Cardiovascular actions of the hypotensive agent, N, N-diallylmelamine (U-7720)

Diallylmelamine is an effective hypotensive agent in hypertensive dogs and rats, having a duration of action exceeding twenty-four hours from a single oral dose. It has limited efficacy in normotensive rats. Hypotensive activity of gradual onset is preceded by a latent period of up to two hours and becomes maximal six hours or more after dosing. This agent does not depress cardiac output or sympathetic vasoconstrictor activity. It is suggested that its hypotensive activity results from a direct effect upon vascular smooth muscle.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46303/1/210_2004_Article_BF00245728.pd

Comparison of Two Thrombin Generation Methods, CAT and ST-Genesia, in Liver Transplant Patients

Background During liver transplantation (LT), thrombin generation (TG) is altered. The most frequently used assay for TG is the Calibrated Automated Thrombogram (CAT). It is designed for series of plasmas and is semi-automated. Complete automation has led to a new device, the ST-Genesia, enabling quantitative standardized TG evaluation. Objective The aim of this observational study was to compare the TG results of the CAT and the ST-Genesia on frozen-thawed plasma samples prepared from the blood of LT patients. Patients and Methods Poor platelet plasma aliquots were prepared from blood samples from six LT patients selected to get the whole range of TG and were assessed with CAT (recombinant human tissue factor [TF] concentration 5 pm) and with ST-Genesia Bleedscreen assay (BS, using ‘low’ recombinant human TF concentration) and Thromboscreen assay (TS, using ‘medium’ recombinant human TF concentration). The TG parameters studied were: lag time, peak, time to peak, endogenous thrombin potential, velocity index and start tail. Results BS and TS did not differ significantly from each other whatever the parameter studied, whereas most of the CAT parameters were significantly different from those obtained with BS and TS. Hierarchical clustering analysis of the different parameters of TG showed three homogeneous groups. One cluster gathered TG quantitative parameters from ST-Genesia. A second cluster gathered all the kinetic parameters. The last cluster isolated the quantitative parameters of CAT. Conclusion In patients undergoing LT, TG performed with CAT and with ST-Genesia provided different results, for unknown reasons

Multiplate® evaluation of acetylsalicylic acid efficacy in carotid surgery: routine and genetic influencing factors

Essentials Acetylsalicylic acid (ASA) is prescribed to patients scheduled for carotid endarterectomy (CEA). We measured ASA efficacy during CEA by Multiplate® and searched for influencing factors. Most patients scheduled for CEA and treated by ASA are sensitive to this therapy. Influencing genomic factors are involved in ASA metabolism and in platelet function modulations. SUMMARY: Background Acetylsalicylic acid (ASA) is recommended before, during and after carotid endarterectomy (CEA). The efficacy of ASA is influenced by numerous biological and genotypic factors. Objectives To determine the biological efficacy of ASA by using the Multiplate® method, and to explore the biological parameters and genomic factors influencing this efficacy. Methods This descriptive cross-sectional study included all patients scheduled for CEA between January 2012 and April 2013. Multiplate® tests were performed at day 0 and day 30. A set of 66 single-nucleotide polymorphisms (SNPs) from 38 genes or DNA regions were selected and studied along with phenotypic parameters by the use of hierarchical clustering (HC) for multidimensional data management. Results Fifty-five patients receiving ASA were analyzed. Of the patients, 95% were found to be sensitive to ASA, with values under the threshold of normality (400 AU min-1 ). However, there were notable differences in residual aggregation among subjects over a wide range. HC revealed four subclusters comprising three categories of parameters: (i) routine and functional parameters - in ASA-treated patients, the ASPItest was highly linked to the ADPtest, to platelet count, and, to a lesser extent, to fibrinogen and hematocrit; (ii) polymorphisms in genes involved in ASA absorption and in the arachidonic acid pathway (ABCB1 and COX-1); and (iii) polymorphisms in genes modulating basal platelet function, i.e. TBXA2R, ADRA2A, PEAR1, ITGA2 and ITGB1. Conclusion Most patients treated with ASA before CEA were sensitive to it, according to Multiplate® ASPItest results. Genomic factors influencing this efficacy are SNPs involved in ASA absorption and metabolic pathway, and in modulations in basal platelet function