Background and Aims : The risk of cardiovascular diseases in patients with a rheumatic background is much higher compared to the normal population. Still, it's etiology is not fully understood. In this study the plasma proteome of patients with a rheumatic background were compared with a group of patients who on top of their rheumatic background suffered from a cardiovascular event (CVE).Methods: The cohort consisted of a rheumatic patient control group (n=10) and a patient group (n=10) with a CVE history. Samples were collected 1 year prior to the CVE and 3-6 months after the CVE. Patients were matched with controls based on age, sex and medication use. Depletion of high abundant plasma proteins (TOP-14) was followed by "bottom up" shotgun proteomics using LC-MS/MS. Rstudio was used for normalization assessment and the relative changes in protein/peptide abundance were investigated using Perseus for comparison between the groups.Results: Principle component analysis (PCA) demonstrated a difference in overall protein and peptide signature between the control group and the CVE group. A total of 282 proteins determined this potential difference. Within the CVE group PCA revealed a more comparable signature before and after the CVE. Nevertheless, still 59 proteins demonstrated significant difference in relative abundancy within the CVE group.Conclusions: Here we demonstrated the existence of potential differences in the plasma proteome of rheumatic patient's who suffered from a CVE. This signature may already exist prior to a CVE. This gives rise to further investigation of potential risk markers which may predict a relative risk for a CVE in rheumatic diseases. Background and Aims : The risk of cardiovascular diseases in patients with a rheumatic background is much higher compared to the normal population. Still, it's etiology is not fully understood. In this study the plasma proteome of patients with a rheumatic background were compared with a group of patients who on top of their rheumatic background suffered from a cardiovascular event (CVE). Methods: The cohort consisted of a rheumatic patient control group (n=10) and a patient group (n=10) with a CVE history. Samples were collected 1 year prior to the CVE and 3-6 months after the CVE. Patients were matched with controls based on age, sex and medication use. Depletion of high abundant plasma proteins (TOP-14) was followed by "bottom up" shotgun proteomics using LC-MS/MS. Rstudio was used for normalization assessment and the relative changes in protein/peptide abundance were investigated using Perseus for comparison between the groups. Results: Principle component analysis (PCA) demonstrated a difference in overall protein and peptide signature between the control group and the CVE group. A total of 282 proteins determined this potential difference. Within the CVE group PCA revealed a more comparable signature before and after the CVE. Nevertheless, still 59 proteins demonstrated significant difference in relative abundancy within the CVE group. Conclusions: Here we demonstrated the existence of potential differences in the plasma proteome of rheumatic patient's who suffered from a CVE. This signature may already exist prior to a CVE. This gives rise to further investigation of potential risk markers which may predict a relative risk for a CVE in rheumatic diseases.

Background and Aims : We aimed to elucidate the cause of hypercholesterolemia in two patients presenting with LDL-C levels >15 mmol/L.Methods: We performed next-generation sequencing (NGS) on FH genes and performed routine and FPLC analysis on lipoprotein subfractions. We assessed liver fat content using controlled attenuation parameter (CAP) based on vibration-controlled transient elastography (FibroScan) and magnetic resonance spectroscopy (MRS). We screened for early atherosclerosis using carotid ultrasound. Dietary intake was verbally assessed by dietary recall.Conclusions: We present two patients with extremely elevated LDL-C levels due to a carnivorous, ketogenic diet. Subjects agreed to reintroduce carbohydrates to their diets and a repeat cholesterol profile is pending. Background and Aims : We aimed to elucidate the cause of hypercholesterolemia in two patients presenting with LDL-C levels >15 mmol/L. Methods: We performed next-generation sequencing (NGS) on FH genes and performed routine and FPLC analysis on lipoprotein subfractions. We assessed liver fat content using controlled attenuation parameter (CAP) based on vibration-controlled transient elastography (FibroScan) and magnetic resonance spectroscopy (MRS). We screened for early atherosclerosis using carotid ultrasound. Dietary intake was verbally assessed by dietary recall. Conclusions: We present two patients with extremely elevated LDL-C levels due to a carnivorous, ketogenic diet. Subjects agreed to reintroduce carbohydrates to their diets and a repeat cholesterol profile is pending.

Background and Aims : Angiopoietin-like 3 (ANGPTL3) is an inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL). The impact of ANGPTL3 lowering has been shown to depend on the type of dyslipidemia: reduced LDL cholesterol in patients with familial hypercholesterolemia and reductions in plasma triglycerides in patients with chylomicronemia. This differential effect may be related to a difference in the association of ANGPTL3 with lipoproteins. We therefore hypothesized that ANGPTL3 resides on lipoproteins and that this affects its ability to suppress lipase activity.Methods: To investigate whether ANGPTL3 resides on LDL and/or HDL ex vivo, recombinant ANGPTL3 was incubated with ultracentrifugation-isolated LDL and HDL fractions derived from healthy volunteers. In addition, plasma from healthy volunteers and HDL deficient patients (due to rare genetic variants in ABCA1 or LCAT) was fractionated by fast protein liquid chromatography and distribution of ANGPTL3 among lipoprotein fractions was determined by ELISA. ANGPTL3 activity was studied by measuring lipolysis and uptake of 3H-trioleate by brown adipocyte T37i cells.Results: Ex vivo binding experiments revealed that ANGPTL3 associates to both HDL and LDL. In healthy volunteers, approximately 75% of lipoprotein-associated ANGPTL3 resides in HDL fractions whereas patients without HDL carried 50% of their ANGPTL3 in LDL fractions. Unbound ANGPTL3 did not suppress T37i lipase activity but when given with HDL or LDL, ANGPTL3 suppressed lipase activity by 21.4±16.4% (p=0.03) and 25.4±8.2% (p=0.006) , respectively.Conclusions: ANGPTL3 preferentially resides on HDL but can also be found on LDL where it has its highest lipase inhibitory activity. Background and Aims : Angiopoietin-like 3 (ANGPTL3) is an inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL). The impact of ANGPTL3 lowering has been shown to depend on the type of dyslipidemia: reduced LDL cholesterol in patients with familial hypercholesterolemia and reductions in plasma triglycerides in patients with chylomicronemia. This differential effect may be related to a difference in the association of ANGPTL3 with lipoproteins. We therefore hypothesized that ANGPTL3 resides on lipoproteins and that this affects its ability to suppress lipase activity. Methods: To investigate whether ANGPTL3 resides on LDL and/or HDL ex vivo, recombinant ANGPTL3 was incubated with ultracentrifugation-isolated LDL and HDL fractions derived from healthy volunteers. In addition, plasma from healthy volunteers and HDL deficient patients (due to rare genetic variants in ABCA1 or LCAT) was fractionated by fast protein liquid chromatography and distribution of ANGPTL3 among lipoprotein fractions was determined by ELISA. ANGPTL3 activity was studied by measuring lipolysis and uptake of 3H-trioleate by brown adipocyte T37i cells. Results: Ex vivo binding experiments revealed that ANGPTL3 associates to both HDL and LDL. In healthy volunteers, approximately 75% of lipoprotein-associated ANGPTL3 resides in HDL fractions whereas patients without HDL carried 50% of their ANGPTL3 in LDL fractions. Unbound ANGPTL3 did not suppress T37i lipase activity but when given with HDL or LDL, ANGPTL3 suppressed lipase activity by 21.4±16.4% (p=0.03) and 25.4±8.2% (p=0.006) , respectively. Conclusions: ANGPTL3 preferentially resides on HDL but can also be found on LDL where it has its highest lipase inhibitory activity.

Background and Aims: Cardiovascular diseases (CVD) are one of the largest causes of death worldwide. The risk for atherosclerosis, the most common cause for CVD is increased specifically in patients with type 2 diabetes (T2DM) and non-alcoholic fatty liver disease (NAFLD). In this pilot study plasma shotgun proteomics was performed to find biomarkers and changes in metabolic proteins in a control group versus a T2DM and NAFLD group prior to bariatric surgery.

Urea cycle disorders (UCDs) are a group of rare inherited metabolic diseases causing hyperammonemic encephalopathy. Despite intensive dietary and pharmacological therapy, outcome is poor in a subset of UCD patients. Reducing ammonia production by changing faecal microbiome in UCD is an attractive treatment approach. We compared faecal microbiome composition of 10 UCD patients, 10 healthy control subjects and 10 phenylketonuria (PKU) patients. PKU patients on a low protein diet were included to differentiate between the effect of a low protein diet and the UCD itself on microbial composition. Participants were asked to collect a faecal sample and to fill out a 24 h dietary journal. DNA was extracted from faecal material, taxonomy was assigned and microbiome data was analyzed, with a focus on microbiota involved in ammonia metabolism. In this study we show an altered faecal microbiome in UCD patients, different from both PKU and healthy controls. UCD patients on dietary and pharmacological treatment had a less diverse faecal microbiome, and the faecal microbiome of PKU patients on a protein restricted diet with amino acid supplementation showed reduced richness compared to healthy adults without a specific diet. The differences in the microbiome composition of UCD patients compared to healthy controls were in part related to lactulose use. Other genomic process encodings involved in ammonia metabolism, did not seem to differ. Since manipulation of the microbiome is possible, this could be a potential treatment modality. We propose as a first next step, to study the impact of these faecal microbiome alterations on metabolic stability. Take home message: The faecal microbiome of UCD patients was less diverse compared to PKU patients and even more compared to healthy controls.

Aims Preliminary evidence from animal and human studies shows that gut microbiota composition and levels of microbiota-derived metabolites, including short-chain fatty acids (SCFAs), are associated with blood pressure (BP). We hypothesized that faecal microbiota composition and derived metabolites may be differently associated with BP across ethnic groups Methods and results We included 4672 subjects (mean age 49.8 +/- 11.7 years, 52% women) from six different ethnic groups participating in the HEalthy Life In an Urban Setting (HELIUS) study. The gut microbiota was profiled using 16S rRNA gene amplicon sequencing. Associations between microbiota composition and office BP were assessed using machine learning prediction models. In the subgroups with the largest associations, faecal SCFA levels were compared in 200 subjects with lower or higher systolic BP. Faecal microbiota composition explained 4.4% of the total systolic BP variance. Best predictors for systolic BP included Roseburia spp., Clostridium spp., Romboutsia spp., and Ruminococcaceae spp. Explained variance of the microbiota composition was highest in Dutch subjects (4.8%), but very low in South-Asian Surinamese, African Surinamese, Ghanaian, Moroccan and Turkish descent groups (explained variance <0.8%). Faecal SCFA levels, including acetate (P < 0.05) and propionate (P < 0.01), were lower in young Dutch participants with low systolic BP Conclusions Faecal microbiota composition is associated with BP, but with strongly divergent associations between ethnic groups. Intriguingly, while Dutch participants with lower BP had higher abundances of several SCFA-producing microbes, they had lower faecal SCFA levels. Intervention studies with SCFAs could provide more insight in the effects of these metabolites on BP.

Objective: To determine the effect of raloxifene (RLX) and hormone replacement therapy (HRT) on non-high density lipoprotein cholesterol (non-HDL-C) levels and the apolipoprotein-B/apolipoprotein-A1 (apo-B/apo-A1) concentration ratio, markers of serum atherogenicity, in postmenopausal women. Methods: Three hundred and ninety healthy postmenopausal women aged 45–72 years were enrolled in a double-blind, randomized, placebo-controlled, parallel trial at eight outpatient sites in the United States. Women were randomly assigned to receive continuous combined HRT (0.625 mg/day conjugated equine estrogen and 2.5 mg/day medroxyprogesterone acetate), 60 or 120 mg/day raloxifene, or placebo for 6 months. Serum concentrations of non-HDL cholesterol and the apo-B/apo-A1 concentration ratio were measured in serum samples obtained at baseline and at 6 months of treatment. Results: At 6 months, non-HDL-C and apo-B/apo-A1 were significantly reduced by 60 mg/day RLX (10 and 11%, respectively), 120 mg/day RLX (9 and 12%, respectively) and HRT (10 and 12%, respectively), compared with placebo. The effect of all treatments to lower non-HDL-C and apo-B/apo-A1 was greatest in women with hypercholesterolemia (total-C>240 mg/dl) at baseline. Among women with undesirable (>160 mg/dl) non-HDL cholesterol at baseline, RLX and HRT lowered the percentage of these women remaining above this threshold after 6 months (placebo, 89%; 60 mg/day RLX, 61%; 120 mg/day RLX, 74%; HRT, 58%). Similar results were observed for women with high (>190 mg/dl) non-HDL cholesterol at baseline. Conclusion: In healthy postmenopausal women, RLX and HRT lower serum non-HDL-C and apo-B/apo-A1, indicators of serum atherogenicity, to a similar extent.

β2-Glycoprotein I (β2-GPI) is a highly abundant protein present in blood, but without a known physiological function. In 1990, β2-GPI became a protein of great interest as it was shown by different groups that the so-called antiphospholipid antibodies present in antiphospholipid syndrome (APS) are in fact directed against this plasma protein [1, 2]. It has been acknowledged that β2-GPI plays an important role in the thrombotic and pregnancy complications observed in APS. Thus, the correct biochemical characterization of β2-GPI is of pivotal importance [3, 4]. In 1979, Polz and Kostner [5] showed the distribution of β2-GPI over different human lipoproteins. Based on these observations, Lee et al. [6] designated β2-GPI as apolipoprotein H (apoH) [6]. Since then, the names β2-GPI and apoH have both been used for the same protein, and the official designation for the β2-GPI gene has become APOH. We were interested in whether the localization of β2-GPI on lipoproteins was influenced by the presence of antiphospholipid antibodies, and so we decided to reinvestigate the distribution of β2-GPI over the different lipoproteins and plasma fractions. We observed that after this original observation no other publications have confirmed the observed association of β2-GPI with lipoproteins. Blood was drawn from five healthy volunteers in a fasting state and 3 h after consuming a classic English breakfast (>1000 kcal), to repeat the original experiments by Polz and Kostner. Moreover, plasmas from two septic patients, two APS patients with antibodies against β2-GPI and pooled plasma from more than 200 healthy volunteers were also investigated. The Institutional Review Boards of the University Medical Centre Utrecht and Academic Medical Centre Amsterdam approved this study and informed consent was obtained from all patients or their caretakers. Citrated blood samples were centrifuged (15 min, 1200 ×g) and plasma was collected. Three millilitres of plasma were brought to a density (D) of 1.250 with KBr and layered with three KBr densities; D = 1.225, D = 1.100, and D = 1.006. A single-step ultracentrifugation (XL-90 Beckman, Beckman Coulter, Fullerton, CA, USA) was performed (96.000 ×g for 19 h at 10 °C), and fractions of 200 μL were collected with a fraction collector. Collected fractions were diluted at least 1000-fold in Tris-buffered saline (TBS; 50 mmol L−1 Tris, 150 mmol L−1 NaCl, 0.1% Tween-20, pH 7.4). Determination of β2-GPI was carried out by a homemade sandwich enzyme-linked immunosorbent assay (ELISA), using a mouse monoclonal antibody 3B7 as the capturing antibody and a rabbit polyclonal α-β2-GPI as a secondary antibody. Serial dilutions of normal pooled plasma (2.000× to 256.000× in TBS) were used as a standard curve. Very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) samples were determined by PAP 250 cholesterol enzymatic methods. Cholesterol reagent (Biomerieux, Le Fontanille, France) was added to 10 μL of the sample and measured on a spectrophotometer. As can be observed in Fig. 1A, no β2-GPI could be detected in the different lipoprotein fractions from a healthy volunteer. These results were confirmed with an additional four healthy volunteers, two septic patients and normal pooled plasma (Fig. 1B). The consumption of a classical English breakfast did not change the distribution of β2-GPI (data not shown). (A) Ultracentrifugation profile of subject 1. Cholesterol (open circles) and β2-glycoprotein I (β2-GPI; closed circles) are depicted. (B) β2-Glycoprotein I distribution over the different human plasma lipoproteins. Lipoproteins were separated after a one-step ultracentrifugation. Subjects 1–5 were normolipemic volunteers. Normal pooled plasma is from more than 200 volunteers. Blood from septic patients were drawn at the time they had sepsis. APS: patients with antibodies against β2-GPI. All fractions were also measured with surface plasmon resonance using a Biacore 2000 (Life Sciences, GE Healthcare, Uppsala, Sweden). To determine the binding of β2-GPI to the lipoproteins, anti-β2-GPI antibodies were coupled to a CM5-chip and the fractions were applied to the chip. In the fractions containing the different lipoproteins, no β2-GPI could be detected (data not shown). Antibodies directed against apoA1 and apoB were also coupled to a CM5-chip. The different lipoproteins were then directly captured from the ultracentrifugation fractions, followed by an injection of anti-β2-GPI antibodies to detect potentially formed complexes between β2-GPI and VLDL, LDL or HDL. No complexes were detected (data not shown). Subsequently, reconstituted HDL (CSL-111, Parkville, Victoria, Australia) was bound to an anti-apoA1 coupled chip and purified β2-GPI, from human plasma as described by Oosting et al. [7], was injected over the chip. No complex formation between purified β2-GPI and purified HDL could be observed (data not shown). To exclude the possibility that the separation technique for the lipoproteins could influence the outcome, lipoproteins from plasmas of three volunteers were separated using gel filtration on a Superose 6 HR 10/30 (Pharmacia Biotech, Uppsala, Sweden) column with inline fluorescence and ultraviolet detection. Fractions were diluted in BSA/TBS (20 mmol L−1 Tris, 150 mmol L−1 NaCl, 3% BSA) and 0.1% Tween-20 and the presence of β2-GPI was detected with an ELISA. Again, β2-GPI was only found in the plasma fractions, not in the fractions that contain the different lipoproteins (data not shown). Since Polz and Kostner published the presence of β2-GPI in human lipoproteins almost 30 years ago, no other studies have confirmed the distribution of β2-GPI over the different lipoprotein. Following this observation, Lee et al. [6] designated the name apoH for β2-GPI and from then on apoH and β2-GPI were used as synonyms for the same protein. Here we show with state-of-the-art techniques that β2-GPI is not present in appreciable quantities in the lipoprotein fractions, neither in fasting healthy persons nor postprandially. Also, when plasmas of two APS patients positive for anti-β2-GPI antibodies were subjected to lipoprotein separation, the presence of anti-β2-GPI antibodies did not result in redistribution of β2-GPI from the plasma fraction over the lipoprotein fractions (Fig. 1B). From these observations and the direct binding experiments using surface plasmon resonance, it is clear that there are no interactions between β2-GPI and LDL or HDL. It cannot be excluded that there is a possible weak interaction with VLDL. We have not studied the effects of oxidation of LDL [8] on the distribution of β2-GPI over the lipoproteins, because we do not know a patient cohort with proven oxidation of lipoproteins, and it is questionable if in vitro oxidation of LDL mimics a physiological condition. We conclude that apoH is not expected to be an integral part of lipoproteins and for this reason the name apolipoprotein H for β2-GPI is clearly a misnomer. We therefore suggest the use of the name β2-GPI only. The authors state that they have no conflict of interest.

OBJECTIVE:Cardiovascular mortality is increased in ankylosing spondylitis (AS), and inflammation plays an important role. Inflammation deteriorates the lipid profile and alters high-density lipoprotein cholesterol (HDL-c) composition, reflected by increased concentrations of serum amyloid A (SAA) within the particle. Anti-tumor necrosis factor (anti-TNF) treatment may improve these parameters. We therefore undertook the present study to investigate the effects of etanercept on lipid profile and HDL composition in AS.METHODS:In 92 AS patients, lipid levels and their association with the inflammation markers C-reactive protein (CRP), erythrocyte sedimentation rate, and SAA were evaluated serially during 3 months of etanercept treatment. HDL composition and its relationship to inflammation markers was determined in a subgroup of patients, using surface-enhanced laser desorption/ionization time-of-flight analysis.RESULTS:With anti-TNF treatment, levels of all parameters of inflammation decreased significantly, whereas total cholesterol, HDL-c, and apolipoprotein A-I (Apo A-I) levels increased significantly. This resulted in a better total cholesterol:HDL-c ratio (from 3.9 to 3.7) (although the difference was not statistically significant), and an improved Apo B:Apo A-I ratio, which decreased by 7.5% over time (P=0.008). In general, increases in levels of all lipid parameters were associated with reductions in inflammatory activity. In addition, SAA was present at high levels within HDL particles from AS patients with increased CRP levels and disappeared during treatment, in parallel with declining plasma levels of SAA.CONCLUSION:Our results show for the first time that during anti-TNF therapy for AS, along with favorable changes in the lipid profile, HDL composition is actually altered whereby SAA disappears from the HDL particle, increasing its atheroprotective ability. These findings demonstrate the importance of understanding the role of functional characteristics of HDL-c in cardiovascular diseases related to chronic inflammatory conditions.

BACKGROUND:High-density lipoprotein (HDL) exerts a variety of anti-atherothrombotic functions, including a potent anti-inflammatory impact. In line, the direct pro-inflammatory effects of C-reactive protein (CRP) can be attenuated by HDL in vitro.OBJECTIVE:To evaluate whether this also holds true in humans, we assessed the ability of reconstituted HDL to neutralize CRP-mediated activation of coagulation and inflammation.METHODS:Fifteen healthy male volunteers received an infusion of recombinant human (rh)CRP (1.25 mg kg(-1) body weight). In eight of these volunteers, an infusion of human apoAI reconstituted with phosphatidylcholine (apoAI-PC; 80 mg kg(-1) body weight) preceded rhCRP infusion.RESULTS:Infusion of rhCRP alone elicited an inflammatory response and thrombin generation. In individuals who received apoAI-PC prior to rhCRP, these effects were abolished. Parallel tests in primary human endothelial cells showed that apoAI-PC preincubation with rhCRP abolished the CRP-mediated activation of inflammation as assessed by IL-6 release. Although we were able to show that rhCRP co-eluted with HDL after size-exclusion chromatography, plasmon surface resonance indicated the absence of a direct interaction between HDL and CRP.CONCLUSION:Infusion of apoAI-PC prior to rhCRP in humans completely prevents the direct atherothrombotic effects of rhCRP. These findings imply that administration of apoAI-PC may offer benefit in patients with increased CRP.

Objectives and background. We here report on a large group of heterozygotes for a novel apoA-l mutation (L178P) that enabled us to assess for the first time to investigate the consequences of an apoA-l gene defect with regards to lipid metabolism, endothelial function, arterial wall thickness as well as coronary artery disease (CAD) risk. Methods. Lipids and lipoproteins could be measured in 54 apoA-l (L178P) carriers and 147 non-affected siblings. Flow-mediated dilatation (FMD) was also assessed in 29 carriers and 45 non-carriers and carotid intima-media thickness (IMT) could be determined in 33 heterozygotes and 40 controls. Moreover, CAD risk was evaluated for all apoA-l mutation carriers. Results. Heterozygotes exhibited lower plasma levels of apoA-l (-50%; p<0.0001) and HDL-C (-63%; p<0.0001). In addition, carriers had impaired FMD (p=0.012) and increased carotid IMT (p<0.001), whereas multivariate analysis revealed that heterozygotes had a striking 24fold increase in CAD risk (p=0.003). Conclusions. Heterozygosity for a novel apoA-l mutation underlies a detrimental lipoprotein profile that is associated with endothelial dysfunction, accelerated carotid arterial wall thickening and severely enhanced CAD risk. Importantly, the extent of atherosclerosis in these subjects was similar to the burden of premature arterial wall abnormalities seen in familial hypercholesterolemia patients. These data illustrate the pivotal role in humans of apoA-l in the protection against CAD.

BACKGROUND:Glucose-insulin-potassium (GIK) administration is advocated on the premise of preventing hyperglycaemia and hyperlipidaemia during reperfusion after cardiac interventions. Current research has focused on hyperglycaemia, largely ignoring lipids, or other substrates. The present study examines lipids and other substrates during and after on-pump coronary artery bypass grafting and how they are affected by a hyperinsulinaemic normoglycaemic clamp.METHODS:Forty-four patients were randomized to a control group (n=21) or to a GIK group (n=23) receiving a hyperinsulinaemic normoglycaemic clamp during 26 h. Plasma levels of free fatty acid (FFA), total and lipoprotein (VLDL, HDL, and LDL)-triglycerides (TG), ketone bodies, and lactate were determined.RESULTS:In the control group, mean FFA peaked at 0.76 (sem 0.05) mmol litre(-1) at early reperfusion and decreased to 0.3-0.5 mmol litre(-1) during the remaining part of the study. GIK decreased FFA levels to 0.38 (0.05) mmol litre(-1) at early reperfusion, and to low concentrations of 0.10 (0.01) mmol litre(-1) during the hyperinsulinaemic clamp. GIK reduced the area under the curve (AUC) for FFA by 75% and for TG by 53%. The reduction in total TG was reflected by a reduction in the VLDL (-54% AUC) and HDL (-42% AUC) fraction, but not in the LDL fraction. GIK prevented the increase in ketone bodies after reperfusion (-44 to -47% AUC), but was without effect on lactate levels.CONCLUSIONS:Mild hyperlipidaemia was only observed during early reperfusion (before heparin reversal) and the hyperinsulinaemic normoglycaemic clamp actually resulted in hypolipidaemia during the largest part of reperfusion after cardiac surgery.

A chronic inflammatory state is a risk factor for accelerated atherogenesis. The aim of our study was to explore whether Crohn's disease (CD), characterized by recurrent inflammatory episodes, is also associated with accelerated atherogenesis. In 60 CD patients and 122 matched controls, carotid intima media thickness (IMT), a validated marker for the burden and progression of atherosclerosis, was assessed ultrasonographically. Additional subgroup analyses, including plasma levels of acute phase reactants and HDL protein profiling, were performed in 11 consecutive patients with CD in remission, 10 patients with active CD, and 15 healthy controls. Carotid IMT in patients with CD was increased compared with healthy volunteers: 0.71 (0.17) versus 0.59 (0.14) mm (P < 0.0001), respectively. In the subgroup analysis, HDL levels in controls and patients in remission were identical [(1.45 (0.48) and 1.40 (0.46) mmol/l; P = 0.797], whereas HDL during exacerbation was profoundly reduced: 1.02 (0.33) (P = 0.022). HDL from patients with active CD and CD patients in remission was characterized by a reduced ability to attenuate oxidation compared with controls (P = 0.008 and P = 0.024 respectively). Patients with CD have increased IMT compared with matched controls, indicative of accelerated atherogenesis. The changes during CD exacerbation in terms of HDL concentration and composition imply a role for impaired HDL protection in these patients.

Bleeding and vascular access site complications are an important cause of morbidity after percutaneous femoral procedures. Together with collagen-based and suture-based vascular closure devices, new hemostatic dressings have been developed to control heavy bleeding.To evaluate safety and efficacy results of the first clinical QuikClot Interventional Hemostatic Bandage use for femoral artery closure after diagnostic or interventional procedures.The first European safety study was performed at the Centro Cardiologico Monzino in Milan, Italy, on January 2010. Forty consecutive patients (75% male, mean age 68 ± 11 years) undergoing diagnostic angiography (62%) or PCI (38%) by femoral approach with a 6- (90%) or 7-Fr (10%) size introducer, received arterial sheath removal with the QuikClot Interventional gauze use. The mean ACT value at hemostasis time was 138 ± 24 s (range 95–186 s). Hemostasis was achieved in a mean time of 4.9 ± 0.5 min. Only one hemostasis failure occurred requiring prolonged mechanical compression. Neither major bleeding, re-bleeding nor hematoma occurred after early (4 h after procedure) ambulation.QuikClot Interventional Bandage obtained prompt hemostasis and allowed for an early ambulation without clinical complications.

De bepaling van vet in faeces wordt tot nu toe binnen onze laboratoria uitgevoerd volgens de 'van de Kamermethode'. Deze methode is zeer bewerkelijk, tijdrovend en een kwaliteitscontrole ontbreekt. In samenwerking met twee andere academische centra (Groningen en Utrecht) hebben we een nieuwe vet in faecesbepaling ontwikkeld die gebruik maakt van mid-infraroodspectroscopie. Deze techniek wordt binnen de klinische chemie al gebruikt voor de niersteenanalyse. Na een korte en eenvoudige voorbewerking van de faecesmonsters, waarbij de vetzuren geïsoleerd worden uit de faeces m.b.v. een aangezuurd mengsel van petroleumether en ethanol, werd een transmissiespectrum opgenomen in het mid-infraroodgebied (400 4000 cm-1). Met behulp van 'Partial Least Square' en multicomponentanalyses van de golflengten, gemeten bij diverse faecesmonsters met een bekende vetconcentratie, werd een model gegenereerd. Tevens werd stearinezuur gebruikt als standaard voor de ijklijn. Er bleek een goede correlatie te zijn tussen de vetconcentraties bepaald met infrarood en gemeten met de 'van de Kamermethode' (n=35, r2> 0,95). Conclusie: de bepaling van vet in faeces met behulp van mid-infraroodspectroscopie biedt, in zijn eenvoud en standaardisatiemogelijkheden, een goed alternatief voor de conventionele 'van de Kamermethode'. Lipiden