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Jozef Vermylen

Other affiliations: University of Leicester
Bio: Jozef Vermylen is an academic researcher from Katholieke Universiteit Leuven. The author has contributed to research in topics: Platelet & Prostacyclin. The author has an hindex of 56, co-authored 394 publications receiving 10840 citations. Previous affiliations of Jozef Vermylen include University of Leicester.


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Journal ArticleDOI
TL;DR: It is concluded that the presence of (ultrafine) particles in the circulation may affect hemostasis and the observed in vivo prothrombotic tendency results, at least in part, from platelet activation by positively charged amine-polystyrene particles.
Abstract: Particulate air pollution is associated with cardiovascular morbidity systems, such as coagulation. The rationale of these studies and mortality. To investigate this association, we studied the effect is that cytokines and other mediators produced in the lungs of ultrafine (60 nm) polystyrene particles on thrombus formation are also released in the circulation and exert extrapulmonary in a hamster model after intravenous and intratracheal administra- effects (6). Thus, in response to particle exposure, heart rate tion of unmodified, carboxylate-polystyrene, or amine-polystyrene or rhythm abnormalities without hypoxia or respiratory disparticles. Unmodified particles had no effect on thrombosis up to tress, as well as an increase in neutrophils and platelets in 5 mg/kg. Carboxylate-polystyrene particles significantly inhibited peripheral blood have been observed (7–9). thrombus formation at 500 and 100 g/kg body weight but not at Another line of research, that has not been pursued much 50 g/kg body weight. In contrast, amine-polystyrene particles sig- so far, consists of studying the possible “direct” effects of nificantly enhanced thrombosis at 500 and 50g/kg body weight but particles that may pass from the lung into the circulation. not at 5 g/kg body weight. Similarly, the intratracheal instillation The rationale for this approach is based on the observation of 5,000 g of amine-polystyrene particles significantly increased that the ultrafine fraction of the particles is probably most thrombus formation. The unmodified particles and carboxylate- hazardous to health (10). Ultrafine particles (UFPs), i.e., polystyrene particles had no effect. During platelet aggregation in particles with a diameter less than 100 nm, deposit in greater human platelet-rich plasma, induced with 1.25M ADP, unmodified numbers and deeper into the lungs than do larger-sized partiparticles had no effect up to 100 g/ml, and carboxylate-polystycles (11). Their small size allows them to translocate from rene particles weakly enhanced platelet aggregation at 25 to 100 the lung into the blood, as we recently demonstrated (12, 13). g/ml. However, amine-polystyrene particles (50 and 100 g/ml) Thromboembolic disease is a major cause of morbidity induced platelet aggregation themselves and strongly increased and mortality in the elderly, i.e., the fraction of the population the ADP-induced aggregation. We conclude that the presence of (ultrafine) particles in the circulation may affect hemostasis. The that is most susceptible to the adverse effects of air pollution observed in vivo prothrombotic tendency results, at least in part, (14). Recently, it has been shown that exposure to particulate from platelet activation by positively charged amine-polystyrene air pollution for as little as 2 hours increased the occurrence particles. of myocardial infarction in people at risk of developing cardiovascular disease (15). The heterogeneous composition of

323 citations

Journal ArticleDOI
15 Sep 1995-Blood
TL;DR: The presence of factor VII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors than patients without inversions.

316 citations

Journal ArticleDOI
TL;DR: It is suggested that inhibition of prostacyclin formation could play a major role in the pathogenesis of thrombosis and obstetrical problems in some patients with this type of anticoagulant, even in the absence of systemic lupus erythematosus.
Abstract: A “lupus” anticoagulant was discovered in 14 patients over a one year period. Only three of them had systemic lupus erythematosus. Bleeding manifestations were only present in one patient with concomitant severe thrombocytopenia. In contrast, eight patients had a history of thrombosis; five of them presented repeated thrombotic episodes. Obstetrical complications (recurrent abortion, fetal death, or intrauterine growth retardation) were observed in six patients. An inhibitory effect of plasma on the production of prostacyclin by vascular tissue was detected in eight patients, six of whom had thrombosis. We suggest that inhibition of prostacyclin formation could play a major role in the pathogenesis of thrombosis and obstetrical problems in some patients with this type of anticoagulant, even in the absence of systemic lupus erythematosus.

304 citations

Journal ArticleDOI
TL;DR: In this paper, the incidence of thromboembolic complications was compared retrospectively in 90 cadaveric kidney allograft recipients treated with cyclosporin and low-dose steroids and the same number of CKG recipient treated with azathioprine, antilymphocyte globulin, and high-dose steroid.

295 citations

Journal ArticleDOI
TL;DR: The intratracheal instillation of DEPs leads to lung inflammation as well as a rapid activation of circulating blood platelets, which provides a plausible explanation for the increase in cardiovascular morbidity and mortality accompanying urban air pollution.
Abstract: Background— Pollution by particulates has consistently been associated with increased cardiovascular morbidity and mortality, but a plausible biological basis for this association is lacking Methods and Results— Diesel exhaust particles (DEPs) were instilled into the trachea of hamsters, and blood platelet activation, experimental thrombosis, and lung inflammation were studied Doses of 5 to 500 μg of DEPs per animal induced neutrophil influx into the bronchoalveolar lavage fluid with elevation of protein and histamine but without lactate dehydrogenase release The same doses enhanced experimental arterial and venous platelet rich-thrombus formation in vivo Blood samples taken from hamsters 30 and 60 minutes after instillation of 50 μg of DEPs yielded accelerated aperture closure (ie, platelet activation) ex vivo, when analyzed in the Platelet Function Analyser (PFA-100) The direct addition of as little as 05 μg/mL DEPs to untreated hamster blood significantly shortened closure time in vitro Conclusi

289 citations


Cited by
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TL;DR: Results of older bio-kinetic studies with NSPs and newer epidemiologic and toxicologic studies with airborne ultrafine particles can be viewed as the basis for the expanding field of nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices.
Abstract: Although humans have been exposed to airborne nanosized particles (NSPs; < 100 nm) throughout their evolutionary stages, such exposure has increased dramatically over the last century due to anthropogenic sources. The rapidly developing field of nanotechnology is likely to become yet another source through inhalation, ingestion, skin uptake, and injection of engineered nanomaterials. Information about safety and potential hazards is urgently needed. Results of older bio-kinetic studies with NSPs and newer epidemiologic and toxicologic studies with airborne ultrafine particles can be viewed as the basis for the expanding field of nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices. Collectively, some emerging concepts of nanotoxicology can be identified from the results of these studies. When inhaled, specific sizes of NSPs are efficiently deposited by diffusional mechanisms in all regions of the respiratory tract. The small size facilitates uptake into cells and transcytosis across epithelial and endothelial cells into the blood and lymph circulation to reach potentially sensitive target sites such as bone marrow, lymph nodes, spleen, and heart. Access to the central nervous system and ganglia via translocation along axons and dendrites of neurons has also been observed. NSPs penetrating the skin distribute via uptake into lymphatic channels. Endocytosis and biokinetics are largely dependent on NSP surface chemistry (coating) and in vivo surface modifications. The greater surface area per mass compared with larger-sized particles of the same chemistry renders NSPs more active biologically. This activity includes a potential for inflammatory and pro-oxidant, but also antioxidant, activity, which can explain early findings showing mixed results in terms of toxicity of NSPs to environmentally relevant species. Evidence of mitochondrial distribution and oxidative stress response after NSP endocytosis points to a need for basic research on their interactions with subcellular structures. Additional considerations for assessing safety of engineered NSPs include careful selections of appropriate and relevant doses/concentrations, the likelihood of increased effects in a compromised organism, and also the benefits of possible desirable effects. An interdisciplinary team approach (e.g., toxicology, materials science, medicine, molecular biology, and bioinformatics, to name a few) is mandatory for nanotoxicology research to arrive at an appropriate risk assessment.

7,092 citations

Journal ArticleDOI
TL;DR: A comprehensive evaluation of the research findings provides persuasive evidence that exposure to fine particulate air pollution has adverse effects on cardiopulmonary health.
Abstract: Efforts to understand and mitigate the health effects of particulate matter (PM) air pollution have a rich and interesting history. This review focuses on six substantial lines of research that have been pursued since 1997 that have helped elucidate our understanding about the effects of PM on human health. There has been substantial progress in the evaluation of PM health effects at different time-scales of exposure and in the exploration of the shape of the concentration-response function. There has also been emerging evidence of PM-related cardiovascular health effects and growing knowledge regarding interconnected general pathophysiological pathways that link PM exposure with cardiopulmonary morbidity and mortality. Despite important gaps in scientific knowledge and continued reasons for some skepticism, a comprehensive evaluation of the research findings provides persuasive evidence that exposure to fine particulate air pollution has adverse effects on cardiopulmonary health. Although much of this research has been motivated by environmental public health policy, these results have important scientific, medical, and public health implications that are broader than debates over legally mandated air quality standards.

5,547 citations

Journal ArticleDOI
TL;DR: It is the opinion of the writing group that the overall evidence is consistent with a causal relationship between PM2.5 exposure and cardiovascular morbidity and mortality.
Abstract: In 2004, the first American Heart Association scientific statement on “Air Pollution and Cardiovascular Disease” concluded that exposure to particulate matter (PM) air pollution contributes to card...

5,227 citations