http://repub.eur.nl/res/aut/3636/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/37999/ 2012-03-01T00:00:00Z http://repub.eur.nl/res/pub/17325/ 2009-10-01T00:00:00Z This paper reports on a qualitative study commissioned by the European Union (EU) and intended to help to improve strategic, pan-European security dialogue and partnership between the private and public sectors. The study draws on interviews with security managers at European level and on a reading of relevant EU policy documents. Most consultees argued for a trusted forum, in which security professionals would trade their knowledge and expertise, rather than representing specific private firms or state agencies. As the study was being conducted, there was a political tilt in ownership within the European Commission, the public-private security dossier being relinquished by its Directorate General for Justice Freedom and Security (Third Pillar) and being gained by DG Enterprise and Industry (First Pillar). Scanning the policy context, the paper suggests that security cooperation, hitherto conceptualised as public-private (public sector lead), should be understood as private-public, as security serves economic concerns. http://repub.eur.nl/res/pub/28811/ 2008-01-01T00:00:00Z BACKGROUND AND PURPOSE - Evidence is accumulating that infection with influenza A virus contributes to atherothrombotic disease. Vaccination against influenza decreases the risk of atherosclerotic syndromes, indicating that inflammatory mechanisms may be involved. We tested the hypothesis that influenza A virus-specific T cells contribute to atherosclerotic plaque inflammation, which mediates the onset of plaque rupture. METHODS - T-cell cultures were generated from atherosclerotic segments and peripheral blood of 30 patients with symptomatic carotid artery disease. The response of plaque and peripheral blood T cells to influenza A virus was analyzed and expressed as a stimulation index (SI). Selective outgrowth of intraplaque influenza A-specific T cells was calculated by the ratio of plaque T cell SI and peripheral blood T cell SI for each patient. Accordingly, the patients were categorized as high- (SI ratio ≥5), intermediate- (5 <SI ratio ≤2), and non- (SI ratio <2) responders. The presence of influenza A virus in the vessel fragments was evaluated by reverse transcription-polymerase chain reaction. RESULTS - High proliferative responses of plaque-derived T cells to influenza A virus were frequently observed. Among the 30 patients, 5 were categorized as high responders, 10 were intermediate responders, and 15 were nonresponders. Live influenza A virus could not be detected in the atherosclerotic plaques by polymerase chain reaction. CONCLUSIONS - Selective outgrowth of influenza A virus-specific T cells occurs within the microenvironment of human atherosclerotic plaques. Influenza virus-derived antigens or alternatively, mimicry antigens, appear to be potential candidates for triggering or sustaining plaque inflammation, which eventually leads to symptomatic plaque complications. http://repub.eur.nl/res/pub/29036/ 2008-01-01T00:00:00Z OBJECTIVE: Alveolar fibrin deposition is a hallmark of pneumonia. It has been proposed that natural inhibitors of coagulation, including activated protein C, antithrombin, and tissue factor pathway inhibitor, exert lung-protective effects via anticoagulant and possibly anti-inflammatory pathways. We investigated the role of these natural anticoagulants in Streptococcus pneumoniae pneumonia. DESIGN: A controlled in vivo laboratory study. SETTING: Research laboratory of a university hospital. SUBJECTS: Total of 98 male Sprague-Dawley rats. INTERVENTIONS: Rats were challenged intratracheally with S. pneumoniae (serotype 3, 10 colony forming units), inducing pneumonia. Rats were randomized to intravenous treatment with normal saline, activated protein C, antithrombin, tissue factor pathway inhibitor, heparin, or tissue-type plasminogen activator. MEASUREMENTS AND MAIN RESULTS: Rats infected with S. pneumoniae had increased thrombin-antithrombin complexes in bronchoalveolar lavage fluid, with decreased levels of antithrombin activity and fibrin degradation products. Administration of activated protein C, antithrombin, and tissue factor pathway inhibitor significantly limited these procoagulant changes. Furthermore, antithrombin treatment resulted in less bacterial outgrowth of S. pneumoniae and less histopathologic damage in lungs. CONCLUSIONS: Anticoagulant treatment attenuates pulmonary coagulopathy during S. pneumoniae pneumonia. Antithrombin seems to exert significant lung-protective effects in pneumococcal pneumonia in rats. http://repub.eur.nl/res/pub/9114/ 1999-01-01T00:00:00Z Cyclosporin A (CsA) has been implicated as one of the factors contributing to the high cardiovascular morbidity and mortality after renal transplantation. This may be mediated by either a high prevalence of conventional risk factors for atherosclerosis, such as hypertension, hypercholesterolemia, and diabetes mellitus, or by impairment of the fibrinolytic activity evoked by CsA, possibly through interference with prostanoid metabolism. We therefore assessed the impact of conversion of CsA to azathioprine immunosuppressive treatment on parameters of fibrinolytic activity and plasma concentration of the prostanoids prostaglandin E2 and thromboxane B2 in 18 stable renal transplant recipients. During CsA, mean arterial pressure and serum creatinine were significantly higher than during azathioprine (116+/-15 mm Hg versus 106+/-13 mm Hg, P=0.0003; and 147+/-34 micromol/L versus 127+/-35 micromol/L, P=0.002; mean+/-SD). On conversion, the plasma tissue plasminogen activator activity increased from 1.2 (1.1 to 1.7; median, 95% CI) to 1.8 (1.6 to 2.0) IU/mL (P=0.011), without a significant change of the plasminogen activator antigen concentration. This was associated with a substantial decrease in plasminogen activator inhibitor-1 activity from 10.4 (8.5 to 16.7) to 6.4 (5.6 to 9.2) IU/mL (P=0.009). Furthermore, plasma levels of prostaglandin E2 and thromboxane B2 markedly decreased (from 9.7 [7.4 to 12.9] to 4.6 [4.3 to 8.1] pg/mL, P=0.0006; and from 106.1 [91.7 to 214.2] to 70.2 [50.3 to 85.6] pg/mL, P=0.002, respectively). During CsA, but not azathioprine, plasma tissue plasminogen activator antigen and plasminogen activator inhibitor-1 levels correlated significantly with prostaglandin E2 (r=0.53, P=0.02; and r=0.60, P=0.008, respectively), and thromboxane B2 (r=0.75, P=0.0001; and r=0.77, P=0.0001, respectively) levels. In conclusion, CsA induced substantial impairment of fibrinolytic activity, which recovered after conversion to azathioprine. The impaired fibrinolysis observed during CsA treatment may be caused by modulation of eicosanoid production or metabolism in vascular endothelial cells and possibly contributes to the high incidence of cardiovascular disease after kidney transplantation.