Diz-Chaves Y.,Instituto Cajal |
Baquedano E.,Autonomous University of Madrid |
Baquedano E.,CIBER ISCIII |
Baquedano E.,Institute Investigacion Sanitaria Princesa |
And 8 more authors.
Psychoneuroendocrinology | Year: 2013
Maternal stress results in behavioral and anatomical alterations that persist during adult life. Here we demonstrate that hippocampal neurons cultured from embryos of stressed mothers exhibit faster development of their soma and neuritic arbor with an increase in the number of presynaptic terminals compared to cultured neurons from embryos of non-stressed mothers. Therefore, the impact of maternal stress on developing neurons is maintained even when these cells are dissociated from the brain and differentiated in vitro. © 2012 Elsevier Ltd.
Martin-Cofreces N.B.,Institute Investigacion Sanitaria Princesa |
Baixauli F.,Institute Investigacion Sanitaria Princesa |
Lopez M.J.,Institute Investigacion Sanitaria Princesa |
Gil D.,Rochester College |
And 3 more authors.
EMBO Journal | Year: 2012
The role of microtubules (MTs) in the control and dynamics of the immune synapse (IS) remains unresolved. Here, we show that T cell activation requires the growth of MTs mediated by the plus-end specific protein end-binding 1 (EB1). A direct interaction of the T cell receptor (TCR) complex with EB1 provides the molecular basis for EB1 activity promoting TCR encounter with signalling vesicles at the IS. EB1 knockdown alters TCR dynamics at the IS and prevents propagation of the TCR activation signal to LAT, thus inhibiting activation of PLCγ1 and its localization to the IS. These results identify a role for EB1 interaction with the TCR in controlling TCR sorting and its connection with the LAT/PLCγ1 signalosome. © 2012 European Molecular Biology Organization | All Rights Reserved.
Bordin D.S.,Moscow Clinical Research and Practical Center |
Yanova O.B.,Moscow Clinical Research and Practical Center |
Abdulkhakov R.A.,Kazan State Medical University |
Tsukanov V.V.,Research Institute for Medical Problems of the North |
And 22 more authors.
Terapevticheskiĭ arkhiv | Year: 2016
AIM: To assess the clinical practice of diagnosis and treatment in patients with Helicobacter pylori infection and to compare this practice with the international guidelines in the European Registry on the management of Helicobacter pylori infection, Hp-EuReg protocol), a multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group. MATERIALs AND METHODS: The data of 813 patients infected with H. pylori and entered in the Hp-EuReg register by the Russian centers in 2013-2015 were analyzed.RESULTS: The most common methods for the primary diagnosis of H. pylori infection are histology (40.3%), rapid urease test (35.7%), and serology (17.2%). The duration of H. pylori eradication therapy was 7, 10, and 14 days in 18.0, 49.3, and 25.1%, respectively. To monitor the effectiveness of treatment, the investigators used a histological examination (34%), a urea breath test (27.3%), H. pylori stool antigen (22.8%), and a rapid urease test (16.3%). A serological test was carried out in 2.5% of the cases. No monitoring was done in 13.5% of the patients. The average eradication efficiency was 82.6%. If the therapy was ineffective, 80% of physicians did not intend to prescribe a new cycle of treatment.CONCLUSION: Significant differences were found between clinical practice and the current guidelines.Abstract available from the publisher.
Garcia-Guerra L.,Complutense University of Madrid |
Garcia-Guerra L.,CIBER ISCIII |
Nieto-Vazquez I.,Complutense University of Madrid |
Nieto-Vazquez I.,CIBER ISCIII |
And 11 more authors.
Diabetes | Year: 2010
OBJECTIVE - Insulin resistance is associated with the pathogenesis of metabolic disorders as type 2 diabetes and obesity. Given the emerging role of signal transduction in these syndromes, we set out to explore the possible role that G protein-coupled receptor kinase 2 (GRK2), first identified as a G protein-coupled receptor regulator, could have as a modulator of insulin responses. RESEARCH DESIGN AND METHODS - We analyzed the influence of GRK2 levels in insulin signaling in myoblasts and adipocytes with experimentally increased or silenced levels of GRK2, as well as in GRK2 hemizygous animals expressing 50% lower levels of this kinase in three different models of insulin resistance: tumor necrosis factor-α (TNF-α) infusion, aging, and high-fat diet (HFD). Glucose transport, whole-body glucose and insulin tolerance, the activation status of insulin pathway components, and the circulating levels of important mediators were measured. The development of obesity and adipocyte size with age and HFD was analyzed. RESULTS - Altering GRK2 levels markedly modifies insulin-mediated signaling in cultured adipocytes and myocytes. GRK2 levels are increased by ∼2-fold in muscle and adipose tissue in the animal models tested, as well as in lymphocytes from metabolic syndrome patients. In contrast, hemizygous GRK2 mice show enhanced insulin sensitivity and do not develop insulin resistance by TNF-α, aging, or HFD. Furthermore, reduced GRK2 levels induce a lean phenotype and decrease age-related adiposity. CONCLUSIONS - Overall, our data identify GRK2 as an important negative regulator of insulin effects, key to the etiopathogenesis of insulin resistance and obesity, which uncovers this protein as a potential therapeutic target in the treatment of these disorders. © 2010 by the American Diabetes Association.
Baquedano E.,Autonomous University of Madrid |
Baquedano E.,Hospital Infantil Universitario Nino Jesus |
Baquedano E.,Institute Investigacion Sanitaria Princesa |
Baquedano E.,CIBER ISCIII |
And 31 more authors.
DMM Disease Models and Mechanisms | Year: 2016
Insulin receptor substrate-2-deficient (IRS2-/-) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2-/- mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2-/- mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2-/- mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, nondiabetic IRS2-/- mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. © 2016. Published by The Company of Biologists Ltd.
Cano-Abad M.F.,Hospital Universitario Of La Princesa |
Cano-Abad M.F.,Autonomous University of Madrid |
Cano-Abad M.F.,Institute Investigacion Sanitaria Princesa |
Herrera-Peco I.,Hospital Universitario Of La Princesa |
And 13 more authors.
International Journal of Developmental Neuroscience | Year: 2011
Primary brain cell cultures are a useful tool for understanding the physiopathology of epilepsy and for searching new potential antiepileptic drugs. These cell types are usually prepared from murine species and few human models have been described. The main goal of this study is the establishment of experimental conditions to isolate and culture neurons and astrocytes from human brain and to test its functionality. The tissues came from antiepileptic drug-resistant epileptic patients undergoing surgery. Human neurons and astrocytes were isolated following an enzymatic and mechanical dissociation protocol. Cultures were viable for 3-6 weeks. Cytological characterization was performed by immunocytochemistry using specific antibodies against both neuron (anti-NeuN) and astrocyte (anti-GFAP) protein markers. In order to test their viability and functionality, cells were loaded with the fluorescent calcium probe fura-2 and variations in cytosolic calcium concentrations ([Ca2+]c) were measured by cell imaging. [Ca2+]c increases were evoked upon cell stimulation with high K+ (KCl 75mM), glutamate (500μM) or bicuculline (100μM). Interestingly, spontaneous [Ca2+]c transients were also observed in some neuron-like cells. A novel unreported finding in this study has been the incorporation of human serum that was critical for cell functionality. The setting of these human cultures open the opportunity to new insights on culture and calcium signalling studies on the mechanism(s) of cell resistance to antiepileptic drugs, as well as to studies on plasticity, maturation and possible neurite emission for graft studies. © 2011 ISDN.
PubMed | Autonomous University of Madrid and Institute Investigacion Sanitaria Princesa
Type: | Journal: The British journal of dermatology | Year: 2016
Indoleamine 2,3-dioxygenase (IDO) is an inducible enzyme that suppresses the immune response. The role of IDO as a negative regulator of inflammatory responses has been documented in several experimental autoimmune diseases.To explore the regulation of IDO by immune cells in psoriasis and its relation with disease severity.The expression and activity of IDO were assessed by reverse-transcriptase polymerase chain reaction, flow cytometry and high-performance liquid chromatography in peripheral blood of patients with moderate-to-severe plaque-type psoriasis. The ability of immune cells to express IDO in response to inflammatory stimuli was studied. The functional role of IDO expression was evaluated in a regulatory T cell (Treg) differentiation assay, using cocultures of immature monocyte-derived dendritic cells with autologous peripheral CD4Analysis of the kynurenine-to-tryptophan ratio in serum samples indicated higher IDO activity in patients with psoriasis than in healthy controls. However, correlation studies showed lower IDO activity in those patients with higher Psoriasis Area and Severity Index (PASI). Although myeloid dendritic cells from patients with psoriasis expressed higher levels of IDO than those from healthy controls, these cells did not upregulate IDO in response to a combination of tumour necrosis factor-, interleukin (IL)-1 and IL-6 cytokines. The defective expression of IDO correlated with PASI. Immature monocyte-derived dendritic cells from patients with psoriasis also expressed low levels of IDO and induced CD4Immune cells from patients with psoriasis have a defect in upregulating IDO in response to inflammation associated with the severity of psoriasis.
Garcia-Monzon C.,Santa Cristina University Hospital |
Vargas-Castrillon J.,Santa Cristina University Hospital |
Porrero J.L.,Santa Cristina University Hospital |
Alonso M.T.,Santa Cristina University Hospital |
And 14 more authors.
Liver International | Year: 2015
Background & Aims: Relationship between gallstones and non-alcoholic fatty liver disease (NAFLD), and largely non-alcoholic steatohepatitis (NASH), is uncertain. Aim: To determine the prevalence, non-invasive fibrosis markers profile and risk factors for biopsy-proven NAFLD and NASH among patients with gallstones. Methods: Anthropometric and laboratory evaluation, an abdominal ultrasound and a liver biopsy were performed to 215 consecutive patients with gallstones referred for cholecystectomy. Results: Prevalence of NASH was 10.2% whereas that of simple steatosis (SS) was 41.4%. In the cohort of NAFLD patients, negative predictive values for advanced fibrosis of FIB-4 and NAFLD fibrosis score were 96 and 95% respectively. Gallstone patients with NASH had a higher mean homeostatic model assessment (HOMA) score than those with SS (P = 0.015). Noteworthy, NASH was 2.5-fold more frequent in patients with gallstones who had metabolic syndrome than in those who did not (P < 0.001). Fatty liver on ultrasound was observed in 90.9% of gallstone patients with NASH compared with 61.8% of those with SS (P = 0.044). Using multivariate logistic regression, increased HOMA score (OR, 3.47; 95% CI, 1.41-8.52; P = 0.007) and fatty liver on ultrasound (OR, 23.27; 95% CI, 4.15-130.55; P < 0.001) were the only factors independently associated with NASH. Conclusions: Prevalence of NASH among patients with gallstones is lower than estimated previously, but NASH is frequent particularly in those patients with concurrent metabolic syndrome. The combination of an increased HOMA score with fatty liver on ultrasound has a good accuracy for predicting NASH in patients with gallstones. © 2015 John Wiley & Sons A/S.
PubMed | Santa Cristina University Hospital, Institute Investigacion Sanitaria Princesa and Hospital del Tajo
Type: Comparative Study | Journal: Liver international : official journal of the International Association for the Study of the Liver | Year: 2015
Relationship between gallstones and non-alcoholic fatty liver disease (NAFLD), and largely non-alcoholic steatohepatitis (NASH), is uncertain.To determine the prevalence, non-invasive fibrosis markers profile and risk factors for biopsy-proven NAFLD and NASH among patients with gallstones.Anthropometric and laboratory evaluation, an abdominal ultrasound and a liver biopsy were performed to 215 consecutive patients with gallstones referred for cholecystectomy.Prevalence of NASH was 10.2% whereas that of simple steatosis (SS) was 41.4%. In the cohort of NAFLD patients, negative predictive values for advanced fibrosis of FIB-4 and NAFLD fibrosis score were 96 and 95% respectively. Gallstone patients with NASH had a higher mean homeostatic model assessment (HOMA) score than those with SS (P = 0.015). Noteworthy, NASH was 2.5-fold more frequent in patients with gallstones who had metabolic syndrome than in those who did not (P < 0.001). Fatty liver on ultrasound was observed in 90.9% of gallstone patients with NASH compared with 61.8% of those with SS (P = 0.044). Using multivariate logistic regression, increased HOMA score (OR, 3.47; 95% CI, 1.41-8.52; P = 0.007) and fatty liver on ultrasound (OR, 23.27; 95% CI, 4.15-130.55; P < 0.001) were the only factors independently associated with NASH.Prevalence of NASH among patients with gallstones is lower than estimated previously, but NASH is frequent particularly in those patients with concurrent metabolic syndrome. The combination of an increased HOMA score with fatty liver on ultrasound has a good accuracy for predicting NASH in patients with gallstones.