The effect of obesity on testicular function by insulin-like factor 3, inhibin B,and leptin concentrations in obese adolescents according to pubertal stages

ObjectivesThe aim of the present study is to investigate the effect of obesity on testicular function by evaluating reproductive hormones, inhibinB, insulin-like 3(INSL3), and leptin, in obese and non-obese adolescents according to pubertal Tanner stages.Design and methodsEighty adolescent boys were grouped (n = 20) as; Group1: obese-Tanner2, Group2: non-obese-Tanner2, Group3: obese-Tanner4, Group4: non-obese-Tanner4. Serum INSL3, luteinizing hormone, follicle-stimulating hormone, total testosterone, free testosterone, estradiol, sex hormone binding globulin, inhibin B and leptin levels were assessed in all groups.ResultsINSL3 levels were significantly lower in obese adolescents compared to non-obese boys (p = 0.003, Tanner2) and (p = 0.031, Tanner4). There was a negative correlation between INSL3 and leptin (r = ?0.468, p = 0.001). The negative correlation between INSL3 and BMISDS indicates that pubertal obesity leads to Leydig cell impairment.ConclusionsThis study demonstrated for the first time in the literature that obesity effects testicular Leydig cell function starting from Tanner stage 2.     

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.     

Plasma visfatin and retinol binding protein-4 levels in patients with type 2 diabetes mellitus and their relationship to adiposity and fatty liver

ObjectivesWe investigated whether plasma visfatin and binding protein-4 (RBP-4) levels correlate with obesity and type 2 diabetes mellitus (T2DM).Design and methodsTwo groups were enrolled: Group 1: 40 patients with T2DM and Group 2: 40 age- and gender-matched healthy controls. Both groups were subdivided according to body mass index (BMI) into non-obese (BMI < 25 kg/m²) and obese subjects (BMI ≥ 30 kg/m²) (20 each).ResultsPlasma visfatin and RBP-4 levels were significantly increased in T2DM patients compared with controls with similar BMI values (for both p < 0.001). Plasma visfatin and RBP-4 concentrations correlated with BMI, waist/hip ratio, insulin and homeostatic model assessment insulin resistance (HOMA_IR). Visfatin and RBP-4 correlated with visceral fat and liver fat in diabetic patients (for both p < 0.001).ConclusionVisfatin level was increased in T2DM, possibly related to hyperglycemia. Plasma RBP-4 correlated positively with liver fat and HOMA_IR which may reflect its effects on hepatic insulin sensitivity.     

Mitochondrial depolarisation and oxidative stress in rheumatoid arthritis patients

ObjectivesTo investigate mitochondrial membrane integrity, lipid peroxidation and cytotoxicity in peripheral lymphocytes (PL) from rheumatoid arthritis (RA) patients.Design and methodsSouth African black RA patients (HIV^?) were recruited into the study. Mitochondrial membrane potential (Δψ_m) was analysed in PL using the JC-1 dye distribution assay and flow cytometry. Correlations between Δψ_m and clinical parameters were tested for statistical significance. Cytotoxicity (LDH) and lipid peroxidation (thiobarbituric acid reactive substances (TBARS)) was also determined.ResultsOur findings show significantly elevated levels of cytotoxicity (p = 0.0029) and lipid peroxidation (p = 0.0030) in RA. A significantly higher percentage of circulating PL contained depolarised mitochondria (p = 0.0003) which correlated with disease activity and C-reactive protein levels in patients. Collapse of Δψ_m also negatively correlated to absolute lymphocyte counts (r = ? 0.4041; p = 0.0197).ConclusionThese findings suggest a possible role for mitochondrial membrane alterations in the pathology of RA.     

Relationship of proprotein convertase subtilisin-kexin type 9 levels with resistin in lean and obese subjects

ObjectivesProprotein convertase subtilisin-kexin type 9 (PCSK9), a key regulator of low density lipoprotein receptor expression, has recently been reported to be upregulated by resistin in HepG2 cells and human primary hepatocytes. Whether this translates into a positive relationship of plasma PCSK9 with resistin levels in humans with varying degrees of obesity is unknown.Design and methodsWe assessed the extent to which plasma PCSK9 levels are determined by resistin in individuals with varying degrees of obesity.ResultsIn 80 subjects (35 women; no diabetes mellitus) with body mass index ranging from 19.4 to 40.4 kg/m², plasma PCSK9 levels were not positively related to resistin (r = ? 0.161, p = 0.154). Despite positive correlations of non-high density lipoprotein cholesterol (r = 0.378, p < 0.001), low density lipoprotein (r = 0.292, p < 0.01) and apolipoprotein B (apoB) (r = 0.266, p < 0.05) with PCSK9, none of these apolipoprotein (apo) B-containing lipoprotein measures was positively related to resistin (p > 0.10 for all). In subjects with BMI < 25.0 kg/m² (n = 38), PCSK9 was even inversely related to resistin (r = ? 0.322, p = 0.049), and this relationship remained present after controlling for either leptin (p = 0.027) or insulin resistance (P = 0.031). In subjects with BMI ≥ 25.0 kg/m² (n = 42), PCSK9 was unrelated to resistin (r = ? 0.064, p = 0.69).ConclusionsThis study demonstrates that there is no positive association of plasma PCSK9 with resistin in lean and moderately obese individuals. Our data question whether circulating resistin is a physiologically important determinant of higher PCSK9 levels.     

Red cell distribution width, C-reactive protein, the complete blood count, and mortality in patients with coronary disease and a normal comparison population

BackgroundRed cell distribution width (RDW) is associated with morbidity and mortality in coronary artery disease (CAD), but the connection of RDW with chronic inflammation is equivocal.MethodsIn 1,489 patients with CAD and 8.4–15.2 years of follow-up all-cause mortality and RDW were studied using Cox regression. RDW and its associations with inflammation, liver function, renal function, and body mass were assessed. A population of 449 normal (No-CAD) patients also was evaluated.ResultsRDW predicted all-cause mortality in a step-wise manner (HR = 1.37 per quintile; 95% CI = 1.29, 1.46; p-trend < 0.001). A significant but meaningless correlation between RDW and high-sensitivity C-reactive protein (hsCRP) was identified (r = 0.181; p < 0.001). With full adjustment, RDW remained significant (p-trend < 0.001) and the strongest predictor of mortality among all factors included in the model. RDW also strongly predicted all-cause mortality in the normal control population (HR = 1.33 per quintile, CI = 1.15, 1.55; p-trend < 0.001), but hsCRP did not predict mortality among normal controls.ConclusionsRDW was associated with mortality in patients with CAD and may provide clinically useful prognostication. Although RDW was correlated with hsCRP, they were independent predictors of mortality. RDW has been incorporated into risk prediction tool using data from basic chemistries available at: http://intermountainhealthcare.org/IMRS.     

Association between indices of body mass and antibody titers to heat-shock protein-27 in healthy subjects

ObjectivesWe have assessed the relationship between indices of adiposity and antibody titers to Hsp-27 in healthy subjects.DesignTwo-hundred and fifty subjects were studied, including 50 normal-weight subjects (body-mass-index (BMI) ?25 kg/m²), 100 overweight subjects (BMI 25 to ?30 kg/m²) (n = 100) and 100 obese subjects (BMI ≥ 30 kg/m²).ResultsAnti-Hsp27-antibody levels in obese subjects were [0.34 (0.20–0.39) absorbency unit], being significantly higher than overweight and normal-weight groups (P < 0.05). Anti-Hsp27-antibody levels in overweight subjects [0.29 (0.15–0.34) absorbency unit] were statistically higher than controls [0.18 (0.10–0.23) absorbency unit] (P < 0.05).ConclusionHigh anti-Hsp-27-antibody levels in obese-subjects without established coronary disease may be related to a heightened state of immunoactivation associated with obesity.     

Association between serum retinol-binding protein 4 and small dense low-density lipoprotein cholesterol levels in young adult women

BackgroundSerum retinol-binding protein 4 (RBP4) and small dense low-density lipoprotein (sdLDL) have been suggested to be associated with insulin resistance, but no information is available on the relationship between RBP4 and sdLDL.MethodsWe determined serum RBP4, sdLDL-cholesterol, and other metabolic variables on 38 young women, aged 19–29 years. The homeostatic model assessment of insulin resistance (HOMA-IR) was used for the estimation of insulin resistance.ResultsIn simple regression analyses, RBP4 levels had significant correlations with total cholesterol (r = 0.354, P = 0.029), LDL-cholesterol (r = 0.396, P = 0.014), and sdLDL-cholesterol (r = 0.510, P = 0.001) levels. The sdLDL-cholesterol levels also correlated significantly with total cholesterol (r = 0.402, P = 0.012), LDL-cholesterol (r = 0.627, P < 0.001) and triglycerides (r = 0.449, P = 0.005). Stepwise multiple regression analyses showed only sdLDL-cholesterol (β coefficient (ß) = 0.510, P = 0.001) level was a significant independent predictor of RBP4 levels (adjusted R² = 0.240), whereas RBP4 (ß = 0.289, P = 0.026) level was one of major factors affecting sdLDL-cholesterol levels (adjusted R² = 0.519). There was no significant association of HOMA-IR with RBP4 or sdLDL levels.ConclusionsWe showed an independent linkage between serum RBP4 and sdLDL-cholesterol levels in young adult women. These findings may contribute to understanding of lipoprotein metabolisms involved in diabetes and cardiovascular disease.     

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.     

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 obesity on the association between ATF3 gene haplotypes and C-reactive protein level in Taiwanese

ObjectiveATF3 has traditionally been related to various inflammatory processes. Our aim was to test the statistical association between variations in the ATF3 gene and levels of nine serum inflammatory markers, including C reactive protein (CRP), in a Taiwanese population using interaction analysis.MethodsA sample population of 604 Taiwanese subjects was enrolled. Five tagging single nucleotide polymorphisms of the ATF3 gene from the Han Chinese HapMap Database were selected and genotyped.ResultsWith or without adjustment for clinical covariates, ATF3 genotypes were found to be associated with CRP levels but not with other inflammatory marker levels. Minor alleles of 2 of the 5 ATF3 SNPs were associated with decreased CRP levels predominantly in non-obese subjects (Bonferoni P = 0.018, and P = 0.002 for rs11571530, and rs10475, respectively). Two haplotypes inferred from the 5 SNPs, GATTA and TACCA, were also associated with increased or decreased CRP levels, respectively, in non-obese subjects (Bonferoni P = 0.012 and P = 0.01, respectively) but not in obese subjects. Interaction analysis revealed interaction of obesity with an ATF3 genotype associated with a high CRP level (interaction P = 0.006 for SNP rs10475). An effect of obesity on CRP level was also noted in haplotype interaction analysis (interaction P = 0.019 for haplotype TACCA).ConclusionsATF3 polymorphisms are independently associated with CRP levels in Taiwanese subjects. Further, ATF3 genotypes/haplotypes interact with obesity to set CRP levels. These findings may have implications for the prediction of atherosclerotic disease.     

Effect of obesity on the association between common variations in the HNF1A gene region and C-reactive protein level in Taiwanese

BackgroundThe level of C-reactive protein (CRP), an inflammatory biomarker that predicts future cardiovascular events, is a heritable trait that has been associated with variants of CRP and hepatic nuclear factor-1α (HNF1A) genes. Our aim was to test the statistical association between HNF1A genotypes/haplotypes and serum CRP level in Taiwanese.MethodsA sample population of 617 Taiwanese subjects (all Han-Chinese origin) was enrolled. Five HNF1A single nucleotide polymorphisms (SNPs) rs1920792, rs1169288, rs7310409, rs2464196, rs1169310 were genotyped and analyzed.ResultsAfter adjusting for clinical covariates, minor alleles of all the 5 study SNPs were associated with decreased CRP level (P = 0.0078, P = 0.0107, P = 0.0006, P = 0.0004 and P = 0.0003, respectively). A common haplotype (TGATA) tagged by the minor alleles of study SNPs was associated with significantly decreased CRP level (P = 0.0112). Subgroup analysis revealed that the association between HNF1A genotypes and CRP level occurred only in non-obese subjects.ConclusionsHNF1A polymorphisms are independently associated with CRP level in Taiwanese. Further, HNF1A genotypes interact with obesity to set CRP level, revealing that genetic determinants for CRP level may be different between obese and non-obese individuals.     

Association among retinol-binding protein 4, small dense LDL cholesterol and oxidized LDL levels in dyslipidemia subjects

ObjectivesTo investigate retinol-binding protein 4 (RBP4), small dense low-density lipoprotein cholesterol (sdLDL-C) and oxidized low-density lipoprotein (ox-LDL) levels and their associations in dyslipidemia subjects.Design and methodsWe determined RBP4, sdLDL-C, ox-LDL levels in 150 various dyslipidemia subjects and 50 controls. The correlation analysis and multiple linear regression analysis were performed.ResultsThe RBP4, sdLDL-C and ox-LDL levels were found increased in various dyslipidemia subjects. The sdLDL-C levels were positively correlated with RBP4 (r = 0.273, P = 0.001) and ox-LDL (r = 0.273, P = 0.001). RBP4 levels were also correlated with ox-LDL (r = 0.167, P = 0.043). The multiple regression analysis showed that only sdLDL-C was a significant independent predictor for RBP4 (β coefficient = 0.219, P = 0.009; adjusted R² = 0.041) and ox-LDL (β coefficient = 0.253, P = 0.003; adjusted R² = 0.057) levels, respectively.ConclusionsThe independent associations of sdLDL-C with RBP4 and ox-LDL were observed in dyslipidemia subjects. RBP4 may play an important role in lipid metabolism of atherosclerosis, particularly in formation of sdLDL.     

Carotid intima media thickness is related positively to plasma pre ß-high density lipoproteins in non-diabetic subjects

BackgroundLipid-poor or lipid-free high density lipoprotein (HDL) particles, designated pre ß-HDL, stimulate removal of cell-derived cholesterol to the extracellular compartment, which is an initial step in the reverse cholesterol transport pathway. Pre ß-HDL levels may be elevated in subjects with established cardiovascular disease. We determined the relationship of carotid intima media thickness (IMT), a marker of subclinical atherosclerosis, with pre ß-HDL in subjects without clinically manifest cardiovascular disease.MethodsIMT and plasma pre ß-HDL, assayed by crossed immuno-electrophoresis, were determined in 70 non-diabetic subjects (aged 56 ± 9 years; non-smokers only; 27 women).ResultsIMT was correlated positively with pre ß-HDL, both expressed as plasma apolipoprotein (apo) A-I concentration (r = 0.271, p = 0.023) and as% of apo A-I (r = 0.341, p = 0.004). In contrast, IMT was correlated inversely with HDL cholesterol (r = ? 0.253, p = 0.035). IMT was also related positively to pre ß-HDL after adjustment for age, sex, systolic blood pressure (in apoA-I concentration, ß = 0.203, p = 0.043; in% of plasma apoA-I, ß = 0.235, p = 0.023). IMT remained associated with pre ß-HDL after additional adjustment for either body mass index, plasma glucose, cholesterol, triglycerides, HDL cholesterol, apoA-I and apoB.ConclusionSubclinical atherosclerosis may relate to higher plasma pre ß-HDL independently of apoA-I and HDL cholesterol levels.     

Diagnostic accuracy, reproducibility and robustness of fibrosis blood tests in chronic hepatitis C: a meta-analysis with individual data

ObjectivesTo evaluate the diagnostic accuracy of liver fibrosis tests and its influencing factors in a meta-analysis with individual data.Design and methodsFour independent centers provided four blood tests and Metavir staging from 825 patients with chronic hepatitis C.ResultsFibroMeter AUROC (0.840) for significant fibrosis was superior to those of Fibrotest (0.803, p = 0.049), APRI (0.789, p = 0.001) and Hepascore (0.781, p < 0.001). The misclassification rate was lower for FibroMeter (23%) than for Fibrotest and Hepascore (both 28%, p < 0.001). The variation in the diagnostic cut-offs of tests among centers, reflecting the overall reproducibility, was: FibroMeter: 4.2%, APRI: 24.0%, Fibrotest: 24.2%, Hepascore: 35.0%. Accordingly, the proportion of patients diagnosed with significant fibrosis changed: FibroMeter: 0.8%, Hepascore: 2.4% (p = 0.02 vs FibroMeter), Fibrotest: 5.8% (p < 10^? 3), APRI: 18.2% (p < 10^? 3).ConclusionsThis study on clinical applicability shows significant differences in diagnostic accuracy, inter-center reproducibility, and robustness of biomarkers to changes in population characteristics between blood tests.     

Effects of a single dose of oral iron on hepcidin concentrations in human urine and serum analyzed by a robust LC-MS/MS method

BackgroundThe measurement of serum hepcidin, a peptide hormone that regulates iron metabolism, is clinically important to the understanding of iron homeostasis in health and disease. To date, the quantification of serum hepcidin levels by conventional immunological detection methods has proven problematic due to challenges in obtaining high quality antibodies which demonstrate good reproducibility. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) has been employed recently for more sensitive quantification of hepcidin; however, this method has high background levels and therefore less than optimal specificity.MethodsIn order to increase the specificity of the mass spectrometry based assay, we developed a robust, ultra-performance liquid-chromatography-tandem mass spectrometry (UPLC-MS/MS) protocol using multiple selected reaction monitoring (mSRM) for quantification of hepcidin levels in urine and serum of human subjects. With this assay, we assessed levels of hepcidin before and for up to 8 h after oral ingestion of ferrous sulfate in ten adult human subjects without known disease.ResultsThe linear response of hepcidin quantitation on each instrument was measured, and the correlation coefficients of these calibrations were r² = 0.9512 ± 0.0202 (n = 5) for urine and r² = 0.9709 ± 0.0291 (n = 5) for serum [r² = mean ± SD]. Compared to baseline, the levels of urinary hepcidin between 2–4 h and 4–8 h of both women and men showed significant increases with p < 0.05 and p < 0.001, respectively. The levels of serum hepcidin between 4 h and 8 h in both women and men showed significant increases, compared with baseline values, with both p < 0.01. Interestingly, we also observed some degree of oscillation of levels, occurring at later time points.ConclusionsWe have developed and validated a new method for measuring hepcidin concentrations in human serum and urine and used it to demonstrate early increases with iron supplement in both urinary and serum levels of hepcidin, which return to baseline levels, except in urine samples from men.     

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.     

Plasma leptin levels and digital pulse volume in obese patients without metabolic syndrome--a pilot study

BackgroundThe mechanism of obesity leading to endothelial function is complex, and involves many adipokines and inflammatory cytokines. The data is especially lacking in obese patients without metabolic syndrome. We assessed the relationship among endothelial dysfunction, anthropometric indices, adipokines and inflammatory cytokines in this population.MethodsObese patients without metabolic syndrome were included in this study. The plasma resistin, leptin, retinol-binding-protein 4 and inflammatory cytokines were examined. Endothelial function was assessed by a fingertip peripheral arterial tonometry (PAT) device. Data are expressed as the natural logarithm (ln) of the PAT ratio. Endothelial dysfunction was defined by a ln (PAT ratio) < 0.30.ResultsA total of 35 patients were enrolled, 11 of whom were with endothelial dysfunction. There was a significant difference of ln leptin (p = 0.007), ln [leptin/visceral fat thickness] (p = 0.004) and ln [leptin/subcutaneous fat thickness] (p < 0.001) between patients with and without endothelial dysfunction. Multivariate linear regression analyses showed that ln [leptin/subcutaneous fat thickness] was significantly related to the ln (PAT ratio) (p = 0.002). Using ln [leptin/subcutaneous fat thickness] to detect endothelial dysfunction, the area of receiver operating characteristic curves was 0.843 (p = 0.002). Using 6.10 as a cutoff point, the sensitivity and specificity to determine endothelial dysfunction were 91% and 78%, respectively.ConclusionAbnormal digital vascular function occurs in obese patients without metabolic syndrome. Low plasma leptin/subcutaneous fat ratio is associated with endothelial dysfunction in this population.     

Butyrylcholinesterase activity and mortality risk in hemodialysis patients: Comparison to hsCRP and albumin

ObjectiveTo test the prediction power of butyrylcholinesterase (BuChE) activity for mortality risk in hemodialysis patients during 12 months follow-up, and made comparison to hsCRP and albumin.Materials and methodsThe study enrolled 62 patients, aged 31–79 years. Serum BuChE, high-sensitivity C-reactive protein (hsCRP) and albumin were measured after 1, 3, 9 and 12 months of dialysis. The Kaplan–Meier survival curves were employed in mortality prediction.ResultsBuChE was positively associated with serum albumin (r = 0.318; p = 0.012) and inversely related to hsCRP (r = ? 0.358; p = 0.004). The highest mortality was in the lowest quartile of basal albumin (< 38.4 g/L; p = 0.027), hsCRP concentrations > 8 mg/L (p = 0.005), and BuChE activity in the lowest tercile of basal values (< 5.92 kU/L; p = 0.0041).ConclusionOur results suggest that low BuChE activity may be a nonspecific risk factor for mortality in patients who are on hemodialysis.     

Evaluation of a novel colorimetric assay for free oxygen radicals as marker of oxidative stress

BackgroundFree oxygen radicals play an important role in the pathogenesis of many diseases including cardiovascular disease, diabetes, hypertension, cancer and aging. Several methods were developed for the direct or indirect measurement of oxygen free radical and its byproducts. The free oxygen radicals monitor (FORM) is a novel point-of-care system for the rapid measurement of free oxygen radicals (FORT) in blood. We have carefully evaluated the use of this assay for batch analysis of plasma samples in a research environment with respect to factors affecting its performance, including storage temperature and duration.MethodsWe determined the effect of storage, hemolysis, variability and reproducibility of the FORT in blood and plasma.ResultsPlasma FORT correlated significantly with hsCRP (P < 0.0001) and CHOL/HDL ratio (P < 0.02). While hsCRP results have shown agreater range of assay variability (27.82%–53.92%), FORT measurements in the same samples have less assay variability (5.63%–9.61%). Collected whole blood can be kept on ice for up to 7 h prior to plasma isolation without affecting FORT values. Storage of plasma has no effect on FORT when stored at 4 °C for up to 3 weeks (R² = 0.685). Comparable values can be obtained in samples stored for up to 3 months at ? 80 °C (R² = 0.5888) but not at ? 20 °C.ConclusionsThe day to day variability of FORT, as assessed by multiple measures in a group of controls over time, is minimal. FORT assay isstable when stored at ? 80 °C for a couple of months or at 4 °C for a few weeks. FORT correlation with hsCRP and other lipid markers provides an interesting insight and a novel link between oxidative stress, inflammation and lipid metabolism.