Syringaresinol causes vasorelaxation by elevating nitric oxide production through the phosphorylation and dimerization of endothelial nitric oxide synthase

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays an important role in vascular functions, including vasorelaxation. We here investigated the pharmacological effect of the natural product syringaresinol on vascular relaxation and eNOS-mediated NO production as well as its underlying biochemical mechanism in endothelial cells. Treatment of aortic rings from wild type, but not eNOS-/- mice, with syringaresinol induced endothelium-dependent relaxation, which was abolished by addition of the NOS inhibitor NG-monomethyl-L-arginine. Treatment of human endothelial cells and mouse aortic rings with syringaresinol increased NO production, which was correlated with eNOS phosphorylation via the activation of Akt and AMP kinase (AMPK) as well as elevation of intracellular Ca2+ levels. A phospholipase C (PLC) inhibitor blocked the increases in intracellular Ca2+ levels, AMPK-dependent eNOS phosphorylation, and NO production, but not Akt activation, in syringaresinol-treated endothelial cells. Syringaresinol-induced AMPK activation was inhibited by co-treatment with PLC inhibitor, Ca2+ chelator, calmodulin antagonist, and CaMKKbeta siRNA. This compound also increased eNOS dimerization, which was inhibited by a PLC inhibitor and a Ca2+-chelator. The chemicals that inhibit eNOS phosphorylation and dimerization attenuated vasorelaxation and cGMP production. These results suggest that syringaresinol induces vasorelaxation by enhancing NO production in endothelial cells via two distinct mechanisms, phosphatidylinositol 3-kinase/Akt- and PLC/Ca2+/CaMKKbeta-dependent eNOS phosphorylation and Ca2+-dependent eNOS dimerization.

Comparing Biological Markers of Alcohol Dependence in the Patients of an Alcohol Counseling Center

OBJECTIVES: Biochemical markers can provide an objective evidence of heavy alcohol drinking. The purpose of this study was to compare and evaluate the usefulness of biological markers detecting alcohol dependence, such as mean corpuscular volume(MCV), gamma-glutamyl transferase(GGT), and carbohydrate-deficient transferrin(CDT) in the patients of an alcohol counseling center. METHODS: This study was done with 64 patients with alcohol dependence and 36 healthy subjects. Relative values(%) of CDT were determined in their sera with turbidimetric immunoassay(Bio-Rad %CDT assay, Axis-Shield ASA, Oslo, Norway), and were compared with conventional markers of alcohol consumption, GGT and MCV. RESULTS: Among the patients with alcohol dependence, 78.1% showed abnormal %CDT levels compared with GGT(61.9%) and MCV(20.7%). The areas under the receiver operating characteristic(ROC) curves(95% confidence interval) for %CDT, GGT, and MCV were 0.934(0.866-0.973), 0.871(0.789-0.930), and 0.575 (0.472-0.673), respectively. CONCLUSION: %CDT seems to be the most reliable biological marker for the detection and monitoring of alcohol consumption in the patients with alcohol dependence of the alcohol counseling center.

Adult-to-Adult Living Donor Liver Transplantation

BACKGROUNDS: Living-donor liver transplantation (LDLT) has been established as an efficacious option to resolve the shortage of cadaveric donor organs for pediatric recipients. This surgical innovation has significantly reduced the pretransplantation mortality for children, but the crisis of increasing scarcity of donor organs in our hospital has led us to extend LDLT to adult recipients. However, the extension of LDLT from pediatric recipients to adult recipients has been made only with limited success largely because of the inability of a relatively small-size left-lobe graft to meet the metabolic demands of an adult recipient. It has been postulated that a left-lobe graft smaller than 40% of the recipient's standard liver volume will not result in a successful adult-to-adult LDLT in chronic parenchymal liver disease. METHODS: From February 1997 to October 1997, 10 LDLTs, using 9 extended left-lobe grafts and 1 right-lobe graft, were performed on patients with end-stage parenchymal liver diseases (9 cases of B-hepatitis-induced cirrhosis with or without an associated hepatocellular carcinoma and 1 case of alcoholic cirrhosis) at the Department of Surgery, Asan Medical Center. The ratios of the graft to the standard liver volume of the recipients were in the range of 30% to 55%. RESULTS: All grafts showed immediate function, but delayed normalization of the serum total bilirubin was demonstrated in all recipients receiving left-lobe grafts. There were no mortalities and serious complications in donors. Two recipients died of sepsis 21 days and 40 days after transplantation, and 8 recipients (80%) are alive with good liver function at a median follow-up of 5.1 months (range 2~10 months). CONCLUSIONS: The aim of this article is to report our experience with adult-to-adult LDLT shows that a graft size greater than 30% of the recipient's standard liver volume is able to meet the metabolic demands of adult recipients with chronic parenchymal liver disease and that LDLT might open a new donor pool for adult recipients when the supply of cadaveric organs is severely restricted.