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Presents abstracts of research published in various medical journals. "Twelve-Month Use of Mental Health Services in the United States: Results From the National Comorbidity Survey Replication"; "Effect of Laparoscopic Colon Resection on Postoperative Glucose Utilization and Protein Sparing: An Integrated Analysis of Glucose and Protein Metabolism During the Fasted and Fed States Using Stable Isotopes"; "Effect of Lowering of Homocysteine Levels on Inflammatory Markers: A Randomized Controlled Trial"; "Variation in the Diagnosis, Treatment, and Management of Melanoma In Situ: A Survey of US Dermatologists"; "Circulating Erythropoietin Levels and Prognosis in Patients With Congestive Heart Failure: Comparison With Neurohormonal and Inflammatory Markers".

Background: Ubiquinol is a sensitive redox marker in the first line of the antioxidative defence mechanism and is increasingly being measured in oxidation studies. Because of its apparent instability during storage and processing, we compared various storage conditions. Method: Blood was collected from three volunteers into tubes containing EDTA; it was then separated at 4°C and cryopreserved with saccharose (final concentration 6 g/L). Aliquots were stored with or without glutathione or butylated hydroxytoluene at -20°C and -80°C. Results and conclusion: Ubiquinol in samples stored at -20°C was not stable; however, it was stable when stored at -80°C, even without addition of antioxidant. By contrast, α-tocopherol was stable under all conditions studied. [ABSTRACT FROM AUTHOR]

Objective: Macrophages are key players in atherogenesis because of their properties to form foam cells that produce a large variety of pro-inflammatory mediators. We addressed the potency of phenotypic different macrophages to accumulate oxidized LDL., Methods and Results: Surprisingly, anti-inflammatory M2 macrophages but not pro-inflammatory M1 macrophages rapidly accumulated oxidized LDL. Simultaneously, expression of Krüppel-like factor 2, a nuclear transcription factor known to suppress inflammation in endothelial cells and monocytes, decreased and the functional phenotype of M2 macrophages shifted towards a pro-inflammatory profile, characterized by higher production of IL-6, IL-8 and MCP-1 and lower expression of IL-10 upon stimulation with LPS. In contrast, Krüppel-like factor 2 expression and the phenotype of M1 macrophages remained largely unchanged upon oxidized LDL exposure. Downregulation of Krüppel-like factor 2 expression of M2 macrophages using siRNA technology led to a significant increase of LPS-induced MCP-1 secretion., Conclusions: We show that (1) anti-inflammatory M2 macrophages are more susceptible to foam cell formation than pro-inflammatory M1 macrophages, (2) exposure to oxidized LDL renders M2 macrophages pro-inflammatory, and (3) Krüppel-like factor 2 is involved in the enhanced secretion of MCP-1 by M2 macrophages loaded with oxidized LDL. The phenotype switch of M2 macrophages from an anti- to a pro-inflammatory profile may play an important role in pathogenesis of atherosclerosis, and could represent a novel therapeutic target., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The incidence of cardiovascular disease is markedly increased in patients with end-stage renal disease (ESRD). High serum cholesterol is widely recognised as a cardiovascular risk factor in the general population. However, in patients with ESRD high concentrations of cholesterol are associated with a better survival. This reverse epidemiology is, amongst others, caused by confounding due to malnutrition and chronic inflammation. In this population, treatment with statins to lower the serum cholesterol remains a matter of debate. In ESRD, LDL cholesterol is modified by increased oxidative stress. These altered LDL particles play a pivotal role in the development of atherosclerosis. Treatment with the antioxidant vitamin E has not equivocally been shown to be beneficial in this population. This review tries to put data from literature on dyslipidaemia and oxidative stress in ESRD in perspective.

Background: Excess body iron is associated with increased cardiovascular disease risk, possibly via non-transferrin-bound iron (NTBI)-mediated enhancement of inflammation and oxidation of low-density lipoprotein (LDL)., Methods: We assessed this proposed atherosclerotic mechanism of body iron by determining the relationship of levels of serum iron parameters, including NTBI, with plasma markers of inflammation and LDL oxidation in 232 subjects who visited the outpatient clinic for hemochromatosis family screening., Results: Plasma level of soluble intercellular adhesion molecule-1 (sICAM-1) was positively related to ferritin (standardized beta coefficient 0.16) and to NTBI (0.185) and negatively to total iron-binding capacity (TIBC, -0.166). Significant higher levels of sICAM-1 were found for subjects in the highest quartile of NTBI compared to the lowest quartile of NTBI (122 microg/L (107-141) and 106 microg/L (89-125), median (interquartile range), p<0.001). Odds ratio of subjects having sICAM-1 level above 134 microg/L (75th percentile) in the highest and lowest quartile of NTBI amounted 2.3. White blood cell count was positively related to ferritin (0.149). High-sensitivity C-reactive protein, interleukin-6, interleukin-8, oxidized LDL, oxidized LDL/apolipoprotein B and IgG and IgM antibodies to oxidized LDL were not related to any of the markers of iron status., Conclusion: Excess body iron, reflected by elevated serum ferritin and NTBI and decreased TIBC, is associated with increased plasma level of sICAM-1 but not with markers of in vivo LDL oxidation.

Objective: Circulating oxidized low-density lipoprotein (LDL) has been shown to be a useful marker for identifying patients with coronary heart disease (CHD) and persons at high cardiovascular risk. The effect of cholesterol-lowering therapy on plasma level of oxidized LDL is not clear., Methods and Results: We investigated effects of cholesterol lowering by therapeutic intervention (2 years) with atorvastatin (80 mg daily) and simvastatin (40 mg daily) on circulating oxidized LDL (absolute level and in proportion to plasma apolipoprotein B) in relation to atherosclerosis progression (carotid intima-media thickness, carotid IMT) and to inflammation (high-sensitivity C-reactive protein, hsCRP) in 115 stable patients with heterozygous familial hypercholesterolemia (FH). Atorvastatin and simvastatin reduced plasma-oxidized LDL (-43 and -35%, respectively) in proportion to the decrease in plasma apolipoprotein B. Neither absolute nor relative level of oxidized LDL correlated with carotid IMT or hsCRP at baseline. Also changes in levels of circulating oxidized LDL were not related to changes in carotid IMT and hsCRP., Conclusions: In familial hypercholesterolemia-oxidized LDL carried in plasma is strongly associated with apolipoprotein B but not with inflammation nor with carotid IMT, and statin treatment does not reduce oxidized LDL relative to apolipoprotein B.

Since the discovery of human serum paraoxonase (PON1), the enzyme has been the subject of various fields of research. Initially, PON1 was identified as an enzyme capable of hydrolysing organophosphate compounds, but there is a growing body of evidence that PON1 plays a role in lipid metabolism and the onset of cardiovascular disease. Still, the precise mechanism by which PON1 functions in vivo remains to be clarified. Here we will briefly review developments in the field of PON1 research which merit further attention.

Objectives: Statins reduce low-density lipoprotein cholesterol (LDL-C) and can raise high-density lipoprotein cholesterol (HDL-C). HDL-bound paraoxonase-1 (PON1) is associated with variations in plasma HDL-C, and may, therefore, contribute to changes of HDL-C during statin therapy., Design: The effects of baseline PON1 status to HDL-C changes because of statin therapy were investigated. PON1 status was determined with (i) PON1 -107C>T and 192Q>R genotype, (ii) PON1 levels and (iii) PON1 paraoxonase, diazoxonase and arylesterase activity., Setting: Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands., Subjects: A total of 134 familial hypercholesterolaemia (FH) patients undergoing atorvastatin or simvastatin therapy., Results: PON1 levels and activities significantly modified the HDL-C increment (P=0.002 for PON1 levels and arylesterase activity and P=0.001 for diazoxonase activity). The effects were even more evident amongst subgroup classifications based on PON1 status and baseline HDL-C concentrations: the HDL-C increment was more pronounced in subgroups of -107CT/TT or 192QR/RR genotype combined with low baseline HDL-C (+13.9%, P<0.001, respectively+15.4%, P<0.001). In contrast, the -107CC or 192QQ genotype in combination with high baseline HDL-C, did not show a significant increase of HDL-C., Conclusions: PON1 status in conjunction with baseline HDL-C levels predicts HDL-C increment during statin therapy in FH patients.

Background: Obesity is characterised by insulin resistance and by elevated levels of proinflammatory markers. We investigated whether, in the absence of changes in glucose, thiazolidinediones (TZDs) have anti-inflammatory effects and whether improvement of insulin sensitivity correlates with suppression of inflammatory markers., Methods: We performed a randomised double-blind placebo-controlled crossover study with troglitazone (400 mg daily for eight weeks) in 15 normoglycaemic obese subjects. We measured plasma high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and tumour necrosis factor-alpha (TNF-alpha) after each of the two treatment periods and in 13 age- and sex-matched lean individuals., Results: Obese subjects were insulin resistant (decreased glucose infusion rate (GIR) during euglycaemic hyperinsulinaemic clamp) and had higher plasma levels of hsCRP, IL-6, leptin, tPA, and PAI-1 compared with lean subjects. TNF-alpha also tended to be higher. Troglitazone improved insulin sensitivity (mean increase in whole body glucose uptake 23.1 +/- 10.5% (p = 0.047)) and normalised plasma concentrations of hsCRP, tPA and TNF-alpha, whereas it did not significantly change IL-6, leptin and PAI-1. Changes in GIR did not correlate with changes in inflammatory markers., Conclusion: Troglitazone induces suppression of some of the inflammatory markers that are elevated in normoglycaemic obese subjects. The suppression of inflammatory markers, however, does not correlate with improvement in insulin sensitivity, suggesting involvement of partially differential mechanisms in these effects of TZDs.