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Biomedical subjects

M Garcia-Maldonado

Publications and source records attributed to M Garcia-Maldonado.

4 recordsLinked to original sources

Decrease in endothelial cell-dependent protein C activation induced by thrombomodulin by treatment with cyclosporine.

The use of cyclosporine has been associated with an increased incidence of thrombosis and endothelial cell perturbation. To explore possible mechanisms involved, we examined the effects of CSA on the activation of protein C by thrombomodulin. Cultured bovine aortic endothelial cell monolayers were incubated for 24 hr with a wide range of CSA concentrations. After removal of CSA and incubation with thrombin and purified protein C, thrombomodulin-dependent protein C activation was measured with an S-2238-based kinetic chromogenic assay. As compared to control, a significant fall in thrombomodulin activity occurred after 24-hr incubation with 100 (70.8 +/- 15.8%, P less than 0.05), 1000 (64.9 +/- 16.6%, P less than 0.05), or 10,000 (28.9 +/- 12.3%, P less than 0.05) ng/ml of CSA. A comparable inhibition of thrombomodulin activity was also observed in cultured renal artery endothelial cells (67.5 +/- 12.6%, P less than 0.05), after 24-hr incubation with 5000 ng/ml CSA. In cells incubated with 5000 ng/ml of CSA for 4 hr, thrombomodulin activity fell by almost 15% (85.6 +/- 8.3%, P less than 0.05) and tended to plateau between 7 hr (73.8 +/- 12.7%, P less than 0.05), and 24 hr of incubation (72.7 +/- 8.9%, P less than 0.05). These results indicate that CSA produces a time- and dose-dependent reduction in thrombomodulin activity of cultured endothelial cells, downregulating the protein C anticoagulant pathway, thereby increasing the risk of thrombosis.

Animals

Mental performance in CAPD.

Impaired cognitive function is part of an array of neurologic manifestations seen in patients with end stage renal disease. We investigated whether a difference exists in mental performance between patients on hemodialysis and on CAPD. The trial test A was administered in standardized fashion, and the time required to complete the test was used as a function of mental performance. A group of age and sex matched healthy controls was included for comparison. The results indicate that performance in the trail test A was markedly different among the three groups; controls did the test in 30.7 +/- 2.4 sec (n = 17), CAPD in 47.2 +/- 6.4 (p less than 0.05) and hemodialysis patients in 82.6 +/- 11 (p less than 0.005). Patients on CAPD completed the test significantly faster than those on hemodialysis (p less than 0.05). This observation of a significantly better mental performance by patients in CAPD than in patients in hemodialysis is likely to be multifactorial, and its significance is unclear, but this may be of interest to the clinician and patients contemplating different dialysis modalities.

Humans

PTH levels correlate with mental performance in CAPD.

Nervous system dysfunction remains a major cause of disability in patients with end stage renal disease. The mechanisms remain unclear, but elevated levels of parathyroid hormone (PTH) have been proposed to act as a neurotoxin in uremia. Previous studies have mainly used electroencephalographic techniques to assess mental performance in patients in dialysis. This study utilized the trail test A and the Pennsylvania bimanual dexterity work sample to evaluate mental performance of patients in CAPD and to correlate their performance with parathyroid hormone levels. Ten male patients from the same CAPD unit, with comparable dialysis dose, underwent standardized testing. Subjects had a mean +/- SE age of 50.8 +/- 3.66 years and had been on CAPD for a mean of 42.4 +/- 12.2 months. Each used 10-12 liters of dialysis per day, with a mean peritoneal dialysis index of 1.04 +/- 0.05 and Kt/V (UN/wk) of 2.35 +/- 0.39. Mental performance of patients with lower intact PTH levels 151.7 +/- 20.8 ng/ml (Group 1) was 34.4 +/- 2.8 min in the trail test A and patients with the higher PTH-mm level (414.0 +/- 21.4 ng/ml) was 58.2 +/- 10.8 min (p = 0.06). Whereas the bi-manual dexterity test was completed in 7.27 +/- 0.5 min by Group 1 and in 11.1 +/- 0.2 by Group 2 (p = 0.003). This study favors the hypothesis that PTH levels may be associated with the impaired mental performance observed in patients with end stage renal disease.

Adult