Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome

BackgroundIt is not elucidated if liver fat deposits associated to metabolic syndrome (MS) aggravate the atherogenic state. We evaluated, in MS patients, if the presence of non-alcoholic hepatic steatosis (HS) determines differences in inflammatory markers and VLDL characteristics.MethodsSeventy-five patients with MS were divided into 2 groups depending on the presence or absence of HS, assessed by ultrasound. Lipid profile, free fatty acids (FFA), VLDL composition, adiponectin, tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), and soluble adhesion molecules (sVCAM-1 and sICAM-1) were measured.ResultsHS patients presented increased triglycerides levels, HOMA-IR and FFA. Patients with HS showed a reduction in adiponectin (p = 0.04) and increase in hs-CRP (p = 0.02), independently of insulin-resistance (IR). FFA correlated positively with TNF-α (p = 0.04) and inversely with adiponectin (p = 0.01). hs-CRP correlated with all inflammatory markers, independently of IR: TNF-α (r = 0.34, p = 0.02), sVCAM-1 (r = 0.29 p = 0.03), sICAM-1 (r = 0.56, p = 0.01), adiponectin (r = ?0.34, p = 0.04). HS patients presented higher VLDL mass and number of particles. Adiponectin correlated with VLDL cholesterol content (r = ?0.47, p = 0.04), independently of IR. VLDL, once secreted, would suffer from changes, becoming more atherogenic.ConclusionsSimple HS would play an important role increasing cardiovascular risk, independently of IR. hs-CRP may represent a useful biomarker of this condition.     

Cytokine elevations in acute coronary syndrome and ovarian cancer: a mechanism for the up-regulation of the acute phase proteins in these different disease etiologies

Objectives:To identify if a common set of cytokines is elevated in both ovarian cancer and acute coronary syndrome (ACS).Design and methods:A cytokine array (Randox Ltd) was measured in healthy women (n = 33), women with ACS (n = 21) and ovarian cancer (n = 45).Results:Women with ACS or ovarian cancer had higher concentrations of IL-6, IL-8, VEGF, MCP-1, and EGF as compared to healthy volunteers.Discussion:Common cytokine elevations are present in both ACS and ovarian cancer.     

Serum soluble Fas levels in patients with autoimmune rheumatic diseases

Objective:The role of the serum soluble Fas (sFAS) system is unclear in diagnosis of several autoimmune rheumatic diseases although there are present contradictory reports on the levels of serum sFas. We therefore assessed levels of sFAS in serum of patients with autoimmune rheumatic diseases.Patients and methods:We analyzed sFas levels and their relationship to clinical and laboratory data in patients with systemic lupus erythematosus (SLE, n = 32), rheumatoid arthritis (RA, n = 28), Sjögren's syndrome (SS, n = 20) systemic sclerosis (SSc, n = 21), polymyositis/dermatomyositis (PM/DM, n = 15). Patients with osteoarthritis (OA, n = 20) and healthy volunteers (n = 20) were used as controls. Serum levels of sFAS were determined by ELISA. sFas levels greater than mean (normals) + 2 SD were considered as elevated.Results:The mean sFas values were found higher in RA, PM/DM and OA than in control although no differences were found in SSc and SS patients. The mean sFas levels in SLE patients were lower than healthy controls. Elevated sFas rates in RA, PM/DM and SS were found to be 21.4%, 60%, 10% higher than in healthy controls, respectively. sFas levels in SLE and SSc did not differ from control values. Mean sFas levels did not show significant difference between active and inactive patients in all disease groups except PM/DM, RA and OA. No correlations of sFas with relevant disease subsets, laboratory findings and treatment modalities were found.Conclusions:The findings indicate that the serum sFas molecule may provide a useful additional marker for presence and assessment of disease in patients with RA and PM/DM.     

Paraoxonase/arylesterase ratio, PON1 192Q/R polymorphism and PON1 status are associated with increased risk of ischemic stroke

Objectives:In recent years, importance of enzyme activity measurements, in addition to genotyping, in epidemiological studies relating paraoxonase 1 (PON1) and vascular disease was emphasized. This is the first report evaluating paraoxonase and arylesterase activities as risk factors for ischemic stroke. In addition, PON1 192Gln(Q)/Arg(R) and 55Leu(L)/Met(M) polymorphisms were also analyzed.Design and methods:The study population was comprised of 108 ischemic stroke patients and 78 controls. Enzyme activities were determined by spectrophotometric assays and for genotyping, standard PCR protocols followed by restriction enzyme digestions were used.Results:The prevalence of the PON1 192RR genotype was increased among stroke patients (16.7%) as compared to controls (9.0%, P = 0.129). Paraoxonase and arylesterase activities and PON1 activity ratio (paraoxonase/arylesterase) were found to be lower in patients than in controls. Logistic regression analysis revealed PON1 activity ratio (odds ratio, OR = 0.697, 95% CI, 0.541 to 0.898, P = 0.005), PON1 192RR genotype (OR = 3.434, 95% CI, 1.159 to 10.178, P = 0.026) and PON1 status (PON1 activity ratio combined with PON1 192RR genotype; OR = 1.406, 95% CI, 1.038 to 1.905, P = 0.028) as significant predictors of stroke.Conclusions:This study identified PON1 activity ratio, PON1 192RR genotype and PON1 status as important risk factors for ischemic stroke.     

Changes of serum adhesion molecules and cytokines in post-ERCP pancreatitis: Adhesion molecules and cytokines in acute pancreatitis

ObjectivesTo assess the early changes of soluble IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-α, TNF-β, IL-17A, IL-22, soluble (s) P-Selectin, sE-Selectin and sICAM-1 in post-ERCP pancreatitis (PEP).MethodsSingle center, prospective study of 318 ERCP procedures. Serum samples were acquired from all patients prior to ERCP, 6 hours and 24 hours after the procedure. For every PEP case, another patient was chosen as a control, matched for gender, age and time period in which ERCP took place.ResultsTotally, 28 cases and 28 controls were studied. Except for significantly higher IL-1b levels in cases at baseline, no significant differences were observed between cases and controls after Bonferroni corrections. An increase in IL-6 was noted between baseline and 6 h in cases alone (p = 0.016). There was a significant fall in sP-selectin levels at 6 and 24 hours compared to baseline in all patients (corrected p = 0.008 and 0.016 for cases and 0.016 and 0.048 for controls respectively). An increase of sE-selectin in cases was observed between 6 and 24 hours post-ERCP (corrected p = 0.03).ConclusionsSoluble forms of cytokines and adhesion molecules studied seem not to play a major role in PEP.     

Measurement of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 after delayed separation of whole blood samples

Objectives:Epidemiological studies benefit from unbiased blood specimens collected with minimal cost and effort of blood collection and storage. We evaluated the stability of IGF-1 and IGFBP-3 in whole blood samples stored at room temperature to justify delays in blood processing.Design and methods:Total IGF-1 and IGFBP-3 levels were measured in EDTA plasma (n = 12), heparin plasma (n = 12) and serum (n = 10) samples of healthy volunteers after blood processing delays up till 14 days. Stability of measured IGF-1 and IGFBP-3 levels was tested by paired t-test and a linear mixed effect model.Results:Longitudinal analysis showed that IGF-1 levels were not significantly affected by blood processing delays in EDTA tubes (p = 0.18) and IGFBP-3 levels were marginally stable (p = 0.06). In heparin plasma and serum, however, IGF-1 increased over time of delayed processing and IGFBP-3 levels tended to decrease (p < 0.01).Conclusion:Total IGF-1 and IGFBP-3 levels are stable in whole blood collected in EDTA tubes at room temperature up till 7 days, allowing a delay in blood processing to reduce costs in large multi-center studies.     

Lipid, protein, DNA oxidation and antioxidant status in rheumatoid arthritis

ObjectivesTo investigate lipid, protein, DNA oxidation and antioxidant status in blood and synovial fluid of rheumatoid arthritis (RA) patients and to determine the importance of oxidative stress parameters in reflecting disease activity.Design and methods20 RA patients and 15 healthy controls were included. Lipid peroxidation (thiobarbituric acid reactive substances (TBARS), lipid hydroperoxide, and conjugated diene), protein oxidation (carbonyl and thiol), DNA oxidation (8-OHdG) and antioxidant status markers (glutathione (GSH), glutathione peroxidase (GSH Px), superoxide dismutase (CuZn SOD), and catalase) were determined in blood and synovial fluid.ResultsTBARS (p < 0.001), lipid hydroperoxide (p < 0.001), conjugated diene (p < 0.001), carbonyl (p < 0.001) and 8-OHdG (p < 0.01) levels were significantly higher; thiol (p < 0.01) and GSH levels (p < 0.01) and GSH Px (p < 0.001) and CuZn SOD (p < 0.01) activities were significantly lower in blood of RA patients. TBARS (p < 0.001), lipid hydroperoxide (p < 0.001), conjugated diene (p < 0.01), carbonyl (p < 0.001) and 8-OHdG (p < 0.05) levels were significantly higher, catalase activity (p < 0.001) significantly lower in synovial fluid of RA patients.ConclusionsIncreased lipid, protein and DNA oxidation markers and impaired antioxidant status confirm the role of oxidative stress in the pathogenesis of RA. Lipid peroxidation markers can serve as surrogate markers for disease activity.     

Butyrylcholinesterase activity is reduced in haemodialysis patients: Is there association with hyperhomocysteinemia and/or oxidative stress?

Objectives:To quantify serum butyrylcholinesterase activity in haemodialysis patients and to evaluate if the homocysteine levels and/or oxidative stress biomarkers have an effect on butyrylcholinesterase.Materials and methods:Blood samples were collected from patients and healthy subjects (control). The plasma homocysteine and TBARS levels; serum butyrylcholinesterase activity; blood δ aminolevulinic acid dehydratase (ALA-D) activity and methahaemoglobin were analyzed. The mortality of the patients was also evaluated after 3 years.Results:The homocysteine was increased and butyrylcholinesterase decreased compared to control (p < 0.05). TBARS and methahaemoglobin were increased and ALA-D decreased (p < 0.05). The following correlations were found: homocysteine with butyrylcholinesterase (? 0.44); methahaemoglobin (0.41); ALA-D (? 0.68); and TBARS (0.66). The partial correlation between homocysteine with butyrylcholinesterase, withdrawn the effect of TBARS, was ? 0.30; all p < 0.05. Moreover, it was observed that 22% of the patients died due to cardiovascular problems.Conclusion:Thus, our findings support a direct association between the reduction of butyrylcholinesterase by the increase of homocysteine and an indirect effect by increase in oxidative stress.     

Plasma resistin levels are associated with homocysteine,endothelial activation,and nitrosative stress in obese youths

ObjectiveTo evaluate whether serum resistin levels are related to cardiovascular risk in obese children.Design and methodsCross-sectional study of 110 children (40 normal weight and 70 severely obese). Clinical and biochemical parameters, including lipid profile, fasting glucose and insulin, and homocysteine, were determined. The levels of adipokines (adiponectin, leptin, and resistin), markers of inflammation (high-sensitivity C-reactive protein (hs-CRP)), endothelial activation (serum concentrations of soluble intercellular and vascular cellular adhesion molecule-1 (sICAM-1, sVCAM-1)), and oxidative/nitrosative stress (malondialdehyde and urinary nitrate/nitrite) were measured.ResultsA partial correlation adjusted by gender, Tanner stage, and body mass index in obese children showed that resistin was significantly related to central obesity (p < 0.002), insulin resistance (p < 0.005), and homocysteine (p < 0.001). No association was found with other metabolic risk factors or hs-CRP levels. Malondialdehyde (p < 0.043) and sVCAM-1 (p < 0.002) were positively correlated whereas urinary nitrate/nitrite was negatively correlated (p < 0.007). In multiple regression analysis homocysteine, sVCAM-1, and urinary nitrate/nitrite remained independent determinants of resistin levels (R² adjusted = 0.347, p = 0.000).ConclusionsResistin could be considered as a promising marker for future cardiovascular disease in obese children.     

Increased urinary level of oxidized nucleosides in patients with mild-to-moderate Alzheimer's disease

Objective:Oxidative stress may play an important role in the pathogenesis of Alzheimer's disease (AD).Design and methods:To investigate the possible role of oxidative DNA damage in the pathogenesis of AD, we measured the metabolite concentrations of oxidized nucleosides (pseudouridine, 1-methyladenosine, 5-methylcytidine, 5-methyl-2′-deoxycytidine, 3-methyluridine, N², N²-dimethylguanosine, 8-hydroxy-2′-deoxyguanosine, 5-deoxyadenosine and 2-deoxyguanosine) in urine between AD (n = 36) and control subjects (n = 34) using liquid chromatography-mass spectrometry (LC-MS) without urine preparation.Results:In AD, the 3-methyluridine, 1-methyladenosine, 8-hydroxy-2′-deoxyguanosine (p < 0.05, respectively), 2-deoxyguanosine (p < 0.01) and pseudouridine, N², N²-dimethylguanosine (p < 0.001, respectively) were significantly increased when compared with the control subjects.Conclusion:The results indicate that oxidized urinary nucleosides may be useful as biomarkers for AD in early stages.     

Influence of diabetes on homocysteine-lowering therapy in chronic hemodialysis patients

IntroductionThe effect of homocysteine (Hcy)-lowering therapy may be different in hemodialysis (HD) patients with and without diabetes mellitus (DM).MethodsStable HD patients with uremia were administered folic acid and vitamin B for 3 months. The impact of treatment was compared in patients with and without DM.ResultsA total of 61 patients (31 men and 30 women) aged 56 ± 13 y completed the study. Among these, 44 patients (72%) did not have DM and 17 (28%) had DM. At baseline, total Hcy and high-sensitivity C-reactive protein (hsCRP) levels were similar. After treatment, the levels of total Hcy and hsCRP were significantly decreased in the nondiabetic group (total Hcy level decreased from 33.63 ± 14.13 μmol/l to 18.94 ± 8.46 μmol/l, p < 0.001; hsCRP level decreased from 0.58 mg/dl [range, 0.21–1.05 mg/dl] to 0.22 mg/dl [range, 0.11–0.53 mg/dl], p < 0.001) but not in the diabetic group (total Hcy level decreased from 34.97 ± 17.12 μmol/l to 29.53 ± 11.36 μmol/l, p = 0.057; hsCRP level decreased from 0.80 mg/dl [range, 0.24–1.47 mg/dl] to 0.49 mg/dl [range, 0.45–0.98 mg/dl], p = 0.28). Serial monitoring of total Hcy level showed a more sustained effect of therapy on patients without DM.ConclusionFolic acid and vitamin B administration significantly lower total Hcy and hsCRP levels in HD patients without DM but not in those with DM.     

Effect of intravenous iron administration frequency on AOPP and inflammatory biomarkers in chronic hemodialysis patients: a pilot study

ObjectivesIntravenous iron administration (IVIR) is effective for correcting anemia in hemodialysis (HD) patients, but it also enhances the generation of hydroxyl radicals. Previously we demonstrated that IVIR increases oxidized serum albumin levels in HD patients. However, the effect of IVIR frequencies on the oxidative stress has never been studied before. Therefore, we compared the two IVIR schedules recommended by the Japanese Society for Dialysis Therapy guideline 2004 by measuring oxidized albumin in chronic HD patients.Design and methodsTwenty-two HD patients were divided into two IVIR protocol groups (group I: 40 mg of iron 3 times a week for 4 weeks, group II: 40 mg of iron once a week for 3 months). These protocols differ in IVIR frequency, but receive the same amount of iron (total 520 mg). We compared these two regimens by determining the levels of hemoglobin, serum ferritin, advanced oxidation protein products (AOPP), and oxidized albumin at 0, 4, 8, 12, 16, and 20 weeks.ResultsBoth patient groups resulted in a similar and significant increase in hemoglobin levels, whereas group I markedly induced AOPP and oxidation of serum albumin than group II at 4 weeks (P < 0.05). AOPP and oxidation of serum albumin was also gradually declined by 20 weeks, while the oxidized albumin and AOPP in group II was not significantly changed during the entire experimental period. Transferrin saturation and serum ferritin levels were also increased in group I compared with group II at 4 weeks (P < 0.001). In addition, we found a strong positive correlation between oxidized albumin and serum ferritin levels (r = 0.615, P < 0.05), suggesting the possibility that the accumulation of iron stores has a causative role in the progression of oxidative stress in HD patients treated with IVIR.ConclusionsThe results of this study indicate that lower frequency IVIR protocol is recommended to reduce IVIR-induced oxidative stress in HD patients.     

Cox proportional hazard model analysis of survival in end-stage renal disease patients with small-sized high-density lipoprotein particles

ObjectiveDyslipidemia is commonly seen in patients with end-stage renal disease (ESRD). This prospective study investigates whether small-sized high-density lipoprotein (HDL) particles alone or in combination with high sensitivity C-reactive protein (hsCRP) are independent determinants of ESRD mortality.Design and methodsWe performed 36 months follow-up study in 122 haemodialysis (HD) patients. HDL size and subclass distribution were determined by gradient gel electrophoresis. Baseline characteristics of the patients were evaluated for the prediction of mortality.ResultsCox regressions analysis showed that patients with small-sized HDL particles had 2.8-fold higher risk of lethal outcome (P < 0.05). Concomitant presence of small-sized HDL particles and increased hsCRP concentration were significantly associated with reduced survival rate (HR = 3.907; P < 0.05). Observed relationships persisted after adjustment for serum lipid and lipoprotein concentrations.ConclusionsOur results indicate that small-sized HDL particles alone and combined with elevated hsCRP concentrations are independent predictors of reduced survival in HD patients.     

Serum heat shock protein 70 levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in women with preeclampsia

BackgroundWe have previously reported that serum levels of 70 kDa heat shock protein (Hsp70, HSPA1A) are increased and reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia. The purpose of this study was to determine whether increased serum Hsp70 concentrations in women with preeclampsia are related to circulating levels of cytokines, chemokines, adhesion molecules and angiogenic factors, the key players in the pathogenesis of the disease.MethodsSixty preeclamptic patients and 60 normotensive, healthy pregnant women were involved in this case-control study. Levels of Hsp70 (HSPA1A) and transforming growth factor (TGF)-beta1 in maternal sera were assessed by ELISA. Serum levels of interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interferon-gamma-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were determined by multiplex suspension array. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were measured by electrochemiluminescence immunoassay. For statistical analyses, the Mann–Whitney U-test, the Fisher exact and Pearson chi-square tests, the Spearman rank order correlation, multiple linear regression and logistic regression were applied.ResultsSerum levels of Hsp70 were significantly higher in preeclamptic patients than in healthy pregnant women. Additionally, most of the measured inflammatory variables differed significantly between the two study groups except for serum IL-1beta and TGF-beta1 levels and IL-18/IL-12p70 and IL-12p70/IL-12p40 ratios, indicating a bias toward a pro-inflammatory status in preeclampsia. Preeclamptic patients had significantly higher sFlt-1 levels and sFlt-1/PlGF ratio and significantly lower PlGF concentrations as compared to healthy pregnant women. In the preeclamptic group, serum Hsp70 concentrations showed significant correlations with serum levels of IL-12p40 (R = 0.59, p < 0.001), MCP-1 (R = 0.43, p < 0.001), ICAM-1 (R = 0.39, p = 0.0020) and VCAM-1 (R = 0.46, p < 0.001). Furthermore, elevated serum Hsp70 level and sFlt-1/PlGF ratio had a synergistic (joint) effect in the risk of preeclampsia, as shown by the substantially higher odds ratios of their combination than of either alone.ConclusionsIncreased serum Hsp70 concentrations in women with preeclampsia were associated with pro-inflammatory changes in circulating cytokine profile, suggesting that circulating Hsp70 might contribute to the development of the excessive systemic inflammatory response characteristic of the maternal syndrome of the disease.     

Normal range of serum Amphiregulin in healthy adult human females

ObjectivesPrior to large studies in breast cancer patients, we have sought to establish the normal range of a potential serum biomarker, Amphiregulin, in healthy women and to determine whether sampling during the menstrual cycle influences the detected Amphiregulin levels.Design and methodsSerum Amphiregulin levels were quantified using a commercially available ELISA in 85 normal female donors.ResultsThe range of circulating Amphiregulin was 0–4467 pg/mL. The majority of women had no detectable circulating Amphiregulin (n = 54), and only five women had levels exceeding 500 pg/mL. Serum Amphiregulin levels did not vary significantly during the menstrual cycle (n = 7 women).ConclusionsDetection of circulating Amphiregulin in a significant minority of healthy women suggests that it may not have the specificity necessary for a population screening tool; however its potential utility for monitoring response to treatment or disease progression should be examined in breast cancer cases.     

A multiplex immunoassay gives different results than singleplex immunoassays which may bias epidemiologic associations

ObjectivesMultiplex immunoassays are increasingly used in epidemiologic studies to measure inflammatory factors, however there are few published evaluations of this technology. Our objective was to compare a common multiplex immunoassay to singleplex immunoassays for measuring inflammatory factors, and to examine how combining data from each affects an epidemiologic association.Design and methodsPlasma IL-1 beta, IFN-gamma, IL-6, and TNF-alpha were measured in 100 samples using a multiplex kit from Mesoscale Discovery (MSD) and singleplex ELISAs from R&;D Systems. Separate samples (n = 80) were collected to compare multiplex and singleplex assays from MSD. We simulated the effect of combining MSD multiplex and R&;D singleplex data on the association between sugar sweetened beverage (SSB) intake and IL-6 in the Health Professionals Follow-up Study (HPFS; n = 1314).ResultsCompared to R&;D ELISAs, the MSD multiplex proportionally and significantly overestimated IL-1 beta (slope = 1.2), and IFN-gamma (slope = 2.9) but underestimated IL-6 (slope = 0.5). Correlations were ≥ 0.81 except for TNF-alpha (r = 0.31). Compared to MSD singleplex, the MSD multiplex proportionally underestimated IFN-gamma (slope = 0.7) and TNF-alpha (slope = 0.5). Correlations were ≥ 0.96. The association between sugar sweetened beverage intake and IL-6 in the HPFS (+ 0.16 pg/mL per serving/day, p = 0.02, all singleplex) was gradually attenuated as multiplex data made an increasing contribution to the data-set. (+ 0.09 pg/mL [? 45%], p = 0.02, all multiplex)ConclusionsA multiplex immunoassay for inflammatory factors yielded significantly different results than singleplex immunoassays—including those from the same company. Correlations were not consistently high, except among assays from the same company. Such differences may distort epidemiologic relationships if data from both methods are merged.     

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.     

Lovastatin enhances paraoxonase enzyme activity and quells low-density lipoprotein susceptibility to oxidation in type 2 diabetic nephropathy

Objectives:To investigate the effect of lovastatin therapy and withdrawal on paraoxonase 1 (PON1) and arylesterase (ARE) activities, and low-density lipoprotein cholesterol (LDL-C) susceptibility to oxidation in people with type 2 diabetic nephropathy (T2DN).Design and methods:Lovastatin (20 mg/day) was administered to 30 people with T2DN for 90 days and then withdrawn for 30 days. PON1 and ARE activities were measured by the spectrophotometric method. Susceptibility of LDL-C to oxidation was determined as the production of conjugated dienes.Results:After 90 days of lovastatin intervention, PON1 and ARE activities and LDL-C lag phase were significantly increased (p = 0.004, 0.002, and < 0.001), while after 30 days of lovastatin withdrawal, PON1 and ARE activities and LDL-C lag phase had not changed significantly.Conclusion:Lovastatin therapy improves PON1 and ARE activities, and LDL-C susceptibility to oxidation. Despite withdrawal of lovastatin, PON1 and ARE activities, and LDL-C susceptibility to oxidation remain unchanged in people with T2DN.     

Association between the -2518G/A polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and hypertension in Tunisian patients

ObjectivesMonocyte chemoattractant protein-1 (MCP-1:CCL2) has been demonstrated to be involved in the pathophysiology of atherosclerosis and hypertension. This study was aimed to investigate whether the single nucleotide polymorphism (SNP) at ?2518 of the MCP-1 gene promoter region is associated to hypertension in a sample of Tunisian population.Design and methodsA total of 290 Tunisian patients with hypertension and 390 normotensive controls were included in the study. The SNP of the MCP-1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.ResultsA significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 7.2% for the GG genotype, 35.2% for the AG genotype and 57.6% for the AA genotype. Normotensive subjects had a frequency of 3.6% for the GG genotype, 29.7% for the AG genotype and 66.7% for the AA genotype (χ² = 8.02, p = 0.01). The hypertension patient group showed a significant higher frequency of the G allele compared to the controls [0.24 vs. 0.18; OR (95%CI), 1.46 (1.11–1.91), p = 0.004]. The association between the ?2518 G/A polymorphism of MCP-1 gene and hypertension remained significant after adjustment for other well-established cardiovascular risk factors.ConclusionThe present study showed a significant and independent association between the ?2518G/A polymorphism of the MCP-1 gene (presence of G allele) and hypertension in the Tunisian population.     

Changes in pro-oxidant-antioxidant balance after bare metal and drug eluting stent implantation in patients with stable coronary disease

ObjectivesIn this study we aimed to assess the changes in pro-oxidant–antioxidant balance (PAB) after the placement of either a drug-eluting-stent (DES) or bare-metal-stent (BMS) in patients with stable coronary artery disease.Design and methodsPercutaneous coronary interventions (PCI) with either BMS or DES were undertaken for 152 patients (82 in the BMS and 70 in the DES groups respectively). PAB values were measured 24 h before and after PCI.ResultsBaseline PAB values were 80.68 (64.98–99.37) and 98.86 (64.70–140.62) for BMS and DES group, respectively, which were not significantly different between the 2 groups (P > 0.05). Following PCI, median PAB values decreased to 72.10 (61.40–96.13) and 81.40 (54.15–121.90) in BMS and DES groups, respectively. The reduction was significant in both BMS and DES groups (P < 0.05). The changes in PAB values were ?2.81 (?12.76 to 2.31) for BMS and ?2.82 (?29.88 to 8.93) for DES group, which were not significantly different between the 2 groups (P > 0.05).ConclusionWe found that the reported difference in clinical outcomes following DES or BMS implantation cannot be attributed to differences in early changes in oxidative stress induction as assessed by changes in PAB values.