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Aim: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) linked to atherogenic dyslipidaemia and postprandial hyperlipidaemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low-density lipoprotein-cholesterol (LDL-C). However, effects of PCK9 inhibitors on other aspects of diabetic dyslipidaemia, particularly in the postprandial situation, are less clear., Material and Methods: Twelve male patients with T2DM on an intensive insulin regimen completed a 6-week randomized, double-blind, placebo-controlled, proof-of-concept study. Participants received three biweekly dosages of subcutaneous alirocumab (150 mg) or placebo. Before and after the intervention, fasting and postprandial triglyceride (TG) plasma levels, apolipoprotein (apo) B48, lipoprotein composition isolated by ultracentrifugation, vascular function and markers of inflammation were evaluated., Results: Alirocumab treatment reduced fasting plasma TG levels (between group median change -24.7%; P = 0.018) and fasting apoB48 serum levels (-35.9%; P = 0.039) compared with placebo. Alirocumab reduced the plasma TG area under the curve (AUC) (-26.4%; P = 0.006) and apoB48 AUC (-55.7%; P = 0.046), as well as plasma TG incremental AUC (-21.4%; P = 0.04) and apoB48 incremental AUC (-26.8%; P = 0.02). In addition, alirocumab reduced fasting and postprandial TG levels in very low-density lipoprotein (VLDL) and LDL. Alirocumab improved fasting pulse wave velocity, but no changes in postprandial markers of inflammation were observed., Conclusions: In addition to the well-known LDL-C-reducing effects, 6 weeks of alirocumab treatment lowered both fasting and postprandial plasma TG levels by reducing the TG levels in VLDL and LDL and the concentration of intestinal remnants., (© 2020 John Wiley & Sons Ltd.)

Background: Women are relatively protected from cardiovascular disease compared with men. Since morbid obesity is an independent risk factor for cardiovascular disease, the current study investigated whether the association between sex and cardiovascular risk factors and outcomes can be demonstrated in subjects suffering from morbid obesity., Materials and Methods: Two hundred subjects enrolled in a study on cardiovascular risk factors in morbid obesity underwent extensive laboratory screening, carotid intima-media thickness (cIMT) and pulse wave velocity (PWV) measurements. Gender differences were analysed using univariate and multivariable linear regression models. In addition, the effect of menopause on cIMT and PWV was analysed. Results of these models were reported as B coefficients with 95% confidence intervals., Results: The group consisted of 52 men and 148 women, with a mean age of 41 (±11.8) years and a mean body mass index (BMI) of 42.7 (±5.2) kg/m 2 . Both, cIMT and PWV were significantly higher in men than in women, although the difference in cIMT disappeared after adjustment for covariables such as waist circumference, age, high-density lipoprotein cholesterol and mean arterial pressure. PWV was associated with sex after adjustments for covariables in morbidly obese patients. Postmenopausal women had significantly increased cIMT and PWV when compared with premenopausal women., Conclusion: Sex differences in PWV persist in subjects suffering from morbid obesity. However, no difference was found in cIMT between morbidly obese men and women after adjustment for classic cardiovascular risk factors. Premenopausal morbidly obese women are protected for cardiovascular disease when compared with postmenopausal morbidly obese women., (© 2019 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Context: Cholecalciferol (vitamin D3) improves vascular function and inflammation, potentially providing an explanation for the proposed cardiovascular protection of vitamin D., Objective: We investigated whether cholecalciferol supplementation reduces postprandial arterial dysfunction and inflammation., Design: Randomized, 1:1, double-blind trial., Setting: Diabetes and Vascular Center, Franciscus Gasthuis, Rotterdam, The Netherlands., Patients: Twenty-four healthy, premenopausal, overweight or obese, vitamin D-deficient women., Interventions: A single high (300,000 IU) or low dose (75,000 IU) of cholecalciferol., Main Outcome Measures: The effect of low- and high-dose cholecalciferol on postprandial leukocyte activation markers, pulse wave velocity (PWV), and augmentation index (AIx) during an oral fat loading test, expressed as area under the curve (AUC)., Results: High- and low-dose supplementation increased vitamin D by 163% ± 134% (P < 0.001) and 66% ± 59% (P < 0.001), respectively. Monocyte CD11b-AUC slightly increased after low but not high dose (6% ± 2%, P = 0.012, and 4% ± 1%, P = 0.339, respectively). There were no significant effects on postprandial PWV or AIx by high- or low-dose vitamin D. Fasting complement component 3 (C3) levels decreased by 5.9% (P = 0.004) in the high-dose group and by 4.0% (P = 0.018) in the low-dose group., Conclusion: A single dose of vitamin D does not seem to reduce arterial stiffness and leukocyte activation in overweight, vitamin D-deficient women. Vitamin D may decrease fasting C3. Possibly, higher vitamin D concentrations may be needed to decrease inflammation and improve vascular function in overweight or obese vitamin D-deficient women., (Copyright © 2017 by the Endocrine Society)

Background: Cell counts in bodyfluids such as ascitic fluid can be difficult to perform and report rapidly. The current gold standard for cell counting in body fluids is a suitable automated cell counter or a manual counting chamber, combined with differential counting on a cytospin. This technique has several disadvantages, so we designed a new flow cytometric test for cell counting in ascites. We compared this with an automatic cell counter (LH750, Beckman Coulter) and manual counting of cytospins., Methods: Ascitic samples (n = 53) from 38 patients were studied. Polymorphonuclear neutrophils (PMN), lymphocytes, eosinophils, and macrophages were defined by flow cytometry. We compared this with our reference method: the absolute cell concentration calculated from the leukocyte concentration of the LH750 combined with a differential cell count performed manually on a cytospin., Results: The outcomes of validation experiments (linearity, reproducibility, and detection limit) of the flow cytometric assay prove it is well suited for cell counting in ascitic fluid., Conclusions: Based on analytical performance, flow cytometry is suited for cell counting in ascitic fluid. An ascitic fluid cell count is frequently ordered to detect spontaneous bacterial peritonitis (SBP). If the PMN count is ≥250 cells/mm 3 , SBP is highly suspected. Using our reference method, we calculated the sensitivities and specificities to detect ≥250 PMN cells/mm 3 for the LH750 (100% and 65%, respectively) and flow cytometric assay (100%, 100%). As flow cytometry is easier and faster we recommend this method for rapid cell counting in ascitic fluid. © 2014 International Clinical Cytometry Society., (© 2014 Clinical Cytometry Society.)

Granulocyte colony-stimulating factor (G-CSF) is the major hematopoietic cytokine involved in the control of neutrophil production and thus serves as a critical regulator of the innate immunity against bacterial infections. G-CSF is applied on a routine basis in the clinic for treatment of congenital and acquired neutropenias, diseases characterized by a critical shortage of neutrophils, leading to severe opportunistic bacterial infections. Very recently, it has become clear that therapeutic application of G-CSF may not be limited to different types of neutropenia, but may extend to non-hematological conditions, in particular cardiac and brain infarctions. G-CSF drives the proliferation, survival and neutrophilic differentiation of myeloid progenitor cells by activation of a receptor of the hematopoietin receptor superfamily, which subsequently triggers multiple signaling mechanisms. These mechanisms exert positive as well as negative effects on the signaling function of the G-CSF receptor. The integrated output of these signaling pathways provide the appropriate balance needed for accurate production of neutrophils under both steady state and "emergency" conditions. Here we review how these mechanisms are thought to act in concert to meet with these demands and how perturbations in the function of the G-CSF receptor are implicated in various types of myeloid disease.