Tejera Segura B.,Hospital Universitario Germans Trias i Pujol |
Holgado S.,Hospital Universitario Germans Trias i Pujol |
Mateo L.,Hospital Universitario Germans Trias i Pujol |
Pego-Reigosa J.M.,Complejo Hospitalario Universitario Of Vigo |
And 3 more authors.
Medicina Clinica | Year: 2014
Background and objective Löfgren's syndrome is characterized by hiliar adenopathies, erythema nodosum and arthritis. It is a benign variant of sarcoidosis, common in the Mediterranean area. To describe the clinical characteristics, treatment and outcome of a series of patients diagnosed with Löfgren's syndrome. Patients and methods Retrospective design (1984-2013). Setting Two university hospitals with a reference population of 1,015,000 inhabitants. Results Eighty patients were diagnosed: 29 men and 51 women (mean age 42.3 years). Forty eight patients (60%) presented with the classical triad: hiliar adenopathies, erythema nodosum and arthritis; 18 (22%) with hiliar adenopathy and arthritis; 13 (16%) hiliar adenopathies and erythema nodosum. All showed abnormalities in the chest study. According to the radiological pattern, patients were classified in stage i-ii. Biopsy was performed in 39 patients and was diagnostic in 28. Treatment was based on non-steroidal anti-inflammatory drugs (54 patients, 67%) and corticosteroids (33 patients, 41%). Fourteen patients (17%) suffered a recurrence of the disease. Conclusions Löfgren's syndrome is a benign form of sarcoidosis with a well defined clinical pattern. Biopsy is usually not required. Recurrence is scarce. The disease has a good prognosis. © 2013 Elsevier Españ a, S.L. All rights reserved.
Cobo-Ibanez T.,Hospital Universitario Infanta Sofia |
Loza-Santamaria E.,Institute for Musculoskeletal Health |
Pego-Reigosa J.M.,Institute Investigacion Biomedica Of Vigo Ibiv |
Marques A.O.,Hospital Universitario Germans Trias i Pujol |
And 5 more authors.
Seminars in Arthritis and Rheumatism | Year: 2015
Objective: To analyse the efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus (SLE). Methods: We systematically searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials up to June 2013. The following were the selection criteria: (1) adult patients with SLE, (2) rituximab treatment, (3) placebo or active comparator, (4) outcome measures assessing efficacy and/or (5) safety. Meta-analysis, systematic literature reviews, randomised control trials (RCT), open clinical trials and cohort studies were included.Independent extraction of articles by 2 authors using predefined data fields was performed. The quality of each study was graded using the Oxford Levels of Evidence and Jadad's scale. Results: A total of 26 articles met our inclusion criteria: one RCT and its exploratory analysis, 2 open studies and 22 cohort studies, which analysed 1,231 patients. Overall, patients had active disease refractory to steroids and/or immunosuppressant drugs. Acceptable evidence suggested improvements in disease activity, arthritis, thrombocytopaenia, complement and anti-dsDNA, with a steroid-sparing effect. But relapses of disease were demonstrated too. Weak evidence suggested a response in anaemia, cutaneous and neuropsychiatric manifestations. Available evidence revealed few major adverse events. Studies had medium methodological quality and in general were applicable to current practice. Conclusion: Rituximab has been shown to be safe and effective in the treatment of non-renal SLE, especially in terms of disease activity, immunologic parameters and steroid-sparing effect. However, it can only be recommended for organ-specific manifestations such as arthritis and thrombocytopaenia. High-quality studies are needed in order to consider the long-term effects of re-treatment on different organ-specific manifestations. © 2014 Elsevier Inc.
Formentini L.,Autonomous University of Madrid |
Formentini L.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer |
Pereira M.P.,Autonomous University of Madrid |
Sanchez-Cenizo L.,Autonomous University of Madrid |
And 9 more authors.
EMBO Journal | Year: 2014
A key transducer in energy conservation and signaling cell death is the mitochondrial H+-ATP synthase. The expression of the ATPase inhibitory factor 1 (IF1) is a strategy used by cancer cells to inhibit the activity of the H+-ATP synthase to generate a ROS signal that switches on cellular programs of survival. We have generated a mouse model expressing a mutant of human IF1 in brain neurons to assess the role of the H+-ATP synthase in cell death in vivo. The expression of hIF1 inhibits the activity of oxidative phosphorylation and mediates the shift of neurons to an enhanced aerobic glycolysis. Metabolic reprogramming induces brain preconditioning affording protection against quinolinic acid-induced excitotoxicity. Mechanistically, preconditioning involves the activation of the Akt/p70S6K and PARP repair pathways and Bcl-xL protection from cell death. Overall, our findings provide the first in vivo evidence highlighting the H +-ATP synthase as a target to prevent neuronal cell death. © 2014 The Authors.
Nishishinya M.B.,Instituto Traumatologico Quiron |
Pereda C.A.,Clinica Mediterraneo |
Munoz-Fernandez S.,Hospital Universitario Infanta Sofia |
Pego-Reigosa J.M.,Complejo Hospitalario Universitario Of Vigo |
And 6 more authors.
Rheumatology International | Year: 2015
To identify risk and predictors of lymphoma or lymphoproliferative disease in patients with primary Sjögren syndrome. Articles were identified through a comprehensive search strategy in Medline, Embase and Cochrane CENTRAL. Studies had to investigate primary Sjögren syndrome patients, 18 years of age or older, with the goal of examining potential clinical, immunological and hematological risk factors for lymphoma or lymphoproliferative disease. The quality of the studies was graded using the Oxford Levels of Evidence Scale. Whenever possible, the authors created evidence tables and performed meta-analysis. Of 900 studies identified, 18 were selected for inclusion. These studies provided data from over 15,000 patients (90 % female) for analysis. Lymphadenopathy, parotid enlargement, palpable purpura, low C4 serum levels and cryoglobulins were the most consistent non-Hodgkin´s lymphoma/lymphoproliferative disease predictors. Additionally, some of the studies identified splenomegaly, low C3 serum levels, lymphopenia and neutropenia as significant prognostic factors. The detection of germinal center-like lesions in primary Sjögren Syndrome diagnostic salivary biopsies was also proposed as highly predictive of non-Hodgkin´s lymphoma. In contrast, anemia, anti-Ro, anti-La, antinuclear antibodies, rheumatoid factor, male gender and hypergammaglobulinemia were not associated with lymphoma or lymphoproliferative disease. Patients with primary Sjögren syndrome have an increased risk of lymphoma or lymphoproliferative disease compared to the general population. Ascertaining relevant and reliable predictors in this patient population would greatly facilitate the identification of patients at elevated risk for closer monitoring in the context of limited resources. © Springer-Verlag Berlin Heidelberg 2014.
Pousada G.,University of Vigo |
Pousada G.,Institute Investigacion Biomedica Of Vigo Ibiv |
Baloira A.,Complexo Hospitalario Universitario Of Pontevedra |
Valverde D.,University of Vigo |
Valverde D.,Institute Investigacion Biomedica Of Vigo Ibiv
Orphanet Journal of Rare Diseases | Year: 2015
Background: Pulmonary arterial hypertension (PAH) is a rare and progressive vascular disorder characterized by increased pulmonary vascular resistance and right heart failure. The aim of this study was to analyze 5'UTR region in canonical transient receptor potential isoform 6 (TRPC6) and 3'UTR region in Angiotensin II type I receptor (AGTR1) genes in patients with idiopathic and associated PAH. Correlation among mutations and clinical and functional parameters was further analyzed. Methods: Analysis of TRPC6 and AGTR1 genes was performed by polymerase chain reaction (PCR) and direct sequencing. We used a non-parametric test to determine if significant differences were found between the groups studied and chi-square test to compare clinical and hemodynamic variables among genotypes. Results: Fifty five patients and fifty two controls were included in this study. We found statistically significant differences for c.1-361A > T (p = 0.0077), c.1-254C > G (p < 0.0001) and c.1-218C > T (p = 0.0021) in TRPC6 gene and c.1166A > C (p < 0.001) in AGTR1 gene, between patients and controls. Idiopathic PAH patients (IPAH) and controls presented significant differences for all 3 TRPC6 polymorphisms (p = 0.020), (p = 0.002) and (p = 0.008) respectively, and also showed differences for AGTR1 gene (p < 0.001). In associated PAH (APAH) patients we found statistical differences for c.1-254C > G (p < 0.001) and c.1-218C > T (p = 0.001) in TRPC6 gene and c.1166A > C (p = 0.001) in AGTR1 gene. Several clinical and hemodynamic parameters showed significant differences between carriers and non-carriers of these single nucleotide polymorphisms (SNPs). Nineteen patients were carriers of all 3 SNPs in TRPC6 gene and presented a more severe phenotype with differences in mean pulmonary arterial pressure (p = 0.016), systolic pulmonary arterial pressure (p = 0.040), cardiac index (p < 0.001) and 6 minute walking test (p = 0.049). 16 of these patients harbored the SNP in AGTR1 gene. These patients showed differences in age at diagnosis (p = 0.049), mean pulmonary arterial pressure (p = 0.033), cardiac index (p = 0.002) and 6 minute walking test (p = 0.039). Conclusions: PAH is a rare disease with pulmonary vascular remodeling caused in part by a heterogeneous constellation of genetic arrangements. This study seems to suggest that c.1-361A > T, c.1-254C > G and c.1-218C > T polymorphisms in TRPC6 gene and c.1166A > C polymorphism in AGTR1 could have a role in the development of this disease. © 2015 Pousada et al.; licensee BioMed Central.
Ortolano S.,Institute Investigacion Biomedica Of Vigo Ibiv |
Vieitez I.,Institute Investigacion Biomedica Of Vigo Ibiv |
Navarro C.,Institute Investigacion Biomedica Of Vigo Ibiv |
Spuch C.,Institute Investigacion Biomedica Of Vigo Ibiv
Recent Patents on Endocrine, Metabolic and Immune Drug Discovery | Year: 2014
Lysosomal storage diseases (LSDs) are a group of rare genetic multisystemic disorders, resulting in deficient lysosomal activity. These pathologies are characterized by progressive accumulation of storage material within the lysosomes, ultimately leading to organ dysfunctions. LSDs patient's clinical outcomes have significantly improved, since the advent of enzyme replacement therapy (ERT). ERT is approved worldwide for 6 LSDs: Gaucher disease, Fabry disease, Mucopolysaccharidosis types I, II, and VI, and Pompe disease. The efficacy and safety of ERT for LSDs has been confirmed by extensive clinical trials, however therapy with infused protein is life-long and disease progression is still observed in treated patients. Obstacles to successful ERT, such as immune reactions against the infused enzyme, miss-targeting of recombinant enzymes, and difficult delivery to crucial tissues (i.e. brain and bone), determine the need for further research, in order to ameliorate therapeutic strategies. Viral gene therapy, stem cell based therapy, pharmacological chaperones and could be considered essential tools for future improvement of recombinant enzyme trafficking and targeting. This review will discuss recent patents and new strategic approaches for enzyme delivery to highlight the most relevant aspects, concerning next generation LSDs treatment. © 2014 Bentham Science Publishers.
Anibarro L.,Complexo Hospitalario Of Pontevedra |
Anibarro L.,Institute Investigacion Biomedica Of Vigo Ibiv |
Pena A.,Complexo Hospitalario Of Pontevedra
Mediterranean Journal of Hematology and Infectious Diseases | Year: 2014
Tuberculosis (TB) is an infectious disease that causes more than 1 million deaths worldwide every year. In addition, it is estimated that one third of the world population is infected with M. tuberculosis in a latent state, which involves an eventual risk of progressing to active TB disease. Patients with immunodeficiencies, such as those suffering from haematological malignancies, have a greater risk of progressing to TB disease once infected. It is estimated that the Relative Risk of TB disease in patients with hematologic malignancies is 2-40 times that of the general population. The diagnosis of TB in these patients is often challenging as they often present clinical characteristics that are distinct to those of patients without any other underlying disease. Mortality due to TB is higher. Therefore, it is recommended to diagnose latent TB infection and consider preventive therapy that could avoid the progression from a latent state to active TB disease. There are currently two methods for diagnosing latent TB infection: the Tuberculin Skin Test (TST) and the Interferon-Gamma Release Assays (IGRA). Due to the lack of sensitivity in patients with immunodeficient conditions, a combined TST-IGRA testing is probably the best way for latent TB diagnosis in order to gain sensitivity. Treatment of latent TB infection and TB disease should follow the general principles to that in the general population.
Martinez C.,Institute Investigacion Biomedica Of Vigo Ibiv |
Lieb M.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire Igbmc |
Alvarez S.,Institute Investigacion Biomedica Of Vigo Ibiv |
Rodriguez-Barrios F.,Institute Investigacion Biomedica Of Vigo Ibiv |
And 4 more authors.
ACS Medicinal Chemistry Letters | Year: 2014
Arotinoids containing a C5,C8-diphenylnaphthalene-2-yl ring linked to a (C3-halogenated) benzoic acid via an ethenyl connector (but not the corresponding naphthamides), which are prepared by Horner-Wadsworth-Emmons reaction of naphthaldehydes and benzylphosphonates, display the rather unusual property of being RXR agonists (15-fold induction of the RXR reporter cell line was achieved at 3- to 10-fold lower concentration than 9-cis-retinoic acid) and RAR antagonists as shown by transient transactivation studies. The binding of such bulky ligands suggests that the RXR ligand-binding domain is endowed with some degree of structural elasticity. © 2014 American Chemical Society.
Sanchez-Garcia E.M.,Complexo Hospitalario Of Pontevedra |
Gamallo R.,Complexo Hospitalario Of Pontevedra |
Blanco-Moure A.,Complexo Hospitalario Of Pontevedra |
Viejo M.A.,Complexo Hospitalario Of Pontevedra |
And 3 more authors.
Infection | Year: 2013
Purpose: Oncohematological patients undergoing chemotherapy who have latent tuberculosis infection (LTBI) are at a high risk of developing active tuberculosis (TB). The identification and treatment of these patients can prevent LTBI progressing to active TB. This study analyzed the degree of adherence with and safety of the treatment of latent tuberculosis infection (TLTBI) in oncohematological patients undergoing antineoplastic chemotherapy. Methods: This is a retrospective study of a cohort of oncohematological patients receiving TLTBI and antineoplastic chemotherapy simultaneously, between January 2007 and June 2010. The proportions of toxicity and adherence to TLTBI in these patients were compared with a non-oncohematological control group, matched for age, sex, and year in which the TLTBI was started. In addition, a minimum 2-year follow-up was carried out for all patients. Results: A total of 105 patients who received TLTBI were included, 21 of whom had received antineoplastic chemotherapy simultaneously. The mean age of the patients was 63 years. There were no significant baseline differences in transaminase values. The percentages of patients completing treatment were 76.2 % in the control group and 71.4 % in the oncohematological group [risk ratio (RR): 1.07, 95 % confidence interval (CI): 0.79-1.43]. The voluntary dropout proportion was similar in both groups (12.3 vs. 11.8 %, RR: 1.05, 95 % CI: 0.25-4.42). Treatment was discontinued because of toxicity in three oncohematological patients and in 11 patients from the control group (RR: 1.14; 95 % CI: 035-3.66). No patient developed TB during the follow-up period. Conclusion: The safety of TLTBI is not influenced by simultaneous antineoplastic chemotherapy in oncohematological patients. © 2013 Springer-Verlag Berlin Heidelberg.
Agis-Balboa R.C.,University of Illinois at Chicago |
Agis-Balboa R.C.,Institute Investigacion Biomedica Of Vigo Ibiv |
Guidotti A.,University of Illinois at Chicago |
Pinna G.,University of Illinois at Chicago
Psychopharmacology | Year: 2014
Rationale The implications of the neurosteroid 3α-hydroxy-5α-pregnan-20-one [allopregnanolone (Allo)] in neuropsychiatric disorders have been highlighted in several recent clinical investigations. For instance, Allo levels are decreased in the cerebrospinal fluid (CSF) of patients with posttraumatic stress disorder (PTSD) and major unipolar depression. Neurosteroidogenic antidepressants [i.e., selective brain steroidogenic stimulants (SBSSs)], including fluoxetine and analogs, correct this decrease in a manner that correlates with improved depressive symptoms. Allo positively and allosterically modulatesGABAaction at postsynaptic and extrasynaptic GABAA receptors. It is synthesized in both the human and rodent brain cortices by principal glutamatergic pyramidal neurons from progesterone by the sequential action of 5α-reductase type I (5α-RI), which is the rate-limiting step enzyme in Allo biosynthesis, and 3α-hydroxysteroid dehydrogenase (3α-HSD), which converts 5α-dehydroprogesterone into Allo.Hypothesis We thus hypothesized that decreased CSF levels of Allo in depressed patients could reflect a brain dysfunction of 5α-RI.Methods In a pilot study of samples from six patients per group [six depressed patients and six nonpsychiatric subjects (NPS)], we studied the expression of 5α-RI messenger RNA (mRNA) in prefrontal cortex Brodmann's area 9 (BA9) and cerebellum from depressed patients obtained from the Maryland Brain Collection at the Maryland Psychiatric Research Center (Baltimore, MD) that were age-matched with NPS. Results The levels of 5α-RI mRNAwere decreased from 25± 5.8 in NPS to 9.1±3.1 fmol/pmol neuronal specific enolase (NSE) (t1,10=2.7, P=0.02) in depressed patients. These differences are absent in the cerebellum of the same patients. The levels of neurosteroids were determined in the prefrontal cortex BA9 of depressed patients obtained from the Stanley Foundation Brain BankNeuropathology Consortium, Bethesda (MD). The BA9 levels of Allo in male depressed patients failed to reach statistical difference from the levels of NPS (1.63±1.01 pg/mg, n=8, in NPS and 0.82±0.33 pg/mg, n=5, in nontreated depressed patients). However, depressed patients who had received antidepressant treatment (three patients SSRI and one TCA) exhibited increased BA9 Allo levels (6.16±2.5 pg/mg, n=4, t1,9=2.4, P=0.047) when compared with nontreated depressed patients.Conclusions Although in a small number of patients, this finding is in-line with previous reports in the field that have observed an increase of Allo levels in CSF and plasma of depressed patients following antidepressant treatment. Hence, the molecular mechanisms underlying major depression may include a GABAergic neurotransmission deficit caused by a brain Allo biosynthesis downregulation, which can be normalized by SBSSs. © 2014 Springer-Verlag Berlin Heidelberg.