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Search Results: 1 - 10 of 188657 matches for " Sanz de Miguel "
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Increased Endoplasmic Reticulum Stress and Decreased Proteasomal Function in Lafora Disease Models Lacking the Phosphatase Laforin
Santiago Vernia, Teresa Rubio, Miguel Heredia, Santiago Rodríguez de Córdoba, Pascual Sanz
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005907
Abstract: Background Lafora progressive myoclonus epilepsy (Lafora disease; LD) is a fatal autosomal recessive neurodegenerative disorder caused by loss-of-function mutations in either the EPM2A gene, encoding the dual specificity phosphatase laforin, or the EPM2B gene, encoding the E3-ubiquitin ligase malin. Previously, we and others have shown that both proteins form a functional complex that regulates glycogen synthesis by a novel mechanism involving ubiquitination and proteasomal degradation of at least two proteins, glycogen synthase and R5/PTG. Since laforin and malin localized at the endoplasmic reticulum (ER) and their regulatory role likely extend to other proteins unrelated to glycogen metabolism, we postulated that their absence may also affect the ER-unfolded protein response pathway. Methodology/Principal Findings Here, we demonstrate that siRNA silencing of laforin in Hek293 and SH-SY5Y cells increases their sensitivity to agents triggering ER-stress, which correlates with impairment of the ubiquitin-proteasomal pathway and increased apoptosis. Consistent with these findings, analysis of tissue samples from a LD patient lacking laforin, and from a laforin knockout (Epm2a-/-) mouse model of LD, demonstrates constitutive high expression levels of ER-stress markers BIP/Grp78, CHOP and PDI, among others. Conclusions/Significance We demonstrate that, in addition to regulating glycogen synthesis, laforin and malin play a role protecting cells from ER-stress, likely contributing to the elimination of unfolded proteins. These data suggest that proteasomal dysfunction and ER-stress play an important role in the pathogenesis of LD, which may offer novel therapeutic approaches for this fatal neurodegenerative disorder.
Bifidobacterium strains suppress in vitro the pro-inflammatory milieu triggered by the large intestinal microbiota of coeliac patients
Marcela Medina, Giada De Palma, Carmen Ribes-Koninckx, Miguel Calabuig, Yolanda Sanz
Journal of Inflammation , 2008, DOI: 10.1186/1476-9255-5-19
Abstract: The effect of faeces of 26 CD patients with active disease (mean age 5.5 years, range 2.1–12.0 years), 18 symptom-free coeliac disease (SFCD) patients (mean age 5.5 years, range 1.0–12.3 years) on a gluten-free diet for 1–2 years; and 20 healthy children (mean age 5.3 years, range 1.8–10.8 years) on induction of cytokine production and surface antigen expression in peripheral blood mononuclear cells (PBMCs) were determined. The possible regulatory roles of Bifidobacterium longum ES1 and B. bifidum ES2 co-incubated with faecal samples were also assessed in vitro.Faeces of both active CD and SFCD patients, representing an imbalanced microbiota, significantly increased TNF-α production and CD86 expression in PBMCs, while decreased IL-10 cytokine production and CD4 expression compared with control samples. Active CD-patient samples also induced significantly higher IFN-γ production compared with controls. However, Bifidobacterium strains suppressed the pro-inflammatory cytokine pattern induced by the large intestinal content of CD patients and increased IL-10 production. Cytokine effects induced by faecal microbiota seemed to be mediated by the NFκB pathway.The intestinal microbiota of CD patients could contribute to the Th1 pro-inflammatory milieu characteristic of the disease, while B. longum ES1 and B. bifidum ES2 could reverse these deleterious effects. These findings hold future perspectives of interest in CD therapy.Coeliac disease (CD) is an enteropathy characterized by an aberrant immune response to ingested wheat-gluten proteins (gliadins) and related prolamins of rye and barley, occurring in genetically predisposed (HLA-DQ2/DQ8) individuals. The pathogenesis of CD involves interaction with genetic, immunological and environmental factors. HLA-DQ2/DQ8 molecules of antigen-presenting cells bind and present gluten peptides to lamina propria CD4+ T cells, triggering a T helper 1 (Th1) biased immune response, mainly with interferon gamma (IFN-γ) production, which e
Nivel de arsénico en abastecimientos de agua de consumo de origen subterráneo en la comunidad de Madrid
Aragonés Sanz Nuria,Palacios Diez Margarita,Avello de Miguel Antonio,Gómez Rodríguez Pilar
Revista Espa?ola de Salud Pública , 2001,
Abstract: Fundamento: En 1998 se detectaron en la Comunidad de Madrid concentraciones de arsénico mayores de 50myg/l en algunos abastecimientos de agua de consumo de origen subterráneo, concentración máxima admisible en el agua de bebida en Espa a. El objetivo de este trabajo fue determinar la concentración de arsénico en el agua procedente de abastecimientos subterráneos en la Comunidad de Madrid. Métodos: Se presentan los resultados de los dos primeros muestreos realizados en el plan de seguimiento de niveles de arsénico establecido. En la primera fase se analizaron muestras de agua de los 353 abastecimientos censados por la Dirección General de Salud Pública de la Comunidad de Madrid. Con estos primeros resultados se realizó una clasificación de riesgo de los abastecimientos. En una segunda fase, seis meses después, se repitieron los análisis en los 35 abastecimientos que se consideró podían suponer un riesgo para la salud pública. Resultados: El 74% de los abastecimientos estudiados en la primera fase presentaron una concentración de arsénico menor de 10myg/l; el 22,6% contenía niveles entre 10 y 50myg/l; y en el 3,7% eran superiores a 50myg/l. La mayoría de los abastecimientos con niveles de arsénico superiores a 10myg/l se encuentran situados en la misma zona geográfica. En el segundo muestreo (6 meses después) se incluyeron los 35 abastecimientos clasificados de riesgo. De ellos, 26 presentaron el mismo nivel de arsénico (10-50myg/l) y 9 cambiaron de categoría: 6 pasaron a tener menos de 10myg/l y 3 más de 50myg/l. Conclusiones: La vigilancia periódica de la calidad del agua realizada por la Dirección General de Salud Pública ha permitido detectar la presencia de 16 abastecimientos de agua de consumo de origen subterráneo con más de 50myg/l de arsénico, nivel máximo admisible según la legislación vigente en nuestro país. Se han adoptado medidas para evitar el consumo de agua en estos abastecimientos.
Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infections among high-risk neutropenic patients in Spain
Santiago Grau, Rafael de la Cámara, Francisco J Sabater, Isidro Jarque, Enric Carreras, Miguel A Casado, Miguel A Sanz
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-83
Abstract: A decision-analytic model, based on a randomised phase III trial, was used to predict IFI avoided, life-years saved (LYS), total costs, and incremental cost-effectiveness ratio (ICER; incremental cost per LYS) over patients' lifetime horizon. Data for the analyses included life expectancy, procedures, and costs associated with IFI and the drugs (in euros at November 2009 values) which were obtained from the published literature and opinions of an expert committee. A probabilistic sensitivity analysis (PAS) was performed.Posaconazole was associated with fewer IFI (0.05 versus 0.11), increased LYS (2.52 versus 2.43), and significantly lower costs excluding costs of the underlying condition (€6,121 versus €7,928) per patient relative to SAT. There is an 85% probability that posaconazole is a cost-saving strategy compared to SAT and a 97% probability that the ICER for posaconazole relative to SAT is below the cost per LYS threshold of €30,000 currently accepted in Spain.Posaconazole is a cost-saving prophylactic strategy (lower costs and greater efficacy) compared with fluconazole or itraconazole in high-risk neutropenic patients.Patients with neutropenia as a result of chemotherapy for acute myelogenous leukaemia (AML) or myelodysplastic syndrome (MDS) are at high risk of developing invasive fungal infection (IFI) [1-7]. Early diagnosis and treatment of IFI are difficult and, as such, are associated with high mortality rates in neutropenic patients. Hence, prophylaxis of IFI has become a commonly used strategy to reduce overall morbidity-mortality rates in patients with haematologic malignancies [8].Posaconazole is a new-generation oral azole [9] that has been demonstrated to be superior to standard azole therapy (SAT; fluconazole or itraconazole) in preventing IFI and reducing overall mortality in high-risk neutropenic patients [10]. In a recent study, posaconazol was shown not only to be as efficacious as fluconazole in the prevention of IFI but also superior to fluc
Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children
Giada De Palma, Inmaculada Nadal, Marcela Medina, Ester Donat, Carmen Ribes-Koninckx, Miguel Calabuig, Yolanda Sanz
BMC Microbiology , 2010, DOI: 10.1186/1471-2180-10-63
Abstract: IgA-coated faecal bacterial levels were significantly lower in both untreated and treated CD patients than in healthy controls. IgG and IgM-coated bacterial levels were also significantly lower in treated CD patients than in untreated CD patients and controls. Gram-positive to Gram-negative bacteria ratio was significantly reduced in both CD patients compared to controls. Bifidobacterium, Clostridium histolyticum, C. lituseburense and Faecalibacterium prausnitzii group proportions were less abundant (P < 0.050) in untreated CD patients than in healthy controls. Bacteroides-Prevotella group proportions were more abundant (P < 0.050) in untreated CD patients than in controls. Levels of IgA coating the Bacteroides-Prevotella group were significantly reduced (P < 0.050) in both CD patients in comparison with healthy controls.In CD patients, reduced IgA-coated bacteria is associated with intestinal dysbiosis, which altogether provide new insights into the possible relationships between the gut microbiota and the host defences in this disorder.Coeliac disease (CD) is a chronic intestinal inflammatory disorder triggered by the ingestion of gluten proteins in susceptible individuals. The active phase of the disease is characterized by a pro-inflammatory intestinal milieu resulting from an aberrant immune response to dietary gluten, along with increased epithelial permeability, which may favour the traffic of luminal antigens to the submucosa [1]. In CD patients, gliadin peptides can activate either an adaptive immune response dominated by Th1 pro-inflammatory cytokines (e.g. IFN-γ) within the mucosa or an innate immune response mediated by IL-15, both of which lead to epithelial cell killing [2]. Gliadin also activates the zonulin pathway leading to an increase in intestinal permeability [1].The aetiology of CD is multifactorial, involving genetic and environmental factors. This disorder is strongly associated to the human leukocyte antigen genes (HLA). Approximately 95% of
Recensiones y crónica científica
Ayarzagüena Sanz, Mariano,Blanco González, Antonio,González Sainz, César,Rubio de Miguel, Isabel
Trabajos de Prehistoria , 2004,
Avances en el tratamiento de los pacientes con Leucemia Promielocítica Aguda en Recaída
A. Sanz Miguel
Iatreia , 2006,
Abstract: Hasta la demostración de la actividad sobresaliente del trióxido de arsénico (ATO) en recaídas de pacientes con leucemia promielocítica (LPA), el tratamiento de rescate en esta enfermedad consistía en la readministración de ácido holo-trans retinóico (ATRA) y quimioterapia para inducir la remisión, generalmente conteniendo citarabina a altas dosis, seguido de consolidación y/o trasplante de progenitores hematopoyéticos (TPH).
Nuevas fronteras en el trasplante de progenitores hematopoyéticos: el trasplante de células de cordón umbilical, una realidad en el tratamiento de Pacientes Adultos con Leucemia
Miguel A. Sanz
Iatreia , 2006,
Abstract: Los continuos avances en el trasplante alogénico de progenitores hematopoyéticos no sólo han mejorado los resultados clínicos en una variedad de enfermedades malignas y no malignas, sino que también han ampliado las indicaciones de tales trasplantes.
Empleo del NMP22 Bladder-Chek en el diagnóstico y seguimiento del cáncer de vejiga
Gonzalo Rodríguez,Victoria; Sanz Justo,Lourdes; Miguel Santamaría,Isabel De; Martínez de Iturrate,Javier; Fernández del Busto,Ernesto;
Archivos Espa?oles de Urología (Ed. impresa) , 2008, DOI: 10.4321/S0004-06142008000300004
Abstract: objectives: the goal of this work is to evaluate the usefulness of nmp22 bladderchek in the diagnosis and follow-up of bladder cancer, comparing it with cystoscopy and urine cytology. methods: group 1: 109 asymptomatic patients on follow up for bladder cancer underwent cystoscopy, cytology and nmp22 bladderchek. group 2: 15 patients with history of hematuria underwent cystoscopy and nmp22 bladderchek. results: group 1: 9 patients had tumor relapse. sensitivity was 25% for nmp22 test, 50% for citology and 100% for cystoscopy. specificity was 91.1%, 94.1% and 95% respectively. group 2: 12 patients had bladder cancer. the sensitivity was of 83.3% for nmp22 bladderchek and 100% for cystoscopy. the specificity was of 100% for nmp22 bladderchek and 66.7% for cystoscopy. conclusions: the low sensitivity of nmp22 bladder-chek invalidates it as alternative method to cystoscopy in the follow-up of bladder cancer. but it can be recommended for screening in patients without history of bladder cancer but with an increased risk (smokers, patients with dysuria and hematuria).
Pau Montesinos,Miguel A Sanz
Mediterranean Journal of Hematology and Infectious Diseases , 2011, DOI: 10.4084/mjhid.2011.
Abstract: Differentiation syndrome (DS), formerly known as retinoic acid syndrome, is the main life-threatening complication of therapy with differentiating agents (all-trans retinoic acid [ATRA] or arsenic trioxide [ATO]) in patients with acute promyelocytic leukemia (APL). The differentiation of leukemic blasts and promyelocytes induced by ATRA and/or ATO may lead to cellular migration, endothelial activation, and release of interleukins and vascular factors responsible of tissue damage. Roughly one quarter of patients with APL undergoing induction therapy will develop the DS, characterized by unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, and/or a vascular capillary leak syndrome leading to acute renal failure. Although the development of the DS, particularly of the severe form, is still associated with a significant increase in morbidity and mortality during induction, the early administration of high-dose dexamethasone at the onset of the first symptoms seems likely to have dramatically reduced the mortality rate of this complication. In this article, we will review the clinical features, incidence, prognostic factors, management, and outcome of the DS reported in the scientific literature. We will make focus in the experience of the three consecutive Programa Espa ol de Tratamientos en Hematología trials (PETHEMA LPA96, LPA99, and LPA2005), in which more than one thousand patients were treated with ATRA plus idarubicin for induction.
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