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PubMed | Hospital Clinico, University of Zaragoza, Clinica Barraquer, Institute Investigacion Sanitaria Of Aragon and 2 more.
Type: Journal Article | Journal: Human molecular genetics | Year: 2014

Mitochondrial DNA mutations at MT-ATP6 gene are relatively common in individuals suffering from striatal necrosis syndromes. These patients usually do not show apparent histochemical and/or biochemical signs of oxidative phosphorylation dysfunction. Because of this, MT-ATP6 is not typically analyzed in many other mitochondrial disorders that have not been previously associated to mutations in this gene. To correct this bias, we have performed a screening of the MT-ATP6 gene in a large collection of patients suspected of suffering different mitochondrial DNA (mtDNA) disorders. In three cases, biochemical, molecular-genetics and other analyses in patient tissues and cybrids were also carried out. We found three new pathologic mutations. Two of them in patients showing phenotypes that have not been commonly associated to mutations in the MT-ATP6 gene. These results remark the importance of sequencing the MT-ATP6 gene in patients with striatal necrosis syndromes, but also within other mitochondrial pathologies. This gene should be sequenced at least in all those patients suspected of suffering an mtDNA disorder disclosing normal results for histochemical and biochemical analyses of respiratory chain.


Vicente E.,Hospital Miguel Servet | Vicente E.,CIBER ISCIII | Vicente E.,Institute Investigacion Sanitaria Of Aragon | Marin J.M.,CIBER ISCIII | And 14 more authors.
European Respiratory Journal | Year: 2016

Obstructive sleep apnoea (OSA) is associated with pharyngeal inflammation, but the coexistence of systemic inflammation is controversial. This study investigated whether local and systemic inflammatory biomarkers are related in patients with OSA. An uncontrolled extension to the study assessed the response to effective treatment. We recruited 89 patients with OSA (apnoea/hypopnoea index (AHI) ≥5 events · h-1), 28 snorers and 26 healthy controls. Pharyngeal lavage (PHAL) and plasma samples were collected at baseline and after a 1-year follow-up. Inflammatory cells were evaluated by flow cytometry; interleukin (IL)-6, IL-8 and tumour necrosis factor-α were evaluated by immunoassay. In PHAL, CD4+ T-cells, IL-6 and IL-8 were higher in OSA patients than in snorers or healthy controls ( p<0.05). The AHI correlated with CD4+, IL-6 and IL-8 in PHAL (all p-values <0.05). There were no differences in the inflammatory biomarkers in plasma between the study groups and no relationship between plasma and PHAL biomarkers. Biomarkers decreased significantly in PHAL but not in plasma after 1 year of therapy with continuous positive airway pressure or surgery. In patients with OSA, increased levels of inflammatory biomarkers were found in PHAL, which were reduced with effective treatment. No simultaneous increase in plasma inflammatory biomarkers was found. Copyright ©ERS 2016.


Garcia-Campayo J.,University of Zaragoza | Perez-Yus M.C.,Institute Investigacion Sanitaria Of Aragon | Garcia-Bustinduy M.,Hospital Universitario Of Canarias | Dauden E.,Hospital Universitario Of La Princesa
Actas Dermo-Sifiliograficas | Year: 2016

Many skin diseases are associated with mental disorders. When the psychological symptoms are mild, as is often the case in dermatology, it can be difficult to distinguish between normality and the manifestations of a mental disorder. To facilitate the distinction we review the concept of mental disorder in the present article. It is also important to have instruments that can facilitate early detection of psychological disease, i.e. when the symptoms are still mild. Short, simple, self-administered questionnaires have been developed to help dermatologists and other health professionals identify the presence of a mental disorder with a high degree of certainty. In this article, we focus on the questionnaires most often used to detect the 2 most common mental disorders: anxiety and depression. Finally, we describe the circumstances in which it is advisable to refer a dermatological patient to a psychiatrist, who can diagnose and treat the mental disorder in accordance with standard protocols. © 2015 Elsevier Espan∼a, S.L.U. and AEDV. All rights reserved.


Sanchez-Marteles M.,Hospital Clinico Universitario Lozano Blesa | Sanchez-Marteles M.,Institute Investigacion Sanitaria Of Aragon Iis Aragon | Rubio Gracia J.,Hospital Clinico Universitario Lozano Blesa | Rubio Gracia J.,Institute Investigacion Sanitaria Of Aragon Iis Aragon | And 2 more authors.
Revista Clinica Espanola | Year: 2016

Our understanding of the pathophysiological mechanisms of heart failure (HF) has changed considerably in recent years, progressing from a merely haemodynamic viewpoint to a concept of systemic and multifactorial involvement in which numerous mechanisms interact and concatenate. The effects of these mechanisms go beyond the heart itself, to other organs of vital importance such as the kidneys, liver and lungs. Despite this, the pathophysiology of acute HF still has aspects that elude our deeper understanding. Haemodynamic overload, venous congestion, neurohormonal systems, natriuretic peptides, inflammation, oxidative stress and its repercussion on cardiac and vascular remodelling are currently considered the main players in acute HF. Starting with the concept of acute HF, this review provides updates on the various mechanisms involved in this disease. © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI).


de Bagues M.P.J.,CSIC - Centro de Investigación y Tecnología Agroalimentaria | de Martino A.,Institute Investigacion Sanitaria Of Aragon | Quintana J.F.,CSIC - Centro de Investigación y Tecnología Agroalimentaria | Quintana J.F.,University of Zaragoza | And 2 more authors.
Infection and Immunity | Year: 2011

A new Brucella species, Brucella microti, has been isolated from wild rodents and found to be pathogenic in mice. The biological relevance of this new mouse pathogen is clear, as it allows us to study Brucella infection in a species-specific model. The course of infection in wild-type (wt) and immunodeficient mice that lack B (Jh), T and B (SCID), or T, B, and NK (SCID.Beige) cells was analyzed over 3 weeks. wt mice completely cleared bacteria from the liver and spleen after that time. However, SCID mice showed a much higher bacterial load in the spleen and liver than wt and Jh mice after 1 week and maintained the same level during the next 2 weeks. All mice tested survived for the 3 weeks. In contrast, the bacterial levels in mice that lacked NK cell activity progressively increased and these mice succumbed to infection after 16 to 18 days. Histopathology analysis of infected mice showed extensive areas of necrotic tissue and thrombosis in liver after 1 week in all infected SCID.Beige mice but were not seen in either SCID or wt animals. These processes were dramatically increased after 21 days, corresponding with the death of SCID.Beige animals. Our results indicate that T and/or B cells are required for the control of infection with the mouse pathogen Brucella microti in liver and spleen but that NK cells are crucial for survival in the absence of B and T cells. In addition, they suggest that controlled granuloma formation is critical to clear this type of infection in wt mice. © 2011, American Society for Microbiology.


Hernandez-Ferrer J.,Institute Carboquimica CSIC | Perez-Bruzon R.N.,University of Zaragoza | Azanza M.J.,University of Zaragoza | Gonzalez M.,Institute Carboquimica CSIC | And 6 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2014

Cultures of primary embryonic rat brain hippocampus neurons with supporting glia cells were carried out on different substrates containing polypyrrole (PPy) and/or single-walled carbon nanotubes (SWCNTs). Neuron adhesion, neurites and dendrites branching elongation, and development of neuron networks on substrates were followed by phase-contrast optical microscopy and quantified to state cell survival and proliferation. Suspensions of as-grown and purified SWCNTs were sprayed on a glass coverslips and PPy/SWCNTs were deposited by potentiodynamic electrochemical deposition. Cell neurotoxicity revealed by neuron death was very high for purified SWCNTs substrates in good agreement with [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) test showing lower viability on SWCNTs containing substrates compared with PPy-substrates and control samples probably due to the metal content and the carboxylic groups introduced during the purification. It is interesting to highlight that neurons grown on PPy-substrates adhere developing neurites and branching dendrites earlier even than on control cultures. On subsequent days the neurons are able to adapt to nanotube substrates developing neuron networks for 14-day cultures with similar patterns of complexity for control, PPy and PPy/SWCNT substrates. PPy/SWCNT substrates show a lower impedance value at frequencies under 1 Hz. We have come to the conclusion that glia cells and PPy added to the culture medium and substrates respectively, improve in some degree nanotube biocompatibility, cell adhesion and hence cell viability. © 2014 Wiley Periodicals, Inc.


Ascaso F.J.,Hospital Clinico Universitario Lozano Blesa | Ascaso F.J.,University of Zaragoza | Ascaso F.J.,Institute Investigacion Sanitaria Of Aragon | Huerva V.,University of Lleida
Optometry and Vision Science | Year: 2016

The incidence of diabetes mellitus is dramatically increasing in the developed countries. Tight control of blood glucose concentration is crucial to diabetic patients to prevent microvascular complications. Self-monitoring of blood glucose is widely used for controlling blood glucose levels and usually performed by an invasive test using a portable glucometer. Many technologies have been developed over the past decades with the purpose of obtaining a continuous physiological glycemic monitoring. A contact lens is the ideal vehicle for continuous tear glucose monitoring of glucose concentration in tear film. There are several research groups that are working in the development of contact lenses with embedded biosensors for continuously and noninvasively monitoring tear glucose levels. Although numerous aspects must be improved, contact lens technology is one step closer to helping diabetic subjects better manage their condition, and these contact lenses will be able to measure the level of glucose in the wearer's tears and communicate the information to a mobile phone or computer. This article reviews studies on ocular glucose and its monitoring methods as well as the attempts to continuously monitor the concentration of tear glucose by using contact lensYbased sensors. © 2015 American Academy of Optometry.


PubMed | Institute Investigacion Sanitaria Of Aragon, University of Zaragoza and Servicio de Bioquimica Clinica
Type: Journal Article | Journal: Clinical biochemistry | Year: 2016

The aim of this study was to compare fourteen non-invasive indexes/scores: AAR, APRI, Fibroindex, MODEL3, Forns index, FIB4, GUCI, FI, FCI, Pohl score, AP index, CDS, HGM-1 and HGM-2, in order to diagnose the hepatic fibrosis stage in a survey of patients with chronic hepatitis C.84 patients with chronic hepatitis C were studied. Liver fibrosis was staged according to the Scheuer scoring system. The diagnostic accuracy of these indexes/scores was evaluated by AUROC, contingency tables and logistic regression analysis.The best AUROCs (>0.9) to discriminate cirrhosis (F=4), were observed for CDS, FI, AAR, MODEL3, FIB4, HGM-2 and FCI. To discriminate at least advance fibrosis (F3), the best AUROCs (>0.89) were for CDS, FI, FIB4, HGM2-2, MODEL3 and FCI. To discriminate at least significant fibrosis (F2), the best AUROCs (>0.8) were for FIB4, GUCI, APRI, FI, Forns index, HGM-2 and FCI. Contingency tables and logistic regression analysis supported the results obtained by AUROC.This study compares the diagnostic performance of fourteen indexes for the diagnosis of liver fibrosis stage in the same group of CHC patients. These results allow the selection of the best indexes for further studies in larger populations, in order to build diagnostic algorithms as an alternative to liver biopsy for fibrosis staging in patients with chronic HCV infection. These algorithms would allow to take therapeutical decisions and the continuous follow-up of hepatic fibrosis in these patients.


PubMed | Institute Investigacion Sanitaria Of Aragon
Type: Journal Article | Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico | Year: 2011

One of the key problems in cancer gene therapy is the inefficient delivery of therapeutic transgenes to tumour sites, after the systemic injection of the viral vector. Hence, new vector discovery is extremely important for the improvement of gene therapy results. Previously, mammalian cells were proposed as new vector systems; however with recent advances in stem cell research this modality makes them more suitable candidates. Tumours are composed of both malignant and benign cells. As benign cell types are able to form blood vessels, and stroma, it has been hypothesised that exogenously administrated cells of a different kind would preferentially engraft at the stromal tumour site and could deliver cancer gene therapy vectors to tumours.


PubMed | Institute Investigacion Sanitaria Of Aragon, Hospital Universitario Of La Princesa, Hospital Universitario Of Canarias and España University
Type: Journal Article | Journal: Actas dermo-sifiliograficas | Year: 2016

Many skin diseases are associated with mental disorders. When the psychological symptoms are mild, as is often the case in dermatology, it can be difficult to distinguish between normality and the manifestations of a mental disorder. To facilitate the distinction we review the concept of mental disorder in the present article. It is also important to have instruments that can facilitate early detection of psychological disease, i.e. when the symptoms are still mild. Short, simple, self-administered questionnaires have been developed to help dermatologists and other health professionals identify the presence of a mental disorder with a high degree of certainty. In this article, we focus on the questionnaires most often used to detect the 2 most common mental disorders: anxiety and depression. Finally, we describe the circumstances in which it is advisable to refer a dermatological patient to a psychiatrist, who can diagnose and treat the mental disorder in accordance with standard protocols.

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