32 results on '"Elena Iglesias"'
Search Results
2. Optimization of universal allogeneic CAR-T cells combining CRISPR and transposon-based technologies for treatment of acute myeloid leukemia
- Author
-
Cristina Calviño, Candela Ceballos, Ana Alfonso, Patricia Jauregui, Maria E. Calleja-Cervantes, Patxi San Martin-Uriz, Paula Rodriguez-Marquez, Angel Martin-Mallo, Elena Iglesias, Gloria Abizanda, Saray Rodriguez-Diaz, Rebeca Martinez-Turrillas, Jorge Illarramendi, Maria C. Viguria, Margarita Redondo, Jose Rifon, Sara Villar, Juan J. Lasarte, Susana Inoges, Ascension Lopez-Diaz de Cerio, Mikel Hernaez, Felipe Prosper, and Juan R. Rodriguez-Madoz
- Subjects
allogeneic CAR-T ,CRISPR ,transposon ,AML ,transcriptomics (RNA sequencing) ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Despite the potential of CAR-T therapies for hematological malignancies, their efficacy in patients with relapse and refractory Acute Myeloid Leukemia has been limited. The aim of our study has been to develop and manufacture a CAR-T cell product that addresses some of the current limitations. We initially compared the phenotype of T cells from AML patients and healthy young and elderly controls. This analysis showed that T cells from AML patients displayed a predominantly effector phenotype, with increased expression of activation (CD69 and HLA-DR) and exhaustion markers (PD1 and LAG3), in contrast to the enriched memory phenotype observed in healthy donors. This differentiated and more exhausted phenotype was also observed, and corroborated by transcriptomic analyses, in CAR-T cells from AML patients engineered with an optimized CAR construct targeting CD33, resulting in a decreased in vivo antitumoral efficacy evaluated in xenograft AML models. To overcome some of these limitations we have combined CRISPR-based genome editing technologies with virus-free gene-transfer strategies using Sleeping Beauty transposons, to generate CAR-T cells depleted of HLA-I and TCR complexes (HLA-IKO/TCRKO CAR-T cells) for allogeneic approaches. Our optimized protocol allows one-step generation of edited CAR-T cells that show a similar phenotypic profile to non-edited CAR-T cells, with equivalent in vitro and in vivo antitumoral efficacy. Moreover, genomic analysis of edited CAR-T cells revealed a safe integration profile of the vector, with no preferences for specific genomic regions, with highly specific editing of the HLA-I and TCR, without significant off-target sites. Finally, the production of edited CAR-T cells at a larger scale allowed the generation and selection of enough HLA-IKO/TCRKO CAR-T cells that would be compatible with clinical applications. In summary, our results demonstrate that CAR-T cells from AML patients, although functional, present phenotypic and functional features that could compromise their antitumoral efficacy, compared to CAR-T cells from healthy donors. The combination of CRISPR technologies with transposon-based delivery strategies allows the generation of HLA-IKO/TCRKO CAR-T cells, compatible with allogeneic approaches, that would represent a promising option for AML treatment.
- Published
- 2023
- Full Text
- View/download PDF
3. Cerebral metabolic pattern associated with progressive parkinsonism in non-human primates reveals early cortical hypometabolism
- Author
-
Francisco Molinet-Dronda, Javier Blesa, Natalia López-González del Rey, Carlos Juri, María Collantes, Jose A Pineda-Pardo, Inés Trigo-Damas, Elena Iglesias, Ledia F. Hernández, Rafael Rodríguez-Rojas, Belén Gago, Margarita Ecay, Elena Prieto, Miguel Á. García-Cabezas, Carmen Cavada, María C. Rodríguez-Oroz, Iván Peñuelas, and José A. Obeso
- Subjects
Parkinson's disease ,Positron emission tomography (PET) ,[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) ,[11C]-dihydrotetrabenazine (11C-DTBZ) ,Glucose metabolism ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Dopaminergic denervation in patients with Parkinson's disease is associated with changes in brain metabolism. Cerebral in-vivo mapping of glucose metabolism has been studied in severe stable parkinsonian monkeys, but data on brain metabolic changes in early stages of dopaminergic depletion of this model is lacking. Here, we report cerebral metabolic changes associated with progressive nigrostriatal lesion in the pre-symptomatic and symptomatic stages of the progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson's Disease. Monkeys (Macaca fascicularis) received MPTP injections biweekly to induce progressive grades of dopamine depletion. Monkeys were sorted according to motor scale assessments in control, asymptomatic, recovered, mild, and severe parkinsonian groups. Dopaminergic depletion in the striatum and cerebral metabolic patterns across groups were studied in vivo by positron emission tomography (PET) using monoaminergic ([11C]-dihydrotetrabenazine; 11C-DTBZ) and metabolic (2-[18F]-fluoro-2-deoxy-d-glucose; 18F-FDG) radiotracers. 11C-DTBZ-PET analysis showed progressive decrease of binding potential values in the striatum of monkeys throughout MPTP administration and the development of parkinsonian signs. 18F-FDG analysis in asymptomatic and recovered animals showed significant hypometabolism in temporal and parietal areas of the cerebral cortex in association with moderate dopaminergic nigrostriatal depletion. Cortical hypometabolism extended to involve a larger area in mild parkinsonian monkeys, which also exhibited hypermetabolism in the globus pallidum pars interna and cerebellum. In severe parkinsonian monkeys, cortical hypometabolism extended further to lateral-frontal cortices and hypermetabolism also ensued in the thalamus and cerebellum. Unbiased histological quantification of neurons in Brodmann's area 7 in the parietal cortex did not reveal neuron loss in parkinsonian monkeys versus controls. Early dopaminergic nigrostriatal depletion is associated with cortical, mainly temporo-parietal hypometabolism unrelated to neuron loss. These findings, together with recent evidence from Parkinson's Disease patients, suggest that early cortical hypometabolism may be associated and driven by subcortical changes that need to be evaluated appropriately. Altogether, these findings could be relevant when potential disease modifying therapies become available.
- Published
- 2022
- Full Text
- View/download PDF
4. Generation of four Isl1 reporter iPSC lines from cardiac and tail-tip fibroblasts derived from Ai6IslCre mouse
- Author
-
Javier Linares, Leyre López-Muneta, Estibaliz Arellano-Viera, Purificación Ripalda-Cemboráin, Elena Iglesias, Gloria Abizanda, Xabier L. Aranguren, Felipe Prósper, and Xonia Carvajal-Vergara
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Islet-1 (Isl1) is a transcription factor essential for life expressed in specific cells with different developmental origins. We have generated iPSC lines from fibroblasts of the transgenic Ai6 x Isl1-Cre (Ai6IslCre) mouse. Here we describe the complete characterization of four iPSC lines: ATCi-Ai6IslCre10, ATCi-Ai6IslCre35, ATCi-Ai6IslCre74 and ATCi-Ai6IslCre80.
- Published
- 2018
- Full Text
- View/download PDF
5. Local Preirradiation of Infarcted Cardiac Tissue Substantially Enhances Cell Engraftment
- Author
-
Gloria Abizanda, Leyre López-Muneta, Javier Linares, Luis I. Ramos, Arantxa Baraibar-Churio, Miriam Bobadilla, Elena Iglesias, Giulia Coppiello, Purificación Ripalda-Cemboráin, Xabier L. Aranguren, Felipe Prósper, Ana Pérez-Ruiz, and Xonia Carvajal-Vergara
- Subjects
myocardial infarction ,cell therapy ,local irradiation ,cell engraftment ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The success of cell therapy for the treatment of myocardial infarction depends on finding novel approaches that can substantially implement the engraftment of the transplanted cells. In order to enhance cell engraftment, most studies have focused on the pretreatment of transplantable cells. Here we have considered an alternative approach that involves the preconditioning of infarcted heart tissue to reduce endogenous cell activity and thus provide an advantage to our exogenous cells. This treatment is routinely used in other tissues such as bone marrow and skeletal muscle to improve cell engraftment, but it has never been taken in cardiac tissue. To avoid long-term cardiotoxicity induced by full heart irradiation we developed a rat model of a catheter-based heart irradiation system to locally impact a delimited region of the infarcted cardiac tissue. As proof of concept, we transferred ZsGreen+ iPSCs in the infarcted heart, due to their ease of use and detection. We found a very significant increase in cell engraftment in preirradiated rats. In this study, we demonstrate for the first time that preconditioning the infarcted cardiac tissue with local irradiation can substantially enhance cell engraftment.
- Published
- 2021
- Full Text
- View/download PDF
6. Generation of a Sprague-Dawley-GFP rat iPS cell line
- Author
-
Giulia Coppiello, Gloria Abizanda, Natalia Aguado, Elena Iglesias, Olalla Iglesias-Garcia, Antonio Lo Nigro, Felipe Prosper, and Xabier L. Aranguren
- Subjects
Biology (General) ,QH301-705.5 - Abstract
We generated a rat iPSC line called ATCi-rSD95 from transgenic Sprague-Dawley GFP fetal fibroblasts. Established ATCi-rSD95 cells present a normal karyotype, silencing of the transgenes and express pluripotency-associated markers. Additionally, ATCi-rSD95 cells are able to form teratoma with differentiated cells derived from the three germ-layers that maintain the GFP expression.
- Published
- 2017
- Full Text
- View/download PDF
7. Isolation and characterization of Sprague-Dawley and Wistar Kyoto GFP rat embryonic stem cells
- Author
-
Giulia Coppiello, Gloria Abizanda, Natalia Aguado, Elena Iglesias, Olalla Iglesias-Garcia, Antonio Lo Nigro, Felipe Prosper, and Xabier L. Aranguren
- Subjects
Biology (General) ,QH301-705.5 - Abstract
We generated two rat embryonic stem cell (ESC) lines: ATCe-SD7.8 from Sprague-Dawley strain and ATCe-WK1 from Wistar Kyoto strain. Cells were marked with enhanced green fluorescent protein (eGFP) by transduction with a lentiviral vector. Cells present a normal karyotype and express pluripotency-associated markers. Pluripotency was tested in vivo with the teratoma formation assay. Cells maintain eGFP expression upon differentiation to the three-germ layers. These cells can be a useful tool for cell therapy studies and chimera generation as they can be easily tracked by eGFP expression.
- Published
- 2017
- Full Text
- View/download PDF
8. Generation of Macaca fascicularis iPS cell line ATCi-MF1 from adult skin fibroblasts using non-integrative Sendai viruses
- Author
-
Giulia Coppiello, Gloria Abizanda, Natalia Aguado, Elena Iglesias, Estibaliz Arellano-Viera, Juan R Rodriguez-Madoz, Xonia Carvajal-Vergara, Felipe Prosper, and Xabier L. Aranguren
- Subjects
Biology (General) ,QH301-705.5 - Abstract
We generated ATCi-MF1 induced pluripotent stem (iPS) cell line from Macaca fascicularis adult skin fibroblasts using non-integrative Sendai viruses carrying OCT3/4, KLF4, SOX2 and c-MYC. Once established, ATCi-MF1 cells present a normal karyotype, are Sendai virus-free and express pluripotency associated markers. Microsatellite markers analysis confirmed the origin of the iPS cells from the parental fibroblasts. Pluripotency was tested with the in vivo teratoma formation assay. ATCi-MF1 cell line may be a useful primate iPS cell model to test different experimental conditions where the use of human cells can imply ethical issues, as microinjection of pluripotent stem cells in pre-implantational embryos.
- Published
- 2017
- Full Text
- View/download PDF
9. Generation of iPSC from cardiac and tail-tip fibroblasts derived from a second heart field reporter mouse
- Author
-
Javier Linares, Estibaliz Arellano-Viera, Olalla Iglesias-García, Carmen Ferreira, Elena Iglesias, Gloria Abizanda, Felipe Prósper, and Xonia Carvajal-Vergara
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Mef2c Anterior Heart Field (AHF) enhancer is activated during embryonic heart development and it is expressed in multipotent cardiovascular progenitors (CVP) giving rise to endothelial and myocardial components of the outflow tract, right ventricle and ventricular septum. Here we have generated iPSC from transgenic Mef2c-AHF-Cre x Ai6(RCLZsGreen) mice. These iPSC will provide a novel tool to investigate the AHF-CVP and their cell progeny.
- Published
- 2016
- Full Text
- View/download PDF
10. Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: A longitudinal in-vivo study
- Author
-
Francisco Molinet-Dronda, Belén Gago, Ana Quiroga-Varela, Carlos Juri, María Collantes, Mercedes Delgado, Elena Prieto, Margarita Ecay, Elena Iglesias, Concepció Marín, Iván Peñuelas, and José A. Obeso
- Subjects
Parkinson's disease ,6-Hydroxydopamine ,Positron emission tomography ,[11C]-dihydrotetrabenazine (11C-DTBZ) ,Nigro-striatal depletion ,Dopaminergic marker ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Carbon-11 labeled dihydrotetrabenazine (11C-DTBZ) binds to the vesicular monoamine transporter 2 and has been used to assess nigro-striatal integrity in animal models and patients with Parkinson's disease. Here, we applied 11C-DTBZ positron emission tomography (PET) to obtain longitudinally in-vivo assessment of striatal dopaminergic loss in the classic unilateral and in a novel bilateral 6-hydroxydopamine (6-OHDA) lesion rat model. Forty-four Sprague–Dawley rats were divided into 3 sub-groups: 1. 6-OHDA-induced unilateral lesion in the medial forebrain bundle, 2. bilateral lesion by injection of 6-OHDA in the third ventricle, and 3. vehicle injection in either site. 11C-DTBZ PET studies were investigated in the same animals successively at baseline, 1, 3 and 6 weeks after lesion using an anatomically standardized volumes-of-interest approach. Additionally, 12 rats had PET and Magnetic Resonance Imaging to construct a new 11C-DTBZ PET template. Behavior was characterized by rotational, catalepsy and limb-use asymmetry tests and dopaminergic striatal denervation was validated post-mortem by immunostaining of the dopamine transporter (DAT). 11C-DTBZ PET showed a significant decrease of striatal binding (SB) values one week after the unilateral lesion. At this point, there was a 60% reduction in SB in the affected hemisphere compared with baseline values in 6-OHDA unilaterally lesioned animals. A 46% symmetric reduction over baseline SB values was found in bilaterally lesioned rats at the first week after lesion. SB values remained constant in unilaterally lesioned rats whereas animals with bilateral lesions showed a modest (22%) increase in binding values at the 3rd and 6th weeks post-lesion. The degree of striatal dopaminergic denervation was corroborated histologically by DAT immunostaining. Statistical analysis revealed a high correlation between 11C-DTBZ PET SB and striatal DAT immunostaining values (r = 0.95, p
- Published
- 2015
- Full Text
- View/download PDF
11. Liposarcoma intraabdominal gigante
- Author
-
Elena Iglesias-Jorquera, Francisco-Javier Álvarez-Higueras, Paula-Tomás Pujante, and Carmen Garre-Sánchez
- Subjects
Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2018
- Full Text
- View/download PDF
12. Anisotropic Cryostructured Collagen Scaffolds for Efficient Delivery of RhBMP–2 and Enhanced Bone Regeneration
- Author
-
Kai Stuckensen, José M. Lamo-Espinosa, Emma Muiños-López, Purificación Ripalda-Cemboráin, Tania López-Martínez, Elena Iglesias, Gloria Abizanda, Ion Andreu, María Flandes-Iparraguirre, Juan Pons-Villanueva, Reyes Elizalde, Joachim Nickel, Andrea Ewald, Uwe Gbureck, Felipe Prósper, Jürgen Groll, and Froilán Granero-Moltó
- Subjects
rhBMP–2 ,collagen sponge ,cryostructured scaffolds ,bone critical size defect ,Technology ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Microscopy ,QH201-278.5 ,Descriptive and experimental mechanics ,QC120-168.85 - Abstract
In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP−2, BMP−7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP−2. In vitro, both scaffolds presented similar mechanical properties, rhBMP−2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP−2 mediated bone healing.
- Published
- 2019
- Full Text
- View/download PDF
13. Enterococcus gallinarum and Chilaiditi syndrome in peritoneal dialysis
- Author
-
Cristina Pérez Melón, Beatriz Ferreiro Álvarez, Elena Iglesias Lamas, María Jesús Camba Caride, María Paz Borrajo Prol, and Enrique Novoa Fernández
- Subjects
Diseases of the genitourinary system. Urology ,RC870-923 - Published
- 2017
- Full Text
- View/download PDF
14. Progression of dopaminergic depletion in a model of MPTP-induced Parkinsonism in non-human primates. An 18F-DOPA and 11C-DTBZ PET study
- Author
-
Javier Blesa, Carlos Juri, María Collantes, Iván Peñuelas, Elena Prieto, Elena Iglesias, Josep Martí-Climent, Javier Arbizu, José L. Zubieta, Mari Cruz Rodríguez-Oroz, David García-García, José A. Richter, Carmen Cavada, and José A. Obeso
- Subjects
PET ,Parkinson's disease ,MPTP-induced parkinsonism ,Non-human primates ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Dopaminergic depletion in the nigrostriatal system is the neurochemical hallmark of Parkinson's disease (PD). Although numerous efforts have been made to determine the evolution of dopaminergic depletion in PD, “in vivo” data concerning the stages of this process are still scarce. We evaluated 6-[18F]-fluoro-l-DOPA (18F-DOPA) and 11C-(+)-α-dihydrotetrabenazine (11C-DTBZ) using PET in a model of chronically MPTP-induced parkinsonism in non-human primates. Methods: Sixty-seven cynomolgus monkeys (Macaca fascicularis) were included in the study. Progressive parkinsonism was induced by repeated administration of small doses of MPTP (iv) over several months. Animals were classified as controls, asymptomatic, recovered (having exhibited parkinsonian features transiently) and stable parkinsonian, according to their motor status. Analysis of striatal dopaminergic activity was conducted by regions of interest (ROI) and statistical parametric mapping (SPM) over normalized parametric images. Results: A progressive loss of striatal uptake was evident among groups for both radiotracers, which correlated significantly with the clinical motor status. Changes occurred earlier, i.e. in the less affected stages, with 11C-DTBZ. Similar results were achieved by ROI and SPM analysis. Uptake was similar with both radiotracers for the asymptomatic and recovered groups. Conclusions: Serial assessment with 18F-DOPA and 11C-DTBZ PETs provides an effective approach to evaluate evolution of dopaminergic depletion in monkeys with MPTP-induced parkinsonism. This approach could be useful to perform studies aiming to test the effect of early therapeutic intervention and putative neuroprotective treatments.
- Published
- 2010
- Full Text
- View/download PDF
15. Daptomycin in peritoneal dialysis, intraperitoneal or intravenous
- Author
-
Cristina Pérez Melón, Maria Borrajo Prol, Elena Iglesias, Beatriz Ferreiro, and Maria Camba Caride
- Subjects
Diseases of the genitourinary system. Urology ,RC870-923 - Published
- 2016
- Full Text
- View/download PDF
16. Overt obscure gastrointestinal bleeding secondary to small bowel gastrointestinal stromal tumor diagnosed by videocapsule endoscopy
- Author
-
Gabriel Carrilero-Zaragoza, Guillermo Carbonell-López-del-Castillo, Gema Ruiz-García, Juan Egea-Valenzuela, Paula Tomas-Pujante, Elena Iglesias-Jorquera, Josefa Parra-García, Antonio Sánchez-Torres, Elena Navarro-Noguera, Esther Estrella-Díaz, and Luis Fernando Carballo-Álvarez
- Subjects
Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2015
17. Recuperación del paisaje con fines de ocio. Parque fluvial del Jarama. Comunidad de Madrid. España
- Author
-
Alejandro Pinedo, Elena Iglesias, and Ana Pilar Espluga
- Subjects
Architecture ,NA1-9428 ,Building construction ,TH1-9745 - Abstract
El plan de recuperación de márgenes y riberas que se describe en el presente artículo, trata de salir al paso y aportar soluciones a los cada vez más frecuentes problemas de restauración y aprovechamiento de terrenos degradados que se plantean en los ámbitos urbanos y periurbano. El plan se localiza geográficamente en un área de la Comunidad de Madrid que posee un alto nivel de degradación y al mismo tiempo un gran potencial recreativo, se trata de el Parque Fluvial del Jarama, situado en el tramo del río Jarama comprendido entre la desembocadura del arroyo de la Vega y la del Manzanares; el Parque Fluvial del Jarama constituye la actuación más ambiciosa dentro del Programa de Recuperación de Márgenes del Plan Integral del Agua en Madrid (PIAM) y en él se contemplan una serie de actuaciones que se pueden agrupar en los bloques siguientes: — Restauración de la explanación del ferrocarril. — Restauración y adecuación del cauce y márgenes. — Restauración de la Laguna del Campillo.
- Published
- 1990
- Full Text
- View/download PDF
18. Un caso de estudio de impacto ambiental: el embalse de Vallfornés. Cataluña-España
- Author
-
Alejandro Pinedo and Elena Iglesias
- Subjects
Architecture ,NA1-9428 ,Building construction ,TH1-9745 - Abstract
Los estudios de impacto ambiental surgen de la necesidad de proyectar las actividades de la forma más adecuada posible, que facilite su integración en el medio natural en que han de inscribirse para que su calidad no se vea afectada. El caso del embalse de Vallfornés, cuya finalidad principal es el abastecimiento de agua para regadío, presenta además la peculiaridad de afectar a terrenos Incluidos dentro del Parque Natural de Montseny, lo que obliga no sólo a un tratamiento cuidadoso de la obra, sino también a la resolución de conflictos inevitables con la normativa existente. En el presente artículo se pasa revista a los principales aspectos del estudio de impacto ambiental de dicho embalse: análisis de las implicaciones derivadas de su ubicación en terrenos del Parque Natural del Montseny, caracterización del medio afectado, identificación de las acciones productoras de impacto, caracterización y valoración de los mismos y recomendaciones respecto a la corrección de los impactos potenciales.
- Published
- 1990
- Full Text
- View/download PDF
19. In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study
- Author
-
Grothe, Michel J., Labrador-Espinosa, Miguel A., Jesús, Silvia, Macías-García, Daniel, Adarmes-Gómez, Astrid, Carrillo, Fátima, Camacho, Elena Iglesias, Franco-Rosado, Pablo, Lora, Florinda Roldán, Martín-Rodríguez, Juan Francisco, Barberá, Miquel Aguilar, Pastor, Pau, Arroyo, Sonia Escalante, Vila, Berta Solano, Foraster, Anna Cots, Martínez, Javier Ruiz, Padilla, Francisco Carrillo, Morlans, Mercedes Pueyo, Aramburu, Isabel González, Ceberio, Jon Infante, Vara, Jorge Hernández, de Fábregues-Boixar, Oriol, de Deus Fonticoba, Teresa, Pascual-Sedano, Berta, Kulisevsky, Jaime, Martínez-Martín, Pablo, Santos-García, Diego, and Mir, Pablo
- Published
- 2021
- Full Text
- View/download PDF
20. Factors associated with the presence of abnormal levels of fecal calprotectin in patients with negative panenteric studies
- Author
-
Valenzuela, Juan Egea, Jorquera, Elena Iglesias, Higueras, Francisco Javier Alvarez, Tornero, Maria Munoz, Lopez, Ana Pereniguez, Diez, Esther Estrella, and de las Parras, Fernando Alberca
- Published
- 2020
- Full Text
- View/download PDF
21. Spontaneous retroperitoneal hematoma in a patient under anticoagulant agents presenting as upper gastrointestinal bleeding
- Author
-
Gabriel Carrilero-Zaragoza, Juan Egea-Valenzuela, María Moya-Arnao, María Muñoz-Tornero, Roxanna Jijón-Crespín, Paula Tomás-Pujante, Elena Iglesias-Jorquera, Josefa Parra-García, Eduardo Sánchez-Velasco, Ana Pereñíguez-López, Manuel Miras-López, Matilde Fuster-Quiñonero, and Fernando Carballo-Álvarez
- Subjects
JAK-2 ,Duodenal ulcer ,Retroperitoneal hematoma ,Gastrointestinal bleeding ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
We present the case of a 44-year-old woman with past history of repeated miscarriage and Budd-Chiari syndrome secondary to primary myelofibrosis. Because of this she was under treatment with oral anticoagulant agents. The patient was admitted in hospital as she presented with gastrointestinal bleeding (melena), asthenia and progressive anemia. In an initial upper endoscopy an extrinsic duodenal compression associated with an ulcer on the posterior face of the first portion of duodenum and upper duodenal knee was observed. In the following days a huge spontaneous retroperitoneal hematoma due to anticoagulation was diagnosed by computed tomography. This was treated with a percutaneous drainage and withdrawal of the antithrombotic drugs. The evolution of the patient was initially satisfactory but she suffered subclavian and jugular vein thrombosis, and reintroduction of anticoagulant agents at the lowest therapeutic doses was required.
- Full Text
- View/download PDF
22. Encefalopatía hepática secundaria a shunt esplenorrenal que se manifiesta tras largo tiempo del trasplante hepático
- Author
-
Paula Tomás-Pujante, Andrés-Francisco Jiménez-Sánchez, Elena Iglesias-Jorquera, and José-Antonio Pons-Miñano
- Subjects
Diseases of the digestive system. Gastroenterology ,RC799-869 - Full Text
- View/download PDF
23. Telomere Length Differently Associated to Obesity and Hyperandrogenism in Women With Polycystic Ovary Syndrome
- Author
-
Mariela Edith Velazquez, Andrea L. Millan, Mailén Rojo, Giselle Adriana Abruzzese, Silvina Ema Cocucci, Andrea Elena Iglesias Molli, Gustavo Daniel Frechtel, Alicia Beatriz Motta, and Gloria Edith Cerrone
- Subjects
Adult ,medicine.medical_specialty ,obesity ,Waist ,endocrine system diseases ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Argentina ,030209 endocrinology & metabolism ,metabolic and endocrine disorders ,Diseases of the endocrine glands. Clinical endocrinology ,Body Mass Index ,hyperandrogenism ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,hemic and lymphatic diseases ,medicine ,telomere length ,Humans ,Testosterone ,Retrospective Studies ,Original Research ,030219 obstetrics & reproductive medicine ,business.industry ,Polycystic ovary syndrome (PCOS) ,Hyperandrogenism ,Telomere Homeostasis ,nutritional and metabolic diseases ,Telomere ,Androgen ,medicine.disease ,RC648-665 ,Obesity ,Polycystic ovary ,female genital diseases and pregnancy complications ,polycystic ovary syndrome ,Case-Control Studies ,Female ,business ,Hormone - Abstract
BackgroundPolycystic Ovary Syndrome (PCOS) often present metabolic disorders and hyperandrogenism (HA), facts that may influence the telomere length (TL).AimsTo compare the absolute TL (aTL) between women with PCOS and control women, and their association with the presence of obesity and HA parameters.Materials and methodsThe PCOS group included 170 unrelated women outpatients and the control group, 64 unrelated donor women. Anthropometric, biochemical-clinical parameters and androgen profile were determined. The PCOS patients were divided accordingly to the presence of obesity and androgenic condition. The aTL was determined from peripheral blood leukocytes by Real Time quantitative PCR.ResultsWomen with PCOS exhibited a significantly longer aTL than controls after age adjustment (p=0.001). A stepwise multivariate linear regression in PCOS women, showed that WC (waist circumference) contributed negatively (b=-0.17) while testosterone levels contributed positively (b=7.24) to aTL. The non-Obese PCOS (noOB-PCOS) presented the longest aTL when compared to controls (p=0.001). Meanwhile, the aTL was significantly higher in the hyperandrogenic PCOS phenotype (HA-PCOS) than in the controls (p=0.001) and non hyperandrogenic PCOS phenotype (NHA-PCOS) (p=0.04). Interestingly, when considering obesity and HA parameters in PCOS, HA exerts the major effect over the aTL as non-obese HA exhibited the lengthiest aTL (23.9 ± 13.13 Kbp). Conversely, the obese NHA patients showed the shortest aTL (16.5 ± 10.59 Kbp).ConclusionsWhilst a shorter aTL could be related to the presence of obesity, a longer aTL would be associated with HA phenotype. These findings suggest a balance between the effect produced by the different metabolic and hormonal components, in PCOS women.
- Published
- 2021
24. Relationship between the IL-1β serum concentration, mRNA levels and rs16944 genotype in the hyperglycemic normalization of T2D patients
- Author
-
Mónica Paula Spalvieri, Andrea Elena Iglesias Molli, María Fernanda Bergonzi, Gustavo Daniel Frechtel, María Amelia Linari, and Gloria Edith Cerrone
- Subjects
0301 basic medicine ,Normalization (statistics) ,Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Genotype ,Molecular biology ,Interleukin-1beta ,lcsh:Medicine ,INFLAMACIÓN ,Article ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,INTERLEUQUINA 1BETA ,Medical research ,purl.org/becyt/ford/3.2 [https] ,Genetics ,Medicine ,Humans ,Hypoglycemic Agents ,Genetic Predisposition to Disease ,Prospective Studies ,lcsh:Science ,Alleles ,Aged ,Gynecology ,Multidisciplinary ,Molecular medicine ,business.industry ,lcsh:R ,Serum concentration ,Middle Aged ,GENETICA ,030104 developmental biology ,Mrna level ,Diabetes Mellitus, Type 2 ,Hyperglycemia ,DIABETES TIPO2 ,Leukocytes, Mononuclear ,lcsh:Q ,purl.org/becyt/ford/3 [https] ,Female ,business ,030217 neurology & neurosurgery - Abstract
To evaluate Interleukin 1-beta (IL-1β) serum and mononuclear leucocyte mRNA levels, also rs16944 (−511C/T) genotype, in relation to hyperglycemic normalization in Type 2 diabetes (T2D) patients, we recruited 30 individuals recently T2D diagnosed with hyperglycemia studied at basal time and after 6 and 12 months of the normalization treatment. At basal time, the T polymorphic allele of the rs16944 was associated with lower IL-1β mRNA expression (p = 0.006); and higher glucose level was positive correlated to IL-1β protein levels (p = 0.015). After treatment, the individuals showed a significant decrease in glucose level (p = 0.003), but they did not express significant changes in the IL-1β serum levels. Surprisingly, we observed that the greater decreases in glucose level were associated to increased IL-1β serum levels (p = 0.040). This is the first follow-up study evaluating IL-1β mRNA expression and serum levels in hyperglycemic T2D individuals and after glycemic normalization treatment. The current results contribute to the knowledge of the relationship between inflammation and glucose metabolism in T2D. Fil: Iglesias Molli, Andrea Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Bergonzi, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Spalvieri, Mónica Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Linari, María Amelia. Union Obrera Metalurgica.; Argentina Fil: Frechtel, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina Fil: Cerrone, Gloria Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
- Published
- 2020
25. Body mass index is negatively associated with telomere length: a collaborative cross-sectional meta-analysis of 87 observational studies
- Author
-
Gil Atzmon, Rosalind Ramsey-Goldman, Barry J. McDonnell, Yun-Ling Zheng, David Gilley, Teresa E. Seeman, Maciej Tomaszewski, Massimo Mangino, Geja J. Hageman, Florian Kronenberg, Iiris Hovatta, Giuseppe Paolisso, Line Rode, Ellen W. Demerath, Jaakko Kaprio, Katarina Nordfjäll, Jonathan N. Hofmann, Peter Willeit, Rosana Maria dos Reis, Barbara Kollerits, Andrea Elena Iglesias Molli, Guo Cheng, Wei Zheng, Karen A. Mather, Daniel Eisenberg, Fadi J. Charchar, Sarah E. Harris, Bianca D’Antono, Jason Y.Y. Wong, Sofia Pavanello, Lisa A. Boardman, Guillaume Paré, Jacob B. H. Hjelmborg, Erik J. Giltay, Tim De Meyer, Evangelia Antoniou, Dmytro Krasnienkov, Maurice P. Zeegers, Marek Kasielski, Audrey E. Hendricks, Linda Broer, Lifang Hou, Andrew Steptoe, Andrew J. Pellatt, Jennifer A. Nettleton, Vanessa A. Diaz, Steven C. Hunt, Marij Gielen, Josine E. Verhoeven, Christian Gieger, Roxanne Schaakxs, Belinda L. Needham, Catherine Duggan, Timo E. Strandberg, Ute Mons, Klelia D. Salpea, Jeremy D. Kark, Raffaela Zannolli, Muthuswamy Balasubramanyam, Michael Chong, Richard P. Ebstein, Daniel Bunout, Amelia Marti, Kristina Sundquist, Lisa Mirabello, Hisham Nassar, David J. Kurz, Ramin Farzaneh-Far, Ilja Demuth, Pim van der Harst, Gielen, Marij, Hageman, Geja J., Antoniou, Evangelia E., Nordfjall, Katarina, Mangino, Massimo, Balasubramanyam, Muthuswamy, De Meyer, Tim, Hendricks, Audrey E., Giltay, Erik J., Hunt, Steven C., Nettleton, Jennifer A., Salpea, Klelia D., Diaz, Vanessa A., Farzaneh-Far, Ramin, Atzmon, Gil, Harris, Sarah E., Hou, Lifang, Gilley, David, Hovatta, Iiri, Kark, Jeremy D., Nassar, Hisham, Kurz, David J., Mather, Karen A., Willeit, Peter, Zheng, Yun-Ling, Pavanello, Sofia, Demerath, Ellen W., Rode, Line, Bunout, Daniel, Steptoe, Andrew, Boardman, Lisa, Marti, Amelia, Needham, Belinda, Zheng, Wei, Ramsey-Goldman, Rosalind, Pellatt, Andrew J., Kaprio, Jaakko, Hofmann, Jonathan N., Gieger, Christian, Paolisso, Giuseppe, Hjelmborg, Jacob B. H., Mirabello, Lisa, Seeman, Teresa, Wong, Jason, Van Der Harst, Pim, Broer, Linda, Kronenberg, Florian, Kollerits, Barbara, Strandberg, Timo, Eisenberg, Dan T. A., Duggan, Catherine, Verhoeven, Josine E., Schaakxs, Roxanne, Zannolli, Raffaela, Dos Reis, Rosana M. R., Charchar, Fadi J., Tomaszewski, Maciej, Mons, Ute, Demuth, Ilja, Molli, Andrea Elena Iglesia, Cheng, Guo, Krasnienkov, Dmytro, D'Antono, Bianca, Kasielski, Marek, Mcdonnell, Barry J., Ebstein, Richard Paul, Sundquist, Kristina, Pare, Guillaume, Chong, Michael, Zeegers, Maurice P., Complexe Genetica, RS: NUTRIM - R3 - Respiratory & Age-related Health, Farmacologie en Toxicologie, Section Eating Disorders and Obesity, RS: FPN CPS II, RS: CAPHRI - R5 - Optimising Patient Care, TELOMAAS Group, Internal Medicine, Psychiatry, APH - Mental Health, and Cardiovascular Centre (CVC)
- Subjects
0301 basic medicine ,Male ,obesity ,Cross-sectional study ,Medicine (miscellaneous) ,BMI ,Low-grade inflammation ,Meta-analysis ,Obesity ,Observational studies ,Telomere length ,Nutrition and Dietetics ,030204 cardiovascular system & hematology ,Body Mass Index ,0302 clinical medicine ,Ethnicity ,Leukocytes ,telomere length ,low-grade inflammation ,Young adult ,Telomere Shortening ,2. Zero hunger ,Aged, 80 and over ,education.field_of_study ,INSULIN-RESISTANCE ,Age Factors ,Middle Aged ,Telomere ,OXIDATIVE DNA-DAMAGE ,Original Research Communications ,CARDIOVASCULAR-DISEASE ,STRONG HEART FAMILY ,CORONARY-ARTERY CALCIFICATION ,Adult ,Adolescent ,Population ,INFLAMAÇÃO ,03 medical and health sciences ,Insulin resistance ,Sex Factors ,Linear regression ,medicine ,Humans ,Meta-analysi ,education ,observational studies ,Aged ,CANCER RISK ,business.industry ,II BASE-II ,medicine.disease ,Observational studie ,AMERICAN-INDIANS ,meta-analysis ,030104 developmental biology ,Cross-Sectional Studies ,PULSE-WAVE VELOCITY ,HELSINKI BIRTH COHORT ,business ,Body mass index ,Demography - Abstract
Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectionalmeta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Studyspecific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a-3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI:-10.03,-5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10-3 unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10-3, -1.01 × 10-3) difference in ageand sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10-3 unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10-3, -1.25 × 10-3). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL arewarranted.
- Published
- 2018
26. Inhibition of osteoblast function by Brucella abortus is reversed by dehydroepiandrosterone and involves ERK1/2 and estrogen receptor
- Author
-
María Virginia Gentilini, Gloria Edith Cerrone, Guillermo H. Giambartolomei, María Victoria Delpino, Paula Constanza Arriola Benitez, Andrea Elena Iglesias Molli, and Ayelén Ivana Pesce Viglietti
- Subjects
lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Immunology ,Ciencias de la Salud ,Estrogen receptor ,Dehydroepiandrosterone ,DEHYDROEPIANDROSTERONE ,cortisol ,03 medical and health sciences ,purl.org/becyt/ford/3.3 [https] ,dehydroepiandrosterone ,0302 clinical medicine ,Glucocorticoid receptor ,Internal medicine ,Bone cell ,medicine ,Immunology and Allergy ,Secretion ,ADRENAL STEROIDS ,BRUCELLA ,Chemistry ,CORTISOL ,adrenal steroids ,Osteoblast ,bacterial infections and mycoses ,IMMUNOENDOCRINOLOGY ,Brucella ,Enfermedades Infecciosas ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Apoptosis ,immunoendocrinology ,030220 oncology & carcinogenesis ,purl.org/becyt/ford/3 [https] ,Cortisone ,lcsh:RC581-607 ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Brucella abortus induces an inflammatory response that stimulates the endocrine system resulting in the secretion of cortisol and dehydroepiandrosterone (DHEA). Osteoarticular brucellosis is the most common presentation of the active disease in humans, and we have previously demonstrated that B. abortus infection inhibits osteoblast function. We aimed to evaluate the role of cortisol and DHEA on osteoblast during B. abortus infection. B. abortus infection induces apoptosis and inhibits osteoblast function. DHEA treatment reversed the effect of B. abortus infection on osteoblast by increasing their proliferation, inhibiting osteoblast apoptosis, and reversing the inhibitory effect of B. abortus on osteoblast differentiation and function. By contrast, cortisol increased the effect of B. abortus infection. Cortisol regulates target genes by binding to the glucocorticoid receptor (GR). B. abortus infection inhibited GRa expression. Cell responses to cortisol not only depend on GR expression but also on its intracellular bioavailability, that is, dependent on the activity of the isoenzymes 11β-hydroxysteroid dehydrogenase (HSD) type-1, 11β-HSD2 (which convert cortisone to cortisol and vice versa, respectively). Alterations in the expression of these isoenzymes in bone cells are associated with bone loss. B. abortus infection increased 11β-HSD1 expression but had no effect on 11β-HSD2. DHEA reversed the inhibitory effect induced by B. abortus infection on osteoblast matrix deposition in an estrogen receptor- and ERK1/2-dependent manner. We conclude that DHEA intervention improves osteoblast function during B. abortus infection making it a potential candidate to ameliorate the osteoarticular symptoms of brucellosis. Fil: Gentilini, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Pesce Viglietti, Ayelén Ivana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Arriola Benitez, Paula Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Iglesias Molli, Andrea Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Cerrone, Gloria Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
- Published
- 2018
27. Common and rare TBK1 variants in early-onset Alzheimer disease in a European cohort
- Author
-
Juan Fortea, Marc Cruts, Tobi Van den Bossche, Jan Versijpt, Alessandro Padovani, Luisa Benussi, Roberta Ghidoni, Alexandre de Mendonça, Elena Lorenzo, Manuel Seijo-Martínez, Jaume Campdelacreu, Sandro Sorbi, Radoslav Matej, Peter Paul De Deyn, Panagiotis Alexopoulos, Olivier Deryck, Albert Lladó, Pau Pastor, Frederico Simões do Couto, Rik Vandenberghe, Estrella Gómez-Tortosa, Zdenek Rohan, Jordi Clarimón, Anne Sieben, Jordi Gascon, Isabel Santana, Maria A. Pastor, Maria Koutroumani, Madalena Martins, Sebastiaan Engelborghs, Janine Diehl-Schmid, Christine Van Broeckhoven, Benedetta Nacmias, Patrick Santens, Lubina Dillen, Ilse Gijselinck, Giuliano Binetti, Silvia Bagnoli, Bruno Bergmans, Agustín Ruiz, Raquel Sánchez-Valle, Barbara Borroni, Maria Rosário Almeida, Kristel Sleegers, Ellen Gelpi, Adrian Ivanoiu, Bavo Heeman, Cristina Razquin, Magda Tsolaki, Elena Iglesias, Caroline Graff, Johan Goeman, Alberto Lleó, Valentina Bessi, Laura Fratiglioni, Jan Verheijen, Alex Michotte, Jan De Bleecker, Rafael Blesa, Julie van der Zee, Eric Salmon, Ramón Reñé, Dirk Nuytten, Mathieu Vandenbulcke, Bart Dermaut, Håkan Thonberg, Christiana Willems, BELNEU Consortium, EU EOD Consortium, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, Clinical sciences, Neurology, and Pathologic Biochemistry and Physiology
- Subjects
0301 basic medicine ,Oncology ,Male ,Aging ,TBK1 ,Early onset Alzheimer's disease ,Frontotemporal dementia ,Loss-of-function ,RNA sequencing ,Neuroscience (all) ,Neurology (clinical) ,Developmental Biology ,Geriatrics and Gerontology ,Disease ,Bioinformatics ,medicine.disease_cause ,AMYOTROPHIC-LATERAL-SCLEROSIS ,Loss of Function Mutation/genetics ,Cohort Studies ,Frontotemporal Dementia/genetics ,0302 clinical medicine ,Loss of Function Mutation ,Medicine and Health Sciences ,Early-onset Alzheimer's disease ,Family history ,Amyotrophic lateral sclerosis ,Medicine(all) ,Mutation ,General Neuroscience ,Homozygote ,Amyotrophic Lateral Sclerosis/genetics ,Middle Aged ,Protein-Serine-Threonine Kinases ,3. Good health ,ddc ,Europe ,Genetic Variation/genetics ,Frontotemporal Dementia ,Cohort ,Female ,Risk ,medicine.medical_specialty ,Heterozygote ,BINDING KINASE 1 ,Protein-Serine-Threonine Kinases/genetics ,Neuroscience(all) ,Clinical Neurology ,IMMUNITY ,Biology ,Protein Serine-Threonine Kinases ,03 medical and health sciences ,Early onset Alzheimer’s disease ,Alzheimer Disease ,Internal medicine ,medicine ,Humans ,BELGIAN COHORT ,Loss function ,Alleles ,Genetic Association Studies ,Aged ,Alzheimer Disease/genetics ,MUTATIONS ,Amyotrophic Lateral Sclerosis ,Biology and Life Sciences ,Genetic Variation ,medicine.disease ,Ageing ,030104 developmental biology ,Human medicine ,030217 neurology & neurosurgery - Abstract
TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are known to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), often combined with memory deficits early in the disease course. We performed targeted resequencing of TBK1 in 1253 early onset Alzheimer's disease (EOAD) patients from 8 European countries to investigate whether pathogenic TBK1 mutations are enriched among patients with clinical diagnosis of EOAD. Variant frequencies were compared against 2117 origin-matched controls. We identified only 1 LoF mutation (p.Thr79del) in a patient clinically diagnosed with Alzheimer's disease and a positive family history of ALS. We did not observe enrichment of rare variants in EOAD patients compared to controls, nor of rare variants affecting NFκB induction. Of 3 common coding variants, rs7486100 showed evidence of association (OR 1.46 [95% CI 1.13-1.9]; p-value 0.01). Homozygous carriers of the risk allele showed reduced expression of TBK1 (p-value 0.03). Our findings are not indicative of a significant role for TBK1 mutations in EOAD. The association between common variants in TBK1, disease risk and reduced TBK1 expression warrants follow-up in FTD/ALS cohorts. ispartof: Neurobiology of Aging vol:62 pages:245- ispartof: location:United States status: published
- Published
- 2018
28. Metabolically healthy obese individuals present similar chronic inflammation level but less insulin-resistance than obese individuals with metabolic syndrome
- Author
-
Jorge Vilariño, Gloria Edith Cerrone, Andrea Elena Iglesias Molli, Alberto Penas Steinhardt, Ariel Pablo Lopez, Claudio Gonzalez, and Gustavo Daniel Frechtel
- Subjects
Male ,Physiology ,medicine.medical_treatment ,Adipose tissue ,lcsh:Medicine ,Cardiovascular Medicine ,030204 cardiovascular system & hematology ,Pathology and Laboratory Medicine ,Biochemistry ,Body Mass Index ,0302 clinical medicine ,Glucose Metabolism ,Immune Physiology ,Medicine and Health Sciences ,lcsh:Science ,Immune Response ,Metabolic Syndrome ,Innate Immune System ,education.field_of_study ,Multidisciplinary ,biology ,purl.org/becyt/ford/3.1 [https] ,Medicina Básica ,Physiological Parameters ,Adipose Tissue ,Cardiovascular Diseases ,Carbohydrate Metabolism ,Cytokines ,purl.org/becyt/ford/3 [https] ,Female ,Anatomy ,Research Article ,Adult ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Immunology ,Population ,Genética Humana ,030209 endocrinology & metabolism ,Young Adult ,03 medical and health sciences ,Signs and Symptoms ,Insulin resistance ,Diagnostic Medicine ,Internal medicine ,medicine ,Humans ,Obesity ,education ,Inflammation ,business.industry ,Insulin ,Body Weight ,C-reactive protein ,lcsh:R ,Biology and Life Sciences ,Molecular Development ,medicine.disease ,Biological Tissue ,Metabolism ,Endocrinology ,Metabolic Disorders ,Immune System ,Chronic Disease ,biology.protein ,lcsh:Q ,Insulin Resistance ,Metabolic syndrome ,business ,Body mass index ,Developmental Biology - Abstract
The Metabolic Syndrome (MetS) is a cluster of cardiometabolic risk factors, usually accompanied by the presence of insulin resistance (IR) and a systemic subclinical inflammation state. Metabolically healthy obese (MHO) individuals seem to be protected against cardiometabolic complications. The aim of this work was to characterize phenotypically the low-grade inflammation and the IR in MHO individuals in comparison to obese individuals with MetS and control non obese. We studied two different populations: 940 individuals from the general population of Buenos Aires and 518 individuals from the general population of Venado Tuerto; grouped in three groups: metabolically healthy non-obese individuals (MHNO), MHO and obese individuals with MetS (MSO). Inflammation was measured by the levels of hs-CRP (high-sensitivity C reactive protein), and we found that MHO presented an increase in inflammation when compared with MHNO (Buenos Aires: p
- Published
- 2017
29. Un caso de estudio de impacto ambiental: el embalse de Vallfornés. Cataluña-España
- Author
-
Elena Iglesias and Alejandro Pinedo
- Subjects
Building construction ,Environmental Engineering ,business.industry ,Building and Construction ,Environmental characterization ,NA1-9428 ,lcsh:TH1-9745 ,Natural park ,Architecture ,Environmental science ,Environmental impact assessment ,lcsh:Architecture ,Project management ,business ,Environmental planning ,Environmental quality ,TH1-9745 ,Civil and Structural Engineering ,lcsh:NA1-9428 ,lcsh:Building construction - Abstract
Environmental impact studies are used as a tool in project development to attain an adequate integration of the proposed activities in their environments so that adverse effects that are likely to affect the environmental quality can be avoided or reduced. The Vallfornés reservoir project case, whose main objective is storing water for irrigation, has al so the peculiarity of being located in the Montseny Natural Park (Catalonia, Spain) thus needing not only a careful treatment of the projected works, but also the resolution of the unavoidable conflicts that can arise related to the Natural Park regulations. This paper focuses on the main aspects of the environmental Impact study of this reservoir project: Natural Park regulations that could affect the project, environmental characterization of the area, Identification, characterization and assessment of environmental impacts, and recommendations for reducing or avoiding impacts.Los estudios de impacto ambiental surgen de la necesidad de proyectar las actividades de la forma más adecuada posible, que facilite su integración en el medio natural en que han de inscribirse para que su calidad no se vea afectada. El caso del embalse de Vallfornés, cuya finalidad principal es el abastecimiento de agua para regadío, presenta además la peculiaridad de afectar a terrenos Incluidos dentro del Parque Natural de Montseny, lo que obliga no sólo a un tratamiento cuidadoso de la obra, sino también a la resolución de conflictos inevitables con la normativa existente. En el presente artículo se pasa revista a los principales aspectos del estudio de impacto ambiental de dicho embalse: análisis de las implicaciones derivadas de su ubicación en terrenos del Parque Natural del Montseny, caracterización del medio afectado, identificación de las acciones productoras de impacto, caracterización y valoración de los mismos y recomendaciones respecto a la corrección de los impactos potenciales.
- Published
- 1990
30. Proteomics analysis of the peritoneal dialysate effluent reveals the presence of calcium-regulation proteins and acute inflammatory response
- Author
-
Elisabete Oliveira, Cristina Perez-Melon, Carlos Lodeiro, Elena Iglesias-Lamas, J.E. Araújo, Alfonso Otero-Glez, Hugo M. Santos, Silvana Gómez-Meire, and José Luis Capelo
- Subjects
Fibrinogen-gamma chain ,Proteomics ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Clinical Biochemistry ,030232 urology & nephrology ,chemistry.chemical_element ,Calcium ,Pharmacology ,Peritoneal dialysis ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Molecular Biology ,030304 developmental biology ,Calcium metabolism ,0303 health sciences ,business.industry ,Research ,Albumin ,General Medicine ,medicine.disease ,3. Good health ,chemistry ,Peritoneal dialysis effluent ,Proteome ,Molecular Medicine ,2D-Gel Electrophoresis ,Protein identification ,business ,Kidney disease - Abstract
Background: Peritoneal dialysis (PD) is a form of renal replacement used for advanced chronic kidney disease. PD effluent holds a great potential for biomarker discovery for diagnosis and prognosis. In this study a novel approach to unravelling the proteome of PD effluent based-on dithiothreitol depletion followed by 2D-SDS-PAGE and protein identification using tandem mass spectrometry is proposed. Results: A total of 49 spots were analysed revealing 25 proteins differentially expressed, among them many proteins involved in calcium regulation. Conclusions: Remarkably, a group of proteins dealing with calcium metabolism and calcium regulation has been found to be lost through peritoneal dialysate effluent, giving thus a potential explanation to the calcification of soft tissues in patients subjected to peritoneal dialysis and kidney injury. Comparison of literature dealing with PD is difficult due to differences in sample treatment and analytical methodologies.
- Full Text
- View/download PDF
31. Metabolically healthy obese individuals present similar chronic inflammation level but less insulin-resistance than obese individuals with metabolic syndrome.
- Author
-
Andrea Elena Iglesias Molli, Alberto Penas Steinhardt, Ariel Pablo López, Claudio Daniel González, Jorge Vilariño, Gustavo Daniel Frechtel, and Gloria Edith Cerrone
- Subjects
Medicine ,Science - Abstract
The Metabolic Syndrome (MetS) is a cluster of cardiometabolic risk factors, usually accompanied by the presence of insulin resistance (IR) and a systemic subclinical inflammation state. Metabolically healthy obese (MHO) individuals seem to be protected against cardiometabolic complications. The aim of this work was to characterize phenotypically the low-grade inflammation and the IR in MHO individuals in comparison to obese individuals with MetS and control non obese. We studied two different populations: 940 individuals from the general population of Buenos Aires and 518 individuals from the general population of Venado Tuerto; grouped in three groups: metabolically healthy non-obese individuals (MHNO), MHO and obese individuals with MetS (MSO). Inflammation was measured by the levels of hs-CRP (high-sensitivity C reactive protein), and we found that MHO presented an increase in inflammation when compared with MHNO (Buenos Aires: p
- Published
- 2017
- Full Text
- View/download PDF
32. Bioimpedance and brain natriuretic peptide in peritoneal dialysis patients.
- Author
-
Crepaldi C, Lamas EI, Martino FK, Rodighiero MP, Scalzotto E, Wojewodzka-Zelezniakowicz M, Rosner MH, and Ronco C
- Subjects
- Electric Impedance, Female, Humans, Hypertension etiology, Ideal Body Weight, Male, Peptide Fragments blood, Body Water metabolism, Natriuretic Peptide, Brain blood, Peritoneal Dialysis adverse effects
- Abstract
Assessment of ideal body weight in peritoneal dialysis (PD) patients is important for clinical practice. Fluid overload may produce hypertension, reduced arterial distensibility, left ventricular hypertrophy. All these are risk factors for mortality in PD patients: cardio- and cerebrovascular events are the main causes of morbidity and mortality in PD population. Nowadays, a clear and widely accepted definition of ideal body weight in PD patients does not exist. Probably the ideal body weight is the weight at which the extra cellular volume is normal. Many different tools have been used to assess the hydration status in dialysis patients. Ultrasonic evaluation of inferior vena cava diameter only assesses intravascular volume, and is also influenced by diastolic dysfunction and is thus a reflection of preload and not of tissue hydration. Direct measurement of extra cellular and total body water by dilution methods is considered as the golden standard, but these techniques are laborious and expensive. Parameters, such as brain natriuretic peptide (BNP) or NT-proBNP can reflect changes in hydration status and may help the nephrologist to estimate it. Natriuretic peptides are influenced both by preload and ventricular abnormalities and in patients with renal failure accumulation can occur. Bioimpedance is an accurate, reproducible, not expensive and not invasive technique that permits a good evaluation of hydration status in PD and can drive the nephrologist in his clinical choices. Clinical evaluation, strict control of body weight, diuresis, sodium and fluids intakes, bioimpedance monitoring and serum levels of natriuretic peptides may all together help us to maintain the PD patient euvolemic., (Copyright © 2012 S. Karger AG, Basel.)
- Published
- 2012
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.