Bencyclane as an anti-sickling agent

A vasodilating Ca²⁺ channel blocker, bencyclane, was used in 18 patients with homozygous sickle cell anaemia (SCD) to test the possible anti-sickling effect. With bencylane intervention the Na⁺-K⁺ ATPase activity increased from 256±29 to 331±37 nmol Pi/mg protein/h ( P <0.0001) and the Ca²⁺-Mg²⁺ ATPase level increased from 172±12 to 222±44 nmol Pi/mg protein/h ( P <0.0001). The intracytoplasmic Ca²⁺ concentration reduced from 3.5±0.6 to 2.7±0.25 μmol/l ( P <0.0001). The patient's blood contained fewer irreversibly sickled cells (ISCs) (a reduction from 21.4% to 14.4%) ( P <0.05). At the same time MCHC of the erythrocytes decreased from 34.5 to 33.0 g/dl ( P <0.05). Bencyclane appears to be a promising anti-sickling agent that can be used orally in SCD.     

Synergistic inhibition of platelet activation by plasmin and prostaglandin I2

Endothelial cell prostacyclin (PGI2) inhibits platelet activation by raising platelet cyclic AMP. Previously, platelet activation was also shown to be blocked by plasmin formed by endothelium-derived tissue plasminogen activator (TPA). We have now studied interactions between PGI2 and plasmin in the control of platelet function. PGI2 and plasmin cause synergistic inhibition of thrombin- and ADP-induced aggregation of washed platelets. Inhibition by PGI2 is similarly potentiated by TPA added to platelet-rich plasma to generate plasmin. Thrombin-stimulated rise in platelet cytosolic Ca2+, measured by fura2 fluorescence, and thromboxane A2 formation, measured by radioimmunoassay (RIA), are likewise synergistically inhibited by PGI2 and plasmin. Plasmin neither increases nor potentiates PGI2-stimulated increases in platelet cyclic AMP. Thus, PGI2 and plasmin cause synergistic inhibition of platelet activation by both cyclic AMP-dependent and independent mechanisms. This interaction between two different endothelium-derived products may play an important role in localizing the hemostatic plug to a site of vascular injury by preventing further thrombin-mediated accrual of platelets.