Publications (14)40.39 Total impact
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Article: Combination of ellipsometry, laser scanning microscopy and Z-scan fluorescence correlation spectroscopy elucidating interaction of cryptdin-4 with supported phospholipid bilayers.
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ABSTRACT: The present study has two main objectives. The first is to characterize antimicrobial peptide (AMP) cryptdin-4 (Crp-4) interactions with biological membranes and to compare those interactions with those of magainin 2. The second is to combine the complementary experimental approaches of laser scanning microscopy (LSM), ellipsometry, and Z-scan fluorescence correlation spectroscopy (FCS) to acquire comprehensive information on mechanisms of AMP interactions with supported phospholipid bilayers (SPBs)-a popular model of biological membranes. LSM shows appearance of inhomogeneities in spatial distribution of lipids in the bilayer after treatment with Crp-4. Ellipsometric measurements show that binding of Crp-4 does not significantly change the lipid structure of the bilayer (increase in adsorbed mass without a change in thickness of adsorbed layer). Furthermore, Crp-4 slows the lateral diffusion of lipids within the membrane as shown by Z-scan FCS. All changes of the bilayer induced by Crp-4 can be partially reversed by flushing the sample with excess of buffer. Bilayer interactions of magainin 2 are significantly different, causing large loss of lipids and extensive damage to the bilayer. It seems likely that differences in peptide mode of action, readily distinguished using these combined experimental methods, are related to the distinctive beta-sheet and alpha-helical structures of the respective peptides.Journal of Peptide Science 05/2008; 14(4):503-9. · 1.80 Impact Factor -
Article: Combination of ellipsometry, laser scanning microscopy and Z‐scan fluorescence correlation spectroscopy elucidating interaction of cryptdin‐4 with supported phospholipid bilayers
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ABSTRACT: The present study has two main objectives. The first is to characterize antimicrobial peptide (AMP) cryptdin-4 (Crp-4) interactions with biological membranes and to compare those interactions with those of magainin 2. The second is to combine the complementary experimental approaches of laser scanning microscopy (LSM), ellipsometry, and Z-scan fluorescence correlation spectroscopy (FCS) to acquire comprehensive information on mechanisms of AMP interactions with supported phospholipid bilayers (SPBs)—a popular model of biological membranes. LSM shows appearance of inhomogeneities in spatial distribution of lipids in the bilayer after treatment with Crp-4. Ellipsometric measurements show that binding of Crp-4 does not significantly change the lipid structure of the bilayer (increase in adsorbed mass without a change in thickness of adsorbed layer). Furthermore, Crp-4 slows the lateral diffusion of lipids within the membrane as shown by Z-scan FCS. All changes of the bilayer induced by Crp-4 can be partially reversed by flushing the sample with excess of buffer. Bilayer interactions of magainin 2 are significantly different, causing large loss of lipids and extensive damage to the bilayer. It seems likely that differences in peptide mode of action, readily distinguished using these combined experimental methods, are related to the distinctive β-sheet and -helical structures of the respective peptides. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.Journal of Peptide Science 03/2008; 14(4):503 - 509. · 1.80 Impact Factor -
Article: Absence of ethanol-induced interdigitation in supported phospholipid bilayers on silica surfaces.
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ABSTRACT: Membranes prepared by the adsorption of phospholipid vesicles on solid supports are much-used model systems in biomedical research. However, there is accumulating evidence that such membranes may not always be equivalent to the free-standing cellular membranes that they are modeling. In the present study, sonicated DOPC/DOPS (80/20 mol %) vesicles were adsorbed on hydrophilic silica surfaces, a system that has been demonstrated to produce confluent bilayers. In addition, pure DOPC and DLPC membranes were studied. It is demonstrated that ethanol-induced membrane interdigitation, as demonstrated for free-standing bilayers, does not occur in these supported membranes.Langmuir 02/2008; 24(1):19-21. · 4.19 Impact Factor -
Article: Plasma markers of activated hemostasis in the early diagnosis of acute coronary syndromes.
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ABSTRACT: Because acute coronary syndromes (ACS) are caused by intracoronary thrombosis, plasma markers of coagulation have relevance for early diagnosis. To provide a critical review of these studies and specific attempts to close the diagnostic time gap left by traditional plasma markers of heart injury. Studies of ACS patients, with at least one control group, were included when blood samples were taken within 24 h after first symptoms prior to medication or intervention. Special attention was paid to studies reporting diagnostic performance, or combination of several markers into a single diagnostic index. Markers with short plasma half-life (FPA, TAT, etc.) reflect ongoing thrombosis and may identify patients at increased risk. Markers with longer half-life (F1+2, D-Dimer, etc.) may be more useful to indicate a single acute thrombotic event. However, results are highly variable and depend on sampling time, clot property, degree of coronary obstruction and physiological condition. Early diagnostic performance of hemostatic markers was poor even when combined with heart injury markers. Early measurement of hemostatic plasma markers in ACS patients provides pathophysiological information and may be helpful in risk stratification or to monitor anticoagulant therapy, but does not seem useful in routine clinical diagnosis of ACS.Clinica Chimica Acta 10/2006; 371(1-2):37-54. · 2.54 Impact Factor -
Article: High-affinity antibodies in a new immunoassay for plasma tissue factor: reduction in apparent intra-individual variation.
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ABSTRACT: Tissue factor, the main initiator of blood coagulation, is shed into plasma by blood cells and endothelium. While studying such circulating plasma tissue factor with a commercially available immunoassay, we found unsatisfactory results and therefore developed a new and highly sensitive enzyme-linked immunosorbent assay (ELISA). High-affinity monoclonal antibodies raised against recombinant soluble tissue factor were used and the new assay had a detection limit of 40 fmol/L, approximately six-fold lower than existing assays. Normal ranges in 20 healthy donors were established in serum and in citrated EDTA and heparinized plasma. Tissue factor was also measured in three successive plasma samples from 43 patients with type 2 diabetes mellitus. In citrated plasma from healthy donors, tissue factor concentrations were 2.5 (1.0-9.3) pmol/L (median with range) and were not significantly different in diabetics. With a commercially available immunoassay, seven plasma samples were below the detection limit. Use of the new assay reduced intra-individual variation in diabetics from 49% to 14% and we conclude that high-affinity antibodies may markedly improve immunoassay performance.Clinical Chemistry and Laboratory Medicine 02/2005; 43(12):1386-91. · 2.15 Impact Factor -
Article: Surface-dependent transitions during self-assembly of phospholipid membranes on mica, silica, and glass.
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ABSTRACT: Formation of supported membranes by exposure of solid surfaces to phospholipid vesicles is a much-used technique in membrane research. Freshly cleaved mica, because of its superior flatness, is a preferred support, and we used ellipsometry to study membrane formation kinetics on mica. Neutral dioleoyl-phosphatidylcholine (DOPC) and negatively charged dioleoyl-phosphatidylserine/dioleoyl-phosphatidylcholine (20% DOPS/80% DOPC) vesicles were prepared by sonication. Results were compared with membrane formation on silica and glass, and the influence of stirring, buffer, and calcium was assessed. Without calcium, DOPC vesicles had a low affinity (Kd approximately 30 microM) for mica, and DOPS/DOPC vesicles hardly adsorbed. Addition of calcium promptly caused condensation of the adhering vesicles, with either loss of excess lipid or rapid additional lipid adsorption up to full surface coverage. Vesicle-mica interactions dominate the adsorption process, but vesicle-vesicle interactions also seem to be required for the condensation process. Membranes on mica proved unstable in Tris-HCl buffer. For glass, transport-limited adsorption of DOPC and DOPS/DOPC vesicles with immediate condensation into bilayers was observed, with and without calcium. For silica, vesicle adsorption was also rapid, even in the absence of calcium, but the transition to condensed layers required a critical surface coverage of about 50% of bilayer mass, indicating vesicle-vesicle interaction. For all three surfaces, additional adsorption of DOPC (but not DOPS/DOPC) vesicles to condensed membranes was observed. DOPC membranes on mica were rapidly degraded by phospholipase A2 (PLA2), which pleads against the role of membrane defects as initial PLA2 targets. During degradation, layer thickness remained unchanged while layer density decreased, in accordance with recent atomic force microscopy measurements of gel-phase phospholipid degradation by PLA2.Langmuir 12/2004; 20(23):10129-37. · 4.19 Impact Factor -
Article: Effects of flow on solute exchange between fluids and supported biosurfaces.
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ABSTRACT: Uptake of nutrients by cultured cells on solid supports, conversion of substrates by surface-bound catalysts and binding of antibodies to microtitre plates are examples of transport processes that are strongly influenced by the flow conditions in the surrounding fluid. The literature on this subject is scattered over widely different research fields and is often found in dated, and not generally available, treatises. Also, the subject is inherently complicated from a mathematical viewpoint, because even the simplest experimental configurations will usually not allow analytical solutions for the diffusion-convection equations describing the solute mass transport in the system. Fortunately, however, relatively simple expressions for the rates of mass transport can often be obtained in physically realistic limiting cases. The present study attempts to give a short overview of the main experimental models used in this field and presents simple equations for the estimation of solute exchange rates between surfaces and fluids. The models considered are: (1) uptake from an unstirred solution; (2) reversible binding from a perfectly stirred solution; (3) reversible binding through an unstirred fluid layer; (4) catalytic conversion at the internal surface of a tube or a slit with laminar flow; (5) adsorption by a surface opposite a rotating stirrer; (6) adsorption from an impinging fluid jet; and (7) uptake by the surface of a rotating disc. In practical situations the property of uniform accessibility proves to be of crucial importance. Stirring by ultrasound, more specifically the use of acoustic streaming in nano-devices, is also discussed.Biotechnology and Applied Biochemistry 07/2004; 39(Pt 3):277-84. · 1.53 Impact Factor -
Article: Prevention of cardiac cell injury during acute myocardial infarction: possible role for complement inhibition.
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ABSTRACT: The purpose of this article is to describe mechanisms of cell death in patients with acute myocardial infarction, particularly the activation of the complement system. Various pro-inflammatory cytokines, released by the inflamed tissue, play a role in the activation of the complement system. Several complement inhibitors have been developed to reduce tissue damage following ischemia. According to animal studies the deleterious effects of activators of the complement system can be diminished by complement inhibition. Several clinical studies have been conducted for the potential treatment of cell injury during acute myocardial infarction. C1 inhibitor dose-dependently inhibited complement activation and appeared to reduce myocardial injury after reperfusion therapy in patients with acute myocardial infarction. C1 inhibitor dose-dependently reduced plasma levels of C4 activation fragments. In addition, cardiac enzymes (troponin T and creatine kinase-MB) returned to baseline levels more rapidly among patients treated with C1 inhibitor, compared with controls. Furthermore, preliminary results from a placebo-controlled trial indicate that treatment with intravenous pexelizumab (anti-C5 antibody) was well tolerated in a large number of patients undergoing coronary artery bypass graft surgery. Further, more randomized trials are necessary to clarify the clinical significance of this new and innovative treatment with complement inhibition.American Journal of Cardiovascular Drugs 02/2003; 3(4):245-51. · 1.77 Impact Factor -
Article: Pharmacokinetics of C1-inhibitor protein in patients with acute myocardial infarction.
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ABSTRACT: C1-inhibitor protein (C1-INH) purified from pooled human plasma is used for the treatment of patients with hereditary angioedema. Recently, the beneficial effects of high-dose C1-INH treatment on myocardial ischemia or reperfusion injury have been reported in various animal models and in humans. We investigated the pharmacokinetic behavior of C1-INH in patients with acute myocardial infarction to calculate the amount of C1-INH required for optimal efficacy. Twenty-two patients received an intravenous loading dose, followed by 48 hours of continuous infusion of C1-INH. Changes in the endogenous production of C1-INH were evaluated in 16 control patients with acute myocardial infarction. A 2-compartment model was used to estimate the fractional catabolic rate constant (FCR), transcapillary escape rate constant (TER), and extravascular return rate constant (ERR) of C1-INH. Software designed to analyze and fit measured data to unknown parameters in a system of differential equations was used to fit the experimental data against the 3-parameter model. With fixed TER and ERR values (0.014 h(-1) and 0.018 h(-1), respectively), 20 of the 22 cases yielded well-determined FCR values, and simultaneous fitting resulted in a median FCR of 0.011 h(-1) (95% confidence interval, 0.010 to 0.012 h(-1)) versus 0.025 h(-1) as reported in healthy control patients. Simultaneous estimation of TER, ERR, and FCR demonstrated weakly defined TER and ERR values, whereas the median FCR value remained unchanged. The use of a 2-compartment model resulted in a significantly better fit compared with the 1-compartment model. Physiologic explanations are offered for discrepancies in the literature. Dose calculation of C1-INH in patients treated with massive doses of C1-INH requires turnover parameters that differ from those found in healthy subjects, possibly because of suppression of continuous C1-INH consumption by target proteases.Clinical Pharmacology & Therapeutics 12/2002; 72(5):498-504. · 6.04 Impact Factor -
Article: Evaluation of "new" cardiac markers for ruling out myocardial infarction after coronary artery bypass grafting.
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ABSTRACT: This study was conducted to evaluate the value of serum troponin T, myoglobin, and creatine kinase (CK)-MB mass concentrations for ruling out perioperative myocardial infarction (poMI) early after cardiac surgery. Retrospective study. Cardiothoracic surgery department in a university hospital. One hundred eighty-one patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass were included. Serum concentrations of troponin T, myoglobin, and CK-MB mass were measured preoperatively (baseline), on arrival at the cardiosurgical ICU (CICU), and at 2, 4, 8, 12, 16, and 20 h after arrival at the CICU. The strength of markers studied for ruling out poMI was studied using receiver operating characteristics curves. Based on these curves, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each marker at every time point were calculated. poMI developed in 14 patients. On arrival at the CICU, all markers were significantly increased from baseline concentrations in both patient groups. In patients with poMI, serum concentrations of troponin T, myoglobin, and CK-MB mass were significantly higher than in control patients from 8, 2, and 0 h after arrival on the CICU, respectively. CK-MB mass was the earliest marker, and its NPV reached 98.6% 12 h after arrival at the CICU. On arrival at the CICU, the NPV for CK-MB mass already reached 96.7%. The NPV for myoglobin reached 98.4% 12 h after arrival at the CICU. Troponin T was not an early marker for ruling out poMI, with an NPV reaching 98.6% 12 h after arrival on the CICU. During the first 8 h after arrival at the CICU, sensitivity, specificity, PPV, and NPV of CK-MB mass exceeded those of myoglobin and troponin T. In later measurements (until 20 h after arrival at the CICU), troponin T gave the most sensitive definition of poMI. For ruling out poMI on the CICU after CABG, CK-MB mass is a better marker than myoglobin and troponin T during the first 12 h after arrival on the CICU. Using these markers, postoperative treatment of cardiac surgical patients might be further improved.Chest 11/2002; 122(4):1316-21. · 5.25 Impact Factor -
Article: Secretory type II phospholipase A(2) binds to ischemic myocardium during myocardial infarction in humans.
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ABSTRACT: An increase of circulating secretory Phospholipase A(2) (sPLA(2)) is a risk factor for coronary artery disease. We hypothesized that this reflects participation of sPLA(2) in local inflammatory reactions ensuing in ischemic myocardium. Therefore, we studied the course of circulating sPLA(2), in patients with acute myocardial infarction (AMI) or unstable angina pectoris (UAP), and investigated the presence of sPLA(2) in infarcted myocardial tissue. Plasma samples of 107 patients with AMI or UAP, collected on admission and at varying intervals thereafter, were tested for the presence of sPLA(2) and C-reactive protein (CRP). Cumulative release values of these parameters were calculated, which allowed for comparison of the results rearranged in time according to the onset of symptoms. By immunohistochemistry we studied the presence of sPLA(2) and CRP in myocardial tissue of 30 patients who died subsequent to AMI. Levels of sPLA(2) became elevated during the disease course in 66 of the 87 patients with AMI, and were higher than those of the patients with UAP of whom 8 of the 20 had elevated levels. By immunohistochemistry sPLA(2) was found to be localized in the infarcted myocardium, particularly in its borderzone, from 12 h after the onset of AMI. Positive staining for sPLA(2) was more extensive than that for CRP. The localization pattern of sPLA(2) in infarcted myocardium as well as its plasma course, in relation to those of CRP, are in line with a supposed pro-inflammatory role during AMI for sPLA(2) as a generator of lysophospholipids serving as ligands for CRP.Cardiovascular Research 02/2002; 53(1):138-46. · 6.06 Impact Factor -
Article: Estimation of Myocardial Infarct Size from Plasma Myoglobin or Fatty Acid-Binding Protein. Influence of Renal Function
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Article: Plasma markers of activated hemostasis in the early diagnosis of acute coronary syndromes
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ABSTRACT: BackgroundBecause acute coronary syndromes (ACS) are caused by intracoronary thrombosis, plasma markers of coagulation have relevance for early diagnosis.Aims and objectivesTo provide a critical review of these studies and specific attempts to close the diagnostic time gap left by traditional plasma markers of heart injury.MethodsStudies of ACS patients, with at least one control group, were included when blood samples were taken within 24 h after first symptoms prior to medication or intervention. Special attention was paid to studies reporting diagnostic performance, or combination of several markers into a single diagnostic index.ResultsMarkers with short plasma half-life (FPA, TAT, etc.) reflect ongoing thrombosis and may identify patients at increased risk. Markers with longer half-life (F1 + 2, D-Dimer, etc.) may be more useful to indicate a single acute thrombotic event. However, results are highly variable and depend on sampling time, clot property, degree of coronary obstruction and physiological condition. Early diagnostic performance of hemostatic markers was poor even when combined with heart injury markers.ConclusionsEarly measurement of hemostatic plasma markers in ACS patients provides pathophysiological information and may be helpful in risk stratification or to monitor anticoagulant therapy, but does not seem useful in routine clinical diagnosis of ACS.Clinica Chimica Acta. -
Article: The role of intrinsic binding rate and transport rate in the adsorption of prothrombin, albumin, and fibrinogen to phospholipid bilayers
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ABSTRACT: The rates of adsorption and desorption of prothrombin, albumin, and fibrinogen are studied by means of ellipsometry. The adsorbing surface consists of a chromium slide covered with a bilayer of negatively charged phospholipid (dioleoylphosphatidylserine) in a stirred buffer solution. Using an unstirred layer model, a simple graphical representation of the results is presented which allows detection of a transport limitation in sorption kinetics and also allows direct estimation of the thickness δ of the unstirred layer. Values of δ ranged from 2.5 to 10 μm, depending on the rate of stirring. The initial rate of prothrombin adsorption is transport-limited under all conditions studied. Adsorption of fibrinogen is much slower and determined by the intrinsic rate of protein binding. However, the adsorption becomes faster after lowering the pH and ionic strength of the buffer solution and eventually becomes transport-limited. Adsorption of albumin is slow and determined by the intrinsic binding rate for all conditions studied. Reversible adsorption is demonstrated for prothrombin, while the adsorption of fibrinogen and albumin was apparently irreversible.Journal of Colloid and Interface Science 111(2):544-554. · 3.07 Impact Factor
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- Langmuir (2)
- Cardiovascular Research (1)
- Clinica Chimica Acta (1)
- Clinical Pharmacology & Therapeutics (1)
- Chest (1)
Institutions
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2002–2008
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Maastricht University
- • Cardiologie
- • Department of Clinical Chemistry
Maastricht, Provincie Limburg, Netherlands
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2004
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Academy of Sciences of the Czech Republic
- Centrum pro biomolekuly a komplexní molekulární systémy
Praha, Hlavni mesto Praha, Czech Republic
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