Triglyceride-rich lipoproteins that circulate postprandially are increasingly being recognized as potentially atherogenic. These particles also have been shown to cause endothelial dysfunction. We recently demonstrated that acute parenteral administration of folic acid restores endothelial function in vivo in patients with increased LDL cholesterol levels. In vitro data suggested that this effect could be mediated by a reduction of radical stress. In the present study, therefore, we evaluated the effect of an acute oral fat load on both endothelial function and oxygen radical production. Next, we studied whether 2 weeks of pretreatment with 10 mg folic acid PO could prevent these fat-induced changes. We conducted a prospective, randomized, placebo-controlled study to evaluate the effect of oral folic acid administration (10 mg/d for 2 weeks) on basal endothelial function as well as endothelial function on an acute fat load in 20 healthy volunteers 18 to 33 years old. Endothelial function was assessed as flow-mediated dilatation (FMD). Endothelium-independent dilatation was measured after sublingual nitroglycerin spray. Oxygen radical stress was assessed by measurement of the urinary excretion of the stable radical-damage end product malondialdehyde. During administration of placebo, FMD decreased significantly after an acute oral fat load, with a median from 10.6% (8.3% to 12.2%) to 5.8% (3.0% to 10.2%), P<0.05. During folic acid administration, FMD was unaffected by a fat load, with a median from 9.6% (7.1% to 12.8%) to 9.9% (7.5% to 14.1%), P=NS. The increase in malondialdehyde excretion in the urine after fat loading was also prevented during folic acid administration (absolute increase after an acute fat load during placebo, 0.11+/-0.1 micromol/L versus folic acid, 0.02+/-0.1 micromol/L, P<0.05). The response to the endothelium-independent vasodilator nitroglycerin remained unaltered throughout the study. Pretreatment with oral folic acid prevents the lipid-induced decrease in FMD as well as the lipid-induced increase in urinary radical-damage end products. Because these observations were made in healthy volunteers with normal folate and homocysteine levels, it is suggested that a higher folate intake in the general population may have vasculoprotective effects.

COPD is characterised by damage to small airways due to an inflammatory process as well as an imbalance between oxidants and antioxidants. Several cytokines and cell adhesion molecules enhancing a mainly neutrophilic inflammation have been associated with COPD. The aim of the study was to investigate whether inflammation or oxidative markers gave an indication of the course of COPD during an exacerbation. Fourteen patients with moderate to severe COPD admitted to the St. Antonius Hospital because of an exacerbation have been monitored during treatment with prednisolone 50 mg intravenously during 24 h at admission, reduced to 25 mg at day 3 and tapered off with oral prednisolone at day 7. On three separate occasions, day 1, 3 and 7, H2O2 in exhaled air, IL-8 and the soluble cell adhesion molecule sICAM and sE-selectin in serum were measured. We compared the patients at day 1 with healthy controls (in both non-smokers and smokers). Furthermore, we examined the changes from the study group in time during therapy. At admission all the markers were raised in comparison with the control groups. During treatment H2O2 concentrations in breath condensate declined significantly (P<0.001) as well as IL-8 and sICAM in serum (P=0.002, respectively, P<0.001). There was no significant change in sE-selectin (P=0.132). No significant improvement has been found in spirometry. These data suggest that the markers H2O2 in exhaled air, IL-8 and sICAM in serum are suitable markers in monitoring exacerbated COPD.

Only mild signs of oxidative stress and no renal dysfunction were found during and after off-pump CABG compared with on-pump CABG.

Our data demonstrate a convenient way to circumvent the use of three reference intervals by introducing a Z-score for ACE activity. It also illustrates the need to re-investigating the possible clinical value of serum ACE activity in sarcoidosis by considering ACE I/D.

Krebs von den Lungen (KL)-6 offers a new perspective as a disease marker in pulmonary diseases. The aim of this study was to analyze whether serum KL-6 levels are dependent on the functional adenosine to guanine mucin-1 (MUC1) gene polymorphism at nucleotide position 568 in a well-characterized white population. Polymorphisms were determined in 327 healthy, white individuals and 74 patients with sarcoidosis, using a PCR-sequence-specific primer assay. The serum KL-6 levels were measured by ELISA. Significant differences between serum KL-6 levels of healthy subjects who were grouped according to MUC1 568 genotype were observed (P<0.0001) (mean+/-SEM): AA (195.2+/-9.9 U/ml; 95% confidence interval [CI], 175.7-214.8), AG (246.0+/-8.6 U/ml; 95% CI, 229.0-263.1), and GG (302.6+/-11.8 U/ml; 95%CI, 279.3-326.0). In the patients with sarcoidosis, the results were (mean+/-SD): AA (550.1+/-411.7; 95% CI, 380.2-720.1), AG (716.3+/-452.4; 95% CI, 547.4-885.2), GG (1,151.0+/-1122; 95% CI, 610.1-1692.0); P=0.02. Comparison of the KL-6 levels in which the 568 genotype was ignored rendered 6 out of 74 (7.5%) misclassifications of "elevated" versus "normal" KL-6 levels or vice versa. In conclusion, the MUC1 568 A to G polymorphism may be of interest for diagnostic purposes because our study delivered in vivo evidence that it contributes to interindividual variations in KL-6 levels.

No abstract

Summary. D-Dimer measurement is a promising tool in the exclusion of venous thrombosis. New D-dimer assays have been introduced, but need clinical validation. Our objective was to evaluate the clinical usefulness of four relatively new D-dimer assays and a classical ELISA in outpatients suspected for deep venous thrombosis. In 537 patients, participants in a large prospective management study using a clinical probability score and a D-dimer measurement (Tina-quant 1 ), additional samples were taken for D-dimer measurement using the Asserachrom ELISA 1 , the VIDAS New 1 , the STA-LIA 1 and the Miniquant 1 assay. Performances of each test were calculated using clinical data during a 3-month follow-up. Thrombosis was detected in 224 patients (42%). The area under the ROC curve was significantly higher for the Tina-quant as compared to the other assays. Using standard cut-off values, sensitivity, negative predictive value (NPV) and specificity of the Asserachrom were 97, 94 and 33%, respectively. For the VIDAS New, values were 100, 96 and 8%, respectively. The Tina-quant showed values of 99, 98 and 41%, respectively, and the STA-LIA 98, 95 and 32%. Values for the Miniquant were 95, 94 and 52%. The D-dimer assays in our study all show a high sensitivity and negative predictive value, but none of the assays reached an NPV of > 98% at standard cut-off values. D-Dimer assays with a low specificity still necessitate additional diagnostic tests in the majority of the patients.

In contrast to conventional on-pump coronary artery bypass grafting only mild increase of parameters of oxidative stress is reported during and after off-pump coronary artery bypass grafting. In an attempt to reduce the side effects of extra corporeal circulation the mini- extra corporeal circulation concept was introduced. In this study peroperative oxidative stress biomarkers were compared using three different techniques for CABG (conventional, mini and off-pump). It concerns a prospective randomized pilot study of 60 aged patients (70+ years) divided over 3 study groups. During the peroperative time points there was a significant increase in the mean concentration of uric acid for the CCABG group. On arrival at the intensive care unit the mean concentrations decreased significantly. During the per-operative period all groups showed significant increase in the concentration of malondialdehyde, however, this increase was the steepest for the CCABG group. On arrival at the intensive care unit the mean concentration decreased significantly for all groups. We found only mild organ ischemia/reperfusion injury and oxidative stress in the OPCAB group and the MCABG group with respect to the CCABG group.