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  • 1
    ISSN: 1432-1440
    Keywords: Granulocyte lysosomal factors ; Elastase ; Acute and chronic uremia ; Catabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In uremic intoxication proteolytic activity in plasma and striated muscle is enhanced. To get further insights into the underlying mechanisms the lysosomal factors of polymorphonuclear (PMN) leukocytes and the plasma elastase-α 1-proteinase inhibitor complex were investigated in patients with acute and chronic renal failure. Lysosomal activity was evaluated in peripheral blood smears by the lysis of erythrocytes and plasma (halo formation) around each neutrophil induced by 0.25 M NaCl borate buffer. In about half of the patients with chronic renal insufficiency on dietary treatment lysosomal activity of PMN leukocytes was reduced. The plasma concentration of elastase-α 1-proteinase inhibitor complex was normal in most subjects, but increased in three patients with the highest serum creatinine levels (〉13 mg/dl). In the patients with acute renal failure (ARF) of various origin (postoperatively, septicemia, pancreatitis, or dye-induced) halo formation was either reduced or absent. The plasma elastase-α 1-proteinase inhibitor complex was increased in 5/6 of the patients by a factor of two to four. Also in the patients on regular hemodialysis treatment halo formation of PMN leukocytes was substantially reduced, whereas the plasma levels of elastase-α 1-proteinase inhibitor complex was slightly increased. The finding of reduced lysosomal activity of PMN neutrophils in uremia may be partly due to an enhanced release of neutral proteinases into the circulation as indicated by the elevated plasma levels of elastase-α 1-proteinase inhibitor complex in some patients. This release might be in part due to the effect of “uremic toxins”. In the patients on hemodialysis treatment the contact of the blood with the dialyzer (cuprophane) membrane might be an additional factor. Moreover, in the patients with acute renal failure the underlying disease (infection, shock, trauma) contributes to the release of proteinases. These disturbances may be harmful to the patient if the blood concentration or function of the most important proteinase inhibitors (α 1-proteinase inhibitor,α 2-macroglobulin) is reduced.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Type-IIa hypercholesteremia ; Lovastatin ; Platelet function ; Fibrinogen ; Clotting inhibitors ; Fibrinolytic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a study of 20 patients with hypercholesterolemia (type IIa) the effects of lovastatin (20–80 mg/ day) on various clotting and thrombosis parameters were monitored for 12 months. On 11 occasions various cholesterol fractions and clotting parameters were determined in each patient. In additon, the clotting inhibitors AT III, protein C, protein S, and C1-esterase inhibitor and the fibrinolysis parameters plasminogen and α2-antiplasmin were examined. Platelet function was monitored on the basis of spontaneous and induced (collagen, ADP, epinephrine, ristocetin) aggregation. Lovastatin in the above dosage brought about a 66 mg/dl (from 320 ± 12.6 to 254 ± 12.0 mg/dl) reduction in the total cholesterol level and a 56 mg/dl (from 244 ± 11.4 to 188 ± 12.1 mg/dl) reduction in LDL cholesterol at the end of the study. Fibrinogen showed a significance decrease during the study period, whereas PT and aPTT remained unaffected. The initial slopes of the ADP-induced platelet aggregation revealed a significant decrease. C-reactive protein and platelet count remained within the normal range, indicating no significant change. Thrombin clotting time, AT III, Cl-esterase inhibitor, plasminogen, and α2-antiplasmin were not modified. Protein C and S behaved in a contradictory way, but remained within the normal range. Long-term treatment with lovastatin was associated with a significant reduction of fibrinogen levels and platelet aggregation induced by ADP in type-IIa hypercholesterolemic patients. These alterations, as well as their role in cardiovascular disease, should be the subject of further investigations.
    Type of Medium: Electronic Resource
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