Endocytosis, Cytotoxicity, and Translocation of Shiga Toxin-2 Are Stimulated by Infection of Human Intestinal (HCT-8) Monolayers With an Hypervirulent E. coli O157:H7 Lacking stx2 Gene

Shiga toxin-producing Escherichia coli (STEC) strains are responsible for multiple clinical syndromes, including hemolytic uremic syndrome (HUS). E. coli O157:H7 is the most prevalent serotype associated with HUS and produces a variety of virulence factors being Stx2 the responsible of the most HUS severe cases. After intestinal colonization by STEC, Stx2 is released into the intestinal lumen, translocated to the circulatory system and then binds to its receptor, globotriaosylceramide (Gb3), in target cells. Thus, Stx2 passage through the colonic epithelial barrier is a key step in order to produce disease, being its mechanisms still poorly understood. We have previously reported that STEC interaction with the human colonic mucosa enhanced Stx2 production. In the present work, we have demonstrated that infection with O157:H7Δstx2, a mutant unable to produce Stx2, enhanced either Stx2 cytotoxicity on an intestinal cell line (HCT-8), or translocation across HCT-8 monolayers. Moreover, we found that translocation was enhanced by both paracellular and transcellular pathways. Using specific endocytosis inhibitors, we have further demonstrated that the main mechanisms implicated on Stx2 endocytosis and translocation, either when O157:H7Δstx2 was present or not, were Gb3-dependent, but dynamin-independent. On the other hand, dynamin dependent endocytosis and macropinocytosis became more relevant only when O157:H7Δstx2 infection was present. Overall, this study highlights the effects of STEC infection on the intestinal epithelial cell host and the mechanisms underlying Stx2 endocytosis, cytotoxic activity and translocation, in the aim of finding new tools toward a therapeutic approach.Fil: Garimano, Nicolás Ezequiel. 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: 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; Argentin

Adenylyl cyclase types I and VI but not II and V are selectively inhibited by nitric oxide

Adenylyl cyclase (AC) isoforms catalyze the synthesis of 3′,5′-cyclic AMP from ATP. These isoforms are critically involved in the regulation of gene transcription, metabolism, and ion channel activity among others. Nitric oxide (NO) is a gaseous product whose synthesis from L-arginine is catalyzed by the enzyme NO synthase. It has been well established that NO activates the enzyme guanylyl cyclase, but little has been reported on the effects of NO on other important second messengers, such as AC. In the present study, the effects of sodium nitroprusside (SNP), a nitric oxide-releasing compound, on COS-7 cells transfected with plasmids containing AC types I, II, V and VI were evaluated. Total inhibition (∼98.5%) of cAMP production was observed in COS-7 cells transfected with the AC I isoform and previously treated with SNP (10 mM) for 30 min, when stimulated with ionomycin. A high inhibition (∼76%) of cAMP production was also observed in COS-7 cells transfected with the AC VI isoform and previously treated with SNP (10 mM) for 30 min, when stimulated with forskolin. No effect on cAMP production was observed in cells transfected with AC isoforms II and V.Fil: Goldstein Raij, Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; ArgentinaFil: Silberstein, Claudia Marcela. Universidad de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentin

Characterization of Stx2 tubular response in a rat experimental model of hemolytic uremic syndrome

In Argentina, hemolytic uremic syndrome (HUS) constitutes the most frequent cause of acute renal failure in children. The aim of our study was to analyze the early tubular response under the effect of Shiga toxin type 2 (Stx2) in a rat experimental model of HUS. METHODS: Adult male Sprague-Dawley rats were injected intraperitoneally with culture supernatant from recombinant Escherichia coli expressing Stx2. Functional, histological, immunohistochemical and Western blot studies were performed at 48 h postinoculation. RESULTS: Renal tubules showed the loss of the epithelial markers E-cadherin and beta-catenin, and an increase in transforming growth factor-beta1 expression. We detected the expression of alpha-smooth muscle actin in the interstitium and fibrosis in the periglomerular areas. CONCLUSION: Our results indicate that the early tubular response to the effects of Stx2 is related to an immunophenotype change of tubular cells and the presence of mild fibrosis in the interstitium.Fil: Ochoa, Federico Claudio. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; ArgentinaFil: Lago, N. R.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Gerhardt, Elizabeth. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Ibarra, Cristina Adriana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Zotta, E.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentin

Chitosan enhances transcellular permeability in human and rat intestine epithelium

The intestinal epithelium regulates the transit of molecules from and into the organism. Several agentsact as absorption enhancers inducing changes in both transcellular and paracellular routes. Chitosan isa non-toxic biocompatible polysaccharide widely used as dietary supplement and mucosal delivery.Chitosan triggers both the activation of intestinal epithelial cells and the release of regulatory factors relevantfor its immunomodulatory activity. Yet, the interaction of chitosan with intestinal epithelial cells ispoorly characterized. We studied the uptake of this polysaccharide, and we evaluated its effects in boththe net water and ion movements across human and rat colon samples and the epithelial permeability.Herein, we demonstrate that chitosan increases the transcellular permeability to ions, water and proteinmarkers in human and rat intestinal mucosa and decreases the water permeability across the paracellularpathway. These findings are relevant to understand the activity of the polysaccharide in the mucosalenvironment.Fil: Canali, María Magdalena. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pedrotti, Luciano Pablo. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Balsinde, Jesús. Universidad de Valladolid; EspañaFil: Ibarra, Cristina Adriana. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Correa, Silvia Graciela. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Shiga toxin-producing Escherichia coli (STEC) O22:H8 isolated from cattle reduces E. coli O157:H7 adherence in vitro and in vivo

Problem addressed Shiga toxin-producing Escherichia coli (STEC) are a group of bacteria responsible for food-associated diseases. Clinical features include a wide range of symptoms such as diarrhea, hemorrhagic colitis and the hemolytic uremic syndrome (HUS), a life-threatening condition. Objective Our group has observed that animals naturally colonized with STEC strains of unknown serotype were not efficiently colonized with E. coli O157:H7 after experimental infection. In order to assess the basis of the interference, three STEC strains were isolated from STEC persistently-colonized healthy cattle from a dairy farm in Buenos Aires, Argentina. Methods and results The three isolated strains are E. coli O22:H8 and carry the stx1 and stx2d genes. The activatable activity of Stx2d was demonstrated in vitro. The three strains carry the adhesins iha, ehaA and lpfO113. E. coli O22:H8 formed stronger biofilms in abiotic surface than E. coli O157:H7 (eae+, stx2+) and displayed a more adherent phenotype in vitro towards HeLa cells. Furthermore, when both serotypes were cultured together O22:H8 could reduce O157:H7 adherence in vitro. When calves were intragastrically pre-challenged with 108 CFU of a mixture of the three STEC strains and two days later challenged with the same dose of the strain E. coli O157:H7 438/99, the shedding of the pathogen was significantly reduced. Conclusions These results suggest that E. coli O22:H8, a serotype rarely associated with human illness, might compete with O157:H7 at the bovine recto-anal junction, making non-O157 carrying-calves less susceptible to O157:H7 colonization and shedding of the bacteria to the environment.Fil: Martorelli, Luisina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Albanese, Adriana Andrea. 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: Vilte, Daniel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Cantet, Rodolfo Juan Carlos. Universidad de Buenos Aires. Facultad de Agronomía; ArgentinaFil: Bentancor, Adriana Beatriz. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Zolezzi, G.. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Chinen, I.. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; 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: Rivas, M.. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Mercado, Elsa Cristina. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias Castelar. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Cataldi, Ángel Adrián. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentin

Intestinal mucus-derived metabolites modulate virulence of a clade 8 enterohemorrhagic Escherichia coli O157:H7

The human colonic mucus is mainly composed of mucins, which are highly glycosylated proteins. The normal commensal colonic microbiota has mucolytic activity and is capable of releasing the monosaccharides contained in mucins, which can then be used as carbon sources by pathogens such as Enterohemorrhagic Escherichia coli (EHEC). EHEC can regulate the expression of some of its virulence factors through environmental sensing of mucus-derived sugars, but its implications regarding its main virulence factor, Shiga toxin type 2 (Stx2), among others, remain unknown. In the present work, we have studied the effects of five of the most abundant mucolytic activity-derived sugars, Fucose (L-Fucose), Galactose (D-Galactose), N-Gal (N-acetyl-galactosamine), NANA (N-Acetyl-Neuraminic Acid) and NAG (N-Acetyl-D-Glucosamine) on EHEC growth, adhesion to epithelial colonic cells (HCT-8), and Stx2 production and translocation across a polarized HCT-8 monolayer. We found that bacterial growth was maximum when using NAG and NANA compared to Galactose, Fucose or N-Gal, and that EHEC adhesion was inhibited regardless of the metabolite used. On the other hand, Stx2 production was enhanced when using NAG and inhibited with the rest of the metabolites, whilst Stx2 translocation was only enhanced when using NANA, and this increase occurred only through the transcellular route. Overall, this study provides insights on the influence of the commensal microbiota on the pathogenicity of E. coli O157:H7, helping to identify favorable intestinal environments for the development of severe disease.Fil: Garimano, Nicolás Ezequiel. 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: Scalise, Maria Lujan. 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: Gómez, 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: 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; Argentin

A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells

Shiga toxin-2 binds to the globotriaosyl-ceramide receptor on the plasma membrane of target cells. The highlevel expression of this receptor in renal epithelial cells may account, at least in part, for acute renal failure observed inchildren with hemolytic uremic syndrome. The cytotoxic effect of Shiga toxin-2 was assayed on primary cultures of humanrenal tubular epithelial cells treated with a new specific inhibitor of glucosylceramide synthase (C-9), the ratelimitingfirst step in the glycosphingolipid biosynthetic pathway. The treatment of the cells with 1-5 M C-9 for at least24 h significantly neutralized the action of 1 ng/ml Shiga toxin-2 on cell viability. The expression levels of globotriaosylceramidesignificantly decreased when cells were incubated with 1 M C-9 for 48 h. We propose here that prevention ofglobotriaosyl-ceramide synthesis by the C-9 could be a novel substrate inhibition therapy to neutralize Shiga toxin-2 actionin renal epithelial cells.Fil: Silberstein, Claudia Marcela. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Copeland, Diane P. No especifíca;Fil: Chiang, Wei Lien. No especifíca;Fil: Repetto, Horacio A.. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Ibarra, Cristina Adriana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Aquaporins can be involved in the swelling caused by shiga toxin type 2 on hgec and hk-2 cells

Hemolytic uremic syndrome related to Shiga toxin?producing Escherichiacoli (STEC-HUS) is the principal etiology of acute kidney injuryin children in Argentina.Previously, we demonstrated that Shiga toxin type 2 (Stx2) damageshuman glomerular endothelial cells (HGEC) and HK-2 human proximaltubular epithelial cell line by inducing swelling and detachment.In this work, we analyzed cell volume changes of HGEC and HK-2exposed or not to Stx2 or a hypoosmotic (HYPO) medium, in thepresence or not of aquaporins (AQPs) inhibitors (mercuric chloride:HgCl2 and tetraethylammonium: TEA), or an inhibitor of Stx2 receptor(Gb3) synthesis, Eliglustat (EG). For controls, an isosmotic (ISO)medium was used.Cells were grown on 12 well plates and pretreated for 30 minuteswith HgCl2 (10 μM) or TEA (100 μM) or pretreated during 24 h withEG (10 μM). Then, HGEC and HK-2 were incubated with Stx2 (50μM) for an additional 40 minutes. Cell volume was analyzed by lightmicroscopy and measuring cell area by using Image J software.After Stx2 and HYPO medium treatments, a significant increase inthe cell volume of HGEC (Stx2: 42%; HYPO: 36%, n= 3, p<0.05) andHK-2 (Stx2: 70%; HYPO: 55%, n= 3, p<0.05) was detected respectto ISO medium. However, when HGEC and HK-2 were pretreatedwith HgCl2 or TEA a significant swelling prevention was obtained forHGEC (Stx2+HgCl2:100%; Stx2+TEA:86%; HYPO+HgCl2: 42.5%;HYPO+TEA: 83%, n=3, p<0.05) and HK-2 (Stx2+HgCl2: 90%; Stx-2+TEA: 85%; HYPO+HgCl2: 55%; HYPO+TEA: 75%, n=3, p<0.05).In addition, EG also was able to prevent HK-2 swelling in 87 % (n=1)with respect to Stx2 treatment.Results show that AQPs may be involved in the water movement insideHGEC and HK-2 induced by Stx2, since HgCl2 and TEA avoidedthis effect. Furthermore, binding of Stx2 to Gb3 could be the initialstep for the development of cellular mechanisms that possibly triggerthe entry of solutes into the cells and the consequent osmoticgradient responsible for the hypotonic effect.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; ArgentinaFil: Repetti, Julieta. 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: Romero, Romina. Hospital Nacional Profesor Alejandro Posadas.; 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; 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: 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; 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 Nanomedicina

Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin

Hemolytic uremic syndrome (HUS) is a consequence of Shiga toxin (Stx)-producingEscherichia coli (STEC) infection and is the most frequent cause of acute renal failure (ARF) in children. Subtilase cytotoxin (SubAB) has also been associated with HUS pathogenesis. We previously reported that Stx2 and SubAB cause different effects on co-cultures of human renalmicrovascular endothelial cells (HGEC) and human proximal tubular epithelial cells (HK-2) relative to HGEC and HK-2 monocultures. In this work we have analyzed the secretion of pro-inflammatory cytokines by co-cultures compared to monocultures exposed or not to Stx2, SubAB, and Stx2+SubAB. Under basal conditions, IL-6, IL-8 and TNF-α secretion was different between monocultures and co-cultures. After toxin treatments, high concentrations of Stx2 and SubAB decreased cytokine secretion by HGEC monocultures, but in contrast, low toxin concentrations increased their release. Toxins did not modulate the cytokine secretion by HK-2 monocultures, but increased their release in the HK-2 co-culture compartment. In addition, HK-2 monocultures were stimulated to release IL-8 after incubation with HGEC conditioned media. Finally, Stx2 and SubAB were detected in HGEC and HK-2 cells from the co-cultures. This work describes, for the first time, the inflammatory responses induced by Stx2 and SubAB, in a crosstalk model of renal endothelial and epithelial cells.Fil: Alvarez, Romina Soledad. 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: 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; ArgentinaFil: Garimano, Nicolás Ezequiel. 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; ArgentinaFil: Paton, Adrienne W.. University of Adelaide; AustraliaFil: Paton, James C.. University of Adelaide; AustraliaFil: 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: 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; Argentin

Obtaining new information on hemolytic uremic syndrome by text mining

El síndroem urémico hemolítico está caracterizado por microangiopatía trombótica, anemia hemolítica, trombocitopenia e insuficiencia renal aguda. Puede causar desde secuelas permanentes hasta muerte, principalmente en niños. En este trabajo, utilizando minería de textos (MT), se analizó el texto explícito e implícito de 16 192 artículos científicos originales sobre SUH indexados en la base de datos de Europe PMC. Los objetivos fueron examinar comportamientos, realizar seguimiento de tendencias, hacer predicciones y cruzar datos con otras fuentes de información. Para el análisis se utilizaron –entre otras herramientas infor-máticas– flujos de trabajo (FT) especialmente desarrollados en la plataforma KNIME. La MT sobre las palabras de los resúmenes de las publicaciones permitió: detectar asociaciones no descritas entre eventos relacionados con SUH; extraer información subyacente; hacer agrupamientos temáticos mediante algoritmos no supervisados; realizar predicciones sobre el curso de las investigaciones asociadas al tema. Tanto el abordaje como los FT desarrollados para realizar Ciencia de Datos sobre SUH pueden aplicarse a otros temas biomédicos y a otras bases de datos científicos, permitiendo analizar aspectos relevantes en el campo de la salud humana para me-jorar la investigación, la prevención y el tratamiento de múltiples enfermedades.Hemolytic uremic syndrome (HUS) is characterized by thrombotic microangiopathy, hemolytic anemia, thrombocytopenia and acute renal failure. It can cause from permanent sequelae to death, mainly in children. In this work, using text mining (TM), we analyzed the explicit and implicit text of 16 192 original scientific articles on HUS indexed in the Europe PMC database. The objectives were to examine behaviors, track trends, and make predictions and cross-check data with other sources of information. For the analysis we used –among other computational tools– specially developed workflows (WF) in the KNIME platform. The TM on the words of the abstracts of the publications made it possible to: detect undescribed associations between events related to HUS; extract underlying information; make thematic clustering using unsupervised algorithms; make forecasting about the course of research associated with the topic. Both the approach and the WFs developed to perform Data Science on HUS can be applied to other biomedical topics and other scientific databases, making it possible to analyze relevant aspects in the field of human health to improve research, prevention and treatment of multiples diseases.Fil: Dorr, Ricardo Alfredo. 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: Silberstein, Claudia Marcela. 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: 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: Toriano, Roxana Mabel. 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; Argentin