Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thromboembolism is a serious complication after Fontan operation, which may be caused by alterations of the coagulation system. We therefore investigated pro- and anticoagulant factors in 20 patients aged 4 to 21 years, 4 to 63 months following total cavopulmonary connection. Furthermore we compared markers of thrombin activation and fibrinolysis and in vitro clotting and clot-lysis to age-matched healthy subjects. Compared to results of age-matched controls, the Fontan operated individuals had significant decreases in levels of protein C (0.88 U/ml in controls, 0.67 U/ml in patients; p <0.001) and protein S (1.05 in controls, 0.93 U/ml in patients; p <0.05). Moreover, half of the patients had high values of FVIII (>1.5 IU/ml), which are associated with an increased thrombotic risk. These changes may result in enhanced generation of thrombin and plasmin, indicated by our finding of increased thrombin-antithrombin III (TAT) and plasmin-antiplasmin (PAP) levels and a similar trend in prothrombin fragments F1+2. Clot lysis tests, global coagulation tests, red blood cell count, liver enzymes AST, ALT, but not GGT, were generally within the normal ranges.
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PMID:Hemostatic changes following the modified Fontan operation (total cavopulmonary connection). 1181 32

This study was conducted to evaluate some anticoagulants' (protein C, protein S and antithrombin) activities among epileptic children treated with VPA and to learn if thromboembolic events occur among these children or their parents. Twenty-five boys and 15 girls using VPA for at least 3 months were included in the VPA group. The control group consisted of 28 boys and 12 girls who had no infection and did not use any medication that could alter protein C activity. Complete blood counts, ALT, AST, PT, aPTT, fibrinogen, protein C, protein S and AT tests were studied in both groups. Serum VPA levels were determined in the VPA group. Protein C and protein S activities of the children in the VPA group were significantly lower than those in the control group (89.5+/-19.3% vs 104.9+/-21.7% and 44.6+/-16.3% vs 59.4+/-28.4%, respectively). Neither children using VPA, nor their parents had any thromboembolic events in medical history. Platelet counts, ALT and fibrinogen levels in the VPA group were significantly lower than those in the controls. A negative correlation was found between serum VPA level and platelet counts. There were also negative correlations between fibrinogen and serum VPA levels, and between fibrinogen level and protein S activity. The children in the VPA group had lower PT and higher aPTT levels than the children in the control group. Since other factors known to alter the anticoagulant activities and liver functions were eliminated initially, the decreases of protein C and protein S activities, thrombocyte counts, ALT, PT and fibrinogen levels and increase in aPTT level may be attributed to VPA. VPA hepatotoxicity can be the cause of decreased pro- and anticoagulant activities.
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PMID:Protein C, protein S and other pro- and anticoagulant activities among epileptic children using sodium valproate. 1684 52

S-nitrosoglutathione reductase is the primary enzyme responsible for the metabolism of S-nitrosoglutathione (GSNO), the body's main source of bioavailable nitric oxide. Through its catabolic activity, GSNO reductase (GSNOR) plays a central role in regulating endogenous S-nitrosothiol levels and protein S-nitrosation-based signaling. By inhibiting GSNOR, we aim to increase pulmonary GSNO and induce bronchodilation while reducing inflammation in lung diseases such as asthma. To support the clinical development of N6022, a first-in-class GSNOR inhibitor, a 14-day toxicology study was conducted. Sprague-Dawley rats were given 2, 10 or 50 mg/kg/day N6022 via IV administration. N6022 was well tolerated at all doses and no biologically significant adverse findings were noted in the study up to 10 mg/kg/day. N6022-related study findings were limited to the high dose group. One male rat had mild hepatocellular necrosis with accompanying increases in ALT and AST and several male animals had histological lung assessments with a slight increase in foreign body granulomas. Systemic exposure was greater in males than females and saturation of plasma clearance was observed in both sexes in the high dose group. Liver was identified as the major organ of elimination. Mechanistic studies showed dose-dependent effects on the integrity of a rat hepatoma cell line.
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PMID:A nonclinical safety and pharmacokinetic evaluation of N6022: a first-in-class S-nitrosoglutathione reductase inhibitor for the treatment of asthma. 2221 Apr 50