Alteration of HDL functionality and PON1 activities in acute coronary syndrome patients

ObjectiveThe functionality of HDL has been suggested as an important factor in the prevention of cardiovascular and coronary artery diseases. The objective of the present study was to investigate the functionality of HDL and the factors that may affect the anti-atherogenic properties of HDL in ACS patients.Methods and resultsOne hundred healthy subjects and 205 ACS patients were recruited. HDL functionality was evaluated by measuring their capacity to mediate cholesterol efflux from J774 macrophages. Oxidative stress status was determined by measuring plasma malondialdehyde (MDA), protein carbonyl, and vitamin E levels by HPLC. The PON1 Q192R polymorphism status and PON1 paraoxonase and arylesterase activities of the healthy subjects and ACS patients were also determined. The HDL of ACS patients displayed a limited capacity to mediate cholesterol efflux, especially via the ABCA1-pathway. MDA (7.06 ± 0.29 μM) and protein carbonyl (9.29 ± 0.26 μM) levels were significantly higher in ACS patients than in healthy subjects (2.29 ± 0.21 μM and 3.07 ± 0.17 μM, respectively, p < 0.0001), while α- and γ-tocopherol (vitamin E) levels in ACS patients were 8-fold (p < 0.001) and 2-fold (p < 0.05) lower than in healthy subjects. Paraoxonase, arylesterase and HDL-corrected PON1 activities (PON1 activity/HDL ratio) were significantly lower in ACS patients. Logistic regression analyses showed that high PON1 paraoxonase and arylesterase activities had a significant protective effect (OR = 0.413, CI 0.289–0.590, p < 0.001; OR = 0.232 CI 0.107–0.499, p < 0.001, respectively) even when adjusted for HDL level, age, BMI, and PON1 polymorphism.ConclusionThe results of the present study showed that the functionality of HDL is impaired in ACS patients and that the impairment may be due to oxidative stress and an alteration of PON1 activities.     

Paraoxonase activity in athletes with depleted iron stores and iron-deficient erythropoiesis

ObjectiveThe aim of this study was to evaluate how conditions that precede anaemia (iron store depletion and iron-deficient erythropoiesis) affect human serum paraoxonase PON1 activity.Design and methodsBased on haemoglobin, transferrin saturation and serum ferritin values 119 athletes were divided into three groups: with iron depletion, with deficient erythropoiesis and controls. The following parameters were measured: paraoxonase activity towards paraoxon (POase) and diazoxon (DZOase), lipid hydroperoxides (LOOH), the pro-oxidant-antioxidant balance (PAB), red blood cells (RBC) and lipid status.ResultsSignificant differences were found between athletes with different stages of iron deficiency and controls with respect to PON 1 activity and oxidative stress status parameters (Wilks' Lambda = 0.712, F = 5.241, p < 0.001, η² = 0.156). There was no significant difference between the PON1 192 Q and R polymorphism distribution in the two groups of athletes with different stages of iron deficiency and controls (χ² = 1.086; p = 0.896). PON1 activity was positively correlated with RBCs, haemoglobin, transferrin saturation (p < 0.001) and ferritin (p = 0.037) and negatively correlated with LOOH (p = 0.044) in all three study groups.ConclusionsDeficient erythropoiesis in athletes contributes to impaired PON1 activity. In contrast, iron depletion, regardless of increased oxidative stress, does not affect PON1 activity.     

A study on serum advanced glycation end products and its association with oxidative stress and paraoxonase activity in type 2 diabetic patients with vascular complications

ObjectivesEnhanced formation of advanced glycation end products (AGEs) formed secondary to hyperglycemic conditions has been linked to diabetes mellitus (DM) associated complications. We investigated the clinical relevance of estimating AGEs and their relationship with oxidative stress (OS) and paraoxonase (PON1) activity in type 2 DM (T2DM) in relation to development of vascular complications.Design and MethodsSerum AGEs along with PON1 activity, protein carbonyl (PCO), advanced oxidation protein products (AOPP), lipid peroxidation (MDA), and total thiol (T-SH) were determined in 157 T2DM patients (DM without complications n = 57, DM micro-vascular complications n = 53, DM macro-vascular complications n = 47) and 40 healthy controls.ResultsSerum AGE level increased significantly in various study groups in following manner: healthy control < DM without complications < DM-macro < DM-micro. Logistic regression analysis using diabetic complications as dependent variable showed significant association with AGE level and PON1 activity even after adjustment for confounding factors. Receiver-operating-characteristics curve analysis showed that 2-fold increased in glycation and 50% decrease in PON1 activity may lead to development of vascular complications in diabetic subjects. PCO, AOPP and MDA were higher and PON1 activity was lower in T2DM with complications than those without complications. Among diabetic patients AGEs showed significant positive correlation with HbA_1C, MDA, AOPP, and negative correlation with PON1 activity and T-SH.ConclusionHigh serum AGE concentration and low PON1 activity may be considered as additional risk factor for development of vascular complications in T2DM. AGE formation plays significant role in induction of OS in diabetes.     

Antioxidative enzymes and increased oxidative stress in depressive women

ObjectivesTo investigate the activities of the main antioxidative enzymes and oxidative stress in women with depressive disorder (DD).MethodsIn 35 drug-naive women with DD and 35 age matched healthy women enzymes superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPX1), glutathione reductase (GR) and paraoxonase (PON1), concentrations of conjugated dienes (CD), reduced glutathione (GSH) and anthropometric and clinical data were investigated.ResultsWomen with DD were found to have decreased activities of GPX1 (p < 0.05), decreased concentrations of GSH (p < 0.05), and increased activities of GR (p < 0.05), CuZnSOD (p < 0.001), and concentrations of CD (p < 0.05). Activity of GPX1 was positively correlated with concentration of GSH (p < 0.05). Concentrations of CD were positively correlated with TG (p < 0.01).ConclusionOur set of depressive women was characterized by changes indicating an increased oxidative stress, as well as by certain features of metabolic syndrome.     

High density lipoprotein-anionic peptide factor effect on reverse cholesterol transport in type 2 diabetic patients with and without coronary artery disease

ObjectivesTo verify if HDL3 Anionic Peptide Factor (HDL3-APF) is as an apolipoprotein that promotes the reverse cholesterol transport.Design and methodsWe investigated a possible association between plasma HDL3-APF concentration, cholesterol efflux from Fu5AH cells and cholesteryl ester transfer protein (CETP) activity in type 2 diabetic patients with coronary artery disease (CAD) (n = 36), those without CAD (n = 20), and 37 healthy subjects.ResultsPlasma APF concentrations were decreased in diabetics with CAD compared to controls (p < 0.01). Cellular cholesterol efflux was decreased in diabetics without and with CAD, (p < 0.01 and p < 0.001 respectively). CETP activity was significantly elevated in all patient groups. Multiple linear regression analysis shows that cholesterol efflux was independently and positively related only to APF concentrations in controls.ConclusionsAPF is likely to be a key independent factor for promoting cellular cholesterol efflux in healthy subjects. However this association is altered in type 2 diabetes.     

Increased large VLDL and small LDL particles are related to lower bilirubin in Type 2 diabetes mellitus

ObjectivesBilirubin may protect against atherosclerotic cardiovascular disease by virtue of its anti-oxidative properties, but lower bilirubin may also be associated to atherogenic lipoprotein abnormalities. We determined associations of plasma (apo)lipoproteins and lipoprotein subfractions in subjects with and without type 2 diabetes mellitus (T2DM).Design and methodsPlasma (apo)lipoproteins, lipoprotein subfractions (nuclear magnetic resonance spectroscopy) and serum total bilirubin levels were determined in 53 T2DM patients and in 53 non-diabetic subjects.ResultsTriglycerides, large VLDL, small LDL and small HDL particles were increased (all p < 0.05), whereas HDL cholesterol, apoA-I and large HDL particles were decreased (all p < 0.05), coinciding lower bilirubin levels in T2DM (p < 0.001). In age- and sex-adjusted analysis, total cholesterol, non-HDL cholesterol, triglycerides, apoB, apoE, large VLDL and small LDL were negatively correlated with bilirubin, but HDL cholesterol was positively correlated with bilirubin in T2DM (p < 0.05 to p < 0.001). Multivariable linear regression analyses demonstrated that in all subjects combined total cholesterol, non-HDL cholesterol, triglycerides and apoE were negatively associated with bilirubin after adjustment for age, sex, T2DM, body mass index and alanine aminotransferase (all p < 0.05). Further multivariable linear regression analysis showed that large VLDL and small LDL particles were negatively associated with bilirubin, whereas large HDL particles were associated positively with bilirubin (p < 0.05).ConclusionsIncreased triglycerides, as well as large VLDL and small LDL particles are associated negatively, whereas HDL cholesterol is associated positively with bilirubin in T2DM. The proposed pro-atherogenic effects of low bilirubin could in part be attributed to relationships with abnormalities in (apo)lipoproteins and lipoprotein subfraction characteristics.     

CYP1A1, CYP1A2 and CYBA gene polymorphisms associated with oxidative stress in COPD

BackgroundThe genetic susceptibility to chronic obstructive pulmonary disease (COPD) depends on detoxification and antioxidant enzymes, which detoxify cigarette smoke reactive components that, otherwise, generate oxidative stress.MethodsIn a case–control study of 346 subjects with and without COPD, we examined the polymorphisms 462Ile/Val, 3801T/C of CYP1A1, ?3860G/A of CYP1A2 and ?930A/G, 242C/T of CYBA individually or in combination and their contribution to oxidative stress markers by measuring malondialdehyde (MDA), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx).ResultsCOPD patients had significantly increased MDA concentration (p < 0.001) and decreased CAT activity, GSH concentration, GPx activity (p ≤ 0.01). The patients were over-represented by the alleles 462Val, 3801C of CYP1A1 and ?930G, 242C of CYBA (p < 0.001, p = 0.003, p = 0.030 and p = 0.031, respectively) and consequently the haplotypes of same alleles i.e. 462Val:3801C, 462Val:3801T and ?930G:242C (p = 0.048, p = 0.016 and p = 0.039, respectively). Similarly, CYP1A1 and CYP1A2 haplotypes, 462Val:3860G and 462Val:3801T:3860G were significantly over-represented (p = 0.001 and p = 0.003), respectively in patients. The same alleles-associated genotype-combinations between genes were more prevalent in patients. Of note, the genotypes, 462Ile/Val+Val/Val, 3801TC+CC of CYP1A1 and ?930AG+GG of CYBA associated with increased MDA concentration (p = 0.018, p = 0.045 and p = 0.017, respectively), decreased CAT activity (p < 0.0001, p = 0.080 and p < 0.0001, respectively) and GSH concentration (p < 0.0001, p = 0.0002 and p = 0.011, respectively) in patients.ConclusionThe identified alleles, its haplotypes and the genotype-combination along with increased oxidative stress, signify the importance in susceptibility to COPD.     

Association of oxidative stress and paraoxonase status with PROCAM risk score

ObjectivesOxidative stress and paraoxonase activity play a significant role in the pathogenesis of cardiovascular disease (CVD). The Prospective Cardiovascular Münster (PROCAM) study evaluated the prevalence of CVD risk factors and postulated the prediction of future CVD events. We therefore investigated the association between plasma markers of oxidative stress and paraoxonase status with PROCAM risk score.Design and methodsOxidative stress status parameters [lipid peroxidation measured as thiobarbituric acid-reacting substances (TBARS), superoxide anion (O₂^?), superoxide dismutase (SOD) activity, total sulphydryl group content] and paraoxonase (PON1) status were assessed in 211 participants. The predicted 10-year risk was calculated according to the PROCAM algorithm.ResultsAs expected subjects with high PROCAM risk score (high CVD risk) had significantly higher concentrations of oxidative stress parameters (TBARS and O₂^? P < 0.001 and P < 0.05, respectively). The PON1₁₉₂ phenotype distribution among CVD risk groups was not significantly different. Logistic regression analyses revealed significant associations of all the examined oxidative stress status parameters with calculated CVD risk score. The potential of the parameters for CVD risk prediction was tested via multivariate analysis. Only the O₂^? level retained a strong association with high CVD risk.ConclusionsOur study demonstrated that high PROCAM risk score is associated with increased oxidative stress, indicating for the first time that elevated O₂^? is independently associated with high CVD risk.     

The paraoxonase L55M and Q192R gene polymorphisms and myocardial infarction in a Tunisian population

ObjectivesIn the present study, we examined a possible association between the PON1 Q192R and L55M polymorphisms and myocardial infarction (MI) in a sample of the Tunisian population.Design and methodsThree hundred and ten patients with MI and 375 controls were recruited. Paraoxonase gene polymorphisms at codon 192 and 55 were analyzed by PCR-RFLP.ResultsGenotype distributions and allele frequencies of L55M were similar among the control and MI groups. For the Q192R polymorphism patients with MI had significantly higher frequency of the RR genotype compared to controls [17.1% vs. 10.9%; OR (95% CI), 1.93 (1.24–3.02); p = 0.004]. The MI patient group showed a significantly higher frequency of the R allele compared to the controls [38% vs. 30%; χ² = 10.74, p = 0.001]. The association between the PON1 Q192R polymorphism and MI remained significant after adjustment for other well-established cardiovascular risk factors.ConclusionsThe present study showed a significant and independent association between the PON1 Q192R polymorphism (presence of R allele) and MI in the Tunisian population.     

Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages after chemotherapy with 5-fluorouracil,doxorubicin and cyclophosphamide

ObjectivesBreast carcinoma is related to the increase of lipid peroxidation in plasma with concomitant decrease of antioxidant (AO) defense capacity in blood cells, which becomes more pronounced during aging of the patients. This work evaluated the potential age-related effect of chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) on the level of lipid hydroperoxides (LP), glutathione (GSH), AO enzyme activities of copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in breast cancer patients. The level of CuZnSOD protein was assessed after the FAC therapy and radiotherapy of breast cancer.Design and methodsAO parameters were measured in the blood of 58 breast cancer patients and 60 healthy age-matched healthy subjects by biochemical and Western blot analyses.ResultsIncreased oxidative stress (LP: p < 0.05) and decreased AO enzyme activities (CuZnSOD: p < 0.01, GPx: p < 0.05, GR: p < 0.01) and GSH level (p < 0.01) in the blood of breast cancer patients in response to FAC chemotherapy seem not to be age-dependent. CuZnSOD enzyme expression decreased after the FAC chemotherapy (p < 0.05), while it increased after the radiotherapy of breast cancer (p < 0.05).ConclusionFAC chemotherapy and radiotherapy promote further oxidative shift, which potentiate already existing chronic oxidative stress linked to breast cancer. In these effects, impaired capacity for H₂O₂ detoxification (CAT, GPX and GSH) seems to have major contribution.     

Increased serum oxidative stress in patients with severe mitral regurgitation: A new finding and potential mechanism for atrial enlargement

ObjectiveThe aim of this study was to examine the serum oxidative stress in patients with severe mitral regurgitation.Design and methodsThis study analyzed serum oxidative stress index in patients with severe mitral regurgitation [persistent atrial fibrillation (AF) or sinus rhythm], paroxysmal lone AF patients and healthy subjects.ResultsThe serum oxidative stress index was significantly higher in the mitral regurgitation AF group and sinus group than in the lone AF group and healthy subjects (p < 0.0001). Left atrial size was significantly larger in the mitral regurgitation AF group and sinus group than in the lone AF group and healthy subjects (p < 0.0001). The oxidative stress index significantly and positively correlated with left atrial size in the overall study population (r = 0.439, p = 0.0008).ConclusionsThis study provides new evidence of increased oxidative stress in human severe mitral regurgitation, probably contributing to atrial enlargement.     

Activity of paraoxonase 1 (PON1) on HDL2 and HDL3 subclasses in renal disease

IntroductionCardiovascular complications, as the main cause of mortality in renal patients, are followed with altered lipoproteins composition. Considering that paraoxonase-1 (PON1) is an anti-oxidative enzyme located mainly on HDL particles, the current study has aim to investigate whether failure of kidney function leads to changes in the distribution of PON1 activity between different HDL subclasses.Materials and methodsIn 77 renal patients (21 chronic kidney disease (CKD) and 56 end stage renal disease (ESRD) patients on dialysis) and 20 healthy subjects PON1 activity on HDL₂ and HDL₃ subclasses was determined by zymogram method that combines gradient gel electrophoresis separation of HDL subclasses and measurement of PON1 activity in the same gel.ResultsSerum paraoxonase (p<0.01) and arylesterase activity (p<0.001) of PON1 as well as its concentration (p<0.01) were significantly lower in CKD and ESRD patients compared to controls. Relative proportion of HDL₃ subclasses was higher in ESRD patients than in healthy participants, while HDL₂ subclasses was significantly decreased in CKD (p<0.05) and ESRD (p<0.001) patients, as compared to controls. Furthermore, control subjects had higher PON1 activity on HDL₂ (CKD and ESRD patients p<0.001) and HDL₃ (CKD p<0.05; ESRD patients p<0.001) subclasses in comparison with the both patients groups. Also, significant negative correlation was found between paraoxonase activity of PON1 in serum and creatinine concentration (ρ=‐0.373, p<0.01).ConclusionsThis study showed that altered HDL subclasses distribution, changed PON1 activities on different HDL subclasses as well as diminished anti-oxidative protection could be important factors in atherosclerosis development in CKD and ESRD patients.     

Relation between riboflavin,flavin mononucleotide and flavin adenine dinucleotide concentrations in plasma and red cells in patients with critical illness

BackgroundThere is some evidence that the relationship between plasma and red cell vitamin B2 concentrations is perturbed in the critically ill patient. The aim of the present study was to examine the longitudinal interrelationships between riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) in plasma and red cells in patients with critical illness.MethodsRiboflavin, FMN and FAD concentrations were measured, by HPLC, in plasma and red cells in healthy subjects (n = 119) and in critically ill patients (n = 125) on admission and on follow-up.ResultsOn admission, compared with the controls, critically ill patients had significantly higher plasma riboflavin and FMN concentrations (p < 0.001) and lower median plasma FAD concentrations (p < 0.001). In the red cell, FAD concentrations were significantly lower in critically ill patients (p < 0.001). In healthy subjects, plasma riboflavin was directly associated with both plasma FMN (r_s = 0.55, p < 0.001) and plasma FAD (r_s = 0.49, p < 0.001). Red cell riboflavin was directly associated with red cell FMN (r_s = 0.52, p < 0.001) but not red cell FAD. In the critically ill patients, plasma riboflavin was not significantly associated with either plasma FMN or FAD. Red cell riboflavin was directly associated with red cell FMN (r_s = 0.79, p < 0.001) and red cell FAD (r_s = 0.72, p < 0.001). Longitudinal measurements (n = 60) were similar.ConclusionsThe relationship between plasma riboflavin, FMN and FAD was significantly perturbed in critical illness. This effect was less pronounced in red cells. Therefore, red cell FAD concentrations are more likely to be a reliable measure of status in the critically ill patient.     

Assessment of paraoxonase activity and lipid peroxidation levels in diabetic and senile subjects suffering from cataract

Objectives:The purpose of this study was to evaluate antioxidant effect of paraoxonase 1 activity and malondialdehyde (MDA) levels as a marker of oxidative stress in patients suffering from cataract due to diabetes and aging.Design and methods:One hundred cataract patients (senile and diabetic) and age- and sex-matched controls were studied. Paraoxonase 1 and arylesterase activities in plasma samples were measured using paraoxon and phenylacetate as substrates, respectively. The magnitude of lipid peroxidation was established by measuring plasma MDA and oxidized low-density lipoprotein (ox LDL) levels. One-way ANOVA was employed for analysis of results.Results:We observed significantly lower plasma paraoxonase and arylesterase activities in senile and diabetic cataractous patients as compared to respective controls (p < 0.001). Plasma MDA and ox LDL levels were found to be higher in patients suffering from cataract (p < 0.001).Conclusions:The results of present study suggest that the observed decrease in PON1 activity may be due to increase in oxidative stress. It can be concluded that lower paraoxonase activity could contribute to the higher risk of cataract formation.     

Proatherogenic disturbances in lipoprotein profile,associated enzymes and transfer proteins in women with iron deficiency anaemia

ObjectiveTo characterize the lipid-related atherogenic risk factors in iron deficiency anaemia (IDA) patients.Design and methodsTwenty IDA women were compared to healthy age-matched controls. Lipoprotein profile, cholesteryl ester transfer protein (CETP), paraoxonase (PON) 1 and lipoprotein-associated phospholipase A₂ (LpPLA₂) activities and plasma levels of oxidized-LDL were evaluated.ResultsTriglycerides were higher (median [range]) (1.0 [0.5–1.9] vs. 0.7 [0.5–1.5] mmol/L, p < 0.05) and HDL-C lower (mean ± SD) (1.3 ± 0.3 vs. 1.6 ± 0.4 mmol/L, p < 0.01) in the patients group. CETP (197 ± 29% vs. 151 ± 29% mL^? 1 h^? 1, p < 0.001), PON 1 (122 ± 17 vs. 140 ± 33 μmol mL^? 1 min^? 1, p < 0.05) and LpPLA₂ (9.6 ± 2.0 vs. 8.1 ± 1.7 μmol mL^? 1 h^? 1, p < 0.05) activities were different in IDA women. No difference was observed in oxidized-LDL. Haemoglobin correlated negatively with triglycerides (r = ? 0.35, p < 0.05), CETP (r =  ?  0.62, p < 0.001) and LpPLA₂ (r =  ?  0.34, p < 0.05), while ferritin was positively associated with HDL-C (r =  0.39, p < 0.05) and inversely with CETP (r =  ?  0.49, p < 0.005).ConclusionThe alterations in lipoprotein profile, CETP, PON 1 and LpPLA₂ activities described in the present study indicate that non-treated IDA might represent a proatherogenic state.     

Oxidative stress and myeloperoxidase activity during bacterial meningitis: Effects of febrile episodes and the BBB permeability

ObjectiveTo investigate participation of extracellular myeloperoxidase (MPO) in oxidative stress during different courses of the bacterial meningitis (BM).Materials and methodsWe sequentially assessed WBC count, blood-brain barrier (BBB) permeability, serum and cerebrospinal fluid (CSF) lipid peroxidation (LPO), MPO and antioxidative activity (AOA) in proven pediatric BM.ResultsBM patients exhibited increased systemic and local LPO and MPO, and reduced AOA, which was exaggerated in the febrile episodes. Serum MPO and LPO products were related to the BBB permeability at the baseline. CSF hydroperoxide level was influenced by the BBB permeability, CSF albumin concentration, and serum hydroperoxide (r = 0.502; p < 0.001, and r = 0.611; p < 0.001, and r = 0.358; p < 0.001, respectively). CSF hydroperoxide and MPO correlated in complicated cases during the study.ConclusionsThese results suggest that CSF LPO and MPO were closely related in BM, had different courses if febrile episodes had occurred, but were partly influenced by the BBB permeability.     

Dysregulation of TH type cytokines in the patients of Parthenium induced contact dermatitis

BackgroundParthenium contact dermatitis is a major health problem caused by a cosmopolitan weed Parthenium hysterophorus. It is a T cell-mediated immune injury and disease manifests as itchy erythematous papules, papulovesicular and plaque lesions on exposed areas of the body. We studied the involvement of T_H1/T_H2/T_H17/Treg type responses by assaying various cytokines in Parthenium dermatitis.MethodsThe study includes 50 patients of Parthenium dermatitis confirmed by patch testing and 50 healthy subjects. The serum levels of T_H1, T_H2, T_H17 and Treg cytokines were estimated by high sensitivity sandwich ELISA and were compared statistically between groups using ANOVA.ResultsThe mean concentration of T_H1 cytokines (p < 0.001) and IL-17 (p < 0.001) were increased significantly as compared to controls. In contrast, decrease in levels of IL-10 (p < 0.002) and TGF-β (p < 0.001) were significant and levels of IL-4 (p < 0.262) were insignificant whereas no alterations in the total IgE concentrations (p < 0.976) was observed.ConclusionThe induction of T_H1 and T_H17 cytokines reinforce the need of detailed analysis of immune dysregulation in Parthenium dermatitis and might add some insight in the pathogenesis, diagnosis and current treatment modalities of this disease.     

Effects of V279F in the Lp-PLA2 gene on markers of oxidative stress and inflammation in Koreans

BackgroundA single nucleotide polymorphism (SNP), V279F, in the lipoprotein-associated phospholipase A₂ (Lp-PLA₂) gene is known to influence enzyme activity. It is unclear whether Lp-PLA₂ exerts pro- or antiatherogenic effects in humans. We investigated the interplay between V279F, Lp-PLA₂ activity, oxidative stress and inflammation.MethodsWe genotyped 2914 healthy Koreans (43–79 years) for the Lp-PLA₂ V279F and measured anthropometric parameters, lipid profile, fatty acid composition, lipid peroxides, inflammatory markers and Lp-PLA₂ levels.ResultsLp-PLA₂ activity was 24% lower in V/F subjects (n = 641) than in those with the V/V genotype (n = 2227). Enzyme activity was undetectable in F/F subjects. Lp-PLA₂ activity was positively correlated with LDL-cholesterol (r = 0.134, P < 0.001), ox-LDL (r = 0.064, P < 0.01), 8-epi-PGF_2α (r = 0.198, P < 0.001), free fatty acid (r = 0.082, P < 0.001), and fibrinogen (r = 0.112, P < 0.01) levels. Additionally, ox-LDL, 8-epi-PGF_2α, free fatty acid, and fibrinogen levels were positively correlated with hs-CRP. V279F was associated with LDL-cholesterol and arachidonic acid (AA) in serum phospholipid. F/F subjects had lower LDL-cholesterol than V/V subjects (V/V: 120.9 ± 0.69, V/F: 119.4 ± 1.26, F/F: 109.2 ± 4.84 mg/dl, P = 0.025). A significant association between the F/F genotype and increasing AA in serum phospholipids was found in subjects with high LDL-cholesterol (≥ 130 mg/dl) (P = 0.003) but not in those with low LDL-cholesterol (< 130 mg/dl). F/F subjects in the high LDL-cholesterol group had CRP concentrations about three times higher than those with V/V or V/F genotypes (V/V: 1.25 ± 0.09, V/F: 0.97 ± 0.12, F/F: 3.20 ± 0.88 mg/dl, P < 0.001).ConclusionsThe recessive effects of Lp-PLA₂ V279F on LDL-cholesterol and significant correlations between Lp-PLA₂ activity and LDL-cholesterol, 8-epi-PGF_2α and fibrinogen support a pro-oxidative or pro-atherogenic role for this enzyme. Paradoxically, the combination of the complete deficiency of Lp-PLA₂ activity and high LDL-cholesterol enhanced lipid peroxidation and inflammation.     

Self-reported physical activity behaviour; exercise motivation and information among Danish adult cancer patients undergoing chemotherapy

BackgroundPhysical activity is considered an important and determining factor for the cancer patient's physical well-being and quality of life. However, cancer treatment may disrupt the practice of physical activity, and the prevention of sedentary lifestyles in cancer survivors is imperative.PurposeThe current study aimed at investigating self-reported physical activity behaviour, exercise motivation and information in cancer patients undergoing chemotherapy.Methods and sampleUsing a cross-sectional design, 451 patients (18–65 years) completed a questionnaire assessing pre-illness and present physical activity; motivation and information received.ResultsPatients reported a significant decline in physical activity from pre-illness to the time in active treatment (p < 0.001). Amongst the respondents, 68% answered that they believed exercise to be beneficial; and 78% claimed not exercising as much as desired. Exercise barriers included fatigue (74%) and physical discomfort (45%). Present physical activity behaviour was associated with pre-illness physical activity behaviour (p < 0.001), exercise belief (p < 0.001), and diagnosis (p < 0.001). More patients <40 years than patients >40 years (OR 0.36, p < 0.001); more men than women (OR 2.12, p < 0.001); and more oncological than haematological patients (OR 0.41, p < 0.001) stated being informed about physical activity. Moreover patients who claimed to have been informed about exercise were more in agreement with being able to exercise while undergoing chemotherapy (OR 1.69, p = 0.023).ConclusionsThis study suggests that Danish adult cancer patients in chemotherapy experience a significant decline in physical activity behaviour. Results indicate a general positive interest in physical activity amongst the patients, which however may be only suboptimally exploited.     

Protein oxidation biomarkers in plasma of type 2 diabetic patients

ObjectivesTo evaluate oxidative stress and the extent of oxidation of plasma proteins in type 2 diabetic patients.Design and methodsStudy was carried out on blood from 31 diabetic patients of both sexes (mean age = 58 ± 7; duration of diabetes 12 ± 5 years) and healthy age and sex matched normal subjects. Biomarkers of protein oxidation; plasma protein carbonyls (PCO), advanced oxidation protein products (AOPPs) and –SH group and free radical scavenging capacity of plasma was measured.ResultsPCO and AOPPS levels were significantly (P < 0.005) higher in diabetic patients in comparison to healthy volunteers. Reduced free radical scavenging capacity (P < 0.001) and –SH group (P < 0.05) was observed in plasma of type 2 diabetic patients.ConclusionsOur data suggest that diabetics are susceptible to protein oxidation. Oxidative modulation of proteins due to reduced radical scavenging activity of plasma patients may be one of the reasons of altered physiological processes in type 2 diabetic patients.