I. Rosa - Academia.edu (original) (raw)

Papers by I. Rosa

Journal of Hepatology, 2015

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 14, 2015

Few direct anti-HCV agents have been studied in difficult-to-treat, null responders and cirrhoti... more Few direct anti-HCV agents have been studied in difficult-to-treat, null responders and cirrhotic HIV co-infected patients. Daclatasvir and asunaprevir combined with pegylated interferon-ribavirin (PR) have shown promising results in HCV mono-infected patients. An open-label, single-arm, phase-2 study was conducted in HIV/HCV genotype 1/4 co-infected patients, null responders to prior PR standard therapy, on a raltegravir-based regimen with HIV RNA<400cp/ml. They received a 4-week lead-in phase with PR, followed by 24 weeks of asunaprevir (100mg bid), daclatasvir (60 mg qd) and PR. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12) using ITT analysis. Seventy-five patients were included, of whom 27 (36%) were cirrhotic. The median baseline CD4 count was 748 (IQR 481 - 930)/mm(3). The global SVR12 rate was 96.0% (72/75; 95%CI: 88.8%-99.2%), 92.6% (25/27; 75.7%-99.1%) in cirrhotic patients, 94.6% (35/37; 81.8%-99.3%) in genotype-1...

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 15, 2014

Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained vir... more Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). Sixty-nine patients ...

European Heart Journal, 2013

Scientific Reports, 2015

Upon stimulation, platelets release a high number of proteins (the releasate). There are clear in... more Upon stimulation, platelets release a high number of proteins (the releasate). There are clear indications that these proteins are involved in the pathogenesis of several diseases, such as atherosclerosis. In the present study we compared the platelet releasate following platelet activation with two major endogenous agonists: thrombin and collagen. Proteome analysis was based on 2D-DIGE and LC-MS/MS. Firstly, we showed the primary role of thrombin and collagen receptors in platelet secretion by these agonists; moreover, we demonstrated that GPVI is the primary responsible for collagen-induced platelet activation/aggregation. Proteomic analysis allowed the detection of 122 protein spots differentially regulated between both conditions. After excluding fibrinogen spots, down-regulated in the releasate of thrombin-activated platelets, 84 differences remained. From those, we successfully identified 42, corresponding to 37 open-reading frames. Many of the differences identified correspond to post-translational modifications, primarily, proteolysis induced by thrombin. Among others, we show vitamin K-dependent protein S, an anticoagulant plasma protein, is up-regulated in thrombin samples. Our results could have pathological implications given that platelets might be playing a differential role in various diseases and biological processes through the secretion of different subsets of granule proteins and microvesicles following a predominant activation of certain receptors. OPEN SUBJECT AREAS: PROTEOMICS MOLECULAR BIOLOGY

Thrombosis Research, 2014

Thrombosis and haemostasis, 2014

Membrane microvesicles (MVs) are released from activated cells, most notably platelets, into the ... more Membrane microvesicles (MVs) are released from activated cells, most notably platelets, into the circulation. They represent an important mode of intercellular communication, and their number is increased in patients with acute coronary syndromes. We present here a differential proteomic analysis of plasma MVs from ST-elevation myocardial infarction (STEMI) patients and stable coronary artery disease (SCAD) controls. The objective was the identification of MVs biomarkers/drug targets that could be relevant for the pathogenesis of the acute event. Proteome analysis was based on 2D-DIGE, and mass spectrometry. Validations were by western blotting in an independent cohort of patients and healthy individuals. A systems biology approach was used to predict protein-protein interactions and their relation with disease. Following gel image analysis, we detected 117 protein features that varied between STEMI and SCAD groups (fold change cut-off ≥2; p<0.01). From those, 102 were successful...

Journal of Thrombosis and Haemostasis, 2009

To cite this article: Senis YA, Antrobus R, Severin S, Parguiñ a AF, Rosa I, Zitzmann N, Watson S... more To cite this article: Senis YA, Antrobus R, Severin S, Parguiñ a AF, Rosa I, Zitzmann N, Watson SP, García A. Proteomic analysis of integrin aIIbb3 outside-in signaling reveals Src-kinase-independent phosphorylation of Dok-1 and Dok-3 leading to SHIP-1 interactions. J Thromb Haemost 2009; 7: 1718-26.

Journal of the American College of Cardiology, 2010

A112.E1047 JACC March 9, 2010 Volume 55, issue 10A ... PROTEOMIC ANALYSIS OF CIRCULATING HUMAN PL... more A112.E1047 JACC March 9, 2010 Volume 55, issue 10A ... PROTEOMIC ANALYSIS OF CIRCULATING HUMAN PLATELETS REVEALS POTENTIAL BIOMARKERS IN NON-ST SEGMENT ELEVATION ACUTE CORONARY SYNDROME ... ACC Poster Contributions Georgia World Congress ...

Journal of Proteomics, 2012

Human Molecular Genetics, 2012

Schizophrenia is a chronic illness of heterogenous biological origin. We hypothesized that, simil... more Schizophrenia is a chronic illness of heterogenous biological origin. We hypothesized that, similar to chronic progressive brain conditions, persistent functional disturbances of neurons would result in disturbed proteostasis in the brains of schizophrenia patients, leading to increased abundance of specific misfolded, insoluble proteins. Identification of such proteins would facilitate the elucidation of molecular processes underlying these devastating conditions. We therefore generated antibodies against pooled insoluble proteome of post-mortem brains from schizophrenia patients in order to identify unique, disease-specific epitopes. We successfully identified such an epitope to be present on collapsin-response mediator protein 1 (CRMP1) in biochemically purified, insoluble brain fractions. A genetic association analysis for the CRMP1 gene in a large Finnish population cohort (n 5 4651) corroborated the association of physical and social anhedonia with the CRMP1 locus in a DISC1 (Disrupted-in-schizophrenia 1)-dependent manner. Physical and social anhedonia are heritable traits, present as chronic, negative symptoms of schizophrenia and severe major depression, thus constituting serious vulnerability factors for mental disease. Strikingly, lymphoblastoid cell lines derived from schizophrenia patients mirrored aberrant CRMP1 immunoreactivity by showing an increase of CRMP1 expression, suggesting its potential role as a blood-based diagnostic marker. CRMP1 is a novel candidate protein for schizophrenia traits at the intersection of the reelin and DISC1 pathways that directly and functionally interacts with DISC1. We demonstrate the impact of an interdisciplinary approach where the identification of a disease-associated epitope in post-mortem brains, powered by a genetic association study, is rapidly translated into a potential blood-based diagnostic marker.

Journal of proteomics, Jan 5, 2012

Platelet-derived microparticles (PMP) are elevated in a number of disorders (e.g. cardiovascular ... more Platelet-derived microparticles (PMP) are elevated in a number of disorders (e.g. cardiovascular disease and cancer). In the present study, we have carried out a high-resolution 2-DE-based proteomic analysis of PMP originated following platelet activation with different stimulus. Flow cytometric analysis revealed a higher average number of microparticles when platelets are activated with shear (1800s(-1)) compared to 0.5U/mL thrombin. Regarding the proteomic analysis, 30 protein features were found to be differentially regulated between shear and thrombin groups in the pI 4-7 range, from which 28 were successfully identified by MS, corresponding to 26 open-reading frames. Signaling proteins constituted the major functional group, including membrane receptors, and adapters. Ingenuity Pathways Analysis (IPA) software revealed that 21 of the 26 differentially regulated unique proteins identified are part of a common network related to cell assembly and organization and cell morphology....

Arteriosclerosis, Thrombosis, and Vascular Biology, 2011

Objective-Our aim in this study was to provide novel information on the molecular mechanisms play... more Objective-Our aim in this study was to provide novel information on the molecular mechanisms playing a major role in the unwanted platelet activation associated with ST-elevation myocardial infarction (STEMI). Methods and Results-We compared the platelet proteome of 11 STEMI patients to a matched control group of 15 stable chronic ischemic cardiopathy patients. In addition, we did a prospective study to follow the STEMI patients over time.