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Background: Cardiovascular (CV) morbidity, mortality and metabolic syndrome are associated with rheumatoid arthritis (RA). A recent trial has suggested increased risk of major CV events (MACE) upon the Janus kinase (JAK) inhibitor tofacitinib compared with anti-tumor necrosis factor α (TNF-α) therapy. In our study, we evaluated lipids and other metabolic markers in relation to vascular function and clinical markers in RA patients undergoing one-year tofacitinib therapy. Patients and methods: Thirty RA patients treated with either 5 mg or 10 mg bid tofacitinib were included in a 12-month follow-up study. Various lipids, paraoxonase (PON1), myeloperoxidase (MPO), thrombospondin-1 (TSP-1) and adipokine levels, such as adiponectin, leptin, resistin, adipsin and chemerin were determined. In order to assess flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and arterial pulse-wave velocity (PWV) ultrasonography were performed. Assessments were carried out at baseline, and 6 and 12 months after initiating treatment. Results: One-year tofacitinib therapy significantly increased TC, HDL, LDL, APOA, APOB, leptin, adipsin and TSP-1, while significantly decreasing Lp(a), chemerin, PON1 and MPO levels. TG, lipid indices (TC/HDL and LDL/HDL), adiponectin and resistin showed no significant changes. Numerous associations were found between lipids, adipokines, clinical markers and IMT, FMD and PWV (p < 0.05). Regression analysis suggested, among others, association of BMI with CRP and PWV (p < 0.05). Adipokines variably correlated with age, BMI, CRP, CCP, FMD, IMT and PWV, while MPO, PON1 and TSP-1 variably correlated with age, disease duration, BMI, RF and PWV (p < 0.05). Conclusions: JAK inhibition by tofacitinib exerts balanced effects on lipids and other metabolic markers in RA. Various correlations may exist between metabolic, clinical parameters and vascular pathophysiology during tofacitinib treatment. Complex assessment of lipids, metabolic factors together with clinical parameters and vascular pathophysiology may be utilized in clinical practice to determine and monitor the CV status of patients in relation with clinical response to JAK inhibition.

Background: Afamin is a liver-produced bioactive protein and features α- and γ-tocopherol binding sites. Afamin levels are elevated in metabolic syndrome and obesity and correlate well with components of metabolic syndrome. Afamin concentrations, correlations between afamin and vitamin E, afamin and lipoprotein subfractions in non-diabetic, obese patients have not been fully examined. Methods: Fifty non-diabetic, morbidly obese patients and thirty-two healthy, normal-weight individuals were involved in our study. The afamin concentrations were measured by ELISA. Lipoprotein subfractions were determined with gel electrophoresis. Gas chromatography–mass spectrometry was used to measure α- and γ tocopherol levels. Results: Afamin concentrations were significantly higher in the obese patients compared to the healthy control (70.4 ± 12.8 vs. 47.6 ± 8.5 μg/mL, p < 0.001). Positive correlations were found between afamin and fasting glucose, HbA1c, hsCRP, triglyceride, and oxidized LDL level, as well as the amount and ratio of small HDL subfractions. Negative correlations were observed between afamin and mean LDL size, as well as the amount and ratio of large HDL subfractions. After multiple regression analysis, HbA1c levels and small HDL turned out to be independent predictors of afamin. Conclusions: Afamin may be involved in the development of obesity-related oxidative stress via the development of insulin resistance and not by affecting α- and γ-tocopherol levels.

Background: Cardiovascular (CV) morbidity, mortality, and metabolic syndrome are associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Here, lipids and other metabolic markers in relation to vascular function and clinical markers were evaluated in RA and AS patients undergoing one-year anti-TNF therapy. Patients and methods: Fifty-three patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Various lipids, paraoxonase (PON) and arylesterase (ARE) activities, myeloperoxidase (MPO) and adipokine levels were determined overtime. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. Results: Anti-TNF therapy decreased ARE activity, MPO, adiponectin, and chemerin levels after 12 months (p &lt, 0.05). Lipids, PON activity, and leptin remained unchanged. Regression analyses suggested variable associations of IMT, PWV, and FMD with ARE, MPO, leptin, and lipids (p &lt, 0.05). On the other hand, these metabolic parameters were significantly associated with disease duration, CV history, CRP, obesity, PWV, and IMT (p &lt, 0.05). One-year anti-TNF treatment together with baseline leptin (p = 0.039) or CRP (p = 0.016) levels determined 12 months of lipid changes overtime. TNF inhibition together with baseline disease activity determined ARE activity changes (p = 0.046). Anti-TNF therapy and baseline chemerin levels determined IMT changes overtime (p = 0.003). Conclusions: Assessment of various metabolic parameters together with disease activity, CRP, and ultrasound-based techniques may exert additional value in determining CV burden and in monitoring the effects of biologics on preclinical vascular pathophysiology.

Background: Diabetes mellitus is a major risk factor of sepsis. The potential role of hemoglobin A1c (HbA1c) in diabetic, septic patients has not yet been studied. Results: In our retrospective study we included diabetic, septic patients - in whom the diagnosis of sepsis was based on the Systemic Inflammatory Response Syndrome (SIRS) criteria (112 patients, SIRS group) - who had HbA1c levels measured either in the previous 30 days (SIRS 30d subgroup – 39 patients) or within 24 hours after their Emergency Department admission (SIRS 24h subgroup – 73 patients). We later selected those patients from the SIRS group, whose Sequential Organ Failure Assessment (SOFA) score was ≥ 2 (55 patients, SOFA group) and these patients were also divided based on the time of HbA1c measurement (SOFA 30d subgroup – 21 patients and SOFA 24h subgroup – 34 patients). We analyzed the relationship between laboratory parameters, length of hospital stay and HbA1c. We found a significant positive correlation between glucose and HbA1c, significant negative correlations between white blood cell count (WBC) and glucose, WBC and HbA1c levels in the SIRS 24h and SOFA 24h subgroups. Furthermore there was a significant positive correlation between length of hospital stay and HbA1c in the SOFA 24h subgroup. No significant correlations were found in the SIRS 30d and SOFA 30d subgroups. Conclusions: Based on our results normal WBC with elevated HbA1c might be considered a positive SIRS criterium in diabetic, SIRS 24h patients. Besides this potential diagnostic role, HbA1c might also be an additional prognostic biomarker in diabetic, SOFA 24h patients.

BACKGROUND Afamin is a plasma vitamin E-binding glycoprotein partially associated with ApoA1-containing high-density lipoprotein (HDL) subfractions. In a previous study, the serum vitamin E decreased after low-density lipoprotein (LDL) apheresis, while vitamin E/cholesterol ratio increased. We aimed to study the effect of LDL apheresis on serum afamin level. METHODS The serum level of afamin and oxidized LDL were measured by enzyme-linked immunosorbent assay in six severe heterozygous FH patients before and after their first LDL apheresis treatments and in seven healthy controls. We also investigated the changes in total cholesterol, LDL-C, HDL-C, ApoB, ApoA1, HDL subfractions, and α- and γ-tocopherol levels during the treatment. HDL subfractions were detected by an electrophoretic method on polyacrylamide gel (Lipoprint). Serum α- and γ-tocopherol levels were detected by gas chromatography-mass spectrometry. RESULTS The first treatment sessions decreased serum afamin levels by an average of 9.4%. Total cholesterol, LDL-C, HDL-C and ApoA1 levels decreased by 52.6; 61.8; 10.5; and 14.1%, respectively. We found that α- and γ-tocopherol levels markedly decreased (by 34.1 and 32.9%, respectively), while α- tocopherol/cholesterol and γ-tocopherol/cholesterol ratios significantly increased (by 41.4 and 40.3%, respectively). Oxidized LDL levels significantly decreased. There was a shift toward the larger HDL subfractions. CONCLUSION LDL apheresis moderately decreases the circulating levels of afamin parallel to lowering HDL-C and ApoA1 levels. Tocopherol levels decreases markedly compared to afamin levels, however, beneficial changes in vitamin E/cholesterol ratios, oxidized LDL levels and HDL subfraction distribution were detected. These additional effects of LDL apheresis may result in further cardiovascular risk reduction in FH patients.

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.

Csaba Papp,1 Krisztian Pak,2 Tamas Erdei,2 Bela Juhasz,2 Ildiko Seres,3 Anita Szentpéteri,3 Laszlo Kardos,4 Maria Szilasi,5 Rudolf Gesztelyi,2 Judit Zsuga1 1Department of Health Systems Management and Quality Management for Health Care, Faculty of Public Health, 2Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, 3Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4Department of Clinical Pharmacology, Infectious Diseases and Allergology, Kenezy Gyula Teaching County Hospital and Outpatient Clinic, 5Department of Pulmonology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Abstract: COPD is accompanied by limited physical activity, worse quality of life, and increased prevalence of depression. A possible link between COPD and depression may be irisin, a myokine, expression of which in the skeletal muscle and brain positively correlates with physical activity. Irisin enhances the synthesis of brain-derived neurotrophic factor (BDNF), a neurotrophin involved in reward-related processes. Thus, we hypothesized that mood disturbances accompanying COPD are reflected by the changes in the irisin–BDNF axis. Case history, routine laboratory parameters, serum irisin and BDNF levels, pulmonary function, and disease-specific quality of life, measured by St George’s Respiratory Questionnaire (SGRQ), were determined in a cohort of COPD patients (n=74). Simple and then multiple linear regression were used to evaluate the data. We found that mood disturbances are associated with lower serum irisin levels (SGRQ’s Impacts score and reciprocal of irisin showed a strong positive association; β: 419.97; 95% confidence interval [CI]: 204.31, 635.63; P

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.

Distress disorder (a collective term for generalized anxiety disorder and major depressive disorder) is a well-known co-morbidity of bronchial asthma. The irisin—brain-derived neurotrophic factor (BDNF) axis is a pathway that influences several neurobehavioral mechanisms involved in the pathogenesis of distress disorder. Thus, the aim of the present study was to quantify the serum irisin and BDNF concentrations in order to investigate the possible link between the irisin/BDNF axis and distress disorder in an asthma patient cohort. Data of 167 therapy-controlled asthma patients were analyzed. Demographic, anthropometric, and anamnestic data were collected, routine laboratory parameters supplemented with serum irisin and BDNF levels were determined, pulmonary function test was performed using whole-body plethysmography, and quality of life was quantified by means of the St. George's Respiratory Questionnaire (SGRQ). Correlation analysis as well as simple and multiple linear regression were used to assess the relationship between the irisin level and the Impacts score of SGRQ, which latter is indicative of the presence and severity of distress disorder. We have found a significant, positive linear relationship between the Impacts score and the reciprocal of irisin level. This association was stronger in patients whose BDNF level was higher, and it was weaker (and statistically non-significant) in patients whose BDNF level was lower. Our results indicate that higher serum irisin level together with higher serum BDNF level are associated with milder (or no) distress disorder. This finding suggests that alteration of the irisin/BDNF axis influences the presence and severity of distress disorder in asthma patients.

Some crucial associations between obesity-related altered adipokine levels and the main factors of atherosclerotic, atherothrombotic processes are not fully known. We analysed the relationships of classic adipokines, namely leptin, resistin, adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) with the markers of platelet activation, including mean platelet volume (MPV), platelet surface/soluble P-selectin, platelet-derived microparticles (PMPs), the parameters of coagulation abnormalities and common carotid intima-media thickness (IMT) in obese patients with or without atherosclerotic comorbidities in comparison to age- and sex-matched controls.We enrolled 154 obese individuals, including 98 suffering from atherosclerotic concomitant conditions, 56 free of atherosclerotic comorbidities and 62 healthy controls. Plasma levels of leptin, resistin, adiponectin, TNF-α, IL-6, soluble P-selectin, and plasminogen activator inhibitor-1 antigen (PAI-1 ag) were analysed by ELISA. Platelet surface P-selectin and PMPs were measured by flow cytometry. IMT was detected by ultrasonography. Adipokines were closely associated with markers of platelet hyperactivity, hypercoagulability, hypofibrinolysis and IMT. Significant independent associations were found between leptin and platelet count (p 0.0001), MPV (p = 0.019), PMPs (p 0.0001), fibrinogen (p = 0.001), factor VIII (FVIII) activity (p = 0.035); adiponectin and PAI-1 ag (p = 0.035); resistin and soluble P-selectin (p = 0.002); TNF-α and PAI-1 ag (p 0.0001); and IL-6 and fibrinogen (p = 0.011). Finally, leptin (p = 0.0005), adiponectin (p = 0.019), IL-6 (p = 0.001), MPV (p = 0.0003), PMP (p = 0.008), and FVIII activity (p = 0.043) were independent predictors of IMT.Overall, we suggest that in obese subjects altered adipokine levels play a key role in common carotid atherosclerosis both directly and through haemostatic parameters.

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Cerebrotendinous xanthomatosis is a rare neurodegenerative disease characterized by the accumulation of cholesterol and cholestanol in the brain and the tendons caused by mutations of the gene encoding sterol 27-hydroxylase (CYP27A1), which is involved in bile acid synthesis. The diagnosis is often missed and delayed because of the variable clinical presentation of the disease. Blood testing for cerebrotendinous xanthomatosis is routinely performed using gas chromatography-mass spectrometry measurement of elevated cholestanol level, and the diagnosis is confirmed by molecular genetic analysis. Early recognition and initiation of chenodeoxycholic acid therapy with hydoxymethyl‑glutaryl‑Coenzyme-A reductase inhibitors is critical to prevent irreversible neurological damage and permanent disability. The authors summarize the current knowledge about the pathomechanism, laboratory diagnosis and therapeutic options of cerebrotendinous xanthomatosis.A cerebrotendinosus xanthomatosis egy ritka, ataxiával, spasticitassal, korai mentális hanyatlással és pszichiátriai tünetekkel járó neurodegeneratív betegség, amelyet a koleszterin és a kolesztanol agyban és az inakban történő felszaporodása jellemez az epesavszintézisben részt vevő szterol-27-hidroxiláz (CYP27A1) génjének mutációja miatt. A diagnózis gyakran hibás vagy megkésett a változatos klinikai megjelenés miatt. A laboratóriumi diagnosztika rutinszerűen az emelkedett kolesztanolszint kimutatását végzi gázkromatográf-tömegspektrométer alkalmazásával, majd a diagnózist a molekuláris genetikai vizsgálat igazolja. A korai felismerés és a kenodezoxikólsav-, valamint a hidroximetil-glutaril-koenzim-A-reduktáz-gátló kezelés megkezdése alapvető jelentőségű az irreverzíbilis neurológiai károsodások és a tartós munkaképtelenség kialakulásának megelőzésében. A szerzők összefoglalják a cerebrotendinosus xanthomatosis patomechanizmusával, laboratóriumi diagnosztikájával és kezelési lehetőségeivel kapcsolatos tudnivalókat. Orv. Hetil., 2014, 155(21), 811–816.

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

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

Obesity is a major risk factor in numerous diseases, in which elevated intracellular Ca 2+ plays a major role in increased adiposity. We examined the difference between Ca 2+ signals in monocytes of lean and overweight subjects and the relationship between leptin induced NADPH oxidase activation and intracellular calcium concentration [Ca 2+ ] i homeostasis. Our results are as follows: (1) The basal level of [Ca 2+ ] i in resting monocytes of overweight subjects (OW monocytes) was higher than that in control cells, whereas the leptin-induced peak of the Ca 2+ signal was lower and the return to basal level was delayed. (2) Ca 2+ signals were more pronounced in OW monocytes than in control cells. (3) Using different inhibitors of cellular signaling, we found that in control cells the Ca 2+ signals originated from intracellular pools, whereas in OW cells they were generated predominantly by Ca 2+ -influx from medium. Finally, we found correlation between leptin induced superoxide anion generation and Ca 2+ signals. The disturbed [Ca 2+ ] i homeostasis in OW monocytes was fully restored in the presence of fluvastatin. Statins have pleiotropic effects involving the inhibition of free radical generation that may account for its beneficial effect on elevated [Ca 2+ ] i and consequently on the pathomechanism of obesity.

Background. Human paraoxonase-1 (PON1) has also been described as a lactonase. Decreased PON1 lactonase activity was found to be a predictor of cardiovascular disease. Homocysteine thiolactonase activity may prevent proteins from homocysteinylation and is thought to be a protective factor against the progression of atherosclerosis. Previous studies have demonstrated decreased PON1 paraoxonase activity in hemodialyzed (HD) and renal transplant (TRX) patients; however, lactonase activity has not been investigated. We aimed to determine the paraoxonase and lactonase activities and to clarify the relationship between lactonase activity and a set of cardiovascular risk factors, such as homocysteine, cystatin C and asymmetric dimethylarginine (ADMA) levels, in HD and TRX patients and in healthy controls. Methods. One hundred and eight HD and 78 TRX patients and 63 healthy controls were involved in the study. Paraoxonase and lactonase activities (paraoxon and gamma-thiobutyrolactone as substrates) were measured spectrophotometrically. ADMA level was determined with sandwich enzyme-linked immunosorbent assay. Results. Both HD and TRX patients had significantly lower lactonase activities compared to the control group (P < 0.05). Significantly lower paraoxonase activities were found in HD patients compared to the TRX group (P < 0.05). Significant negative correlation was found between lactonase activity and ADMA level in the whole study population (P < 0.001), while paraoxonase and lactonase activities showed significant positive correlation (P < 0.001). Multiple regression analysis identified paraoxonase activity and homocysteine level as independent predictors of lactonase activity. Conclusion. Lactonase activity is a potential new predictor of cardiovascular risk in renal failure. Measurement of lactonase activity is recommended in future studies on HD and TRX patients.

The prevalence of obesity is increasing in adult and child populations throughout the world. Childhood obesity has a great impact on adult cardiovascular morbidity and mortality; treatment of this pathological state is important given the significant health consequences. We investigated the effect of short-term lifestyle changes on the alteration of human serum paraoxonase-1 (PON1) activities, leptin, adiponectin, E-selectin, and asymmetric dimethylarginine (ADMA) as atherogenic and antiatherogenic factors in obese children. PON1 protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low density lipoprotein (LDL) and therefore may protect against atherosclerosis.A total of 23 white obese and overweight children (age, 11.43 ± 1.78 years; 8 girls, 15 boys) participated in a 2-week-long lifestyle camp based on a diet and exercise program. Overweight and obesity were defined according to the national body mass index (BMI) reference tables for age and sex.After a 2-week-long supervised diet and aerobic exercise program, obese children had significantly lower leptin (55.02 ± 33.42 ng/ml vs 25.37 ± 19.07 ng/ml; p0.0001), ADMA (0.68 ± 0.15 μmol/l vs 0.55 ± 0.16 μmol/l; p0.01), and E-selectin levels (67.19 ± 30.35 ng/ml vs 46.51 ± 18.40 ng/ml; p0.0001), whereas they had significantly higher PON1 paraoxonase activity (110.48 ± 72.92 U/l vs 121.75 ± 93.48 U/l; p0.05) besides the antiatherogenic alteration of the lipid profile and significant weight change (70.32 ± 19.51 kg vs 67.01 ± 18.75 kg, p0.0001; BMI, 28.95 ± 5.05 kg/m(2) vs 27.43 ± 4.82 kg/m(2), p0.0001). Adiponectin and PON1 arylesterase activity did not change significantly.Our investigation suggests that modifications in dietary habits and physical activity induce antiatherogenic changes in childhood obesity. These findings emphasize the major role of primary prevention and nonpharmaceutical treatment of childhood obesity through lifestyle changes based on diet and increased physical activity.

Objective.Studies indicate that ankylosing spondylitis (AS), as well as rheumatoid arthritis, may be associated with accelerated atherosclerosis and vascular disease. We assessed endothelial dysfunction, carotid atherosclerosis, and aortic stiffness in AS in context with clinical and laboratory measurements.Methods.Forty-three patients with AS and 40 matched healthy controls were studied. We assessed common carotid intima-media thickness (ccIMT), flow-mediated vasodilation (FMD), and pulse-wave velocity (PWV) in association with age, disease duration, smoking habits, body mass index, patient’s assessment of pain and disease activity, Bath AS Disease Activity Index, Bath AS Functional Index (BASFI), metric measurements, erythrocyte sedimentation rate, C-reactive protein, and HLA-B27 status.Results.We found impaired FMD (6.85 ± 2.98% vs 8.30 ± 3.96%; p = 0.005), increased ccIMT (0.65 ± 0.15 vs 0.54 ± 0.15 mm; p = 0.01), and higher PWV (8.64 ± 2.44 vs 8.00 ± 1.46 m/s; p = 0.03) in patients with AS compared to controls, respectively. We also found that ccIMT negatively correlated with FMD (r = −0.563; p = 0.0001) and positively correlated with PWV (r = 0.374; p = 0.018). Both ccIMT and PWV correlated with disease duration (r = 0.559; p = 0.013 and r = 0.520; p = 0.022, respectively), BASFI (r = 0.691; p = 0.003 and r = 0.654; p = 0.006), decreased lumbar spine mobility (r = −0.656; p = 0.006 and r = −0.604; p = 0.013), chest expansion (r = −0.502; p = 0.047 and r = −0.613; p = 0.012), and increased wall-occiput distance (r = 0.509; p = 0.044 and r = 0.614; p = 0.011).Conclusion.In this well characterized AS population, impaired FMD and increased ccIMT and PWV indicate abnormal endothelial function and increased atherosclerosis and aortic stiffness, respectively. The value of noninvasive diagnostic tools needs to be further characterized.

Background: Altered secretion of adipokines and non-esterified fatty acid (NEFA) seems to play a pivotal role in the abdominal obesity-related insulin resistance (IR). Aim: To determine semi-quantitatively the impact of serum NEFA, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin, and resistin levels on IR measured by homeostasis model assessment (HOMA-IR). Material/subjects: Seventy-four Caucasian subjects forming 3 age-, and sex-matched groups were included into the study [Group 1 and 2: non-diabetic obese patients, no.= 25, body mass index (BMI): 28–39.9 kg/m2, no.=25, BMI≥40 kg/m2, respectively, and Group 3: 24 healthy, normal weight control subjects]. Methods: Serum levels of NEFA and adipokines as well as other metabolic variables including HOMA-IR were measured. Results: HOMA-IR was associated positively with BMI, waist circumference, serum NEFA, leptin, IL-6, and TNF-α levels, negatively with adiponectin, with no significant relation to resistin. In multiple regression analyses, of these factors leptin was a strong, IL-6 and adiponectin were weak independent predictors of HOMA-IR, while the others were not significant determinants of HOMA-IR. However, even together, they explained only 35–36% of variance of HOMA-IR. Conclusions: Although IR has associations with many of the investigated parameters, of these, only serum level of leptin, and in lesser degree IL-6 and adiponectin are independent determinants of the severity of IR. Moreover, even together they explain only a minority of variance IR.