physical and chemical parameters were explored in order to fine-tune the microstructure and the incidence on both swelling and dissolution behavior in aqueous media. Gentamicin-loaded HA matrices with tuned drug release properties were also prepared; their inherent properties and behavior in solution are discussed in the framework of thermal analysis and scanning electron microscopy inspection.
Author affiliation: Minaberry, Yanina Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Author affiliation: Chiappetta, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Author affiliation: Sosnik, Alejandro Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Jobbagy, Matias. Centro Interdisciplinario de Nanociencia y Nanotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Valva, Pamela; Rios, Daniela Alejandra; Casciato, Paola; Gadano, Adrián Carlos; Galdame, Omar; Mullen, Eduardo; Bertot, Gustavo; de Matteo, Elena Noemí; Preciado, María Victoria
Publication Date: 2017.
Language: English.
Abstract:
Background Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has been increasing constantly and linked to the global obesity epidemic. The NAFLD histologic spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Liver biopsy is the only reliable means to diagnose and stage NASH, but its invasive nature limits its use. Therefore, the prediction of hepatic injury by means of the development of new noninvasive tests represents a growing medical need. Our aim was to evaluate matrix deposition and cell-death markers, which correlate with liver injury in an NAFLD patient cohort. Patients and methods Liver biopsies and serum from 34 NAFLD adult patients were analyzed. Histological parameters were evaluated. Matrix deposition [hyaluronic acid (HA) and tissue inhibitor of matrix metalloproteinase inhibitor-1 (TIMP-1)] and cell-death markers [cytokeratin-18 (M65) and caspase-cleaved cytokeratin-18 (M30)] were measured in serum samples. Results HA showed an association with fibrosis severity (P=0.03) and M30 with steatosis (P=0.013), inflammation (P=0.004), and fibrosis severity (P=0.04). In contrast, TIMP-1 and M65 showed no association with any histological parameter of liver injury. The evaluation of diagnostic accuracy showed good performance as less invasive markers of significant fibrosis of both HA (area under the receiver operating characteristic curve: 0.928) and M30 (area under the receiver operating characteristic curve: 0.848). Conclusion Biomarkers are essential tools that may provide a quick and accurate diagnosis for patients with life-threatening NAFLD and NASH. HA and M30, together or determined sequentially, have been found to be straightforward tests that may be sufficient to predict significant fibrosis even in a primary care center of an underdeveloped country.
Author affiliation: Valva, Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Author affiliation: Rios, Daniela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Author affiliation: Casciato, Paola. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Gadano, Adrián Carlos. Hospital Italiano; Argentina
Author affiliation: Galdame, Omar. Hospital Italiano; Argentina
Author affiliation: Mullen, Eduardo. Hospital Italiano; Argentina
Author affiliation: Bertot, Gustavo. Instituto Universidad de la Fundación "Héctor Barceló"; Argentina
Author affiliation: de Matteo, Elena Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Author affiliation: Preciado, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas