CD36 gene polymorphism and plasma sCD36 as the risk factor in higher cholesterolemia.

INTRODUCTION: The receptor CD36 has been reported to play an important role in atherogenicity. The aim of this study was to gain insight into the relationship between CD36 gene polymorphisms or the plasma concentration of sCD36 and clinical or biochemical parameters in children. PATIENTS AND METHODS: The study groups comprised Caucasian children with and without hypercholesterolemia. The alterations in the CD36 gene were detected by DHPLC and the plasma concentrations of sCD36 were measured by ELISA. RESULTS: The data presented suggest that the IVS4-10A allele of CD36 (rs3211892) is associated with a lower risk of hypercholesterolemia. We observed a negative correlation of the sCD36 concentration with uric acid and insulin concentrations, the HOMA-IR ratio, weight, waist and hip circumference, systolic blood pressure, body mass index, waist-hip ratio and mean arterial pressure ratio, but a positive correlation with HDL cholesterol and ApoA1 concentrations. Female gender was a significant independent predictor of a higher plasma sCD36 concentration. CONCLUSIONS: The data presented suggest a possible protective effect of a higher sCD36 concentration in relation to metabolic syndrome components.

Inhibition of erythrocyte phosphoribosyltransferases (APRT and HPRT) by Pb2+: a potential mechanism of lead toxicity.

Many reports show that red blood cells of people exposed to lead have a decreased ATP concentration, decreased adenylate energy charge value and many metabolic and morphological abnormalities. Since the synthesis of nucleotides in erythrocytes occurs only through salvage pathways, we hypothesized that a decrease in nucleotide concentrations may be caused by lead-induced inhibition of erythrocyte phosphoribosyltransferases: adenine APRT (EC 2.4.2.7) and hypoxanthine-guanine HPRT (EC 2.4.2.8). These enzymes enable the reutilization of purine bases (adenine, guanine, hypoxanthine) converting them to mononucleotides (AMP, GMP, IMP), substrates for the synthesis of high-energy nucleotides. To confirm the hypothesis two experiments were performed: (i) in vitro, using a lysate of human erythrocytes incubated (5, 10, 30min) with lead ions (100microM, 10microM, 1microM, 500nM, 100nM lead acetate) and 100microM sodium acetate for the control, (ii) in vivo, using a lysate of rat erythrocytes taken from rats chronically exposed to lead (0.1% lead acetate in drinking water for 9 months, resulting in whole blood lead concentration 7microg/dL). The activities of APRT and HPRT were determined using HPLC method, which allowed concurrent determination of the activity of both enzymes in erythrocyte lysates. We have shown that, lead ions: (i) moderately inhibit both phosphoribosyltransferases in erythrocytes, this influence being detectable even at very low concentrations (ii) participate in hemolysis, the intensity of which negatively correlates with the activity of phosphoribosyltransferases. Our results indicate the necessity of further research on the role of lead-induced APRT and HPRT inhibition as one of the mechanisms of lead toxicity.

Hypoxanthine as a graft ischemia marker stimulates catalase activity in the renal vein during reperfusion in humans.

BACKGROUND: The impairment of organ function derived from ischemia-reperfusion injury is still an important problem in solid organ transplantation. Cell alterations induced by ischemia prime the tissue for subsequent damage occurring during the reperfusion phase. Purine nucleotides and oxypurines are products of adenine nucleotide degradation. Reperfusion and reoxygenation are characterized by great production of reactive oxygen species and free radicals. On the contrary, superoxide dismutase, catalase, glutathione, and glutathione peroxidase are involved in protecting against free radicals. The aim of the study was to examine the correlation between concentrations of ischemia markers (hypoxanthine or inosine) and the activity of erythrocyte superoxide dismutase, catalase, or glutathione peroxidase. PATIENTS AND METHODS: The study included 40 renal transplant recipients. Before anastomosis of the kidney vessels with the recipient's iliac vessels, a "0" blood sample was taken from the iliac vein. Then, after anastomosis, the renal vein of the graft was cannulated and blood samples I, II, and III were obtained. The reperfusion of the transplanted kidney was measured with a thermovision camera ThermaCAM SC500. RESULTS: The plasma concentrations of hypoxanthine and inosine increased in statistically significant fashion immediately after total tissue reperfusion (P < .0001). Catalase activity at 4 minutes after total tissue reperfusion correlated positively with hypoxanthine concentrations immediately after total tissue reperfusion (Rs = +0.49), 2 minutes after total tissue reperfusion (Rs = +0.47), and 4 minutes after total tissue reperfusion (Rs = +0.46). There were no statistically significant correlations between hypoxanthine or inosine concentrations or superoxide dismutase or glutathione peroxidase activities. CONCLUSIONS: The results of the present study suggest that catalase activity may correlate with the concentration of hypoxanthine in the graft renal vein and other mediators of oxidative stress.

Myocardial and coronary sinus purines as indicators of pig heart energy metabolism during reperfusion after extracorporeal circulation.

AIM: The precise understanding of myocardial metabolism is crucial for the optimization of cardiosurgical procedures. We attempted to gain a comprehensive insight into the purine metabolism of the porcine heart during reperfusion by measuring concentrations of nucleotides, nucleosides and oxypurines simultaneously in the myocardium and coronary sinus. METHODS: Twenty-five pigs were subjected to sham cardiosurgery with extracorporeal circulation and cold cardioplegic arrest of 60 min. Myocardial biopsies, as well as coronary sinus and arterial blood samples were taken before aortic clamping and at 5, 20, 60 and 120 min of reperfusion. HPLC was used to measure concentrations of 17 purines in the bioptates and of 5 in plasma. RESULTS: Reperfusion rapidly normalized the ischaemic decrease in the adenylate energy charge of the myocardium, but during 120 min failed to restore the reduced adenylate pool, because of irreversible loss of nucleosides by cardiomyocytes. Low adenylate energy charge and depletion of the adenylate pool were accompanied by analogous changes in the guanylates and growing deficit of NAD and NADP. Reperfusion was marked by significant release of inosine and guanosine from the heart, without any noticeable effect on hypoxanthine and xanthine. CONCLUSIONS: Coronary sinus concentrations of purines provide only a limited insight into the metabolism of the porcine heart. Repeated biopsies of the heart muscle and HPLC determinations of purine profiles represent a comprehensive and unique method for the study of purine metabolism during ischaemia and reperfusion. Future research on myocardial metabolism in disease and during cardiosurgical procedures should additionally be oriented to deficits in guanine and pyridine nucleotides.