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ABSTRACT: INTRODUCTION: Changes in leukocyte cell population data have been reported in various infectious diseases, but little is known in other inflammatory conditions such as the postprandial state. We investigated whether leukocyte cell population data change during postprandial leukocyte activation. METHODS: Healthy volunteers underwent a standardized oral fat loading test (OFLT). Flowcytometric quantitation of leukocyte activation markers CD11b, CD66b, CD35, and CD36, together with leukocyte cell population data from LH750 hematology analyzers were measured fasting and at 4 and 8 h postprandially. RESULTS: Twelve volunteers were included. Postprandial leukocyte activation was confirmed by increased expression of CD11b by monocytes (+11.7%) and neutrophils (+15.0%) and by increased expression of CD66b (+14.7%) and CD35 (+16.6%) by neutrophils at T = 4 h. The mean scatter from neutrophils, reflecting granularity, significantly decreased at T = 4 h (P < 0.05) and returned to baseline at T = 8 h (P-anova 0.048). The mean volume of monocytes increased significantly at T = 4 h (P < 0.001) and returned to baseline at T = 8 h (P-anova 0.0008). At T = 4 h, CD11b expression on neutrophils was associated with a reduction in mean scatter of neutrophils (Pearson's r: -0.677, P = 0.016). CONCLUSION: Postprandial leukocyte activation is accompanied by temporary changes in leukocyte cell population data, similar to changes observed during various infections, but to a lesser extent.
International journal of laboratory hematology 05/2013; · 1.30 Impact Factor
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ABSTRACT: Hypertriglyceridemia is a common lipid disorder associated to different, highly prevalent metabolic derangements like diabetes mellitus, the metabolic syndrome and obesity. The choice of treatment depends on the underlying pathogenesis and the consequences for atherosclerosis or pancreatitis. A family history, physical examination and analysis of the lipid profile including measurement of apolipoprotein B or non-HDL-C are necessary to establish the underlying primary or secondary cause. Due to physiological diurnal variations of triglycerides (TG), the time of measurement (fasting or postprandial) should be taken into account when evaluating TG values. Increased awareness arises concerning the impact of postprandial hypertriglyceridemia on the development of atherosclerosis. Hypertriglyceridemia is strongly associated to postprandial hyperlipidemia, remnant accumulation, increased small dense LDL concentrations, low HDL-C, increased oxidative stress, endothelial dysfunction, leukocyte activation and insulin resistance. All these factors are strongly linked to the development of atherosclerosis. Treatment should be aimed at reducing the secretion of triglyceride-rich lipoproteins, increasing intravascular lipolysis and reducing the number of circulating remnants. The main intervention is a change of lifestyle with decreased alcohol consumption, increased physical activity, dietary changes and, if applicable, adaptation of used medication. Fibrates, fish oil and nicotinic acid are the first choice of treatment in sporadic and familial hypertriglyceridemia to reduce the risk of pancreatitis, whereas high dose statins, sometimes in combination with fibrates, nicotinic acid, or fish oil capsules, are indicated for familial combined hyperlipidemia. Statins are necessary to reach low LDL-C concentrations in patients with type 2 diabetes mellitus and statin dosage should be increased when hypertriglyceridemia is present to reach secondary treatment targets for apolipoprotein B or non-HDL-C. Finally, family screening is mandatory to detect familial lipid disorders for early intervention in other family members.
Panminerva medica 06/2012; 54(2):91-103. · 1.11 Impact Factor
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ABSTRACT: The intestines have been proposed as the 'new player' in the field of atherosclerosis as a result of recent discoveries on intestinal cholesterol absorption and excretion. 'Niemann-Pick C1-like 1' is one of the most important transport proteins in the process of intestinal and biliary cholesterol absorption. Cholesterol is not only excreted via the hepato-biliary route but is also excreted directly into the intestinal lumen; this transintestinal cholesterol excretion is particularly important in mice. Other cholesterol transporters have also been identified, including the ABC transporters, which have been linked to rare disorders such as sitosterolemia. Inhibition of intestinal cholesterol absorption increases the hepatic synthesis of cholesterol and vis versa; several different genes and hormones play an important role in this process. When the effect of statins is insufficient or they cause too many side-effects, additional inhibition of intestinal cholesterol absorption is indicated.
Nederlands tijdschrift voor geneeskunde 01/2011; 155:A2503.
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ABSTRACT: Lipoprotein transport is thought to occur in the plasma compartment of the blood, where lipoproteins are modulated by various enzymatic reactions. Subsequently, lipoproteins can migrate through the endothelial barrier to the subendothelial space or are taken up by the liver. The interaction between pro-atherogenic (apoB-containing) lipoproteins and blood cells (especially monocytes and macrophages) in the subendothelial space is well known. This lipoprotein-inflammatory cell interplay is central in the development of the atherosclerotic plaque. In this review, a novel interaction is described between lipoproteins and both leukocytes and erythrocytes in the blood compartment. This lipoprotein-blood cell interaction may also be related to the process of atherosclerosis by inducing inflammatory changes in the case of leukocytes (pro-atherogenic) and as an anti-atherogenic transport-system by adherence to erythrocytes. Triglyceride rich lipoprotein (TRL)-mediated leukocyte activation can lead to an inflammatory situation with generation of oxidative stress and the production of cytokines, ultimately resulting in acute endothelial dysfunction. Binding of apoB containing lipoproteins to erythrocytes may be a potential anti-atherogenic mechanism protecting the vessel wall from the pro-inflammatory effects of these lipoproteins and also playing a role in the removal of these particles from the circulation. One of the proposed mechanisms of this interaction implies complement activation on the lipoprotein surface and binding to the Complement Receptor 1 (CR1) on erythrocytes and leukocytes, followed by clearance by the liver.
Atherosclerosis. Supplements 06/2010; 11(1):25-9. · 4.94 Impact Factor
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ABSTRACT: In autoimmune hypothyroidism (Hashimoto's disease), TPO (thyroid peroxidase) antibodies may be detected, while in autoimmune hyperthyroidism (Graves' disease) thyroid-stimulating hormone (TSH ) receptor antibodies (TSH -R-AB s) are frequently present. Less well known is the fact that autoimmune hypothyroidism can present with TSH-R-ABs and ophthalmic Graves' disease (OGD). This condition is also known as hypothyroid Graves' disease. In this report we describe four patients with this uncommon phenomenon. These four cases demonstrate that differences between Hashimoto and Graves' disease are less clear than expected. Hypothetically the thyroid cell might be 'attacked' by blocking and stimulating antibodies. Dependent on the relative concentrations, hypothyroidism or hyperthyroidism may occur. So the differences between Hashimoto's disease and Graves' disease, at least in these cases, may be gradual and small.
The Netherlands Journal of Medicine 04/2010; 68(4):178-80. · 2.07 Impact Factor
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ABSTRACT: It has recently been proposed that other hormones than ACTH can control cortisol production in Cushing's syndrome with bilateral adrenal hyperplasia. We present a case of food-dependent Cushing's syndrome. After a positive response of cortisol production during mixed meals, several tests identified glucose-dependent insulinotropic polypeptide (GIP) as the driving hormone responsible for the cortisol overproduction. Identification of aberrant hormone receptor expression is of importance because it may create a possibility for pharmacological treatment.
The Netherlands Journal of Medicine 06/2009; 67(5):187-90. · 2.07 Impact Factor
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ABSTRACT: Mannose binding lectin (MBL) is one of the three initiators of complement activation and is therefore closely linked to inflammation. MBL deficiency has been associated with the generation of atherosclerosis. Since atherosclerosis, the complement system and postprandial lipemia are linked to inflammation, we studied postprandial lipoprotein metabolism in MBL deficiency. An observational study was carried out in 107 volunteers (21% MBL deficient). Classical cardiovascular risk factors were not different between subjects with and without MBL deficiency. Oral fat loading tests in 8 MBL deficient and 14 MBL sufficient subjects showed similar postprandial triglyceride, free fatty acid, hydroxybutyric acid and complement component 3 concentrations. MBL deficient subjects had 2.4 times lower postprandial Sf>400 (chylomicron)-apoB48 concentrations, but in contrast a 2-3.5 times increased Sf 60-400 (VLDL1-TG) and Sf 60-400-apoB100 response. MBL activity was inversely related to the postprandial Sf 60-400-TG increase. Despite lower postprandial Sf>400-apoB48 concentrations, MBL deficient subjects show an accumulation of Sf 60-400 lipoproteins.
Atherosclerosis 04/2009; 206(2):444-50. · 3.79 Impact Factor
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Atherosclerosis 02/2009; 204(2):348-9; author reply 350-1. · 3.79 Impact Factor
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ABSTRACT: Postprandial hyperlipidaemia has been associated with coronary artery disease (CAD). We investigated which of the generally used methods to test postprandial lipaemia differentiated best between patients with premature CAD (50+/-4 years, n=20) and healthy controls. Furthermore, the effects of rosuvastatin 40 mg/day on postprandial parameters were assessed. Standardised oral fat-loading tests (OFLT) and ambulant self-measurements of daylong capillary triglycerides (TGc) were performed. Total responses of individual lipoproteins, plasma TG (TGp) and remnant-like particle cholesterol (RLP-C) were estimated as area under the curve (AUC). Most AUCs were highest in untreated patients and reached control levels after rosuvastatin. From all AUCs, RLP-C-AUC was best associated to TGp-AUC in untreated patients and controls (adjusted R2=0.84, beta=0.92, p.
The Netherlands Journal of Medicine 01/2009; 67(1):13-20. · 2.07 Impact Factor
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European Journal of Internal Medicine 12/2008; 19(7):e64-6. · 2.00 Impact Factor
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ABSTRACT: Postprandial hyperlipidemia is considered to be a substantial risk factor for atherosclerosis. Interestingly, this concept has never been supported by randomized clinical trials. The difficulty lies in the fact that most interventions aimed to reduce postprandial lipemia, will also affect LDL-C levels. The atherogenic mechanisms of postprandial lipids and lipoproteins can be divided into direct lipoprotein-mediated and indirect effects; the latter, in part, by inducing an inflammatory state. Elevations in postprandial triglycerides (TG) have been related to the increased expression of postprandial leukocyte activation markers, up-regulation of pro-inflammatory genes in endothelial cells and involvement of the complement system. This set of events is part of the postprandial inflammatory response, which is one of the recently identified potential pro-atherogenic mechanisms of postprandial lipemia. Especially, complement component 3 levels show a close correlation with postprandial lipemia and are also important determinants of the metabolic syndrome. In clinical practice, fasting TG are frequently used as reflections of postprandial lipemia due to the close correlation between the two. The use of serial capillary measurements in an out-of-hospital situation is an alternative for oral fat loading tests. Daylong TG profiles reflect postprandial lipemia and are increased in conditions like the metabolic syndrome, type 2 diabetes and atherosclerosis. Studies are needed to elucidate the role of postprandial inflammation in atherogenesis and to find new methods in order to reduce selectively the postprandial inflammatory response. Future studies are needed to find new methods in order to reduce selectively the postprandial inflammatory response.
Atherosclerosis Supplements 07/2008; 9(2):39-44. · 1.70 Impact Factor
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ABSTRACT: Morbid obesity is a serious disease as it is accompanied by substantial co-morbidity and mortality. The prevalence is increasing to an alarming extent, in Europe as well as in the United States. In the past few decades, bariatric surgery has developed and gained importance. It currently represents the only long-lasting therapy for this group of patients, resulting in an efficient reduction in body weight and obesity-related medical conditions, mostly cardiovascular in nature. The importance of a standardized protocol, the use of selection criteria, and a multidisciplinary approach have been stressed but not yet described in detail. Therefore, in this article, the multidisciplinary approach and the treatment protocol that have been applied in our hospital for more than 20 years are set out in a detailed manner. The application of a strict protocol may help to select and follow-up motivated patients and to organize multidisciplinary research activities.
European Journal of Internal Medicine 04/2008; 19(2):92-8. · 2.00 Impact Factor
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ABSTRACT: Cushing's syndrome results from lengthy and inappropriate exposure to excessive concentrations of either endogenous or exogenous glucocorticoids. This case report describes a patient with a novel type of Cushing's syndrome due to the use of party drugs. A 35-year-old woman had gained 8 kg body weight in 5 months and complained of anxiety. She showed a Cushing-like appearance and mild hypertension (blood pressure, BP 150/95 mmHg). She reported daily use of increasing doses of gamma-hydroxybutyric acid (GHB), a popular party drug. ACTH plasma levels were in the upper normal range (41 ng/l), with normal plasma cortisol (0.36 micromol/l). She showed an abnormal overnight 1 mg dexamethasone suppression test (cortisol 0.38 micromol/l). The urinary excretion of free cortisol in 24 h was also increased (0.47 micromol/24 h). CT scanning of the abdomen showed normal adrenals. After stopping GHB intake she lost 7 kg body weight and her BP normalized (BP 135/80 mmHg). GHB is a popular party drug in the Netherlands, but it is also used as a narcotic and for the treatment of narcolepsy. We hypothesize that GHB may bind to the pituitary gland gamma-aminobutyric acid-B receptors leading to ACTH overproduction.
European Journal of Endocrinology 01/2008; 157(6):779-81. · 3.42 Impact Factor
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ABSTRACT: Risk factors for coronary heart disease (CHD) include decreased insulin sensitivity and glucose intolerance, hypertension,
increased body fat mass, unfavorable body fat distribution, the prothrombotic state and dyslipidemia. A clustering of these
metabolic disturbances is also seen in Insulin Resistance and the metabolic syndrome. It has been shown that lipoproteins,
triglycerides (TG), fatty acids and glucose can activate endothelial cells most likely due to the production of reactive oxygen
species (ROS). Elevation of TG, fatty acids and glucose are common disturbances in the metabolic syndrome and are most prominent
in the postprandial phase. Furthermore, postprandial lipemia has been associated with decreased HDL-C concentrations. The
postprandial phase is therefore considered to be a pro-atherogenic and pro-oxidative condition. Paraoxonase 1 (PON1) is a
HDL-associated enzyme with the ability to hydrolyze oxidized lipids, reducing oxidative stress in lipoproteins and in macrophages.
Postprandial HDL-C decrease is associated with a decrease of PON1 activity. Subjects at risk for CHD, such as type 2 diabetics
and patients with hypercholesterolemia have low PON1 activity. Furthermore, expression of PON1 inhibits the development of
atherosclerosis in mice. Classic determinants of postprandial lipemia such as fasting TG, apolipoprotein B (apoB) and central
obesity do not predict the postprandial PON1 activity and drugs like statins, glitazons and metformin do not affect the postprandial
PON1 changes, although some effects on fasting concentrations may be seen. Lifestyle interventions using the Mediterranean
diet increase PON1 activity and may thereby decrease the risk fro atherosclerosis
12/2007: pages 129-138;
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ABSTRACT: Postprandial hyperlipidaemia is a common metabolic disturbance in atherosclerosis. During the postprandial phase, chylomicrons and their remnants can penetrate the intact endothelium and cause foam cell formation. These particles are highly atherogenic after modification. People in the Western world are non-fasting for most of the day, which consequently leads to a continuous challenge of the endothelium by atherogenic lipoproteins and their remnants. Furthermore, atherosclerosis is considered a low-grade chronic inflammatory disease. Many studies have shown that the process of atherogenesis in part starts with the interaction between the activated leucocytes and activated endothelium. Postprandial lipoproteins can activate leucocytes in the blood and up-regulate the expression of leucocyte adhesion molecules on the endothelium, facilitating adhesion and migration of inflammatory cells into the subendothelial space. Another inflammatory process associated with postprandial lipaemia is the activation of the complement system. Its central component C3 has been associated with obesity, coronary sclerosis, the metabolic syndrome and fasting and postprandial TAGs (triacylglycerols). Moreover, chylomicrons are the strongest stimulators of adipocyte C3 production via activation of the alternative complement cascade. A postprandial C3 increment has been shown in healthy subjects and in patients with CAD (coronary artery disease) and with FCHL (familial combined hyperlipidaemia). Postprandial lipaemia has been related to TAG and free fatty acid metabolism. All of these mechanisms provide an alternative explanation for the atherogenicity of the postprandial period.
Biochemical Society Transactions 07/2007; 35(Pt 3):466-9. · 3.71 Impact Factor
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ABSTRACT: We postulated that in type 2 diabetes, the postprandial phase is a pro-inflammatory state that can be modulated by PPAR-gamma agonists. For this purpose, we determined the effects of rosiglitazone (8 mg/d) on postprandial leukocyte counts and pro-inflammatory cytokines (IL-6 and IL-8) in patients with type 2 diabetes.
A randomized, 8-week, cross-over, placebo-controlled, double-blind clinical trial was performed in 19 patients with type 2 diabetes. Standardized 6-h oral fat-loading tests were performed after each treatment period. During placebo treatment, blood leukocytes increased to a maximum 6-h postprandially, due to significant increases in neutrophils and lymphocytes. Concomitant postprandial increases were observed for IL-6 and IL-8, the major chemokines responsible for leukocyte recruitment. Rosiglitazone reduced the incremental area under the curves (dAUCs) for IL-6 (-63%, p<0.01) and IL-8 (-16%, p<0.05). The dAUC for leukocytes decreased with 37% (p<0.05), due to a specific reduction of neutrophils (-39%, p<0.05).
Rosiglitazone attenuated the postprandial increases of neutrophils, IL-6 and IL-8 in patients with type 2 diabetes. Since inflammation is a major force driving atherosclerosis, and man lives in a postprandial period most part of the day, a reduced inflammatory response after a meal may delay progression of atherosclerosis.
We postulated that in type 2 diabetes, the postprandial phase is a pro-inflammatory state that can be modulated by PPAR-gamma agonists. Rosiglitazone attenuated the postprandial increases of neutrophils, IL-6 and IL-8 in patients with type 2 diabetes. These effects may contribute to cardiovascular risk reduction.
Atherosclerosis 06/2006; 186(1):152-9. · 3.79 Impact Factor
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ABSTRACT: A new method based on self-measurement of diurnal capillary triglycerides (TG) facilitates the study of postprandial lipemia (PL). The objectives of our study are: to evaluate the effect of gender and obesity on PL measured by self-determination of diurnal capillary TG with Accutrend GCT in normolipidemic non-diabetic subjects and subjects with familial combined hyperlipidemia (FCH).
We studied 23 FCH subjects (10 males) and 45 normolipidemic non-diabetic subjects (29 males). All subjects self-determine 3 diurnal capillary TG profiles during a week.
In normolipidemic non diabetic subjects significantly higher diurnal TG profiles and area under the curve of TG (AUCTGc) (25.25 +/-9.09 vs 19.71 +/- 6.16 mmolh/l) were found in males compared to females. In FCH subjects these differences were not found and the AUCTGc correlated with BMI (r = 0.510, p < 0.05) and waist circumference (r = 0.453, p < 0.05). Obese subjects (BMI >or= 27 kg/m2) showed diurnal TG profiles and AUCTGc significantly higher than the non-obese.
Normolipidemic non diabetic females showed a lower PL compared to males, probably due to the effect of estrogens in PL metabolism. Obesity negatively influences PL in normolipidemic non diabetic subjects and subjects with FCH.
Revista Clínica Española 05/2006; 206(5):213-9. · 2.01 Impact Factor
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ABSTRACT: We investigated whether pro-inflammatory aspects of the postprandial phase can be modulated by rosuvastatin in premature coronary artery disease (CAD) patients. Herefore standardized 8 h oral fat loading tests were performed off-treatment and after rosuvastatin 40 mg/d in 20 male CAD patients (50 +/- 4 years). The expression of leukocyte activation markers CD11a, CD11b, CD62L and CD66b was studied using flowcytometry. Migration of isolated neutrophils towards chemoattractants was determined in a fluorescence-based assay. Rosuvastatin did not affect baseline leukocyte counts nor the postprandial neutrophil increment (maximum mean increase +10% pre- and +14% post-treatment, P < 0.01 for each). Rosuvastatin reduced baseline platelets (from 266 +/- 78 to 225 +/- 74 x 10(9) cells/L, P < 0.001) and blunted the postprandial platelet count change (maximum mean increase +6%, P = 0.01, and 0%, respectively). The baseline expression of CD11a, CD11b and CD62L increased on most types of leukocytes by rosuvastatin, whereas the postprandial responses were unaffected. Pretreatment, postprandial neutrophil migration increased dose-dependently, but there were no postprandial changes after rosuvastatin. The latter effect was unrelated to changes in lipoprotein concentrations. In conclusion, in CAD patients postprandial pro-inflammatory and pro-coagulant changes can be modified by rosuvastatin. These apparently lipid-lowering independent effects may render protection against atherosclerosis.
Atherosclerosis 04/2006; 185(2):331-9. · 3.79 Impact Factor
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P J Barter,
C M Ballantyne,
R Carmena, M Castro Cabezas,
M John Chapman,
P Couture,
J de Graaf,
P N Durrington,
O Faergeman,
J Frohlich, [......],
K Srinath Reddy,
R Rosenson,
N Sarrafzadegan,
A D Sniderman,
A F Stalenhoef,
E Stein,
P J Talmud,
A M Tonkin,
G Walldius,
K M S Williams
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ABSTRACT: There is abundant evidence that the risk of atherosclerotic vascular disease is directly related to plasma cholesterol levels. Accordingly, all of the national and transnational screening and therapeutic guidelines are based on total or LDL cholesterol. This presumes that cholesterol is the most important lipoprotein-related proatherogenic risk variable. On the contrary, risk appears to be more directly related to the number of circulating atherogenic particles that contact and enter the arterial wall than to the measured concentration of cholesterol in these lipoprotein fractions. Each of the atherogenic lipoprotein particles contains a single molecule of apolipoprotein (apo) B and therefore the concentration of apo B provides a direct measure of the number of circulating atherogenic lipoproteins. Evidence from fundamental, epidemiological and clinical trial studies indicates that apo B is superior to any of the cholesterol indices to recognize those at increased risk of vascular disease and to judge the adequacy of lipid-lowering therapy. On the basis of this evidence, we believe that apo B should be included in all guidelines as an indicator of cardiovascular risk. In addition, the present target adopted by the Canadian guideline groups of an apo B <90 mg dL(-1) in high-risk patients should be reassessed in the light of the new clinical trial results and a new ultra-low target of <80 mg dL(-1) be considered. The evidence also indicates that the apo B/apo A-I ratio is superior to any of the conventional cholesterol ratios in patients without symptomatic vascular disease or diabetes to evaluate the lipoprotein-related risk of vascular disease.
Journal of Internal Medicine 03/2006; 259(3):247-58. · 5.48 Impact Factor
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ABSTRACT: The use of antiretroviral combination therapy in HIV has been associated with lipodystrophy and several metabolic risk factors. We postulated that patients with HIV-lipodystrophy have impaired adipose tissue free fatty acid (FFA) trapping and, consequently, increased hepatic FFA delivery. We investigated FFA, hydroxybutyric acid (HBA; reflecting hepatic FFA oxidation), and triglyceride (TG) changes after a high fat meal in HIV-infected males with (LIPO; n = 26) and without (NONLIPO; n = 12) lipodystrophy and in healthy males (n = 35). Because defective peripheral FFA trapping has been associated with impaired action of complement component 3 (C3), we also determined postprandial C3 concentrations. The LIPO group had higher homeostasis model assessment scores compared with the other groups. Areas under the curve (AUCs) for FFA, HBA, and TG were higher in the LIPO group than in the NONLIPO group or the controls. No differences in TG-AUC, FFA-AUC, and HBA-AUC were observed between the NONLIPO group and controls. In HIV-infected patients, FFA-AUC and HBA-AUC were inversely related to sc adipose tissue area. Plasma C3 showed a postprandial increase in healthy controls, but not in the HIV-infected groups. C3 was not related to body fat distribution, postprandial FFA, or HBA. The present data suggest disturbed postprandial FFA metabolism in patients with HIV-lipodystrophy, most likely due to inadequate incorporation of FFA into TG in sc adipose tissue, but do not support a major role for C3 in these patients. The higher postprandial HBA levels reflect increased hepatic FFA delivery and may aggravate insulin resistance and dyslipidemia, leading to increased cardiovascular risk.
Journal of Clinical Endocrinology & Metabolism 07/2005; 90(6):3575-82. · 6.50 Impact Factor
