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The impact of skin decontamination on the time window for effective treatment of percutaneous VX exposure

Joosen, M.J.A. (author), van den Berg, R.M. (author), de Jong, A.L. (author), van der Schans, M.J. (author), Noort, D. (author), Langenberg, J.P. (author)

The main goal of the present study was to obtain insight into depot formation and penetration following percutaneous VX poisoning, in order to identify an appropriate decontamination window that can enhance or support medical countermeasures. The study was executed in two phases, using the hairless guinea pig as an animal model. In the first...

article 2017

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Timing of decontamination and treatment in case of percutaneous VX poisoning: A mini review

Joosen, M.J.A. (author), van der Schans, M.J. (author), Kuijpers, W.C. (author), van Helden, H.P.M. (author), Noort, D. (author)

Low volatile organophosphorous nerve agents such as VX, will most likely enter the body via the skin. The pharmacokinetics of drugs such as oximes, atropine and diazepam, are not aligned with the variable and persistent toxicokinetics of the agent. Repeated administration of these drugs showed to improve treatment efficacy compared to a single...

article 2013

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Percutaneous exposure to the nerve agent VX: Efficacy of combined atropine, obidoxime and diazepam treatment

Joosen, M.J.A. (author), van der Schans, M.J. (author), van Helden, H.P.M. (author), TNO Defensie en Veiligheid (author)

The nerve agent VX is most likely to enter the body via liquid contamination of the skin. After percutaneous exposure, the slow uptake into the blood, and its slow elimination result in toxic levels in plasma for a period of several hours. Consequently, this has implications for the development of toxic signs and for treatment onset. In the...

article 2010

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Dexamethasone-eluting stents for the prevention of in-stent restenosis: Evidence for a differential effect in insulin-dependent and non-insulin-dependent diabetic patients

van der Hoeven, B.L. (author), Pires, N.M.M. (author), Warda, H.M. (author), Putter, H. (author), Quax, P.H.A. (author), Schalij, M.J. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)

Diabetes mellitus (DM) is a strong predictor of in-stent restenosis. This may be due to a higher level of vascular inflammation. We hypothesized that diabetic patients will benefit from dexamethasone-eluting stents, since local inflammation and consequently neointimal growth are suppressed and no systemic side effects will occur. Methods: 21...

article 2008

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Interleukin 10: A new risk marker for the development of restenosis after percutaneous coronary intervention

Monraats, P.S. (author), Kurreeman, F.A.S. (author), Pons, D. (author), Sewgobind, V.D.K.D. (author), de Vries, F.R. (author), Zwinderman, A.H. (author), de Maat, M.P.M. (author), Doevendans, P.A. (author), de Winter, R.J. (author), Tio, R.A. (author), Waltenberger, J. (author), Huizinga, T.W.J. (author), Eefting, D. (author), Quax, P.H.A. (author), Frants, R.R. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)

Genetic factors appear to be important in the process of restenosis after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. An important mediator in the inflammatory response is interleukin (IL)-10. Our aim was to study whether genetic variants in IL-10 predispose to the risk of restenosis. The...

article 2007

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The influence of established genetic variation in the haemostatic system on clinical restenosis after percutaneous coronary interventions

TNO Kwaliteit van Leven (author), Pons, D. (author), Monraats, P.S. (author), de Maat, M.P.M. (author), Pires, N.M.M. (author), Quax, P.H.A. (author), van Vlijmen, B.J.M. (author), Rosendaal, F.R. (author), Zwinderman, A.H. (author), Doevendans, P.A.F.M. (author), Waltenberger, J. (author), de Winter, R.J. (author), Tio, R.A. (author), Frants, R.R. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author)

Since activation of the haemostatic system is an important feature of the wound healing response triggered by arterial injury, variations in genes involved in thrombus formation may play a role in restenosis after percutaneous coronary interventions (PCI). Therefore, our aim was to examine the relationship between polymorphisms that are known to...

article 2007

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Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies

Wilkinson, S.C. (author), Maas, W.J.M. (author), Nielsen, J.B. (author), Greaves, L.C. (author), van de Sandt, J.J.M. (author), Williams, F.M. (author), TNO Kwaliteit van Leven TNO Voeding (author)

Objectives: To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Methods: Percutaneous penetration of caffeine (log P -0.01), testosterone ...

article 2006

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Dermal absorption of chlorpyrifos in human volunteers

Meuling, W.J. (author), Ravensberg, L.C. (author), Roza, L. (author), van Hemmen, J.J. (author), TNO Kwaliteit van Leven (author)

Objective: The methods and results are described of a study on the dermal absorption of chlorpyrifos (CPF) in humans established via urinary excretion of the metabolite 3,5,6-trichloro-2-pyridinol (TCP). Methods: Two dermal, single, doses of CPF were applied in two study groups (A and B) each comprising three apparently healthy male volunteers...

article 2005

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Genetic inflammatory factors predict restenosis after percutaneous coronary interventions

Monraats, P.S. (author), Pires, N.M.M. (author), Agema, W.R.P. (author), Zwinderman, A.H. (author), Schepers, A. (author), de Maat, M.P.M. (author), Doevendans, P.A. (author), de Winter, R.J. (author), Tio, R.A. (author), Waltenberger, J. (author), Frants, R.R. (author), Quax, P.H.A. (author), van Vlijmen, B.J.M. (author), Atsma, D.E. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)

Background - Restenosis is a negative effect of percutaneous coronary intervention (PCI). No clinical factors are available that allow good risk stratification. However, evidence exists that genetic factors are important in the restenotic process as well as in the process of inflammation, a pivotal factor in restenosis. Association studies have...

article 2005

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Endothelial function and baroreflex sensitivity according to the oral glucose tolerance test in patients with coronary artery disease and normal fasting glucose levels

Wykretowicz, A. (author), Guzik, P. (author), Bartkowiak, G. (author), Krauze, T. (author), Kasinowski, R. (author), Dziarmaga, M. (author), Wesseling, K.H. (author), Wysocki, H. (author), TNO Biomedical Instrumentation (author)

Endothelial dysfunction and reduced BRS (baroreflex sensitivity) may be present in patients with CAD (coronary artery disease). The normal fasting glucose level does not exclude abnormal glucose metabolism in patients with CAD. The aim of present study was to evaluate endothelial function and BRS according to glucose metabolism in patients with...

article 2005

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Tumor necrosis factor-α plays an important role in restenosis development

Monraats, P.S. (author), Pires, N.M.M. (author), Schepers, A. (author), Agema, W.R.P. (author), Boesten, L.S.M. (author), de Vries, M.R. (author), Zwinderman, A.H. (author), de Maat, M.P.M. (author), Doevendans, P.A.F.M. (author), de Winter, R.J. (author), Tio, R.A. (author), Waltenberger, J. (author), 't Hart, L.M. (author), Frants, R.R. (author), Quax, P.H.A. (author), van Vlijmen, B.J.M. (author), Havekes, L.M. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)

Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNFα, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER)...

article 2005

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Lipoprotein lipase gene polymorphisms and the risk of target vessel revascularization after percutaneous coronary intervention

TNO Kwaliteit van Leven (author), Monraats, P.S. (author), Rana, J.S. (author), Nierman, M.C. (author), Pires, N.M.M. (author), Zwinderman, A.H. (author), Kastelein, J.J.P. (author), Kuivenhoven, J.A. (author), de Maat, M.P.M. (author), Rittersma, S.Z.H. (author), Schepers, A. (author), Doevendans, P.A.F. (author), de Winter, R.J. (author), Tio, R.A. (author), Frants, R.R. (author), Quax, P.H.A. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author)

OBJECTIVES: We sought to identify polymorphisms in genes that predispose to restenosis. BACKGROUND: Variations in the lipoprotein lipase (LPL) gene have been implicated in a number of pathophysiologic conditions associated with coronary heart disease. The present study examines the impact of polymorphisms in the LPL gene on restenosis (defined...

article 2005

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Human systemic exposure to a [14C]-para-phenylenediamine- containing oxidative hair dye and correlation with in vitro percutaneous absorption in human or pig skin

Hueber-Becker, F. (author), Nohynek, G.J. (author), Meuling, W.J.A. (author), Benech-Kieffer, F. (author), Toutain, H. (author), TNO Voeding (author)

We investigated the absorption of a commercial [14C]-PPD- containing oxidative dark-shade hair dye in human volunteers as well as in vitro using human or pig ear skin. The hair of eight male volunteers was cut to a standard length, dyed, washed, dried, clipped and collected. Hair, washing water, materials used in the study and a 24-h scalp wash...

article 2004

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Current PTCA practice and clinical outcomes in the Netherlands: The real world in the pre-drug-eluting stent era

Agema, W.R.P. (author), Monraats, P.S. (author), Zwinderman, A.H. (author), de Winter, R.J. (author), Tio, R.A. (author), Doevendans, P.A.F.M. (author), Waltenberger, J. (author), de Maat, M.P.M. (author), Frants, R.R. (author), Atsma, D.E. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author), Gaubius Instituut TNO (author)

Aims To document the practice of interventional cardiology and the clinical restenosis rate, as well as the risk factors for clinical restenosis in an unselected population of patients in daily practice and to provide a perspective for the need of new devices such as drug-eluting stents. Methods and results A total of 3177 consecutive patients,...

article 2004

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Evaluation of the Retrievability of the OptEase IVC Filter in an Animal Model

Reekers, J.A. (author), Hoogeveen, Y.L. (author), Wijnands, M. (author), Bosma, G. (author), Mulder, R. (author), Oliva, V.L. (author), TNO Voeding (author)

PURPOSE: A new inferior vena cava filter was evaluated in vivo to determine the percutaneous retrievability after an implantation period of up to 18 days. MATERIALS AND METHODS: The inferior venae cavae of six goats were percutaneously implanted with three filters, and one animal received two filters. To assess filter stability, a plain...

article 2004

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Percutaneous absorption of mexoryl SX® in human volunteers: Comparison with in vitro data

Benech-Kieffer, F. (author), Meuling, W.J.A. (author), Leclerc, C. (author), Roza, L. (author), Leclaire, J. (author), Nohynek, G. (author), TNO Voeding (author)

The potential human health risk of UV filters depends on their toxicity and the human systemic exposure which is a function of the extent of percutaneous absorption of the topically applied substance into the human organism. Using a 'mass balance' approach, a study was designed to investigate the systemically absorbed dose of [14C]-Mexoryl SX®...

article 2003

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Toxicokinetics of the nerve agent (±)-VX in anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration

van der Schans, M.J. (author), Lander, B.J. (author), van der Wiel, H. (author), Langenberg, J.P. (author), Benschop, H.P. (author), Prins Maurits Laboratorium TNO (author)

In continuation of our investigations on the toxicokinetics of the volatile nerve agents C(±)P(±)-soman and (±)-sarin, we now report on the toxicokinetics of the rather nonvolatile agent (±)-VX. A validated method was developed to determine blood levels of (±)-VX by means of achiral gas chromatography at blood levels ≥10 pg/ml. The ratio of the...

article 2003

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Percutaneous penetration studies for risk assessment

Sartorelli, P. (author), Andersen, H.R. (author), Angerer, J. (author), Corish, J. (author), Drexler, H. (author), Göen, T. (author), Griffin, P. (author), Hotchkiss, S.A.M. (author), Larese, F. (author), Montomoli, L. (author), Perkins, J. (author), Schmelz, M. (author), van de Sandt, J. (author), Williams, F. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

During the last few years the general interest in the percutaneous absorption of chemicals has increased. It is generally accepted that there is very few reliable quantitative and qualitative data on dermal exposure to chemicals in the general population and in occupationally exposed workers. In order to predict the systemic risk of dermally...

article 2000

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Dermal route in systemic exposure

Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author), Benford, D.J. (author), Cocker, J. (author), Sartorelli, P. (author), Schneider, T. (author), van Hemmen, J. (author), Firth, J.G. (author)

To evaluate risk from dermal exposure, the amount of material on the skin must first be measured. The potential for dermal uptake must then be assessed for the potential health effects from systemic exposure. No standard methods exist for studying these processes, and published data are not comparable because of the different techniques used....

article 1999

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Long-term endothelial dysfunction is more pronounced after stenting than after balloon angioplasty in porcine coronary arteries

van Beusekom, H.M.M. (author), Whelan, D.M. (author), Hofma, S.H. (author), Krabbendam, S.C. (author), van Hinsbergh, V.W.M. (author), Verdouw, P.D. (author), van der Giessen, W.J. (author), Gaubius Instituut TNO (author)

Objectives. To compare percutaneous transluminal coronary angioplasty (PTCA) and stent implantation with respect to the long-term changes they induce in the newly formed endothelium in porcine coronary arteries by studying both morphological and functional parameters of the endothelium at 2 weeks and 3 months after intervention. Background....

article 1998