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Biomedical subjects

A Sturk

Publications and source records attributed to A Sturk.

At least 19 recordsLinked to original sources
PubMed2006

Two consecutive high-fat meals affect endothelial-dependent vasodilation, oxidative stress and cellular microparticles in healthy men.

BACKGROUND: A large body of evidence has accumulated indicating a relation between postprandial hyperglycemia and hypertriglyceridemia, and the risk of cardiovascular disease. OBJECTIVE: We studied possible mechanisms underlying the postprandial proatherogenic state by exposing healthy males to two consecutive high-fat mixed meals. PATIENTS/METHODS: Seventeen healthy males [age 25.4 +/- 3 years, body mass index 23.6 +/- 2 kg m(-2)] were studied during two randomized visits. During the meal visit, subjects consumed standardized meals (50 g of fat, 55 g of carbohydrates and 30 g of proteins) as breakfast and 4 h later as lunch. During the control visit, subjects remained fasted. Prior to each blood collection (before and every 2 h after the first meal), flow-mediated dilation (FMD) of the brachial artery was measured. RESULTS: Although within the normal range, postprandial plasma glucose and triacylglycerol concentrations increased significantly, especially after the second meal, as compared with baseline (4.8 +/- 0.3 to 5.4 +/- 0.4, 0.8 +/- 0.2 to 1.7 +/- 0.7 mmol L(-1), respectively; both P < 0.05) and the fasting visit. After the second meal, FMD was significantly impaired (6.9% vs. 3.7%, P < 0.05) whereas oxidized low-density lipoprotein (oxLDL)/LDL cholesterol ratio and malondialdehyde concentrations were markedly elevated (both P < 0.01). Finally, an increase in total microparticle (MP) numbers was observed during the meal visit (P < 0.05). CONCLUSIONS: In healthy males, after two consecutive fat-rich meals, mild elevations in plasma glucose and triacylglycerol were paralleled by impaired FMD, increased markers of oxidative stress and circulating MPs, in particular, after the second meal. These findings may have consequences for subjects with postprandial dysmetabolism, including those with Type 2 diabetes.

Adult↗
PubMed2005

Congenital deficiency of factor XIII caused by two missense mutations in a Dutch family.

We present the clinical, biochemical and genomic findings of a family with congenital factor XIII (FXIII) deficiency. Congenital FXIII deficiency is a very rare autosomal recessive bleeding disorder, characterized by umbilical cord bleeding at birth and spontaneous intracranial haemorrhage. Routine clotting tests are normal, which may delay the diagnosis, leading to an increased chance of severe sequelae. The propositus and her brother, known with haemorrhagic diathesis, were found to be compound heterozygous with a known missense mutation (1050 G --> T transversion in exon 7, Val316Phe substitution) and a novel mutation 889 G --> A in exon 6, which predicts a Gly262Glu substitution. As these mutations were known in the family, DNA obtained from cord blood of the youngest sister was analysed for mutations in exons 6 and 7 only. We postulate that the diagnosis was facilitated by determining the two different mutations in the genotype of this family. The analysis showed that she was heterozygous for the exon 7 mutation. Hence, she was not at risk of experiencing haemorrhagic diathesis. This diagnosis avoided the administration of FXIII concentrate to the newborn.

Adult↗
PubMed2005

Cell-derived microparticles contain caspase 3 in vitro and in vivo.

BACKGROUND: Microparticles (MP) from endothelial cells (endothelial microparticles; EMP) circulate in disease states, but the processes such as apoptosis or cell activation underlying their release are unclear. OBJECTIVES: We investigated whether adherent (viable) or detached (apoptotic) endothelial cells are the possible source of EMP in vitro, i.e. under control and interleukin (IL)-1alpha activation conditions, and in vivo. METHODS: Adherent and detached endothelial cells, and EMP, were isolated from human umbilical vein endothelial cell cultures (n = 6), treated without or with IL-1alpha (5 ng mL(-1); 24 h). Cell fractions were analyzed by flow cytometry for annexin V binding, propidium iodide (PI) and caspase 3 staining (n = 3). Caspase 3 in EMP was studied using Western blot (n = 6) and flow cytometry (n = 6). Plasma from healthy subjects and systemic lupus erythematosus patients (both n = 3) were analyzed for caspase 3-containing (E)MP. RESULTS: Detached but not adherent cells double-stained for annexin V and PI, confirming the apoptotic conditions of the detached cells and the viable nature of the adherent cells. Caspase 3 was solely present in the detached cells and procaspase 3 in the adherent cells. Caspase 3 was present in EMP from both control and IL-1alpha-treated cultures. Counts of EMP and detached cells, but not adherent cells, highly correlated (r = 0.959, P < 0.0001). In vivo circulating MP from nucleated (endothelial cells, monocytes) and anucleated cells (platelets, erythrocytes) contained caspase 3. CONCLUSIONS: EMP contain caspase 3 and may be mainly derived from detached (apoptotic) endothelial cells in vitro. The presence of caspase 3 in MP from anucleated cell types, however, suggests that its presence may not necessarily be related to apoptosis in vivo but may be associated with caspase 3 activation unrelated to apoptosis.

Annexin A5↗
PubMed2005

The phospholipid composition and cholesterol content of platelet-derived microparticles: a comparison with platelet membrane fractions.

BACKGROUND: The processes that govern the distribution of molecules between platelets and the microparticles (MP) they release are unknown. Certain proteins are sorted selectively into MP, but lipid sorting has not been studied. OBJECTIVES: To compare the phospholipid composition and cholesterol content of platelet-derived MP obtained with various stimuli with that of isolated platelet membrane fractions. METHODS: Washed platelets from venous blood of healthy individuals (n = 6) were stimulated with collagen, thrombin, collagen plus thrombin, or A23187. Platelet activation, MP release and antigen exposure were assessed by flow cytometry. MPs were isolated by differential centrifugation. Platelet plasma-, granule- and intracellular membranes were isolated from platelet concentrates (n = 3; 10 donors each) by pressure homogenization and Percoll density gradient fractionation. The phospholipid composition and cholesterol content of MPs and membrane fractions were analyzed by high performance thin layer chromatography. RESULTS: The phospholipid composition of MPs was intermediate compared with that of platelet plasma- and granule membranes, and differed significantly from that of intracellular membranes. There were small but significant differences in phospholipid composition between the MPs produced by the various agonists, which paralleled differences in P-selectin exposure in case of the physiological agonists collagen, thrombin, or collagen plus thrombin. The cholesterol content of MPs tended to be higher than that of the three-platelet membrane fractions. CONCLUSIONS: Regarding its phospholipid content, the MP membrane is a composite of the platelet plasma- and granule membranes, showing subtle differences depending on the platelet agonist. The higher cholesterol content of MPs suggests their enrichment in lipid rafts.

Blood Platelets↗
PubMed2004

[Cellular microparticles and blood-vessel damage. I. Structure, detection and origin].

In virtually all eukaryotic cells, activation and apoptosis lead to the formation of vesicles or microparticles by intracellular mechanisms which as yet are not completely understood. Flow cytometry, electron microscopy and ELISA techniques can be used to detect microparticles. Microparticles are a heterogeneous population and their numbers, cellular origin, composition and functional characteristics, both in vitro and in vivo, depend on the circumstances under which they were generated. Microparticles derived from various cells, primarily platelets but also lymphocytes, granulocytes, monocytes, erythrocytes and endothelial cells, are present in the circulation of healthy subjects. Elevated numbers of microparticles can be found in a wide variety of diseases, all of which are associated with hypercoagulability and blood-vessel damage, thus suggesting their role in the pathogenesis of vascular disease.

Apoptosis↗
PubMed2004

[Cellular microparticles and blood-vessel damage. II. Functional characteristics and clinical significance].

Cellular microparticles support coagulation by exposure of negatively charged phospholipids and sometimes tissue factor. They are involved in inflammatory processes, the transfer of membrane antigens and bioactive molecules, and in the modulation of endothelial functions. Patients with disturbances in membrane vesiculation, leading to decreased numbers of circulating microparticles, present clinically with an increased bleeding tendency. In contrast, elevated numbers of microparticles are found in a great variety of diseases involving blood-vessel damage and hypercoagulability. Microparticles are also a major component of human atherosclerotic plaques. In view of their functional properties, cellular microparticles may be a missing link between cellular and plasmatic processes underlying atherosclerotic blood-vessel damage.

Blood Coagulation↗
PubMed2004

[Extent and quality of anti-coagulation treatment with coumarin derivatives by the Dutch Thrombosis Services].

OBJECTIVE: To obtain an impression of the extent and quality of the anti-coagulation treatment with coumarin derivatives carried out by the Thrombosis Services in the Netherlands. DESIGN: Descriptive. METHOD: Data were drawn from the medical annual reports of 62 of the 63 Thrombosis Services in the Netherlands over the period 1998-2002. In 2002 the Thrombosis Services treated 325,072 patients and performed 4,469,730 INR laboratory tests. The half-yearly figures produced by the Thrombosis Services were calculated as an average percentage per year per thrombosis service and then recalculated as a percentage per year. RESULTS: Seventy-three per cent of the patients were treated for an arterial and 27% for a venous indication. Depending on the required intensity of anticoagulation a mean of 74-78% of the long-term treated patients fell within the therapeutic range and a mean of 6-10% below. The mean number of major bleedings per 100 treatment years was 1.0. A mean of 79% of the patients was treated with acenocoumarol and 21% with phenprocoumon. When acenocoumarol was used, a mean of 72-77% fell within the therapeutic range and in the case of phenprocoumon 79-82%. In the last few years the number of patients had increased due to a growing number of patients treated for atrial fibrillation. The percentages of INR within the therapeutic range were unchanged or showed a slight increase. CONCLUSION: The quality of the anticoagulation therapy with coumarin derivatives was good or acceptable.

Acenocoumarol↗
PubMed2004

Cellular microparticles: new players in the field of vascular disease?

Microparticles are small membrane vesicles that are released from cells upon activation or during apoptosis. Cellular microparticles in body fluids constitute a heterogeneous population, differing in cellular origin, numbers, size, antigenic composition and functional properties. Microparticles support coagulation by exposure of negatively charged phospholipids and sometimes tissue factor, the initiator of coagulation in vivo. Microparticles may transfer bioactive molecules to other cells or microparticles, thereby stimulating cells to produce cytokines, cell-adhesion molecules, growth factors and tissue factor, and modulate endothelial functions. Microparticles derived from various cells, most notably platelets but also leucocytes, lymphocytes, erythrocytes and endothelial cells, are present in the circulation of healthy subjects. Rare hereditary syndromes with disturbances in membrane vesiculation leading to a decreased numbers of microparticles clinically present with a bleeding tendency. In contrast, elevated numbers of microparticles are encountered in patients with a great variety of diseases with vascular involvement and hypercoagulability, including disseminated intravascular coagulation, acute coronary syndromes, peripheral arterial disease, diabetes mellitus and systemic inflammatory disease. Finally, microparticles are a major component of human atherosclerotic plaques. In view of their functional properties, cell-derived microparticles may be an important intermediate in the cascade of cellular and plasmatic dysfunctions underlying the process of atherogenesis.

Apoptosis↗
PubMed2003

Comparison of the quality of oral anticoagulant therapy through patient self-management and management by specialized anticoagulation clinics in the Netherlands: a randomized clinical trial.

BACKGROUND: Several studies have demonstrated that patient self-management of oral anticoagulant therapy (OAT) can improve treatment quality. However, most of these studies were not conducted within a specialized anticoagulation care system. The objective of the present study was to determine whether patient self-management of OAT improves the quality of care delivered by anticoagulation clinics. METHODS: In this randomized study by 2 Dutch anticoagulation clinics 341 patients aged between 18 and 75 years and receiving long-term OAT were divided into 4 groups: an existing routine care group of patients untrained in self-management; a routine care group of trained patients; a group managed weekly at an anticoagulation clinic where international normalized ratios were measured by trained patients; and weekly patient self-management. A 2-step randomization procedure was followed: first, a Zelen-design randomization was performed to distribute patients (without informing them) to the existing care group or to receive training in self-management; second, trained patients were randomized to the 3 other study groups. RESULTS: Only 25.6% of invited patients agreed to participate in the training program. Patients who remained in the existing care group were within the international normalized ratio target range 63.5% of the time. The type of coumarin taken was a major predicting factor of OAT quality. In all study groups phenprocoumon outperformed acenocoumarol by 11.6% (95% confidence interval [CI], 6.6%-16.5%). Weekly management with phenprocoumon led to a 6.5% improvement (95% CI, 0.0%-13.1%) in time in the international normalized ratio target range when patients were managed at an anticoagulation clinic and to an 8.7% improvement (95% CI, 1.6%-15.9%) when patients were self-managed. Weekly management with acenocoumarol did not improve the quality of OAT. CONCLUSION: With selected patients, the quality of OAT obtained through patient self-management is at least as high as that delivered by specialized physicians at anticoagulation clinics. Weekly management of OAT with long-acting phenprocoumon has to be preferred at anticoagulation clinics or, where possible, through patient self-management.

Adult↗
PubMed2003

Microparticles in cardiovascular diseases.

Microparticles are membrane vesicles released from many different cell types. There are two mechanisms that can result in their formation, cell activation and apoptosis. In these two mechanisms, different pathways are involved in microparticle generation. Microparticle generation seems to be a well regulated process. Microparticles vary in size, phospholipid and protein composition. They have a potent pro-inflammatory effect, promote coagulation and affect vascular function. Since these processes are all involved in the pathogenesis of cardiovascular disease and circulating microparticle numbers are altered in many cardiovascular diseases, a role for microparticles in the pathogenesis of cardiovascular diseases is likely. Although hard evidence for a role of microparticles in cardiovascular diseases at present is still only limited, new evidence is accumulating rapidly to support this theory. Elucidation of the microparticle composition and the mechanisms involved in exertion of their effects will supply this evidence and enable us to develop additional intervention strategies for prevention and treatment of cardiovascular diseases.

Abciximab↗
PubMed2003

Lipoprotein(a) and ultrasonographically determined early atherosclerotic changes in the carotid and femoral artery.

Recent studies suggest that high lipoprotein(a) [Lp(a)] plasma levels are associated with symptomatic ischemic cardiovascular disease. We examined whether Lp(a) plasma levels are associated with early atherosclerotic vessel wall changes in a group of asymptomatic subjects. In a group of 142 asymptomatic men, the intima-media thickness (IMT) in the common carotid artery, the carotid bifurcation and the common femoral artery was determined by B-mode ultrasonography. In addition to Lp(a) levels, established risk factors, such as blood pressure and cholesterol levels were determined. Lipoprotein(a) values ranged from 2 mg L(-1) to 900 mg L(-1) (median 145 mg L(-1)). Linear regression analysis showed a clear association of IMT with the established risk factors but not with Lp(a) [regression coefficient carotid artery -0.0003, 95% confidence interval (CI) -0.002-0.001; regression coefficient femoral artery -0.0003, 95% CI -0.004-0.003]. We found no increased intima-media thickness in the carotid or femoral artery at high levels of Lp(a). Lipoprotein(a) levels are not associated with early atherosclerotic vessel wall changes in the carotid or femoral artery.

Adult↗
PubMed2003

Pro- and non-coagulant forms of non-cell-bound tissue factor in vivo.

BACKGROUND: Concentrations of non-cell-bound (NCB; soluble) tissue factor (TF) are elevated in blood collecting in the pericardial cavity of patients during cardiopulmonary bypass (CPB). Previously, we reported microparticles supporting thrombin generation in such blood samples. In this study we investigated the extent of microparticle association of the NCB form of TF in pericardial and systemic blood, and whether this microparticle-associated form is active in thrombin generation compared with non-microparticle-bound, (fluid-phase) TF. METHODS: Systemic and pericardial blood samples were collected before and during CPB from six patients undergoing cardiac surgery. Microparticles were isolated by differential centrifugation and their thrombin-generating capacity measured in a chromogenic assay. Microparticle-associated and fluid-phase forms of NCB TF were measured by ELISA. Microparticle-associated TF was visualized by flow cytometry. RESULTS: In pericardial samples, 45-77% of NCB TF was microparticle-associated, and triggered factor VII (FVII)-mediated thrombin generation in vitro. Microparticles from systemic samples triggered thrombin generation independently of FVII, except at the end of bypass (P = 0.003). The fluid-phase form of TF did not initiate thrombin generation. Both forms of NCB TF were, at least in part, antigenically cryptic. CONCLUSIONS: We demonstrate the occurrence of two forms of NCB TF. One form, which is microparticle-associated, supports thrombin generation via FVII. The other form, which is fluid-phase, does not stimulate thrombin formation. We hypothesize that the microparticle-associated form of NCB TF may be actively involved in postoperative thromboembolic processes when pericardial blood is returned into the patients.

Blood Circulation↗
PubMed2003

Antigenic characterization of endothelial cell-derived microparticles and their detection ex vivo.

BACKGROUND: Endothelial activation and dysfunction are associated with several diseases. However, hardly any specific markers are available. Microparticles (MP) from endothelial cells (EC; EMP) were reported in patient groups and healthy individuals. The antibodies used to detect EMP, however, were mainly directed against antigens without EC specificity. OBJECTIVES: We evaluated the antigens on EC and EMP to establish proper markers for EMP detection. METHODS: EMP were isolated from supernatants of resting and interleukin (IL)-1alpha activated human umbilical vein EC (HUVEC; n=3; 0-72 h), stained with annexin V and monoclonal antibodies, and analyzed by flow cytometry. Human platelet-MP (PMP), the main MP population in plasma, were prepared in vitro. EMP and PMP were studied in plasma from systemic lupus erythematosus (SLE) patients (n=11) and healthy individuals (n=10). RESULTS: Platelet-endothelial cell adhesion molecule-1 (PECAM-1), alphanu and beta3 were constitutively exposed on HUVEC, but (almost) absent on EMP (<15% positive for alphanu and beta3), or only exposed on a subpopulation (PECAM-1; 30-60%). Activated HUVEC (>80%) and (subpopulations of) EMP exposed E-selectin and tissue factor. PMP strongly exposed PECAM-1, beta3, and glycoprotein (GP)Ib (CD42b), but not alphanu or E-selectin. GPIb and P-selectin (CD62P) were absent on EMP. Plasma samples contained 0.5% MP staining for E-selectin and/or alphanu. Plasma from one SLE patient contained E-selectin exposing MP (21%), but little alphanu-positive MP. CONCLUSIONS: EC release EMP in vitro. The antigenic phenotype of EMP released from resting and IL-1alpha-stimulated EC differs among each other as well as from resting and stimulated EC, respectively. E-selectin exposed on IL-1alpha-stimulated EC is a valid marker for EMP detection ex vivo to establish endothelial cell activation.

Adult↗
PubMed2003

Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner.

BACKGROUND: Circulating microparticles of various cell types are present in healthy individuals and, in varying numbers and antigenic composition, in various disease states. To what extent these microparticles contribute to coagulation in vivo is unknown. OBJECTIVES: To examine the in vivo thrombogenicity of human microparticles. METHODS: Microparticles were isolated from pericardial blood of cardiac surgery patients and venous blood of healthy individuals. Their numbers, cellular source, and tissue factor (TF) exposure were determined using flow cytometry. Their in vitro procoagulant properties were studied in a fibrin generation test, and their in vivo thrombogenicity in a rat model. RESULTS: The total number of microparticles did not differ between pericardial samples and samples from healthy individuals (P = 0.786). In both groups, microparticles from platelets, erythrocytes, and granulocytes exposed TF. Microparticle-exposed TF antigen levels were higher in pericardial compared with healthy individual samples (P = 0.036). Pericardial microparticles were strongly procoagulant in vitro and highly thrombogenic in a venous stasis thrombosis model in rats, whereas microparticles from healthy individuals were not [thrombus weights 24.8 (12.2-41.3) mg vs. 0 (0-24.3) mg median and range; P < 0.001]. Preincubation of pericardial microparticles with an inhibitory antibody against human TF abolished their thrombogenicity [0 (0-4.4) mg; P < 0.01], while a control antibody had no effect [19.6 (12.6-53.7) mg; P > 0.05]. The thrombogenicity of the microparticles correlated strongly with their TF exposure (r = 0.9524, P = 0.001). CONCLUSIONS: Human cell-derived microparticles promote thrombus formation in vivo in a TF-dependent manner. They might be the direct cause of an increased thromboembolic tendency in various patient groups.

Adult↗
PubMed2003

Lipopolysaccharide concentration and bone resorption in cholesteatoma.

HYPOTHESIS: There is a relationship between the local lipopolysaccharide (LPS) concentration in cholesteatoma and local bone resorption in chronic otitis media (COM) with cholesteatoma. BACKGROUND: During the past decade, it has become known that the recruitment of osteoclasts is the main causative factor that induces bone destruction in COM with cholesteatoma. Cellular inflammation factors like cytokines may trigger the osteoclast. Sequel to this, LPS is able to up-regulate cytokines. This makes it of interest to study whether the local LPS concentration is related to bone resorption in cholesteatoma. MATERIALS AND METHODS: Twenty-four cholesteatoma samples and control tissue from COM patients without cholesteatoma were collected. During surgery, the degree of bone resorption was established and classified. Retrospectively, the authors checked whether patients had chronic purulent otorrhea. LPS concentration of the tissue samples was measured by the limulus amebocyte lysate test. The one-way analysis of variance test was used to determine the relation between LPS concentration, otorrhea, and local bone resorption. RESULTS: A significantly higher concentration of LPS was measured in samples from patients with cholesteatoma with bone resorption and otorrhea compared with cholesteatoma without bone resorption and control tissue. There were no significant differences between the LPS levels of the different groups of patients with bone resorption. CONCLUSION: It is suggested that LPS is one of the first factors in the cascade of bone resorption in COM with cholesteatoma.

Bone Resorption↗
PubMed2002

Monitoring of unfractionated heparin with the activated partial thromboplastin time: determination of therapeutic ranges.

The purpose of the present study was to determine therapeutic ranges for unfractionated heparin therapy using the activated partial thromboplastin time (APTT) by calibration against anti-Xa concentration. APTT assays were performed locally, i.e. at the institution of blood collection, on fresh plasma samples from patients treated with intravenous unfractionated heparin. The measurements were performed by 25 Dutch clinical laboratories using 11 different APTT reagents and 10 different types of coagulometers. After the local APTT measurement, the samples were frozen and transported to a central laboratory for measurement of anti-Xa activity. The number of samples from the participating laboratories ranged from 10 to 48. Local APTT results were correlated with the central anti-Xa measurements. Orthogonal regression analysis of log-transformed values was used to calculate APTT therapeutic ranges corresponding to anti-Xa concentrations of 0.29-0.47 IU/ml. The calculated APTT ranges were different between laboratories, even when the same reagent was used. In many laboratories, the therapeutic APTT range in use was much wider than the calculated range. Imprecision of the calculated APTT range was influenced by the wide scatter of the measurement points and by the selection of samples for the orthogonal regression equation. The present results show that, if anti-Xa concentrations of 0.29-0.47 IU/ml reflect the true therapeutic range, many laboratories do not use the proper therapeutic APTT range.

Dose-Response Relationship, Drug↗