Assessment of the relationship between serum paraoxonase activity and epicardial adipose tissue in hemodialysis patients.

PURPOSE: Paraoxonase-1 (PON-1) is a high-density lipoprotein-associated (HDL) enzyme, which has been shown to reduce susceptibility to low-density lipoprotein (LDL) peroxidation. Epicardial adipose tissue (EAT) is a marker of atherosclerosis. The aim of this study was to determine the relationship between PON-1 activity and EAT in hemodialysis (HD) patients. METHODS: This is a cross-sectional study conducted on 72 (43 males) HD patients with end-stage renal disease. Serum levels for lipid profiles, C-reactive protein, calcium, phosphate, and parathyroid hormone were measured. PON-1 activity was also measured and compared to the rate of enzymatic hydrolysis of paraoxon to p-nitrophenol. Echocardiography was used to measure EAT thickness (EATT). The correlation between PON-1 and EATT was assessed, while independent predictors of EATT in HD patients were similarly assessed using multivariate regression analysis. RESULTS: There was a significant low mean value of PON-1 activity in HD patients compared with the control group (82.1 ± 31.6 vs. 164.3 ± 61.5 U/l, p = 0.0001) and significant high mean value of EATT in HD patients, compared with controls (6.2 ± 1.7 vs. 3.9 ± 1.1 mm, p = 0.0001). In addition, there was a significant negative correlation between PON-1 activity and EATT (r = -0.484, p = 0.0001) and a significant positive correlation between PON-1 activity and HDL-C (r = 0.417, p = 0.0003). PON-1, total cholesterol, triglycerides, LDL, HDL, age, and body mass index were found to be independent predictors of EATT. CONCLUSION: Our study demonstrated that PON-1 activity was significantly lower in HD patients compared with healthy controls and that PON-1 activity was inversely correlated with EATT in this population.

Assessment of the relationship between serum soluble Klotho and carotid intima-media thickness and left ventricular dysfunction in hemodialysis patients.

BACKGROUND: The aim of our study was to assess the relationship between soluble Klotho (s-Klotho) and carotid intima-media thickness (CIMT) and left ventricular (LV) dysfunction in hemodialysis (HD) patients. METHODS: This is a cross-sectional study conducted on 88 patients with end-stage renal disease on regular HD. Serum levels of calcium, phosphorus, parathyroid hormone, and C-reactive protein were measured. The serum levels of s-Klotho and fibroblast growth factor-23 (FGF-23) were measured using an Enzyme linked immunosorbent assay (ELISA) kit. Echocardiography and measurement of CIMT were also conducted. The studied patients were divided according to the median s-Klotho level into 2 groups: patients with low s-Klotho (Group I) and patients with high s-Klotho (Group II). RESULTS: Mean value of s-Klotho was significantly low in HD patients compared to controls (P = 0.001), and mean value of FGF-23 was significantly high in HD patients compared to controls (P = 0.001). The mean values of parathyroid hormone, FGF-23, and phosphorus were significantly high in Group I compared to Group II, whereas the mean value of serum calcium was significantly low in Group I compared to Group II. The mean values of CIMT, LV mass (LVM), LVM index, and LV ejection fraction (LVEF) were high in Group I compared to Group II. Patients with low s-Klotho had significantly more coronary artery disease (CAD). In a regression analysis of s-Klotho with different markers of cardiovascular diseases, s-Klotho showed significant association with CIMT, LVEF, and CAD, but not with LVM and LVM index. CONCLUSION: The present study showed that patients with a low s-Klotho were more often associated with increased CIMT, LV dysfunction, and CAD, and it seems that there was independent association between s-Klotho and CIMT, LVEF, and CAD.

Anticoagulants affect matrix metalloproteinase 9 levels in blood samples of stroke patients and healthy controls.

OBJECTIVES: Matrix metalloproteinase-9 (MMP-9) represents a promising marker for acute stroke management. In clinical studies MMP-9 has been quantified by ELISA using differing protocols. We aimed to establish a valid protocol by evaluation of preanalytics. DESIGN AND METHODS: Blood from stroke patients (n=28) and healthy controls (n=28) was drawn into tubes containing different anticoagulants (EDTA, citrate, lithium-heparin (heparin) and heparin with proteinase inhibitors) and processed after 0, 60 and 240 min. MMP-9 plasma protein and mRNA from mononuclear leukocytes were determined. RESULTS: In regard to anticoagulants used, samples showed different MMP-9 protein baseline values and kinetics. Stable MMP-9 protein concentrations were only measured from EDTA samples. Particularly in samples with proteinase inhibitors protein and mRNA concentrations increased over time. Kinetics did not differ between patients and controls. CONCLUSIONS: Preanalytics plays a key role for determination of MMP-9. EDTA seems to be a valid anticoagulant for MMP-9 protein measurement.

Adiponectin and cardiovascular outcomes among hemodialysis patients.

BACKGROUND: Adiponectin (ADPN) levels are consistently elevated among patients with advanced chronic kidney disease, but its relationship with cardiovascular outcomes in this population remains controversial. The aim of our study was to measure the plasma levels of ADPN in patients with end-stage renal disease on maintenance hemodialysis (HD) and we studied its correlates to cardiovascular outcomes and mortality. METHODS: Our study included 133 HD patients (79 male and 54 female patients) with a mean age of 54.6 ± 17.3 years who had been receiving regular HD for at least 6 months in the nephrology units of Theodor Bilharz Research Institute, Cairo, Egypt. The clinical and biochemical correlates of plasma ADPN levels were investigated and the predictive power of ADPN levels with respect to cardiovascular events and mortality was prospectively tested in HD patients, who were monitored for 24 ± 9 months. Plasma ADPN levels were measured by using a sensitive enzyme-linked immunosorbent assay. RESULTS: Plasma ADPN levels were 3 times higher (p < 0.0001) among HD patients (18.1 ± 6.8 µg/ml) than among healthy subjects (6.2 ± 1.8 µg/ml). Plasma ADPN levels were lower (p < 0.007) among patients who experienced new cardiovascular events (13.9 ± 6.4 µg/ml) than among event-free patients (18.6 ± 8.4 µg/ml). The relative risk of cardiovascular events was 1.96 times (95% confidence interval 1.290-2.977, p = 0.0016) higher among patients in group 1 (ADPN <15.1 µg/ml), compared with those in group 2 (ADPN ≥15.1 µg/ml). Plasma ADPN levels were inversely related to BMI, insulin levels, homeostatic model assessment index values, triglyceride and LDL-C, CRP and left ventricular mass index. Furthermore, plasma ADPN levels were directly related to HDL-C. CONCLUSION: Plasma ADPN is an independent (inverse) predictor of cardiovascular events and mortality among HD patients. The directions of the RELATIONSHIPS between ADPN and several metabolic risk factors indicate that ADPN has a protective role in prevention of CVD.

Homing of transplanted bone marrow cells in livers of Schistosoma mansoni-infected mice.

The efficiency of differentiation of bone marrow cells (BMCs) into hepatocytes in vivo and its importance in physiopathological processes is still debated. Murine schistosomiasis was used as a liver injury model and unfractionated male mice BMCs were transplanted through intrahepatic injection into non-irradiated Schistosoma mansoni-infected female mice on their 16th week post-infection. Two weeks after bone marrow transplantation, mice were sacrificed on a weekly basis until 10 weeks. Tracing of male donor-derived cells in female recipient mice livers was carried out by the detection of Y chromosome expression by fluorescent in situ hybridization (FISH) and also of chromodomain Y-linked (CDYL) protein by indirect immunofluorescence (IF). Their transformation into hepatocytes was studied by double labelling indirect IF using antibodies directed against CDYL and mouse albumin. Histopathological and electron microscopic examinations revealed the presence of small hepatocyte-like cells in the periportal tracts and in between the hepatocytes facing the sinusoids. Donor-derived cells showing Y chromosome by FISH and expressing CDYL protein by IF were recovered in the infected transplanted livers. The initial number of these cells increased with increased post-transplantation time. Cells were mainly localized in the periphery of schistosoma granuloma. Few donor-derived cells appeared within the hepatic parenchymal tissue and showed positivity for albumin secretion by double labelling with IF. We suggest that transplanted bone marrow stem cells can repopulate the Schistosoma-infected liver of immunocompetent mice. Their differentiation is a complex event controlled by many factors and needs to be further characterized extensively. The extent and type of liver injury and the number of transplanted cells are important variables in the process of stem cell engraftment and differentiation into functioning hepatic cells that still need to be defined.