Factors responsible for cerebral hypoxia in hemodialysis population.

Brain tissue oxygenation (rSO(2)) measured by near-infrared spectroscopy (NIRS) is lower in hemodialysis patients than in the healthy population and is associated with cognitive dysfunction. The involved mechanisms are not known. We conducted this study to identify the factors that influence the rSO2 values in end-stage renal disease (ESRD) patients and to describe rSO2 changes during hemodialysis. We included a cohort of ESRD patients hemodialyzed in our institution. We recorded rSO2 using INVOS 5100C oximetry system (Medtronic, Essex, U.K.) and analyzed changes in basic laboratory values and hemodynamic fluctuations. Baseline rSO2 was lower in patients with heart failure (45.2±8.3 % vs. 54.1±7.8 %, p=0.006) and was significantly linked to higher red cell distribution width (RDW) (r=-0.53, p?0.001) and higher BNP level (r=-0.45, p=0.01). The rSO(2) value decreased in first 15 min of hemodialysis, this decrease correlated with drop in white blood count during the same period (r=0.43, p=0.02 in 10 min, r=0.43, p=0.02 in 20 min). Lower rSO(2) values in patients with heart failure and higher RDW suggest that hemodynamic instability combined with vascular changes probably leads to worse cerebral oxygenation in these patients. Decrease of rSO(2) in 15th minute of hemodialysis accompanied with a significant drop in leukocyte count could be explained by complement activation.

Reduction of DNA-damaging effects of anti-HIV drug 3'-azido-3'-dideoxythymidine on human cells by ursolic acid and lignin biopolymer.

In this study we verified our assumption that the genotoxicity of the effective anti-HIV drug 3'-azido-3'-dideoxythymidine (AZT) on human cells could be reduced by non-toxic concentrations of two antioxidants that occur frequently in nature (ursolic acid and lignin biopolymer). Cytotoxicity of these natural compounds, well-known by their antimutagenic effects, was evaluated by the trypan blue exclusion technique. Genotoxic activity of AZT was measured on the basis of AZT-induced single and double strand breaks to DNA in two histopathologically different types of human cells, hepatoma cells HepG2 and colonic cells Caco-2. Induction of DNA strand breaks was measured by the comet assay processed in parallel at pH > or = 13.0 (standard alkaline technique which enables to recognize single strand DNA breaks of different origin) and at pH = 9.0 (neutral technique which enables to recognize double strand DNA breaks). As the level of AZT-induced double strand DNA breaks was rather low, protective effects of the antioxidants tested were evaluated only against AZT-induced single strand DNA breaks by the standard alkaline comet assay. Our findings showed that 1 h pre-incubation of cells with ursolic acid or lignin preceding to 3 h treatment of cells with AZT (3 mg/ml) significantly decreased in both cell types the level of AZT-induced single strand DNA breaks. Pre-incubation of HepG2 or Caco-2 cells with a mixture of both natural antioxidants did not increase the effects of individual treatments. This study confirms that AZT is genotoxic toward both used cell types of human origin and that ursolic acid and biopolymer lignin can protect the cells studied against genotoxic effect of AZT.