Plasma high sensitivity C-reactive protein and its relationship with cytokine levels in children with newly diagnosed type 1 diabetes and ketoacidosis

BackgroundHigh-sensitivity C-reactive protein (hs-CRP) and pro-inflammatory cytokines have been suggested as sensitive markers of endothelial dysfunction. Our aim was to monitor plasma hs-CRP levels at different time-points and in different degrees of ketoacidosis severity, its association with cytokine levels and its role as a marker of severe ketoacidosis complications.Patients and methodsWe studied in 38 newly diagnosed children with type 1 diabetes and ketoacidosis, aged 7.7 ± 3.1 years, hs-CRP, white blood cell count (WBC), and plasma levels of cytokines IL-1β (interleukin-1β), IL-2, IL-6, IL-8, IL-10, TNF-α (tumor necrosis factor-α) prior to and during DKA management.ResultsOn admission, the levels of WBC, PMN, IL-6 and IL-10 were elevated, but were all reduced within 120 h after ketoacidosis management. In the group with moderate/severe ketoacidosis, but not in mild ketoacidosis, hs-CRP levels were significantly reduced at 24 h (p = 0.021), WBC and IL-6 at 120 h (p = 0.003), while IL-10 was prematurely reduced at 6–8 h (p = 0.008). Moreover hs-CRP was significantly associated with WBC (p = 0.023) and IL-6 (p = 0.028) on admission, with IL-6 (p = 0.002) and IL-8 (p = 0.014) at 24 h and with IL-10 (p = 0.027) at 120 h. The above were not observed in the group with mild ketoacidosis.ConclusionsIn the children with moderate/severe diabetic ketoacidosis of our study, increased levels of hs-CRP and IL-6 were observed, together with leukocytosis and neutrophilia, without the presence of infection. As hs-CRP was found to be strongly associated with the inflammatory IL-6, the prolonged elevation of hs-CRP levels in children with severe ketoacidosis could serve as a marker for the development of its severe complications.     

Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial

BackgroundCytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS.MethodsThis study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1 g/day) or a matched placebo for a period of 8 weeks.ResultsOne hundred and seventeen subjects were assigned to either curcumin (n = 59) or placebo (n = 58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 following curcumin supplementation (p < 0.001). In the placebo group, serum levels of TGF-β were decreased (p = 0.003) but those of IL-6 (p = 0.735), TNF-α (p = 0.138) and MCP-1 (p = 0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 in the curcumin versus placebo group (p < 0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines.ConclusionResults of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.     

Interleukin-1β genotype and circulating levels in cancer patients: Metastatic status and pain perception

ObjectivesProinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/B/RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients.Design and methodsSerum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters.ResultsIL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p = 0.032, Mann–Whitney test) and presented a trend for lower levels of pain (p = 0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR = 4.074, p = 0.010, Pearson χ² test). Among the female patients presenting metastatic disease and carriers of the TT genotype we observed a trend to lower levels of IL1-β (p = 0.053, Pearson χ² test).ConclusionsOur results indicate that genetic variation at IL1-β gene may influence serum levels of IL1-β, with proportional consequences in cancer-related pain.     

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.     

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.     

Serum carotenoids in relation to risk factors for development of atherosclerosis

ObjectiveTo explore associations between serum carotenoids and risk factors for development of atherosclerosis.Design and methodsWe studied 40 early atherosclerosis patients without clinical cardiovascular events and comparable healthy controls aged 45–68 years. Intima-media thickness (IMT) and arterial stiffness were simultaneously measured by carotid ultrasonography, and serum carotenoids and cytokines were determined by high-pressure liquid chromatograph (HPLC) and ELISA kits respectively. We evaluated the associations between serum carotenoids, early atherosclerosis and serum cytokines.ResultsSerum concentrations of lutein and zeaxanthin in early atherosclerosis patients were significantly lower than those of control subjects. PCA logistic analysis found that serum carotenoids were associated with decreased risk of atherosclerosis. In contrast, blood pressure, body mass index and serum triglyceride were positively related to the risk of atherosclerosis. Ridge regression analysis revealed that serum carotenoids were associated with inflammatory cytokines and apoE. More specifically, serum lutein was inversely associated with IL-6 (P < 0.001) and positively associated IFN-γ (P = 0.002). In contrast, zeaxanthin had a significant negative association with VCAM-1 (P = 0.001) and apoE (P = 0.022) .Lycopene was inversely associated with VCAM-1(P = 0.011) and LDL (P = 0.046).ConclusionsThe results suggested that early atherosclerosis patients had lower serum concentrations of lutein and zeaxanthin than healthy subjects. Serum carotenoids were associated with reduced risk of atherosclerosis. The associations between serum carotenoids and inflammatory cytokines may help to explain the possible protective effects of carotenoids on atherosclerosis.     

Prognostic value of cytokines and chemokines in addition to the GRACE Score in non-ST-elevation acute coronary syndromes

BackgroundIncreased cytokine and chemokine levels are associated with cardiovascular events in patients with non-ST-elevation acute coronary syndromes (ACS), but the incremental prognostic value of these inflammatory markers is not known. We determined if cytokine and chemokine assessment adds prognostic information to the GRACE Score in patients with ACS.MethodsFive cytokines (interleukin (IL)-1β, IL-6, IL-10, IL-12p70, and tumor necrosis factor (TNF)-α soluble receptor I), five chemokines (IL-8, CCL5, CXCL9, CCL2, and CXCL10) and C-reactive protein (CRP) were measured at admission of 87 patients admitted with ACS.ResultsDuring hospitalization, the incidence of cardiovascular events was 13% (7 deaths, 1 nonfatal acute myocardial infarction, and 3 refractory unstable angina). Individuals who developed events had significantly greater levels of CRP, IL-1β, IL-12, TNF-α, IL-8, CXCL9 and CCL2, compared with those free of events. Thus, these markers were used to build an Inflammatory Score, by the input of one point for each of these variables above the 75th percentile. After adjustment for the GRACE Score, the Inflammatory Score independently predicted events (OR = 1.80; 95% CI = 1.12–1.88). Incorporation of the Inflammatory Score into the GRACE Score promoted a C-statistics improvement from 0.77 (95% CI = 0.58–0.96) to 0.85 (95% CI = 0.71–1.0). Net reclassification improvement obtained with GRACE–Inflammatory Score was 13% (P = 0.007), indicating a significant reclassification. When only CRP was incorporated into GRACE, the increase on C-statistics was not relevant (from 0.77 to 0.80).ConclusionCytokines and chemokines measured at admission add prognostic information to the GRACE Score in patients admitted with ACS.     

Increased serum levels of microvesicles in nonvalvular atrial fibrillation determinated by ELISA using a specific monoclonal antibody AD-1

BackgroundMicrovesicles are involved in different pathological processes such as inflammation, coagulation and tumor progression. We intended to establish an immunoaffinity capture method for detecting microvesicles and bioactive effectors carried on them using a specific homemade monoclonal antibody AD-1. By this method we investigated the association of inflammation with platelet activation in patients with nonvalvular atrial fibrillation (NVAF).MethodsA case–control study of 90 Chinese subjects selected in 3 groups: control, paroxysmal AF, and persistent AF. After capturing the microvesicles of serum using a specific monoclonal antibody AD-1, the amounts of LAP, IL-1β and P-selectin loaded on these microvesicles were quantified by either enzyme activity assay (LAP) or ELISA respectively.ResultsCompared with normal controls, the patients with persistent AF showed significantly increased serum levels of microvesicles (P < 0.001), microvesicle-bound IL-1 β (P = 0.019) and microvesicle-bound P-selectin (P = 0.001). The latter two were significantly correlated with each other (r² = 0.371, r = 0.616, P < 0.001). The microvesicle-bound IL-1β (β = 0.570, P < 0.001) and body weight (β = 0.427, P = 0.002) were as independent predictors of platelet activation.ConclusionsThe method was easy and reproducible. Inflammation may be involved in the activation of platelets in NVAF.     

Plasma concentrations of Gas6 and soluble Axl correlate with disease and predict mortality in patients with critical limb ischemia

IntroductionCritical limb ischemia (CLI) is a severe peripheral arterial disease, characterized by rest pain, ulcers and gangrene in the legs. Gas6 is a vitamin K-dependent protein, which binds and activates the tyrosine kinase receptor Axl. Gas6-mediated Axl-signaling influences endothelial activation, neointima formation and immune regulation. Axl can be cleaved and soluble Axl (sAxl) is detectable in circulation.Design and methodsWe quantified plasma concentrations of Gas6 and sAxl in 189 CLI patients and 204 controls.ResultsGas6 and sAxl concentrations were increased in the CLI patients (p < 0.0001) and correlated to C-reactive protein, interleukin-6, tumor necrosis factor α and neopterin. Patients who died within 3 years of sampling (n = 84) had increased concentrations of Gas6 and sAxl as compared to survivors (p = 0.0009 and p = 0.0011).ConclusionsPlasma concentrations of Gas6 and sAxl correlate to inflammation and predict survival. This indicates that Gas6 and sAxl have a role in CLI, presumably connected to the inflammatory process.     

Effects of activated protein C on postcardiac arrest microcirculation: An in vivo microscopy study

BackgroundThe clinical symptoms and pathophysiologic mechanisms during and after ischaemia–reperfusion following cardiac arrest (CA) and successful cardiopulmonary resuscitation (CPR) closely resemble those observed in patients with severe sepsis. Impairment of microcirculation and endothelial leakage seem to play key roles in the underlying pathophysiology. Recombinant human activated protein C (rhAPC) is the first drug being licensed for the treatment of severe sepsis in patients. Therefore, for the first time, we investigated effects of rhAPC on microhaemodynamic changes and endothelial leakage applying in vivo microscopy of postcapillary mesenteric venules after CA and CPR in rats.MethodsAfter 6 min of CA, male Wistar rats were randomised into two groups (n = 10) to receive rhAPC or placebo (0.9% NaCl). Sham-operated animals (n = 10) served as non-ischaemic controls. At 360, 420, and 480 min after CA in vivo microscopy was performed to assess wall shear rate (WSR) and plasma extravasation (PE).ResultsBoth treatment groups showed typical signs of impaired microcirculation and a severe endothelial leakage after CA at all time points studied when compared to the sham group. However, no significant differences between the treatment groups were observed with regard to WSR and PE.ConclusionOur results show that CA with consecutive successful CPR leads to a microcirculatory impairment closely resembling experimentally induced sepsis. Intriguingly, despite these similarities, rhAPC had no significant effects on WSR and PE. Our results strongly suggest that further mechanisms such as mast cell activation might play an important role and have therefore to be studied to elucidate the pathophysiology of “postresuscitation disease”.     

The effect of sodium bicarbonate on cytokine secretion in CKD patients with metabolic acidosis

The incidence of acidosis increases with the progression of chronic kidney disease (CKD). Correction of acidosis by sodium bicarbonate may slow CKD deterioration. Inflammation, which is common in CKD, may be related to acidosis. Whether the slower rate of GFR decline following the correction of acidosis is related to changes in inflammatory markers is unknown. The current study examined whether correcting CKD-acidosis affected inflammatory cytokines secretion. Thirteen patients with CKD 4–5 and acidosis were tested for cytokines secretion from peripheral-blood mononuclear cells at baseline and after one month of oral sodium bicarbonate. Following treatment with sodium bicarbonate there was no change in weight, blood pressure, serum creatinine, albumin, sodium, calcium, phosphate, PTH, hemoglobin and CRP. Serum urea decreased (134 ± 10–116 ± 8 mg/dl, P = 0.002), potassium decreased (5.1 ± 0.4–4.8 ± 0.1 mequiv./l, P = 0.064), pH increased (7.29 ± 0.01–7.33 ± 0.01, P = 0.008), and serum bicarbonate increased (18.6 ± 0.4 mequiv./l to 21.3 ± 0.3 mequiv./l, P = 0.001). The secretion of the anti-inflammatory cytokine IL-10 decreased (2.75 ± 0.25 ng/ml to 2.29 ± 0.21 ng/ml, P = 0.041). There was no significant change in the secretion of the other pro-inflammatory and anti-inflammatory cytokines, including IL-1β, IL-2, IL-6, TNFα, IFNγ, IL-1ra. Thus, correcting acidosis in CKD with bicarbonate decreases IL-10 secretion. Its significance needs to be further investigated.     

Serum activated leukocyte cell adhesion molecule and intercellular adhesion molecule-1 in patients with gastric cancer: Can they be used as biomarkers?

Cellular adhesion molecules might be used as markers in diagnosis and prognosis in some types of malignant tumors. The purpose of this study was to determine the clinical significance of the serum levels of activated leukocyte cell adhesion molecule-1 (ALCAM) and intercellular adhesion molecule-1 (ICAM-1) in gastric cancer (GC) patients. Fifty-eight GC patients and 20 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). The median age at diagnosis was 59.5 years (range 32–82 years). Tumor localizations of the majority of the patients were antrum (n = 42, 72.4%) and tumor histopathologies of the majority of the patients were diffuse (n = 43, 74.1%). The majority of the patients had stage IV disease (n = 41, 70.7%). Thirty six (62.1%) patients had lymph node involvement. The median follow-up time was 66 months (range 1–97.2 months). At the end of the observation period, 26 patients (44.8%) were dead. The median survival for all patients was 21.4 ± 5 months (%95 CI, 11.5–31.3). The 1-year survival rates were 66.2%.The baseline serum ALCAM levels of the patients were significantly higher than those of the controls (p = 0.001). There was no significant difference in the serum levels of ICAM-1 between the patients and controls (p = 0.232). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p > 0.05). Tumor localization (p = 0.03), histopathology (p = 0.05), and response to chemotherapy (p = 0.003) had prognostic factors on survival. Neither serum ALCAM levels nor serum ICAM-1 levels were identified to have a prognostic role on overall survival (ICAM-1 p = 0.6, ALCAM p = 0.25). In conclusion, serum levels of ALCAM were found to have diagnostic value in GC patients.     

The plasma levels of relaxin-2 and relaxin-3 in patients with diabetes

ObjectivesRelaxin-2 has been found to alleviate fibrosis in experimental diabetic cardiomyopathy. In addition, the levels of serum relaxin-3 were increased and correlated with all the component traits of metabolic syndrome. We investigated the levels of plasma relaxin-2 or relaxin-3 and their relationship to component traits in patients with diabetes.Design and methodsWe studied 33 newly diagnosed type 2 diabetes patients and 38 age-matched healthy subjects. Blood samples were taken at study entry, and relaxin-3, relaxin-2, fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, serum insulin and hemoglobin A_1c (HbA_1c) levels were measured.ResultsRelaxin-2 levels were significantly lower in patients with diabetes than in controls: the median plasma relaxin-2 concentration was 34.68 pg/mL (range, < 29.00–50.81 pg/mL) in patients with diabetes and 45.80 pg/mL (range, < 37.42–54.46 pg/mL) in controls (p = 0.0150). However, no differences in relaxin-3 levels were observed between the diabetes group and controls (p = 0.6550). The plasma levels of relaxin-2 or relaxin-3 were not correlated with systolic blood pressure (BP), diastolic BP, total cholesterol, LDL-C, HDL-C, triglyceride, fasting blood glucose, fasting insulin and HbA_1c in patients with diabetes. Additionally, there was no correlation between the plasma concentrations of relaxin-2 and relaxin-3 in patients with diabetes (r_s = 0.225; p = 0.208).ConclusionsWe conclude that the plasma levels of relaxin-2 in diabetes patients were lower than in controls, however, there are no difference in plasma relaxin-3 concentrations between controls and patients with diabetes. Relaxin-2 or relaxin-3 levels are not related to component traits in patients with diabetes.     

Association of serum carotenoids with high molecular weight adiponectin and inflammation markers among Japanese subjects

BackgroundSeveral studies have reported that serum concentrations of carotenoids and adiponectin are inversely associated with the risk for cardiovascular disease (CVD). However, no studies have investigated the association between serum concentrations of adiponectin and carotenoids in the general population.MethodsWe investigated cross-sectionally whether serum carotenoids are associated with serum high molecular weight (HMW) adiponectin and some inflammatory markers in 437 Japanese subjects (116 men and 321 women) who attended a health examination.ResultsIn multiple linear regression analysis adjusted for confounding factors, serum β-carotene concentrations were significantly associated with serum HMW adiponectin concentrations in both sexes (standardized β coefficient = 0.197, p = 0.036 for men; standardized β coefficient = 0.146, p = 0.012 for women). Serum α-carotene and β-carotene concentrations were significantly associated with serum C-reactive protein (CRP) concentrations in men. In women, there were significant negative associations between serum carotenoids concentrations and serum interleukin-6 (IL-6) concentrations. Additional adjustment for serum concentrations of IL-6 or CRP did not significantly affect the association between carotenoids and HMW adiponectin in non-smoking men as well as in women.ConclusionSerum β-carotene concentrations were positively associated with serum HMW adiponectin concentrations even after adjustment for possible confounding factors including inflammatory markers.     

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.     

Correlation of endothelin 1 plasma levels with plasma antioxidant capacity in elderly patients treated for hypertension

Experimental studies confirmed that reactive oxygen species increase endothelin-1 (ET-1) synthesis, and modulate ET-1 signaling pathway resulting in vasoconstriction and vascular remodeling.The aim of this study was to evaluate the relationship between plasma ET-1 concentration and antioxidant status in patients with essential hypertension and type 2 diabetes mellitus.Methods78 hypertensive patients, 53.8% diabetic, mean age 72.1 ± 7.07 were examined. The plasma concentration of glucose, creatinine, uric acid, bilirubin, cholesterol, insulin, HbA1c and ET-1 were measured. Antioxidant status was assessed by Ferric Reducing Ability of Plasma (FRAP), vitamin C concentration and erythrocyte superoxide dismutase (SOD) activity.ResultsWith diabetes ET-1 concentration was higher (1.35 ± 0.51 vs 1.12 ± 0.46 pg/mL, p = 0.04). The negative correlations between ET-1 concentration and FRAP (r = ? 0.50, p < 0.0001), vitamin C (r = ? 0.296, p = 0.01) and SOD (r = ? 0.44, p = 0.001) were found. Concentration of ET-1 correlated positively with SBP (r = 0.33, p = 0.005) but not with DBP. The relationship between DBP and ET-1 only in subjects with DBP > 110 mm Hg and FRAP < 0.40 mmol/L was found. In multiple regression analysis plasma ET-1 levels were associated independently with FRAP (beta = ? 0.583, p = 0.003) and plasma vitamin C (beta = ? 0.407, p = 0.04).ConclusionsIn hypertensive and diabetic patients higher plasma endothelin-1 level was independently associated with lower plasma antioxidant status measured by FRAP and decreased vitamin C concentration, which may be a result of increased oxidative stress in these diseases.     

Gender-specific effect of Pro12Ala polymorphism in peroxisome proliferator-activated receptor γ-2 gene on obesity risk and leptin levels in a Tunisian population

ObjectivesThis study was undertaken to investigate the impact of the Pro12Ala (rs1801282) polymorphism of the peroxisome proliferator-activated receptor γ-2 (PPARγ-2) gene on obesity or body mass index (BMI) and plasma leptin, insulin, adiponectin and lipid levels in a sample of the Tunisian population.Design and MethodsThe study included 387 obese patients and 288 control subjects. The Pro12Ala genotype was determined by polymerase chain reaction followed by a digestion with the restriction of endonuclease BstUI.ResultsIn the whole population, there is no significant difference in genotype frequencies of the Pro12Ala polymorphism between obese patients and controls. However, separate analysis by gender revealed that obese men (but not women) had significantly higher frequency of Pro/Ala genotypes compared to controls (12.2% vs. 4.1%; χ² = 6.76, p = 0.009). In comparison to Pro/Pro homozygotes, Ala-allele bearers had a significantly higher risk of obesity [OR (95% CI) = 3.26 (1.28–8.33)]. When obese subjects were stratified according to type 2 diabetes status, the association with obesity was only significant in obese non-diabetic patients [OR (95% CI) = 3.74 (1.43–9.74), p =  0.007]. Additionally, obese male patients carrying the Ala-allele had significantly higher body mass index (p =  0.007) and plasma leptin levels (p =  0.023) compared to those homozygous for Pro-allele. The significant effect of Pro12Ala polymorphism on plasma leptin levels disappeared after adjustment for age and BMI.ConclusionThe present study provides evidence that the Pro12Ala polymorphism of the PPARγ-2 gene is associated with obesity in non-diabetic men from Tunisian origin.     

Effects of anticoagulants on human plasma soluble corin levels measured by ELISA

BackgroundRecently, soluble corin was detected in human plasma. In patients with heart failure, plasma corin levels were lower than that of normal controls. In this study, we analyzed experimental conditions for measuring plasma or serum corin by an immunoassay.MethodsSerum and plasma corin levels were measured by ELISA. Effects of different anticoagulants (EDTA, heparin and sodium citrate) on plasma corin levels were examined.ResultsCorin levels in serum were similar to that in plasma with heparin (950 ± 305 vs. 929 ± 301 pg/ml, n = 40, p = 0.73), but were significantly higher than those in plasma with sodium citrate (735 ± 237 pg/ml, p < 0.01) or EDTA (716 ± 261 pg/ml, p < 0.001). Native and recombinant human corin proteins were stable in human plasma with EDTA at 4 °C or underwent freezing-and-thawing. In 348 healthy Chinese individuals, plasma corin levels ranged from 216 to 1663 pg/ml. The levels were higher in males than that in females (842 ± 283 vs. 569 ± 192 pg/ml, p < 0.001).ConclusionSoluble corin was stable in plasma samples. Plasma soluble corin levels vary depending on anticoagulants used. Samples containing heparin had significantly higher levels of corin than that in samples with EDTA or sodium citrate.     

Post-treatment circulating plasma BMP6 mRNA and H3K27 methylation levels discriminate metastatic prostate cancer from localized disease

BackgroundWe evaluated the utility of post-treatment plasma levels of the circulating bone-morphogenetic protein-6-specific mRNA (cBMP6 mRNA), cell-free DNA (cf-DNA), apoptotic nucleosomes and Histone H3 lysine 27 trimethylation (H3K27me3), in discriminating metastatic prostate cancer (PCa) from organ confined, locally controlled disease.MethodsPeripheral blood was taken from the patients at the end of therapy, and quantitative PCR was performed to amplify cBMP6 mRNA or cf-DNA from plasma while apoptotic nucleosomes and H3K27me3 were determined by ELISA-based approaches. Following blinded measurements, the markers were compared between the patients with local (n = 22), local advanced (n = 11) or metastatic disease (n = 28).ResultsOf the four markers investigated, the cBMP6 mRNA and H3K27me3 levels revealed significant differences between the three subgroups. We found higher levels of cBMP6 mRNA in the patients with metastases than in those with localized (p = 0.001) or local advanced disease (p = 0.05). When compared to cBMP6, H3K27me3 displayed an inverse distribution and was significantly lower in the patients with metastatic disease than in those with localized (p = 0.05) or local advanced disease (p = 0.024). There was no correlation between the different markers and total PSA levels or Gleason score at diagnosis.ConclusionOur study provides evidence that post-treatment analysis of cBMP6 mRNA and H3K27me3 may be used to distinguish metastatic PCa from organ confined, locally controlled disease.     

Serum interleukin measurement may help identify thyroid cancer patients with active disease

BackgroundInvestigate the clinical utility of serum interleukin dosages of IL-2, IL-2R, IL-4, IL-6, IL-6R, IL-8, IL-10 and IL-12 in the diagnosis and characterization of patients with DTC. In particular, verify ILs utility in the identification of individuals who are evolving disease-free or with the active disease.MethodsWe evaluated 200 patients with malignant nodules (100 patients disease-free and 100 patients with recurrence/active disease); 60 benign nodules and 100 healthy controls, serum levels were assessed by ELISA.ResultsAll ILs, but not IL-4, differentiated these three groups. We observed that IL-2, 2R and 10 serum concentrations were associated with thyroglobulin levels. Serum IL-2 was able to differentiate patients with active disease from the disease-free with a sensitivity of 98%, specificity of 58%, positive predictive value (PPV) of 70% and negative predictive value (NPV) of 97% (p = 0.0007). IL-6R levels differentiated patients with active disease from the disease-free patients with 56% sensitivity, 63% specificity, PPV of 60% and NPV of 59% (p < 0.0001). IL-8 values also distinguished patients with active disease from the disease-free ones with sensitivity of 50%, specificity of 76%, PPV of 68% and NPV of 60% (p = 0.0025); using IL-12, we obtained a sensitivity value of 73%, specificity of 66%, PPV of 68% and NPV of 71% (p < 0.0001). Furthermore, interleukin levels showed association with some tumor characteristics of aggressiveness.ConclusionWe suggest that the serum concentration of ILs may assist in the diagnosis and characterization of tumor malignancy helping identify patients with active disease who deserve closer medical attention.