Hurtado, V. (Verónica)
- Publications
- item.page.relationships.isContributorAdvisorOfPublication
- item.page.relationships.isContributorOfPublication
5 results
Search Results
Now showing 1 - 5 of 5
- Interleukin (IL)-8 and growth related oncogene-alpha in severe endotoxemia and the effects of a tumor necrosis factor-alpha/IL-1beta inhibitor on these chemokines(Elsevier, 2002) Matsukawa, A. (Akihiro); Rodriguez-Wilhelmi, P. (Pablo); Rocha, E. (Eduardo); Hermida, J. (José); Montes, M. (Marta); Hurtado, V. (Verónica); Montes, R. (Ramón)FR167653 inhibits the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, powerful inducers of CXC chemokines IL-8 and growth related oncogene (GRO)-alpha. The production of IL-8 and GRO-alpha was investigated and the effects of FR167653 were examined in a rabbit model of endotoxin shock. Male New Zealand rabbits were given endotoxin at a dose sufficient to induce DIC. Three groups of rabbits received FR167653 at different doses. TNF-alpha, IL-1beta, IL-8, and GRO-alpha levels were measured, several pathologic features were evaluated, and the results were compared with those obtained in control rabbits, which received only endotoxin. Endotoxin increased serum levels of IL-8 and GRO-alpha, which were associated with hypotension, renal dysfunction, and mortality, peaking at 4 h. FR167653 improved mortality, an event that was associated with decreased levels of not only TNF-alpha and IL-1beta but also IL-8 and GRO-alpha. TNF-alpha peaked at 2 h, at a time point before IL-8 and GRO-alpha reached their peak, and the TNF-alpha level was tightly correlated with that of IL-8 and GRO-alpha. Altogether, these data suggest the possible involvement of IL-8 and GRO-alpha in endotoxin shock, and FR167653 may foster a beneficial outcome in part by modulating the chemokines level by inhibiting TNF-alpha and IL-1beta.
- Autoantibodies against the endothelial receptor of protein C are associated with acute myocardial infarction in young women(Wiley-Blackwell, 2005) Foco, L. (L.); Hermida, J. (José); Alonso, A. (Andrés); Zonzin, P. (P.); Hurtado, V. (Verónica); Montes, R. (Ramón); Mannucci, P.M. (P.M.)BACKGROUND: Acute myocardial infarction (AMI) is rare among young women. The search for unknown risk factors is warranted. Endothelial protein C receptor (EPCR) is largely present at the endothelial surface of large arteries. No studies about association of anti-EPCR autoantibodies (anti-EPCR) with AMI are available. METHODS: Plasma IgA, IgM and IgG anti-EPCR levels were measured by enzyme-linked immunosorbent assay in 165 women younger than 45 years who survived a first AMI and 165 healthy women, matched by age and geographical origin. RESULTS: Using the 90th percentile of IgA anti-EPCR in the control group, IgA anti-EPCR were independently associated with AMI after adjustment for cardiovascular risk factors (OR 5.1; 95% CI 1.7-15.6; P = 0.004). The risk apparently conferred by IgA anti-EPCR increased dose-dependently (P for trend =0.0002). IgM anti-EPCR were less consistently associated with AMI: a significant increase in the risk was found when women above the 90th percentile were compared with those in the lowest quartile (OR 3.6; 95% CI 1.2-11.5; P = 0.03). IgG anti-EPCR were similar in patients and controls. A total of 145 patients underwent coronary arteriography. IgA or IgM anti-EPCR were not different among patients with different degrees of atherosclerotic lesion (anova, P = 0.77 and 0.24, respectively). CONCLUSIONS: High levels of IgA and, to a lesser extent, IgM anti-EPCR, are associated with AMI in young women.
- Tumor necrosis factor-alpha inhibition reduces CXCL-8 levels but fails to prevent fibrin generation and does not improve outcome in a rabbit model of endotoxic shock(Elsevier, 2003) Matsukawa, A. (Akihiro); Rodriguez-Wilhelmi, P. (Pablo); Rocha, E. (Eduardo); Hermida, J. (José); Montes, M. (Marta); Hurtado, V. (Verónica); Montes, R. (Ramón); Nariuchi, H. (Hideo)The effects of a monoclonal antibody (mAb) to tumor necrosis factor-alpha (TNF-alpha) were examined in a rabbit model of endotoxic shock. Intravenous administration of lipopolysaccharide (100 microg/kg/hr) for 6 hours (n = 11) increased TNF-alpha levels. Fibrinogen was partially consumed, and fibrin deposits were seen in kidney and lungs at 24 hours. Mortality at 24 hours was 64%. Levels of interleukin-8 (aka CXCL-8) were notably increased. Mean arterial pressure (MAP) and leukocyte counts decreased, whereas creatinine levels were enhanced. The anti-TNF-alpha mAb (20 mg/kg i.v. bolus + 5 mg/kg/h i.v. for the first 90 minutes) (n = 10) efficiently inhibited the TNF-activity. Rabbits exhibited lower CXCL-8 levels; MAP improved, the decrease in leukocyte counts was partially prevented and creatinine levels were lower, but fibrinogen, fibrin deposits in kidneys and lungs and mortality, 55%, were similar to the LPS group. Rabbits that did not survive exhibited lower fibrinogen levels, more fibrin in kidneys and lungs and higher CXCL-8 and creatinine levels than survivors, while there were no differences in TNF-alpha, MAP and leukocytes. Thus, the inhibition of TNF-alpha, although beneficial through lowering CXCL-8 levels, is not enough to improve the outcome, which could be partly due to the inability to prevent the fibrin deposits formation in kidneys and lungs.
- Identification and characterization of a natural R96C EPCR variant(Wiley-Blackwell, 2003) Hermida, J. (José); Hurtado, V. (Verónica); Philippou, H. (Helen); Villegas-Mendez, A. (Ana); Catto, A.J. (A.J.)
- Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for fetal death(American Society of Hematology, 2004) Bertolaccini, M.L. (María L.); Martinez-Gonzalez, M.A. (Miguel Ángel); Gris, J.C. (Jean-Christophe); Hermida, J. (José); Lane, D.A. (David A.); Hurtado, V. (Verónica); Khamashta, M.A. (Munther A.); Alonso, A. (Alvaro); Montes, R. (Ramón); Fukudome, K. (Kenji)The antiphospholipid syndrome (APS) is associated with thrombosis and fetal death but the pathologic mechanisms are poorly understood. Since endothelial protein C receptor (EPCR) plays a role in the anticoagulant system and in placental development, we hypothesized that anti-EPCR autoantibodies may be involved in clinical manifestations of APS and in fetal loss. The levels of immunoglobulin M (IgM) and IgG anti-EPCR autoantibodies were analyzed by enzyme-linked immunosorbent assay (ELISA) in 43 patients with APS and 43 controls. Anti-EPCR levels were higher in APS patients than in controls. Interestingly, one of the IgM anti-EPCR autoantibodies inhibited the generation of activated protein C on endothelium. Since markedly high anti-EPCR levels were found in women with fetal death, 87 patients with a first episode of unexplained fetal death were subsequently analyzed and their anti-EPCR levels were compared with 87 matched controls. We found that anti-EPCR autoantibodies constitute an independent risk factor for a first fetal death episode: the adjusted odds ratios (ORs) for anti-EPCR autoantibodies above the 95th percentile were 23.0 (95% confidence interval [CI], 2.0-266.3) for IgM and 6.8 (95% CI, 1.2-38.4) for IgG. Anti-EPCR autoantibodies can be detected in APS patients and are independent risk factors for fetal death.