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In order to test the existence of a possible oxidative damage during hemodialysis, plasma conjugated dienes (CD), plasma and red blood cell (RBC) thiobarbituric acid (TBA) reactants were investigated in 25 patients receiving regular dialysis treatment (RDT). The RBC TBA reactant concentration was significantly increased in RDT patients in comparison with healthy subjects. The extracellular antioxidant systems were evaluated by the assay of plasma antioxidant activity, plasma tocopherol, urate, transferrin, haptoglobin and ceruloplasmin levels. Except urate and transferrin, none of these parameters were different between the two groups. On the other hand, in RDT patients, RBC superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were significantly lower than in healthy subjects. There was an inverse correlation between decreased RBC GPX and RBC TBA reactant concentration. These results show in RDT patients the existence of an oxidizing stress, mainly intracellular, which could be due, in part, to a decrease in SOD and GPX activities.

Two series of compounds, substituted benzoselenazolinones and their opened analogs, diselenides, were prepared. The diselenides were designed according to the available SAR about glutathione peroxidase mimics and were expected to have activity. An initial series of tests was performed in order to assess the glutathione peroxidase and antioxidant activity of the diselenides compared to their cyclized analogs. The diselenides were shown to be very potent (up to 3 times the activity of ebselen), whereas the benzoselenazolinones were inactive, thus confirming our hypothesis. A second series of tests was done to determine the anti-inflammatory potency of the two series. Both were found to be potent on cyclooxygenase and 5-lipoxygenase pathways (up to 95% inhibition at 10(-5) M). Some compounds were selective, and the variations in the activity allowed us to draft some structure-activity relationships. The most interesting compound of each series, 6-benzoylbenzoselenazolinone and bis[(2-amino-5-benzoyl)phenyl] diselenide, was tested in vivo on the rat foot edema induced with different phlogistic agents and was shown to have some anti-inflammatory properties.

No abstract

Background-Prognostic evaluation of patients with primary pulmonary hypertension (PPH) requires right heart catheterisation. The development of accurate non-invasive methods for monitoring these patients remains an important task. Cyclic guanosine monophosphate (cGMP) is an indicator of the action of natriuretic peptides and nitric oxide on target cells. Plasma and urinary cGMP concentrations are raised in patients with congestive heart failure in whom they correlate closely with haemodynamic parameters and disease severity. The aim of the present study was to determine whether the urinary concentration of cGMP could be used as a non-invasive marker of haemodynamic impairment in patients with severe PPH. Methods-Urinary