No abstract

To elucidate some of the links between homocysteine and vascular disease, we have evaluated the effect of the amino acid on the formation (by kinetics studies), structure (by electron microscopy) and lysis of the fibrin network, using tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). We have studied whether homocysteine could alter the activity of the components involved in fibrinolysis (by amidolytic and thrombolytic methods). The results showed that homocysteine-associated networks were more compact and branched than controls (52 +/- 6 vs 44 +/- 5 fibers/field, P = 0.008), and were formed by shorter and thicker fibers. This clot proved to be more resistant to fibrinolysis with u-PA than control [lysis time 50%: 257 +/- 16 (homocysteine) vs 187 +/- 6 min (control); P < 0.004], but there were no differences with t-PA. Homocysteine did not affect the biological activities of plasmin, or plasminogen activation by t-PA and u-PA. Defective fibrinolysis with u-PA was therefore associated with homocysteine-fibrin structural alterations rather than the homocysteine effect on the biological activities of the fibrinolytic components evaluated. Results suggest that hyperhomocysteinemic patients could produce tight clots, were more resistant to lysis, and generated a procoagulant environment in situ. We believe that our findings may contribute to understanding the mechanisms involved in the homocysteine harmful effect.

Based on our results, we propose 12 micromol/L as the hyperhomocysteinemia cutoff value.

Aluminium (All toxicity has been associated with anaemia in exposed patients with chronic renal failure (CRF). The present study was undertaken to determine whether the ingestion of A1 citrate was able to affect erythropoiesis in rats with normal or impaired renal function. The renal insufficiency was induced by surgical procedures and control rats were sham operated. Twenty-four rats were allocated to four groups of six rats each: (A) Sham; (B) Sham+Al; (C) CRF; and (D) CRF+Al. The groups B and D received daily doses of A1 citrate (0.5 pmol/g bodyweight) and the groups A and C, deionized water, via the intragastric route. At the end of the experimental period (15 weeks) cultures of late erythroid progenitor cells (CFU-E) stimulated with erythropoietin were performed and haematological parameters determined. The liver, kidney, brain, bone and serum A1 amounts were quantified. The results are expressed as median and interquartile range. The CFU-E growth was found inhibited in B and D groups (A: 100; B: 74/54-83; C: 86/54-98; D: 46/39-53 %). The haematocrit values were significantly diminished in rats with renal insufficiency when compared to controls (A: 42/40-43; B: 45/42-46; C: 37/32-40 and D: 37/24-39 %). Serum A1 accumulation was observed in B and D groups receiving A1 (A: 8/5-12; B: 36/3644; C: 5 / 5 4 D: 45/26-132 pg Al/I). No differences among groups were found in the liver and kidney A1 contents, but uraemic state favoured A1 accumulation in brain (A: 6/5.0-9.0; B: 4/3.84.3; C: 2/2.0-3.0; D: 15/12.0-21.0 pg Al/g tissue) and bone (A: 29/27-31; B: 30/29-39; C: 42/33-48; D: 68/56-79pg Al/g tissue). We suggest that the heavy accumulation of A1 in the bone compartment may result in a protracted endogenous exposure of bone marrow cells, affecting the erythropoiesis in uiuo.