Ischemia leads to impaired ATP metabolism, with increased production of purine degradation products, such as hypoxanthine and xanthine, which are useful markers of tissue hypoxia. These extracellular markers of ischemia have been studied extensively in many clinical conditions of oxidative stress, including perinatal asphyxia, acute respiratory distress syndrome, cerebral ischemia, and preeclampsia. The aim of this study was to explore the usefulness of urinary hypoxanthine and xanthine as ischemia markers in acute coronary syndromes. Urinary excretion of hypoxanthine and xanthine was assessed by high-performance liquid chromatography in 30 patients with acute coronary syndromes and in 30 age- and sex-matched controls. Serum and urine uric acid, creatinine, and urea concentrations were also determined. Hypoxanthine excretion was significantly elevated in patients compared with healthy controls (84.37+/-8.63 and 42.70+/-3.97 nmol/mg creatinine, mean+/-SEM, P<0.0001). Urinary xanthine levels were also increased in patients with acute coronary syndromes (100.13+/-12.14 and 34.74+/-4.07 nmol/mg creatinine patients and controls, respectively; P<0.0001). Hypoxanthine and xanthine excretion showed a strong positive correlation in both groups. Significant negative correlations between urinary hypoxanthine and uric acid and xanthine and uric acid were observed in the patients, but not in controls. In conclusion, increased levels of ATP degradation products hypoxanthine and xanthine are observed in various hypoxic clinical conditions. This study suggests that these parameters may be useful markers of ischemia in patients with acute coronary syndromes.

Background/Aims: To compare the effects of saturated, monounsaturated and polyunsaturated n–6 fatty acid-enriched diets on the development of atherosclerosis and thrombosis in New Zealand white male rabbits, 3- to 6-month-old animals were supplemented daily (10 g/100 g diet) with butter (n = 8), olive oil (n = 8) or corn oil (n = 8) by oral administration for 7 weeks. Methods: Total cholesterol (TC), HDL- (HDL-C) and LDL-cholesterol (LDL-C), triglycerides (TG), apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoB), lipid peroxides as thiobarbituric acid-reactive substances (TBARS), thromboxane B₂ (TXB₂) and 6-ketoprostaglandin F_1α (6-ketoPGF_1α) concentrations were determined in blood samples drawn before and after each group was fed the different dietary regimens. Histological examination was performed on the aortic tissues. Results: After 7 weeks, TC, ApoB and TXB₂ increased significantly (p < 0.05) in the butter-fed animals compared to pre-experimental concentrations. Olive oil administration lead to a significant (p < 0.05) decrease in TC and ApoB levels. The corn oil-enriched diet decreased TC, LDL-C concentrations, TC/HDL-C ratios and 6-ketoPGF_1α (stable metabolite of prostacyclin-PGI_2; p < 0.05 for all) but increased TBARS levels and TXB₂/6-ketoPGF_1α ratios. Light microscopic findings were in accordance with these biochemical alterations. Conclusion: Although effective in lipid lowering, corn oil increased oxidant stress as evidenced by increased TBARS and induced endothelial damage which lead to a reduction in PGI₂ synthesis and consequently to an increase in the TXB₂/6-ketoPGF_1α ratio. Olive oil administration did not induce oxidant stress and it had no affect on PGI₂ and TXB₂ levels which are implicated in platelet aggregation. These findings suggest that oleic acid is more effective than linoleic acid in the protection of endothelial integrity.

Background: Renal involvement in Takayasu’s arteritis (TA) effects the disease outcome and endovascular treatment is an effective treatment of choice. We investigated nitric oxide (NO) levels and the effect of endovascular treatment in renovascular hypertensive TA patients. Methods: In five hypertensive patients with renal artery stenosis due to TA, serum creatinine, nitrite, nitrate; urinary microalbumin, nitrite, nitrate measurements and blood pressures were recorded at entry and after 24 h and 6 weeks of endovascular treatment. Results: Serum NO levels were higher in patients than controls (p = 0.008). Serum and urine NO levels increased 24 h after the treatment and decreased after 6 weeks (p = 0.015; p = 0.01, respectively). After the treatment blood pressures decreased. Urinary microalbumin excretions increased after the intervention (p = 0.02) and returned to normal in patients 1 and 4, and decreased in the others. There were no significant differences in estimated glomerular filtration rate (EGFR), serum creatinine, urinary sodium and potassium levels. Conclusion: Increased NO secretion in these patients may contribute to improve the prognosis of renal function through its vasodilator and antiproliferative activities possibly by counterbalancing the excessive vasoconstrictor actions. Endovascular treatment causes a dilatation-induced shear stress that may be responsible for the increased NO release, which in turn leads to the rapid hypotensive response.

Background/Aim: Nitric oxide supplementation and antioxidant therapy modulate gut barrier function, but the relationships between enhanced nitric oxide production, antioxidant administration, and biliary obstruction remain unclear. We evaluated the role of nitric oxide and α-tocopherol supplementation in bile duct ligated rats. Methods: Fifty male Wistar albino rats underwent sham operation (group I; control animals) or bile duct ligation (groups II, III, IV, and V). The ligation groups received the following regimens: standard pellet diet (group II), pellet diet plus intramuscularly administerd α-tocopherol (group III), and L-arginine-enriched pellet diet without (group IV) or with (group V) α-tocopherol. Nitric oxide, malondialdehyde, and α-tocopherol concentrations were assessed at the end of 3 weeks. Liver and intestinal samples were scored histologically. Mesenteric lymph node and liver cultures were assessed for bacterial translocation. Results: The liver malondialdehyde concentration was highest in group III. The nitric oxide content in the liver was higher in groups III and V, as were the blood α-tocopherol levels. Bacterial translocation was evident following bile duct ligation, but did not differ among the treatment groups. Intestinal histology revealed that group III had the lowest villus height, that group V had the least villus count, and that group II had the highest mucous cell count. The fibrosis scores were higher in groups IV and V. Conclusions: An obvious effect of α-tocopherol (with or without L-arginine) on the gut barrier could not be demonstrated. Moreover, the L-arginine-enriched diet promoted fibrosis in the liver. Thus, while biliary duct obstruction triggers bacterial translocation, nitric oxide and/or α-tocopherol supplementation did not seem to improve the gut barrier in our model.