Association of high sensitivity C-reactive protein (hsCRP) and tumour necrosis factor-alpha (TNF-alpha) with carotid intimal medial thickness in subjects with different grades of glucose intolerance--the Chennai Urban Rural Epidemiology Study (CURES-31)

ObjectiveTo assess the association of high sensitivity C-Reactive Protein [hsCRP] and Tumour Necrosis Factor-α [TNF-α] with IMT in Asian Indians with different grades of glucose intolerance.Design and methodsSubjects with normal glucose tolerance [NGT](n = 150), impaired glucose tolerance [IGT] (n = 150) and type 2 diabetes (DM) (n = 150) were recruited from the Chennai Urban Rural Epidemiology Study [CURES], in south India. hsCRP was estimated by nephelometry and TNF-α by enzyme linked immunosorbent assay. Carotid IMT was assessed by high resolution B-mode ultrasonography.ResultshsCRP and TNF-α levels were higher in those with DM [p < 0.001] and IGT [p < 0.001] compared to NGT. In linear regression analysis, both hsCRP [p = 0.003] and TNF-α [p =0.001] showed an association with IMT among NGT subjects even after adjusting for age and gender. Among IGT subjects, TNF-α was associated with IMT [p < 0.001], while no association was observed either with hsCRP or TNF-α in diabetic subjects. In NGT subjects, mean IMT was highest in those with high values [III tertile] of both TNF-α and hsCRP [0.83 ± 0.1 mm; p < 0.001] followed by those with high TNF-α + low hsCRP [0.74 ± 0.09 mm; p < 0.001], high hsCRP  low TNF-α [0.67 ± 0.09 mm; p < 0.001], and lowest in those with both low TNF-α and hsCRP [I tertile] [0.63 ± 0.05 mm.ConclusionWe conclude that in Asian Indians 1. Levels of hsCRP and TNF-α increase with increasing severity of glucose intolerance 2. Both hsCRP and TNF-α are associated with IMT in NGT subjects while TNF-α alone is associated with IMT in IGT subjects 3. hsCRP and TNF-α have a cumulative effect on mean IMT values in NGT subjects.     

Serum Fetuin-A and Pentraxin3 in hemodialysis and renal transplant patients

ObjectiveThe aim of the present study was to evaluate of Fetuin-A and Pentraxin3 (PTX3) as the main factors for vascular calcification and inflammation in hemodialysis (HD) and renal transplant (RT) patients.MethodSerum was obtained from 45 stable chronic HD patients and 44 stable RT recipients. Biochemical factors, intact Parathormone, high-sensitive C-reactive protein (hsCRP), Fetuin-A and PTX3 levels were determined by standard methods.ResultsIn the RT recipients PTX3 level was significantly higher than the HD patients [5.78(1.09–20.36) ng/mL vs. 1.65(0.24–7.89) ng/mL, p ≤ 0.001]. Serum Fetuin-A concentration was significantly higher in the HD compared to RT group [43.39(27.75–81.48) ng/mL vs. 38.76(22.26–89.07) ng/mL, p = 0.020]. hsCRP level was also higher in the HD than the RT group [2.90(0.1–8.50) mg/L vs. 1.1(0.1–7.9) mg/L, p = 0.003].ConclusionAlthough our study shows that serum PTX3 is increased and Fetuin-A is decreased after successful RT, their direct role on atherosclerosis needs further studies in the future.     

Effects of temperature and light on the stability of bilirubin in plasma samples

BackgroundAlthough it is known that bilirubin is photo-sensitive, detailed effects of both temperature and artificial light exposure on bilirubin stability in plasma have not been well investigated. We determined the impact of temperature and artificial light on bilirubin stability in plasma.MethodsPlasma total and direct bilirubin were analyzed using a diazo method. The aliquots of 38 samples were stored at 3 °C and 22 °C with light protection for 2, 4, 8, and 24 h respectively before analysis. The aliquots of 20 samples with normal bilirubin and additional 20 with elevated bilirubin were exposed to artificial light for 2, 4, 8, 24, and 48 h at 22 °C, and total and direct bilirubin were measured. The differences between the baselines and subsequent measurements were analyzed with analysis of variance.ResultsThe baseline total bilirubin was 9.6 ± 8.1 mg/dl (mean ± SD) and the concentrations were 9.6 ± 8.2, 9.0 ± 7.4, 9.0 ± 7.5, and 8.8 ± 7.5 mg/dl at 3 °C and 9.5 ± 8.1, 9.0 ± 7.4, 9.6 ± 8.1, and 9.5 ± 8.0 mg/dl at 22 °C after 2, 4, 8, and 24 h (p > 0.05, n = 38). The baseline direct bilirubin was 1.3 ± 1.2 mg/dl and the concentrations after 2, 4, 8, and 24 h were 1.4 ± 1.2, 1.4 ± 1.2, 1.5 ± 1.2, and 1.3 ± 1.1 mg/dl at 3 °C and 1.4 ± 1.1, 1.3 ± 1.1, 1.3 ± 1.1, and 1.3 ± 1.0 mg/dl at 22 °C (p > 0.05, n = 19). In samples with elevated bilirubin exposed to light at 22 °C, the baseline total and direct bilirubin concentrations were 10.2 ± 1.7 mg/dl and 5.0 ± 1.9 mg/dl, respectively. After 2, 4, 8, 24, and 48 h, total bilirubin concentrations were 10.1 ± 1.8, 10.0 ± 1.8, 10.0 ± 1.8, 9.3 ± 2.0 (p > 0.05, n = 20), and 8.4 ± 2.3 (p < 0.01, n = 20) mg/dl and direct bilirubin concentrations were 4.9 ± 1.8, 4.9 ± 1.9, 4.8 ± 1.8, 4.2 ± 1.6 (p > 0.05, n = 20), and 3.5 ± 1.5 (p < 0.01, n = 20) mg/dl. For samples with normal bilirubin levels under the same conditions, the average baseline total and direct bilirubin concentrations were 0.7 ± 0.1 mg/dl and below the lower limit of quantification (LLOQ), respectively. After 2, 4, 8, 24, and 48 h, the average total bilirubin concentrations were 0.7 ± 0.1, 0.6 ± 0.1, 0.6 ± 0.1 (p > 0.05, n = 20), 0.5 ± 0.1, and 0.4 ± 0.1 mg/dl (p < 0.01, n = 20) and direct bilirubin concentrations were still below LLOQ.ConclusionsBilirubin in plasma is stable in refrigerator or at room temperature without light exposure for at least 24 h. In normal laboratory environment, a delay of up to 8 h in the measurement of bilirubin left unprotected from light at room temperature does not significantly affect the results. Under these conditions, the changes in bilirubin concentration are not clinically significant until 24 h (direct bilirubin) and after 48 h (total bilirubin).     

Glutamine, ornithine, citrulline and arginine levels in children with phenylketonuria: The diet effect

BackgroundPhenylketonuria (PKU) therapeutic diet is characterized by the great replacement of natural protein with a phenylalanine-free formula.AimTo investigate the effect of diet on the amino acid serum levels in PKU patients and their total antioxidant status (TAS).MethodsThirty-seven poorly controlled patients (group A), 43 patients who strictly adhered to their diet (group B) and 50 controls were included in the study. In patients and controls blood chemistry, TAS and serum amino acid level determinations were performed.ResultsPhenylalanine levels significantly differed among the groups. Glutamine and ornithine levels were significantly higher in group A, while TAS (416 ± 30 vs 228 ± 23 μmol/L, p < 0.001), citrulline (39 ± 15 vs 26 ± 5 μmol/L, p < 0.001) and arginine levels (61 ± 11 vs 80 ± 12 μmol/L, p < 0.001) were higher in group B. The other determined amino acid serum levels did not differ among the groups of patients and controls.ConclusionsThe high glutamine and ornithine levels in group A may reflect the high natural protein intake. High phenylalanine levels in these patients may locally affect the hepatocyte, enterocyte, and/or renal function resulting in low citrulline and arginine levels contributing to their low TAS.     

Small dense LDL cholesterol is a robust therapeutic marker of statin treatment in patients with acute coronary syndrome and metabolic syndrome

BackgroundSmall dense low-density lipoprotein (sd-LDL) is an atherogenic LDL subfraction and often increased in metabolic syndrome (MetS). This study aimed to determine whether sd-LDL cholesterol (sd-LDL-C) is a therapeutic marker of statin treatment in patients with acute coronary syndrome (ACS) and MetS.MethodsWe examined 71 patients with ACS and 50 non-ACS subjects with normal coronary arteries (controls). The patients with ACS were treated with life-style modifications (n = 36) or those plus 20 mg atorvastatin daily (n = 35) for 6 months. We measured sd-LDL-C by a novel detergent-based homogenous assay and calculated buoyant LDL-C (b-LDL-C).ResultsThe patients with ACS had higher sd-LDL-C than did the controls (30 ± 14 vs. 22 ± 8 mg/dl, p < 0.001). Furthermore, sd-LDL-C was higher in the patients with ACS and MetS (n = 31) than in those without MetS (n = 40) (35 ± 17 vs. 27 ± 11 mg/dl, p < 0.05). Atorvastatin reduced LDL-C and sd-LDL-C by 31% (102 ± 23 to 70 ± 28 mg/dl, p < 0.0001) and 24% (29 ± 15 to 22 ± 13 mg/dl, p < 0.01). The reduction in sd-LDL-C by atorvastatin was 5.5-fold greater in the patients with ACS and MetS than in those without MetS (p < 0.001). Contrary, that in b-LDL-C was similar between the groups.Conclusionssd-LDL-C is a superior therapeutic marker of statin treatment in patients with ACS and MetS.     

A 96-well plate assay for high-throughput analysis of holocarboxylase synthetase activity

BackgroundHolocarboxylase synthetase (HCS) catalyzes the covalent binding of biotin to both carboxylases and histones. Biotinylated carboxylases and biotinylated histones play crucial roles in the metabolism of fatty acids, amino acids, and glucose, and in gene regulation and genome stability, respectively. HCS null mammals are not viable whereas HCS deficiency is linked to developmental delays in humans and phenotypes such as short life span and low stress resistance in Drosophila.MethodsHCS-dependent biotinylation of the polypeptide p67 was detected and quantified in a 96-well plate format using IRDye-streptavidin and infrared spectroscopy.ResultsBiotinylation of p67 by recombinant HCS (rHCS) and HCS from human cell extracts depended on time, temperature, and substrate concentration, all consistent with enzyme catalysis rather than non-enzymatic biotinylation. The Michaelis–Menten constant of rHCS for p67 was 4.1 ± 1.5 μmol/l. The minimal concentration of rHCS that can be detected by this assay is less than 1.08 nmol/l. Jurkat cells contained 0.14 ± 0.02 U of HCS activity [μmol of biotinylated p67 formed/(nmol/l HCS h)] in 400 μg of total protein.ConclusionsWe developed a 96-well plate assay for high-throughput analysis of HCS activity in biological samples and studies of synthetic and naturally occurring HCS inhibitors.     

Serum uric acid levels and the clinical characteristics of depression

ObjectiveThis study was designed to investigate the correlation between serum uric acid (UA) levels and the clinical characteristics of depression.Design and methodsThe serum UA levels were measured in 124 patients with depression, 660 patients with different types of other mental disorders (OMD) and 42 healthy subjects. Clinical characteristics of depression and OMD were also investigated.ResultsDepressive patients (271.97 ± 77.50 μmol/L) had significantly lower UA levels than those with delirium, dementia, amnesia and other cognitive disorders (339.95 ± 141.74 μmol/L, P = 0.004), substances related disorders (359.61 ± 125.02 μmol/L, P = 0.022), schizophrenia (341.03 ± 106.84 μmol/L, P = 0.000), schizoaffective disorder (336.78 ± 155.49 μmol/L, P = 0.024), bipolar disorder (323.04 ± 108.70 μmol/L, P = 0.008) and the healthy control group (315.76 ± 87.50 μmol/L, P = 0.012). We also found that the UA levels of depressive patients normalised after a five week treatment with antidepressants.ConclusionOur data suggested that a lowered UA level is another characteristic of depression.     

Pediatric reference values for serum zinc concentration in Iranian subjects and an assessment of their dietary zinc intakes

ObjectivesTo determine pediatric reference values for serum zinc concentration in Iranian subjects.Design and methodsSerum zinc concentration was measured by flame atomic absorption spectrometry in 699 children and adolescents. Reference values for serum zinc were determined according to the Clinical and Laboratory Standards Institute/International Federation of Clinical Chemistry guidelines. Dietary zinc intake was assessed using a validated semiquantitative food frequency questionnaire.ResultsOverall 95% reference values for serum zinc concentrations were 9.7–31.5, 9.2–30.9, and 9.3–31.1 μmol/L in boys, girls, and total population respectively. Serum zinc concentrations were comparable in boys and girls (17.5 ± 5.3 μmol/L vs. 17.2 ± 5.6 μmol/L, p = 0.242). The dietary zinc intake of 7.6% (4.9% boys and 10.2% girls, p < 0.01) was lower than the estimated average requirement.ConclusionsThis study presents pediatric reference values for serum zinc concentrations, values that could help diagnose and manage zinc deficiency in pediatrics.     

Plasma ceruloplasmin as a biomarker for obesity: a proteomic approach

ObjectivesThis study aimed to investigate new biomarkers of obesity particularly in relation with inflammation-associated proteins using protein differential display techniques.Design and methodsComparison of protein expression in plasma between non-obese (n = 109, body mass index, BMI < 25 kg/m²) and obese (n = 32, BMI ≥ 25 kg/m²) groups was carried out using two-dimensional gel electrophoresis (2-DE) analysis. ELISA was also performed for validation.ResultsAmong six differentially expressed protein spots, ceruloplasmin (Cp) and fibrinogen were over-expressed in obese group. Plasma Cp levels were significantly higher in obese group than non-obese group (34.0 ± 8.6 vs. 41.3 ± 12.7 mg/dL, p < 0.001) and positively correlated with age (r = 0.253, p < 0.005), BMI (r = 0.265, p < 0.001) and hsCRP (r = 0.385, p < 0.001). In stepwise multiple linear regression analysis, plasma Cp along with hsCRP were found predictors for obesity (adjusted β-coefficient = 0.266, p < 0.01).ConclusionElevated plasma Cp levels were significantly associated with obesity, which may be suggested to be a marker of obesity.     

Closing the anion gap: contribution of D-lactate to diabetic ketoacidosis

BackgroundA high anion gap in diabetic ketoacidosis (DKA) suggests that some unmeasured anions must contribute to the generation of the anion gap. We investigated the contribution of d-lactate to the anion gap in DKA.MethodsDiabetic patients with and without DKA and high anion gap were recruited. Plasma d-lactate was quantified by HPLC. Plasma methylglyoxal was assayed by liquid chromatography-tandem mass spectrometry.ResultsThe plasma fasting glucose, β-hydroxybutyrate, and blood HbA1c levels were highly elevated in DKA. Plasma anion gap was significantly increased in DKA (20.59 ± 6.37) compared to either the diabetic (7.50 ± 1.88) or the control group (6.53 ± 1.75) (p < 0.001, respectively). Moreover, plasma d-lactate levels were markedly increased in DKA (3.82 ± 2.50 mmol/l) compared to the diabetic (0.47 ± 0.55 mmol/l) or the control group (0.25 ± 0.35 mmol/l) (p < 0.001, respectively). Regression analysis demonstrated that d-lactate was associated with acidosis and anion gap (r = 0.686, p < 0.001).ConclusionsPlasma d-lactate levels are highly elevated and associated with metabolic acidosis and the high anion gap in DKA. Laboratory monitoring of d-lactate will provide valuable information for assessment of patients with DKA.     

Anserine inhibits carnosine degradation but in human serum carnosinase (CN1) is not correlated with histidine dipeptide concentration

BackgroundWe reported an association of a particular allele of the carnosinase (CNDP1 Mannheim) gene with reduced serum carnosinase (CN1) activity and absence of nephropathy in diabetic patients. Carnosine protects against the adverse effects of high glucose levels but serum carnosine concentration was generally low.MethodsWe measured the concentration of two further histidine dipeptides, anserine and homocarnosine, via HPLC. CN1 activity was measured fluorometically and for concentration we developed a capture ELISA.ResultsWe found an association between the CNDP1 Mannheim allele and reduced serum CN1 activity for all three dipeptides but no correlation to serum concentrations although anserine and homocarnosine inhibited carnosinase activity. Patients with liver cirrhosis have low CN1 activity (0.24 ± 0.17 μmol/ml/h, n = 7 males; normal range: 3.2 ± 1.1, n = 104; p < 0.05) and CN1 concentrations (2.3 ± 1.5 μg/ml; normal range: 24.9 ± 8.9, p < 0.05) but surprisingly, histidine dipeptide concentrations in serum are not increased compared to controls.ConclusionsSerum histidine dipeptide concentrations are not correlated to CN1 activity. The protective effect of low CN1 activity might be related either to turnover of CN1 substrates or a protective function of dipeptides might be localized in other tissues.     

Determination of protein-incorporated methylated arginine reference values in healthy subjects whole blood and evaluation of factors affecting protein methylation

ObjectivesProtein arginine methylation is a post-translational modification involved in the regulation of signal transduction, RNA export, and cell proliferation. Reference values of arginine methylation of whole blood proteome remain to be determined.Design and methodsAsymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and monomethylarginine (MMA) incorporated in whole blood protein and methionine, cysteine and homocysteine plasma levels from 134 healthy subjects were measured by capillary electrophoresis.ResultsThe mean protein-incorporated concentration of the selected population was 4.11 ± 0.77 nmol/mg protein for ADMA; 1.66 ± 0.42 nmol/mg protein for SDMA and 4.31 ± 1.17 nmol/mg protein for MMA. Multiple correlation analysis showed that plasma Hcy was positively related to incorporated protein ADMA (P = 0.002) and MMA (P = 0.049).ConclusionsThe study was able to define a reference value for protein-incorporated ADMA, SDMA and MMA levels and found a positive association between protein-incorporated ADMA and plasma homocysteine.     

Measurement of serum remnant-like lipoprotein particle-triglyceride (RLP-TG) and RLP-TG/total TG ratio using highly sensitive triglyceride assay reagent

BackgroundSerum concentration of remnant-like lipoprotein particles (RLP) have been measured by cholesterol as RLP-C for clinical diagnostic purpose. However, the measurement of TG in RLP and the ratio of RLP-TG/total TG has not been well established.MethodHighly sensitive triglyceride assay reagent (TG-EX) was used for RLP-TG assay and compared with the previously used TG reagent (Determiner LTGII). Sera in health check-up populations, cardiovascular disease, diabetes and oral fat load cases were used for the evaluation of the new RLP-TG assay. Serum TC, TG, HDL-C, LDL-C and RLP-C concentrations were also determined in above cases.ResultsThe detection limit of new RLP-TG using TG-EX was 2.0 mg/dl. The within-run imprecision (n = 10) was CV = 3.0% (RLP-TG: 4.1 mg ± 0.7 mg/dl), CV = 1.4% (RLP-TG: 42.0 ± 0.6 mg/dl) and CV = 0.5% (RLP-TG: 100.6 ± 0.6 mg/dl). Cut-off value (75 percentile) of RLP-TG determined in the fasting Japanese population was 13.1 mg/dl in men and 9.9 mg/dl in women. In patients with metabolic syndrome, cardiovascular disease and diabetes, RLP-TG levels were significantly higher than those in normal control subjects. RLP-TG levels increased significantly after an oral fat load and the ratio of RLP-TG/total TG increased > 3-fold compared to the ratio in the fasting state. Approximately 80% of TG increased after an oral fat load was TG derived from remnant lipoproteins.ConclusionNormal range of plasma RLP-TG in the fasting Japanese population was first determined using a highly sensitive TG assay reagent. RLP-TG was shown to be higher in cases with metabolic syndrome, cardiovascular disease, etc and a better marker than RLP-C for the measurement of postprandial remnant lipoproteins, together with total TG for RLP-TG/total TG ratio.     

Gingival crevicular fluid PGE2, IL-1beta, t-PA, PAI-2 levels in type 2 diabetes and relationship with periodontal disease

ObjectivesTo evaluate if type 2 diabetes mellitus increase gingival crevicular fluid (GCF) levels of prostaglandin E₂ (PGE₂), interleukin-1beta (IL-1ß), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-2 (PAI-2).Design and methodsSeventeen type 2 diabetic patients with periodontal disease (DM), 17 otherwise healthy periodontally diseased patients (PD) and 17 systemically and periodontally healthy control subjects (H) were enrolled. Clinical periodontal measurements were recorded at six sites/tooth. GCF samples were analyzed by ELISA. Data were tested by statistical tests.ResultsDM group revealed lower IL-1ß levels than PD group (p < 0.01). PGE₂, t-PA and PAI-2 levels were similar in DM and PD groups (p > 0.05). PGE₂, t-PA levels were higher in DM and PD groups than H group (p < 0.05). PAI-2 level was higher in DM group than H group (p < 0.05). GCF total amount of PGE₂ in DM group exhibited significant correlations with all clinical periodontal measurements (p < 0.05).ConclusionType 2 diabetes in this study seems not to increase GCF levels of the evaluated inflammatory mediators.     

Total and bone-specific alkaline phosphatases in haemodialysis patients with chronic liver disease

ObjectiveThe Kidney Disease: Improving Global Outcomes “KDIGO” recommends regular sampling of bone turnover markers (BTMs) such as total alkaline phosphatases (t-ALP) and bone-specific alkaline phosphatase (b-ALP) in the case of haemodialysis (HD) patients.Design and methodsWe present our results of the regular assessment of t-ALP, b-ALP, and PTH, obtained for existing HD patients with chronic liver disease (LD).Results76 prevalent HD patients were examined. Linear regression showed that b-ALP and t-ALP levels were closely related (r²: 0.6; p < 0.0001), even when the serum PTH level was < 250 pg/mL (r²: 0.56; p < 0.001). The b-ALP/t-ALP ratio was 0.07 ± 0.12 and correlated poorly with PTH levels (r²: 0.03; p = 0.01). Both b-ALP and t-ALP levels did not correlated with PTH levels.ConclusionOur results did not confirm the KDIGO recommendation for using b-ALP as BTM in the special cases of HD patients with LDs.     

Inflammatory marker levels in obese adolescents with glucose intolerance: increased chitotriosidase activity

ObjectivesExistance of low grade persistent inflammation in obese children may increase the risk of metabolic and cardiovascular events. The aim was to determine whether glucose intolerance has an influence on inflammatory markers in obese adolescents.Designs and methods45 obese adolescents (mean BMI: 30.34 ± 5.42 kg/m²) were grouped as normal or impaired glucose tolerance. IL-6 and CRP levels were analyzed by commercially available kits. Chitotriosidase activity was measured by a fluorescence method and neopterin levels were determined by ELISA. Data were expressed as mean ± SD.ResultsIL-6 and CRP levels were similar in the two groups. Serum neopterin levels were not different between the groups. The chitotriosidase activity was significantly higher in the IGT group than NGT (124.33 ± 51.97 μmol/L/h vs 84.50 ± 53.99 μmol/L/h, p = 0.04).ConclusionSerum chitotriosidase activity is increased in obese adolescents with impaired glucose tolerance.     

Decreased serum brain-derived neurotrophic factor concentration in young nonobese subjects with low insulin sensitivity

ObjectiveInsulin resistance and type 2 diabetes are associated with an increased risk of neurodegenerative diseases. Decreased brain-derived neurotrophic factor (BDNF) levels might play a role in the pathogenesis of neuropsychiatric disorders. The aim of our study was to estimate serum BDNF concentration in nonobese women divided into subgroups according to their insulin sensitivity.Design and methodsWe studied 46 young, healthy, nonobese women. Insulin sensitivity was estimated with the euglycemic–hyperinsulinemic clamp technique. Then, participants were divided into subgroups of high (mean, 12.79 ± 2.01 mg/kg fat-free mass/min) and low insulin sensitivity (mean, 7.33 ± 1.66 mg/kg fat-free mass/min).ResultsWe observed decreased serum BDNF concentration in women with low insulin sensitivity in comparison to high insulin sensitivity group (3306.11 ± 603.10 vs 4141.91 ± 755.37 pg/mL, p = 0.001). Serum BDNF was positively related to insulin sensitivity (r = 0.43, p = 0.003). This correlation remained significant after adjustment for other estimated parameters.ConclusionsSerum BDNF is decreased in young nonobese women with low insulin sensitivity. Early detection and prevention of insulin resistance might be useful in the prevention of neurodegenerative disorders.     

Association of haptoglobin phenotypes with ceruloplasmin ferroxidase activity in β-thalassemia major

BackgroundHaptoglobin (Hp) and ceruloplasmin (CP) are 2 plasma antioxidants playing a role in preventing iron-induced oxidative damage. This study presents data related to Hp phenotypes and ceruloplasmin ferroxidase activity in relation to iron store markers in patients with β-thalassemia major.MethodsBlood specimens were collected from 196 subjects (124 β-thalassemia major patients and 72 healthy controls). Serum levels of iron, total iron binding capacity (TIBC), ferritin, high sensitivity C-reactive protein (hs-CRP), ceruloplasmin, and ferroxidase activity were determined using conventional methods. Haptoglobin phenotypes were determined by polyacrylamide gel electrophoresis.ResultsAs expected, the mean levels of iron store markers, except TIBC, were significantly higher in patients than in controls. Ceruloplasmin concentrations (mg/dl) and its ferroxidase activity (U/l) were significantly higher in patients than in controls (57.9 ± 18.8 vs 46.9 ± 14.2 and 159.9 ± 47.8 vs 95.3 ± 20.9; p < 0.001, for CP and Hp, respectively). As for Hp phenotypes, no significant differences were observed between iron store markers and ferroxidase activity among the control group. In the patients group however, significantly higher concentrations of ceruloplasmin and its ferroxidase activity were observed among patients with Hp2-2 phenotype as compared to patients with the other phenotypes. Additionally, correlations according to Hp phenotypes revealed strong association between ceruloplasmin ferroxidase activity and serum ferritin in patients with Hp 2-2 phenotype and not in the others (r = 0.331, p < 0.05).ConclusionThalassemia patients with Hp 2-2 phenotype are under greater iron-driven oxidative stress than patients with other phenotypes.     

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.     

Glycated albumin is independently associated with estimated glomerular filtration rate in nondiabetic patients with chronic kidney disease

BackgroundGlycated albumin (GA) may contribute to diabetic nephropathy, but the clinical significance of GA in patients with chronic kidney disease (CKD) is unknown.MethodsPatients were classified with the NKF/DOQI classification system as mild (stage I, II), moderate (stage III), or advanced CKD (stage IV). Those undergoing dialysis or with CKD stage V were excluded. GA was measured using the Lucica TM GA-L assay kit. The relationship between GA and renal dysfunction was analyzed in patients with or without diabetes.ResultsA total of 187 subjects were enrolled. GA values in those with normal, mild, moderate and advanced CKD were 18.4 ± 1.4%, 18.4 ± 3.1%, 19.0 ± 3.8%, 20.4 ± 6.4%, respectively, in diabetic patients (N = 67, p = 0.5), and were 14.1 ± 1.9%, 14.2 ± 2.2%, 15.9 ± 1.9%, 15.0 ± 1.7%, respectively, in nondiabetic patients (N = 120, p = 0.004). GA value was negatively correlated to eGFR in nondiabetic patients (r = ?0.35, p < 0.001) but not in diabetic patients (r = ?0.11, p = 0.39). In the adjusted model, GA is independently correlated to eGFR only in nondiabetic subjects.ConclusionsIncreased GA concentrations are independently associated with renal dysfunction in nondiabetic patients with CKD.