Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein S is a vitamin K-dependent glycoprotein acting as a cofactor for activated protein C and thereby exerting an antithrombotic effect. When compared to values recorded in the 10 healthy normal weight normolipidemic control subjects (80.1% +/- 5.16; mean +/- SEM), plasma protein S-antigen (PS:Ag) level was found to be significantly (p < 0.01) decreased in the 11 patients with decompensated cirrhosis of the liver (54.72% +/- 4.89) and in the 12 surgical patients in critical condition (59.2 +/- 4.96), while obviously (p < 0.001) increased plasma levels were noted in the group including 20 overweight and hyperlipidemic subjects (113% +/- 3.1). Since the low PS:Ag level was associated with a decreased serum cholinesterase (CHE) activity, while both plasma PS:Ag and serum CHE activity were increased in overweight and hyperlipidemic subjects it is considered that impaired or respectively enhanced hepatic protein synthesis is at least partially responsible for changes affecting this antithrombotic plasma protein.
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PMID:Plasma protein S-antigen (PS:Ag) in selected disease states. 808 8

Irinotecan [7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11)] is a promising water-soluble analogue of camptothecin [S. Sawada et al., Chem. & Pharm. Bull. (Tokyo), 39: 1446-1454, 1991]. We have reported previously the presence of an important polar metabolite, in addition to 7-ethyl-10-hydroxycamptothecin (SN-38) beta-glucuronide, in samples of plasma taken from patients undergoing treatment with CPT-11 (L.P. Rivory and J. Robert, Cancer Chemother. Pharmacol. 36: 176-179, 1995; L. P. Rivory and J. Robert, J. Cromatogr., 661: 133-141, 1994). Plasma samples (0.5 ml) containing comparatively large amounts of this metabolite were extracted by solid-phase columns and subjected to high-performance liquid chromatography and mass spectrometry in parallel to fluorometric detection. The metabolite yielded [M + 1] ions with a m/z of 619, representing the addition of 32 atomic mass units to CPT-11. Purified fractions were subjected to proton nuclear magnetic resonance, and the structure determined, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycampothecin (APC), was further validated following synthesis. Like CPT-11, APC was found to be only a weak inhibitor of the cell growth of KB cells in culture (IC50, 2.1 versus 5.5 micrograms/ml for CPT-11 and 0.01 microgram/ml for SN-38, the active metabolite of CPT-11) and was a poor inducer of topoisomerase I DNA-cleavable complexes (100-fold less potent than SN-38). In contrast to CPT-11, APC was not hydrolyzed to SN-38 by human liver microsomes or purified human liver carboxylesterase. Furthermore, APC did not inhibit the hydrolysis of CPT-11 in these preparations. Interestingly, APC was only a weak inhibitor of acetylcholinesterase in comparison to CPT-11 and neostigmine. It appears likely, therefore, that APC does not contribute directly to the activity and toxicity profile of CPT-11 in vivo.
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PMID:Identification and properties of a major plasma metabolite of irinotecan (CPT-11) isolated from the plasma of patients. 870 9

Liver cirrhosis is associated with alterations of the coagulation system commonly causing bleeding as well as thromboembolic complications. The potential pathophysiological roles of tissue factor (TF) (the initiator of the extrinsic coagulation pathway) and thrombomodulin (TM) (an initiator of the anticoagulatory protein C pathway) are unknown. We therefore measured plasma concentrations of TF and TM in 111 patients with liver diseases who were evaluated for liver transplantation. We could demonstrate that the levels of both molecules increased with the Child's class of liver cirrhosis, independently of aetiology. TM was significantly elevated in Child A, B and C patients compared with patients without cirrhosis; TF only in Child C patients. The plasma TM and TF concentrations correlated with prothrombin time, activated partial thromboplastin time, and inversely with factor VII activity, cholinesterase serum activity, and serum albumin concentration. TM was elevated in patients with a bleeding tendency, but TM and TF did not differ between patients with or without prior thrombotic events. Further studies are warranted to clarify the underlying mechanisms that raise TM and TF plasma levels in liver disease with possible clinical consequences.
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PMID:Tissue factor and thrombomodulin levels are correlated with stage of cirrhosis in patients with liver disease. 1168 41

Studies initiated 30 years ago emphasized that dilute blood clot lysis time was longer in obese diabetic patients than in normal weight diabetics. It was also later reported that when compared to obese women with gluteal and femoral adiposity, the age matched men with abdominal obesity displayed a more delayed clot lysis, higher triglyceride levels and higher cholinesterase activity, as well as more increased concentration of plasminogen activator inhibitor-1 (PAL-1). According to authors' investigations and data in the literature, impaired fibrinolysis in overweight hypertriglyceridemic subjects are mainly due to increased plasma levels of coagulation factor XIII and PAI-1. It could also be demonstrated that plasma clotting factors VII and VIII activities as well as plasma fibrinogen and von Willebrand factor levels were higher in patients with type 2 diabetes and abdominal obesity than in diabetics without obesity. Such findings are supporting data in the literature, insisting on the pathogenic relevance of intraabdominal obesity and of the subsequently enhanced release of fatty acids and of proinflammatory cytokines in the portal flow. Surprisingly anticoagulant plasma proteins C and S levels were found to be increased in overweight and hyperlipidemic patients considered to be at risk for thrombotic complications. Recent data in the literature had however demonstrated that circulating protein C zymogen acquires anticoagulant activity only after its binding to specific receptors on endothelial cell membrane, while proinflammatory cytokines may disrupt this activating interaction with vascular endothelia.
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PMID:Thrombotic tendency in diabetes mellitus. Revisiting and revising a study initiated 30 years ago. 2332 54

In this work, the in vitro tests of biological activity of benzimidazoles were conducted. This group of benzimidazole derivatives was evaluated as potential bioreductive agents and their characteristic pro-apoptosis activity and cell cycle interruption on the human lung adenocarcinoma A549 cells were discussed. Their toxicity on the healthy human erythrocytes and their influence on the healthy human erythrocytes acetylcholinesterase enzyme (AChE) were established. Their apoptosis activity on A549 cells line was determined by Annexin V-APC test, and it was visualized by Hoechst test. In the next stage, their influence on the cell cycle interruption was determined by using the ribonuclease reagent. The AChE inhibition test was defined by the Ellman method, and the red blood cell lysis was defined by erythrotoxicity test. The results proved the pro-apoptosis properties of all tested compounds in normoxia and hypoxia. The DNA content assay showed that the benzimidazoles possess the ability to interrupt S phase of tumor cell cycle. The best activity in this action was presented by compound 1, especially in hypoxia, and it proves that the N-oxide analogs are predispositioned to the hypoxic target. In this study, the benzimidazoles were found as potentially biocompatible and their inhibition of acetylcholinesterase was lower than tirapazamine and much lower than tacrine which constitutes their desired effect of potential biological activity.
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PMID:Biological evaluation of the toxicity and the cell cycle interruption by some benzimidazole derivatives. 2703 17