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Abstract. Background: In hyperlipidaemic state, increased levels of myeloperoxidase (MPO) and decreased paraoxonase-1 (PON1) activity have been reported; however, their relationships with other atherosclerotic biomarkers have not been completely clarified. Patients and methods: Serum concentrations of lipid and inflammatory parameters, MPO levels, and PON1 activities were investigated in 167 untreated hyperlipidaemic patients with and without vascular complications and in 32 healthy controls. Additionally, levels of CD40 ligand (sCD40L) and asymmetric dimethyl arginine (ADMA), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1, and oxidized LDL were determined. Results: We found elevated C-reactive protein (CRP), ADMA, sCD40L, sICAM-1 concentrations, and higher MPO levels in patients with vascular complications compared to those without. The PON1 arylesterase activity correlated negatively with sCD40L, ADMA, and sICAM-1 levels, respectively. In contrast, MPO concentrations showed positive correlations with sCD40L, ADMA, and sICAM-1 levels, respectively. Conclusions: It can therefore be stated that PON1 activity and MPO level correlate strongly with the vascular biomarkers, highlighting the importance of the HDL-associated pro- and antioxidant enzymes in the development of endothelial dysfunction and atherogenesis.

Our objective was to investigate the impact of low-intensity aerobic training on cognitive functions in severely deconditioned subacute and chronic stroke patients. For this purpose, a randomized, controlled pilot study was designed involving subacute and chronic stroke patients. Thirty-seven eligible patients participated in the 4-week-long randomized, controlled pilot study. Patients were randomized into study group and control group and both groups participated in conventional physiotherapy included occupational therapy. Only the study group's patients participated in a low-intensity aerobic training by cycle ergometer. Cognitive evaluations (Functional Independence Measure Cognitive part - FIM-cog; Coding and Symbol Search tasks of the Processing Speed index and Digit Span task of Working Memory index of Wechsler Adult Intelligence Scale-Fourth Edition) were performed before and after the programme. In-group analysis showed a significant improvement in study group patients regarding Coding subtest of Processing Speed domain (P = 0.003). Symbol Search subtest of Processing Speed showed significant improvements in both groups by the end of the programme (study group, P = 0.041; control group, P = 0.006). There were no significant changes in the FIM-cog and Digit Span task. The intergroup analysis did not find significant difference between the two groups. It was concluded that even the low-intensity aerobic training may improve special domains of cognitive function after stroke. Further studies are needed to confirm the impact of low-intensity aerobic training on cognitive functions.

Oxidative stress and chronic low-grade inflammation are major characteristics of obesity-related disorders. The dominance of pro-oxidant and pro-inflammatory mechanisms triggers insulin resistance and enhances the progression of atherosclerosis. Discovered first as an esterase that hydrolyze organophosphates, human paraoxonase-1 is bound to high-density lipoprotein and inhibits the oxidation of lipoproteins and reduces the degree of inflammation, hence it is considered to act against atherosclerosis. In contrast, the majority of the adipokines secreted from the enlarged white adipose tissue promote the atherosclerotic process; and altered adipokine secretion is now regarded as one of the major contributors of increased cardiovascular morbidity and mortality in obesity. In this review, we detail the correlations between paraoxonase-1 and some selected adipokines, namely leptin, adiponectin and chemerin. Adipokine imbalance leads to decreased paraoxonase-1 activity that results in enhanced atherosclerosis; therefore, altered adipokine secretion may be predictive of cardiovascular complications in obesity. As an active organ secreting biological active substances, white adipose tissue may also act as a "fine-tuner" of immune and endocrine actions attenuating or enhancing reactions triggered by pathogens, inflammation and metabolic stimuli; and obesity, as a chronic noxious state may perturb the proper functioning of this fine-tuning process. Further investigations are of major importance to elucidate the associations between adipokines and paraoxonase-1 and to establish accurate interventions against obesity-related disorders.

Myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were shown to contribute to atherogenesis, while human paraoxonase-1 (PON1) protects against oxidative stress. Although several studies investigated these biomarkers, their associations have not been completely clarified yet. We aimed to investigate these parameters in overweight hyperlipidemic, lipid-lowering therapy-naive patients (n=167) with and without vascular complications.MPO, MMP-9 and TIMP-1 levels were measured by ELISA. PON1 activities were detected spectrophotometrically. PON1 phenotype was calculated by using a dual substrate method.Patients with vascular complications (VC) had significantly higher MPO and TIMP-1 levels compared to those without (patients with no vascular complications; NVC) (728 (367.25-1177.90) mg/ml vs. 315.9 (176.05-687.40) mg/ml; p0.001; and 172.7 (157.7-197.7) ng/ml vs. 152.6 (129.3-172.3) ng/ml; p0.0001; respectively). MPO levels showed a significant negative correlation with PON1 arylesterase activity (whole patient group (W): r=0.42, p0.0001; VC: r=0.44, p=0.01; NVC: r=0.39, p0.0001) and positive correlations with MMP-9 (W: r=0.37, p0.0001; VC: r=0.29, p=0.07; NVC: r=0.42, p0.0001) and TIMP-1 (W: r=0.42, p0.0001; VC: r=0.33, p0.05; NVC: r=0.41, p0.0001), respectively. PON1 arylesterase activity was found to be an independent predictor of MPO levels in the whole patient group (β=-0.350, p0.0001) or when studied separately in the subgroups with or without cardiovascular complications (VC: β=-0.57, p0.05; NVC: β=-0.33, p0.0001).Our results suggest that parallel investigation of MPO, MMP-9 and TIMP-1 levels and PON1 arylesterase activity may be a more accurate indicator of atherosclerosis, which may allow earlier treatment and therefore, improvement of treatment efficacy.

Background and aims Familial hypercholesterolemia (FH) is one of the most frequent diseases with monogenic inheritance. Previous data indicated that the heterozygous form occurred in 1:250 people. Based on these reports, around 36,000–40,000 people are estimated to have FH in Hungary, however, there are no exact data about the frequency of the disease in our country. Therefore, we initiated a cooperation with a clinical site partner company that provides modern data mining methods, on the basis of medical and statistical records, and we applied them to two major hospitals in the Northern Great Plain region of Hungary to find patients with a possible diagnosis of FH. Methods Medical records of 1,342,124 patients were included in our study. From the mined data, we calculated Dutch Lipid Clinic Network (DLCN) scores for each patient and grouped them according to the criteria to assess the likelihood of the diagnosis of FH. We also calculated the mean lipid levels before the diagnosis and treatment. Results We identified 225 patients with a DLCN score of 6–8 (mean total cholesterol: 9.38 ± 3.0 mmol/L, mean LDL-C: 7.61 ± 2.4 mmol/L), and 11,706 patients with a DLCN score of 3–5 (mean total cholesterol: 7.34 ± 1.2 mmol/L, mean LDL-C: 5.26 ± 0.8 mmol/L). Conclusions The analysis of more regional and country-wide data and more frequent measurements of total cholesterol and LDL-C levels would increase the number of FH cases discovered. Data mining seems to be ideal for filtering and screening of FH in Hungary.

SummaryObjective Chemerin is a recently described adipokine expressed primarily in the white adipose tissue. Compared with lean subjects, circulating chemerin levels are significantly elevated in obese individuals and correlate positively with the prevalence of various cardiovascular risk factors including altered lipoprotein levels. To date, the impact of chemerin on lipoprotein subfractions and its role in atherosclerotic processes are still unclear. Patients and Methods Fifty nondiabetic obese (NDO) patients and 38 lean controls matched in age and gender were enrolled. Chemerin level was measured by ELISA. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were detected by nongradient polyacrylamide gel electrophoresis (Lipoprint). Results We detected significantly higher serum chemerin levels in NDO patients compared with healthy controls (590·1 ± 190·3 ng/ml vs 405 ± 127·1 ng/ml, P

Changes in high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels have been linked to residual cardiovascular risk, whereas non-HDL-C levels have been shown to be more predictive of cardiovascular risk than are low-density lipoprotein cholesterol (LDL-C) levels. We aimed to investigate the impact of HDL-C, TG, and non-HDL-C levels on acute coronary syndrome (ACS) risk with on-target LDL-C levels. In all, 424 Caucasian patients aged over 50 years who had LDL-C levels below 3.4 mmol/l with a first or subsequent ACS event were enrolled in a multicenter, retrospective study. Lipid samples were collected within 4 days after the cardiovascular event. The subjects of the age-matched, gender-balanced control group (n = 443) had LDL-C levels below 3.4 mmol/l and were free of cardiovascular diseases. Patients with ACS had significantly higher TG and lower HDL-C levels compared with the control patients; however, we did not find any significant difference regarding non-HDL-C levels between the two groups. In regression analysis, the risk of coronary heart disease increased significantly with 1 standard deviation (SD) increase in TG and 1 SD decrease in HDL-C levels. High TG and low HDL-C levels may contribute to residual cardiovascular risk in patients with well-controlled LDL-C levels; however, non-HDL-C levels at admission did not seem to be predictive for patients with ACS. Detection and treatment of secondary lipid targets such as high TG and low HDL-C levels may be important for the prevention of cardiovascular diseases.

Background The causes of increased cardiovascular risk in systemic lupus erythematosus (SLE) are not understood thoroughly, although presence of traditional cardiovascular risk factors and disease-specific agents were also proposed. In this study, we investigated the quantitative changes in the lipid profile, as well as qualitative characteristics of high-density lipoprotein (HDL) and markers of inflammation and disease activity in SLE patients. Methods Lipoprotein levels were determined in 51 SLE patients and 49 healthy controls, matched in age and gender. HDL antioxidant capacity was determined spectrophotometrically with a cell-free method of hemin-induced low-density lipoprotein (LDL) oxidation. Polyacrylamide gel-electrophoresis was used for HDL subfraction analysis. Human paraoxonase-1 (PON1) activity, apolipoprotein A1 (ApoA1) and oxidized LDL concentrations, as well as interleukin-6, high-sensitivity C-reactive protein, serum amyloid A and monocyte chemotactic protein-1 levels were determined. Results HDL-cholesterol and ApoA1 concentrations decreased significantly in SLE subjects. Also, PON1 arylesterase activity (125.65 ± 26.87 vs. 148.35 ± 39.34 U/L, p = 0.001) and total HDL antioxidant capacity (165.82 ± 58.28 % vs. 217.71 ± 54.36 %, p

Oxidative stress has a complex effect on cancer development. To further study this process, we induced colon tumors with azoxymethane (AOM) in mice deficient for uncoupling protein-2 (UCP2). UCP2 has recently emerged as a negative regulator of mitochondrial oxidant production. When overexpressed, UCP2 protects cells from oxidative stress, while its absence may cause abundance of reactive oxygen species, release of pro-inflammatory cytokines and persistent activation of nuclear factor kappaB (NF-kappaB), a pleiotropic transcription factor with an increasingly recognized role in cancer. Here we show that Ucp2-/- mice develop more aberrant crypt foci and colon tumors than Ucp2+/+ littermates when examined 24 weeks after the completion of treatment with AOM (10 mg/kg i.p. weekly for a total of 6 weeks, n = 8-12). This effect is primarily seen in the proximal colon of Ucp2-/- mice (P < 0.05), in association with changes indicative of increased oxidative stress (increased staining for malondialdehyde and inducible nitric oxide synthase), enhanced NF-kappaB activation (increased levels of phosphorylated IkappaB and increased nuclear presence of p65) and a disrupted balance between intestinal epithelial cell proliferation (greater 5-bromo-2'-deoxy-uridine incorporation rates and increased phosphorylation of ERK1/2 and AKT) and apoptosis (decreased number of terminal deoxynucleotidyltransferase-mediated nick-end-labeling (TUNEL)-positive cells and increased expression of Bcl-2). In conclusion, our findings provide the first in vivo evidence for a link between UCP2 and tumorigenesis and indicate the need for additional studies to assess the role of mitochondrial uncoupling in cancer development.

Fatty liver is vulnerable to conditions that challenge hepatocellular energy homeostasis. Lipid-laden hepatocytes highly express uncoupling protein-2 (UCP2), a mitochondrial carrier that competes with adenosine triphosphate (ATP) synthesis by mediating proton leak. However, evidence for a link between UCP2 expression and susceptibility of liver to acute injury is lacking. We asked whether absence of UCP2 protects ob/ob mice from Fas-mediated acute liver damage. UCP2-deficient ob/ob mice (ob/ob:ucp2-/-) and UCP2-competent littermates (ob/ob:ucp2+/+) received a single dose of agonistic anti-Fas antibody (Jo2). Low-dose Jo2 (0.15 mg/kg intraperitoneally) caused less serum alanine aminotransferase (ALT) elevation and lower apoptosis rates in ob/ob:ucp2-/- mice. High-dose Jo2 (0.40 mg/kg intraperitoneally) proved uniformly fatal; however, ob/ob:ucp2-/- mice survived longer with less depletion of liver ATP stores, indicating that fatty hepatocytes may benefit from lack of UCP2 during Jo2 challenge. Although UCP2 reportedly controls mitochondrial oxidant production, its absence had no apparent effect on fatty liver tissue malondialdehyde levels augmented by Jo2. This finding prompted us to determine UCP2 expression in Kupffer cells, a major source of intrahepatic oxidative stress. UCP2 expression was found diminished in Kupffer cells of untreated ob/ob:ucp2+/+ mice, conceivably contributing to increased oxidative stress in fatty liver and limiting the impact of UCP2 ablation. In conclusion, whereas UCP2 abundance in fatty hepatocytes exacerbates Fas-mediated injury by compromising ATP stores, downregulation of UCP2 in Kupffer cells may account for persistent oxidative stress in fatty liver. Our data support a cell-specific approach when considering the therapeutic effects of mitochondrial uncoupling in fatty liver disease.

The prevalence of obesity has been increasing worldwide. Chemerin is a recently discovered adipokine secreted by the enlarged adipose tissue with diverse biological effects that are not well detailed yet. This study aimed to elucidate the potential role of chemerin in oxidative stress and inflammation that are characteristics for excess weight and may eventually lead to insulin resistance and atherosclerotic complications. We also analysed the associations between chemerin and classical adipokines, namely leptin and adiponectin. Therefore, we investigated non-diabetic obese patients without manifest cardiovascular disease and compared their data to healthy lean individuals. Chemerin correlated positively with markers of oxidative stress and inflammation, while it showed a negative correlation with the measure of antioxidant status, characterized by the HDL-linked paraoxonase-1 enzyme. Chemerin also correlated positively with leptin and negatively with adiponectin respectively. In our study population, oxidized low-density lipoprotein and high-sensitivity C-reactive protein were found to be the strongest predictors of chemerin level. We conclude that chemerin may contribute to chronic inflammation and increased oxidative stress in obese individuals, even in the absence of manifest insulin resistance.

Obesity and its co-morbidities as metabolic syndrome, type 2 diabetes mellitus and cardiovascular diseases are major health problems worldwide. Several reports indicated that nutrient excess and metabolic syndrome are linked with altered immune response. Indeed, metabolic syndrome is characterized by insulin resistance and chronic low-grade inflammation, which conditions are the consequences of the complex interaction between adipocytes and immune cells. Enlarged white adipose tissue is infiltrated by immune cells and secretes various bioactive substances, like adipokines, cytokines and other inflammatory mediators. Due to its special architecture in which metabolic and immune cells are in intimate proximity, metabolic and immunologic pathways are closely integrated in adipose tissue. With the contribution of altered gut microbiota, adipokines and cytokines modulate insulin signaling and immune response leading to adipose tissue inflammation and systemic insulin resistance. In this chapter, we focus on the cellular and molecular mechanisms that lead to impaired insulin sensitivity and chronic low-grade inflammation in obesity. We also detail the potential role of adipokines and immune cells in this deleterious process, and the concerns of vaccination in metabolic syndrome. Finally, we address the links between obesity and gut microbiota as an emerging new field of interest, and scratch the surface of potential therapeutic opportunities.

Selenium is an essential trace element with potential anti-atherogenic and antioxidant effects. Experimental data suggest that selenium might be beneficial in the prevention of atherosclerosis and its complications, whereas human epidemiological studies have yielded conflicting results. Data on hair selenium status in hyperlipidemic patients are still lacking. Therefore, we analysed selenium concentrations by X-ray fluorescence in the hair of 81 statin-naive patients with newly diagnosed Fredrickson-type IIa and IIb hyperlipoproteinemia and compared their data with 43 healthy volunteers. We also assessed the frequency of other classical risk factors of atherosclerosis. Hair selenium levels were found to be significantly higher in hyperlipidemic patients compared with volunteers with normal lipid levels. Also, a significantly increased number of traditional atherosclerosis risk factors were observed in hyperlipidemic patients with hair selenium concentrations above the median in contrast to those with below. Our results suggest that high hair selenium status might be associated with adverse blood lipid profile together with an increased number of traditional risk factors in a selenium-deplete population. These findings warrant further investigations to study the impact of selenium supplementation on the incidence of cardiovascular events.

Az elhízás és hozzá társuló kórállapotok, így az inzulinrezisztenciát kísérő nem alkoholos zsírmájbetegség a világ egészségügyi rendszereire jelentős terhet rónak. A betegség kialakulásának első lépése a májban történő trigliceridlerakódást kísérő elzsírosodás, amely később gyulladáshoz, illetve májzsugorhoz és májrákhoz is vezethet. A steatosis hátterében a májba történő nagy mennyiségű zsírsavbeáramlás és a szervben megfigyelhető fokozott lipogenesis, valamint a zsírsav-oxidációs és -szekréciós utak relatív csökkenése áll. Jelen összefoglalónkban ezen molekuláris mechanizmusokra világítunk rá. Ezek megértése fontos adalékul szolgálhat az elhízás és az inzulinrezisztencia mellett kialakuló májbetegség, illetve a következményes kardiometabolikus következmények hátterének tisztázásához.

Uncoupling protein-2 (UCP2) regulates insulin secretion by controlling ATP levels in β-cells. Although UCP2 deficiency improves glycemic control in mice, increased expression of UCP2 interferes with glucose-stimulated insulin secretion. These observations link UCP2 to β-cell dysfunction in type 2 diabetes with a perplexing evolutionary role. We found higher residual serum insulin levels and blunted lipid metabolic responses in fasted ucp2−/−mice, supporting the concept that UCP2 evolved to suppress insulin effects and to accommodate the fuel switch to fatty acids during starvation. In the absence of UCP2, fasting initially promotes peripheral lipolysis and hepatic fat accumulation at less than expected rates but culminates in protracted steatosis, indicating diminished hepatic utilization and clearance of fatty acids. We conclude that UCP2-mediated control of insulin secretion is a physiologically relevant mechanism of the metabolic response to fasting.

Angiotensin II (Ang II) is able to induce free radical generation in neutrophils, which is more elevated in neutrophils of patients with hypercholesterolemia (HC). In addition, the signal processing through angiotensin I (Ang I) receptors is altered. In present study, we compared the Ang II-triggered free radical generation of neutrophils obtained from patients with relatively isolated forms of metabolic syndrome (MS) with membrane-bound cholesterol content and membrane fluidity. We determined the enhancement of Ang II-induced superoxide anion and leukotriene C(4) (LTC(4)) generation, membrane fluidity and cell-bound cholesterol content of neutrophils obtained from 12 control subjects, 11 patients with obesity (Ob), 10 patients with type 2 diabetes mellitus (t2-DM) and 12 patients with HC. The alteration of signal processing was studied after preincubation with different inhibiting drugs. Superoxide anion, LTC(4) production and membrane rigidity were increased in the following order: controlObt2-DMHC. Both Ang II-induced superoxide anion and LTC(4) generation were decreased in control cells by pertussis toxin and fluvastatin (Flu), whereas in each patient group, mepacrin, verapamil and Flu were effective, suggesting alterations in signal pathways, which may be attributed to isoprenylation. The enhancement of superoxide anion and LTC(4) generation correlated significantly with membrane rigidity, independently from the experimental groups and membrane-bound cholesterol content. Membrane rigidity of neutrophils, obtained from patients with MS, plays a role in Ang II-induced free radical generation independent of intracellular cholesterol homeostasis.

Background and aim Previous studies have demonstrated that oxidative stress is increased in obese patients. The high-density lipoprotein (HDL) associated human paraoxonase 1 (PON1) can inhibit low-density lipoprotein oxidation and has an antiatherogenic effect. Our objective was to assess the effects of orlistat therapy combined with diet on body mass index (BMI), waist circumference, lipid parameters, blood pressure, serum glucose level and PON1 activity. Methods and results A longitudinal, multicenter, randomized study with and without orlistat treatment was performed. One hundred thirty nine otherwise healthy, obese subjects were divided in to two groups: 78 persons received orlistat (120 mg three times a day) combined with diet while 61 persons were kept on diet only. Anthropometrical parameters, serum lipid levels and PON1 activity were measured at baseline and after 6 months of treatment. BMI and waist circumference were reduced more pronouncedly in the orlistat group than in the control group. Patients receiving orlistat also had significantly greater improvements in fasting blood glucose levels and blood pressure. The orlistat-treated group showed a greater reduction in total cholesterol and triglyceride levels. In addition, the serum PON1 activity in these patients was significantly increased compared to the diet-only group. Conclusions The 6-month treatment with orlistat had a beneficial effect on the lipid profile and improved the antioxidant status by increasing serum PON1 activity. However, because of the limited therapeutic effectiveness, obese patients with hypercholesterolemia should receive additional lipid lowering medications.

Rats (FLF1) were pretreated with 2 and 20 mg/kg/day fluvastatin (Flu), and after 6 weeks, hepatocellular tumor cells were inoculated under the left renal capsule. At different times, growth and pyruvate kinase (PK) activity of the primary tumors and lymph node metastases were determined. Flu had a dose-dependent inhibitory effect on primary and metastatic tumors, and the inhibitiory effect on growth and PK activity in metastases were higher than in primary tumors. Finally, Flu had an earlier inhibitory effect on the early appeared PK activity in metastases than in primary tumors.

Background Selective low-density lipoprotein (LDL) apheresis is commonly used to treat patients with familial hypercholesterolemia (FH). Chemerin is an adipokine with putative roles in the regulation of lipid metabolism. Methods In our pilot study, we measured serum chemerin levels by enzyme-linked immunosorbent assay in six severe heterozygous FH patients before and after their first LDL apheresis treatments using the technique of direct adsorption of lipoproteins (DALI). Results The first treatment sessions decreased serum chemerin levels by an average of 27.26 %. While following one patient, 12 months of regular LDL apheresis resulted in a permanent reduction in his serum chemerin level. Changes in the lipoprotein subfractions measured by gel electrophoresis (Lipoprint) correlated with the reduction of chemerin levels. Furthermore, we eluted and then measured chemerin bound to the DALI column. Conclusion We conclude that LDL apheresis decreases the circulating level of chemerin by binding the protein to the column and thus improves lipoprotein subfraction pattern.

High density lipoprotein (HDL)-associated paraoxonase activity may play an important role in the inhibition of low density lipoprotein (LDL) oxidation. Previous studies have demonstrated that serum paraoxonase activity is decreased in patients with hyperlipoproteinaemia and coronary heart disease, and a few investigators have suggested that the lipid-lowering statins may increase paraoxonase levels. To examine the effect of short-term treatment with simvastatin on lipids and paraoxonase activity in patients with hyperlipoproteinaemia. Prospective nonblind single-group sequential study. 112 (52 male and 60 female) hyperlipoproteinaemic patients with Fredrickson type IIa and IIb hyperlipoproteinaemia (mean age 52.15 ± 7.99 years, mean body mass index 27.53 ± 4.30 kg/m2). Serum cholesterol, lipoproteins, triglycerides, apolipoproteins and liver function were measured, and serum paraoxonase activity was determined spectrophotometrically using paraoxon as substrate. Simvastatin 20 mg/day was administered for 1 month, and measurements were repeated. Simvastatin significantly decreased serum cholesterol [from 10.25 ± 2.73 (SD) to 8.85 ± 2.02 mmol/L], triglyceride (from 3.95 ± 2.51 to 3.15 ± 1.47 mmol/L), LDL (from 6.36 ± 1.70 to 4.94 ± 1.48 mmol/L) and apolipoprotein B100 (from 1.93 ± 0.41 to 1.56 ± 0.35 g/L) levels, whereas HDL and apo A1 levels did not change significantly (from 1.19 ± 0.34 to 1.22 ± 0.39 mmol/L, and from 1.56 ± 1.99 to 1.64 ± 0.24 g/L, respectively). HDL-associated paraoxonase activity did not change significantly (from 182.25 ± 37.21 to 166.49 ± 35.01 U/L) after simvastatin therapy. Short-term administration of simvastatin did not increase the activity of the HDL-associated antioxidant enzyme paraoxonase.