Rocha, E. (Eduardo)

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    Prevention of renal fibrin deposition in endotoxin-induced DIC through inhibition of PAI-1
    (Schattauer, 2000) Muñoz, M.C. (María Carmen); Rocha, E. (Eduardo); Hermida, J. (José); Montes, M. (Marta); Declerck, P.J. (Paul J.); Montes, R. (Ramón); Calvo-González, A. (Alfonso)
    Plasminogen activator inhibitor-1 (PAI-1) increases in endotoxemia thus possibly cooperating in altering the hemostatic balance in a prothrombotic direction. The effect of the inhibition of PAI-1 with the monoclonal antibody MA-33B8 was studied systemically and in kidneys in a lapine model of endotoxin-induced disseminated intravascular coagulation (DIC). The increase in plasmatic PAI activity in the control group (n = 9) was inhibited in the MA-33B8 treated rabbits (n = 5). Control rabbits showed renal fibrin deposits, whereas only one of the MA-33B8 rabbits did so. These results were confirmed immunohistochemically in kidneys as PAI-1 immunostaining was seen inside the glomeruli and larger vessels in the control group, whereas MA-33B8 rabbits showed a remarkable decrease, demonstrating that MA-33B8 successfully inhibited PAI-1 in the kidneys as well. Therefore evidence for the important role of PAI-1 in fibrin generation in endotoxin-induced DIC is presented, suggesting that strategies aiming at its reduction can be useful in this pathology.
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    Endotoxin-induced intravascular coagulation in rabbits: effect of tissue plasminogen activator vs urokinase of PAI generation, fibrin deposits and mortality
    (Schattauer, 1995) Paramo, J.A. (José Antonio); Rocha, E. (Eduardo); Paloma, M.J. (María José)
    We have evaluated the effect of plasminogen activators (t-PA and urokinase) on an experimental model of disseminated intravascular coagulation (DIC) in rabbits by injection of 20 micrograms/kg/h of E. coli lipopolysaccharide during 6 h t-PA (0.2 mg/kg and 0.7 mg/kg), urokinase (3000 U/kg/h) and saline (control) were given simultaneously with endotoxin. Results indicated that urokinase and low dose of t-PA significantly reduced the increase of plasminogen activator inhibitor (PAI) activity observed 2 h after endotoxin (p < 0.001). High t-PA dose also diminished the PAI levels at 6 h (p < 0.001). A significant reduction of fibrin deposits in kidneys was observed din both t-PA treated groups as compared with findings in the group of rabbits infused with saline solution (p < 0.005), whereas urokinase had no significant effect on the extent of fibrin deposition. Finally, the mortality rate in the control group (70%) was reduced to 50% in rabbits receiving high doses of t-PA. In conclusion, treatment with t-PA resulted in reduced PAI generation, fibrin deposits and mortality in endotoxin-treated rabbits.
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    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.
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    Effect of DDAVP on endotoxin-induced intravascular coagulation in rabbits
    (Schattauer, 1992) Paramo, J.A. (José Antonio); Rocha, E. (Eduardo); Paloma, M.J. (María José)
    We have evaluated the effect of 1-Deamino-8D-arginine vasopressin (DDAVP) on an experimental model of intravascular coagulation (DIC) induced in rabbits by injection of 20 micrograms kg-1 h-1 during 6 h of E. coli lipopolysaccharide. DDAVP significantly ameliorated the platelet drop and fibrinogen decrease (p less than 0.01) induced by endotoxin in control animals. A significant reduction in factor XII consumption (p less than 0.01) and a decrease in the generation of endotoxin induced PAI-1 activity in rabbits circulation was also observed (p less than 0.005). Moreover, fibrin deposition in kidneys of rabbits receiving DDAVP was significantly reduced as compared to control animals. Finally, the mortality rate in the control group was significantly higher than in DDAVP-treated rabbits (p less than 0.01). The hemostatic changes induced by DDAVP correlated with lower fibrin deposition and reduction in mortality rates.
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    Prevalence of FVR506Q and prothrombin 20210A mutations in the Navarrese population
    (Schattauer, 1998) Paramo, J.A. (José Antonio); Rocha, E. (Eduardo); Orbe, J. (Josune); Medarde, A. (A.); Montes, R. (Ramón); Ayape, M.L. (M. L.); Zabalegui, N. (Natalia)
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    Nuevos agentes trombolíticos: presente y futuro
    (Universidad de Navarra, 1987) Paramo, J.A. (José Antonio); Rocha, E. (Eduardo); Fernandez, J. (Javier); Cuesta, B. (Braulia); Aranda, A. (Alejandro); Paloma, M.J. (María José)
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    Fibrinogen and fibrin degradation products in patients undergoing open-heart surgery
    (Lippincott, Williams & Wilkins, 1990) Paramo, J.A. (José Antonio); Rifon, J. J. (Jose J.); Rocha, E. (Eduardo); Fernandez, J. (Javier); Cuesta, B. (Braulia)
    We have determined fibrinogen and fibrin degradation products (FgDP and FbDP respectively) by an ELISA method using specific monoclonal antibodies in 100 patients undergoing cardiopulmonary bypass (CPB) for valvular heart disease and in 60 patients undergoing aorto-coronary bypass surgery. Blood samples were taken pre-operatively and on post-operative days 1 and 5. Post-operative evolution was similar in both patient groups, with a significant increase in FgDP on post-operative days 1 and 5 with respect to baseline value (P less than 0.01). FbDP were also significantly higher on post-operative days 1 and 5 (P less than 0.001), especially the day after surgery in patients with valvular disease as compared with coronary patients (P less than 0.01). Our results indicate that fibrinolysis is more important than fibrinogenolysis after open-heart surgery, which may have pathophysiological implications.
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    Evan's syndrome, chronic active hepatitis and focal glomerulonephritis in IgA deficiency
    (Karger, 1986) Paramo, J.A. (José Antonio); Rocha, E. (Eduardo); Fernandez, J. (Javier); Cuesta, B. (Braulia); Gomez, C. (C.); Pardo, J. (Javier)
    A 10-year-old female with a complete selective IgA deficiency and recurrent autoimmune disease (chronic active hepatitis, focal glomerulonephritis, hemolytic anemia and thrombopenic purpura) is presented. Both serum IgA and saliva secretory IgA were below the detection limit. The small bowel biopsy using a peroxidase-antiperoxidase technique showed absence of plasma cells secreting IgA. Circulating antibodies against mitochondria, microsomal thyroid antigen were detected as well as rheumatoid factor. Circulating immune complexes were present. A positive Coombs' test and a slightly positive reaction for cryoagglutinins were demonstrated. No alterations in cellular immunity were observed. Clinical and analytical improvement with prednisone and azathioprine was obtained.
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    Tratamiento profiláctico de la enfermedad tromboembólica en el paciente quirúrgico
    (Universidad de Navarra, 1987) Paramo, J.A. (José Antonio); Hernández, M. (M.); Rocha, E. (Eduardo); Fernandez, J. (Javier); Cuesta, B. (Braulia); Aranda, A. (Alejandro)
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    Prevalencia de los estados de la hipercoagulabilidad en pacientes con thrombosis en Navarra Septentrional
    (Aran, 1997) Paramo, J.A. (José Antonio); Rocha, E. (Eduardo); Benedicto-Aguirre, E. (E.); Prieto, J. (Jesús); Yuste, J.R. (José Ramón)