Effect of Cordycepin-Enriched WIB801C from Cordyceps militaris Suppressing Fibrinogen Binding to Glycoprotein IIb/IIIa

In this study, we investigated the effects of cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha on collagen-stimulated platelet aggregation. CE-WIB801C dose dependently inhibited collagen-induced platelet aggregation, and had a synergistic effect together with cordycepin (W-cordycepin) from CE-WIB801C on the inhibition of collagen-induced platelet aggregation. CE-WIB801C and cordycepin stimulated the phosphorylation of VASP (Ser157) and the dephosphorylation of PI3K and Akt, and inhibited the binding of fibrinogen to glycoprotein IIb/IIIa (alphaIIb/beta3) and the release of ATP and serotonin in collagen-induced platelet aggregation. A-kinase inhibitor Rp-8-Br-cAMPS reduced CE-WIB801C-, and cordycepin-increased VASP (Ser157) phosphorylation, and increased CE-WIB801C-, and cordycepin-inhibited the fibrinogen binding to alphaIIb/beta3. Therefore, we demonstrate that CE-WIB801C-, and cordycepin-inhibited fibrinogen binding to alphaIIb/beta3 are due to stimulation of cAMP-dependent phosphorylation of VASP (Ser157), and inhibition of PI3K/Akt phosphorylation. These results strongly indicate that CE-WIB801C and cordycepin may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

Cordycepin-Enriched WIB801C from Cordyceps militaris Inhibits Collagen-Induced Ca2+i Mobilization via cAMP-Dependent Phosphorylation of Inositol 1, 4, 5-Trisphosphate Receptor in Human Platelets

In this study, we prepared cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha, and investigated the effect of CE-WIB801C on collagen-induced human platelet aggregation. CE-WIB801C dose-dependently inhibited collagen-induced platelet aggregation, and its IC50 value was 175 microg/ml. CE-WIB801C increased cAMP level more than cGMP level, but inhibited collagen-elevated [Ca2+]i mobilization and thromboxane A2 (TXA2) production. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased the CE-WIB801C-downregulated [Ca2+]i level in a dose dependent manner, and strongly inhibited CE-WIB801C-induced inositol 1, 4, 5-trisphosphate receptor (IP3R) phosphorylation. These results suggest that the inhibition of [Ca2+]i mobilization by CE-WIB801C is resulted from the cAMP/A-kinase-dependent phosphorylation of IP3R. CE-WIB801C suppressed TXA2 production, but did not inhibit the activities of cyclooxygenase-1 (COX-1) and TXA2 synthase (TXAS). These results suggest that the inhibition of TXA2 production by WIB801C is not resulted from the direct inhibition of COX-1 and TXAS. In this study, we demonstrate that CE-WIB801C with cAMP-dependent Ca2+-antagonistic antiplatelet effects may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

Inhibitory Effects of Epigallocatechin-3-Gallate on Microsomal Cyclooxygenase-1 Activity in Platelets

In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins from green tea leaves, on activities of cyclooxygenase (COX)-1 and thromboxane synthase (TXAS), thromboxane A2 (TXA2) production associated microsomal enzymes. EGCG inhibited COX-1 activity to 96.9%, and TXAS activity to 20% in platelet microsomal fraction having cytochrome c reductase (an endoplasmic reticulum marker enzyme) activity and expressing COX-1 (70 kDa) and TXAS (58 kDa) proteins. The inhibitory ratio of COX-1 to TXAS by EGCG was 4.8. These results mean that EGCG has a stronger selectivity in COX-1 inhibition than TXAS inhibition. In special, a nonsteroid anti-inflammatory drug aspirin, a COX-1 inhibitor, inhibited COX-1 activity by 11.3% at the same concentration (50 microM) as EGCG that inhibited COX-1 activity to 96.9% as compared with that of control. This suggests that EGCG has a stronger effect than that of aspirin on inhibition of COX-1 activity. Accordingly, we demonstrate that EGCG might be used as a crucial tool for a strong negative regulator of COX-1/TXA2 signaling pathway to inhibit thrombotic disease-associated platelet aggregation.

Clinical Analysis of Neonatal Microtia

PURPOSE: Neonatal microtia is an external ear deformity that takes various forms in degrees from minor deformity to aural atresia. Microtia causes not only simple deformity of the auricle but also the deformity of the middle ear or/and the internal ear leading to hearing loss. We intended to analyze the clinical manifestation of microtia in neonate period. METHODS: 17 neonates born with microtia who were admitted to Kyung Hee Hospital from January 1994 to June 2003 were evaluated for clinical characteristics including associated anomalies, outcomes, findings of temporal computer tomogram (CT) and auditory brainstem response test. RESULTS: The most common type of microtia was grade III (64.7%) followed by grade II (29.4%) and grade I (5.9%) according to the Marx classification. Temporal CT was carried out in 15 cases which showed external ear abnormalities in 7 cases, external and middle ear abnormalities in 5 cases, and external middle and internal ear abnormalities in 3 cases. 7/15 (46.7%) cases had partial hearing loss, followed by 4/15 (26.7%) cases of total hearing loss and 4/15 (26.7%) cases of normal hearing. Associated anomalies among 8/17 (47%) cases included congenital heart disease, celft palate and lip, microcephaly, micrognathia, CONCLUSION: Neonate born with microtia should be evaluated and followed closely for combined anomalies such as middle or internal ear deformities as these may lead to hearing loss affecting language and emotional development.

Two Cases of Rotor Syndrome in Siblings / 소아과

Rotor syndrome is a rare benign familial disorder characterized by chronic, fluctuating, nonhemolytic and predominantly direct bilirubinemia with normal liver tissue. We have recently experienced two cases of Rotor syndrome in a brother and sister. They revealed icteric sclerae with mild hepatomegaly in physical examination. Laboratory findings showed increased serum bilirubin with direct bilirubin predominance. The urinary excretion of total coproporphyrin was slightly elevated. The 99mTc-DISIDA scan showed a markedly decreased hepatic uptake and poor visualization of gallbladder and biliary tree which could be compatible to the Rotor syndrome. We report two cases with a review of the literature.