Pharmacokinetic modeling of tranexamic acid for patients undergoing cardiac surgery with normal renal function and model simulations for patients with renal impairment

Tranexamic acid (TXA), an effective anti-fibrinolytic agent that is cleared by glomerular filtration, is used widely for cardiopulmonary bypass (CPB) surgery. However, an effective dosing regimen has not been fully developed in patients with renal impairment. The aims of this study were to characterize the inter-patient variability associated with pharmacokinetic parameters and to recommend a new dosing adjustment based on the BART dosing regimen for CPB patients with chronic renal dysfunction (CRD). Recently published data on CPB patients with normal renal function (n = 15) were re-examined with a two-compartment model using the ADAPT5® and NONMEMVII® to identify covariates that explain inter-patient variability and to ascertain whether sampling strategies might affect parameter estimation. A series of simulations was performed to adjust the BART dosing regimen for CPB patients with renal impairment. Based on the two-compartmental model, the number of samples obtained after discontinuation of TXA infusion was found not to be critical in parameter estimation (p > 0.05). Both body weight and creatinine clearance were identified as significant covariates (p < 0.005). Simulations showed significantly higher than normal TXA concentrations in CRD patients who received the standard dosing regimen in the BART trial. Adjustment of the maintenance infusion rate based on the percent reduction in renal clearance resulted in predicted plasma TXA concentrations that were safe and therapeutic (~100 mg·L(-1) ). Our proposed dosing regimen, with consideration of renal function, is predicted to maintain effective target plasma concentrations below those associated with toxicity for patients with renal failure for CPB

Localisation of exogenous surfactants in cell membranes in the air-blood barrier: rat model

The use of exogenous surfactants has been introduced into the therapy of patients of different ages. Much better results have been obtained in the treatment of respiratory distress syndrome with surfactants enriched with surfactant proteins. In the following study we used protein-containing surfactants (survanta and curosurf). The aim of the following study was to determine the localisation of artificial surfactants in the lung tissue. Using the Immunogold Technique, biotinylated surfactant proteins were traced in the air-blood barriers. In all lungs the exogenous surfactant was present only in some alveoli. In these parts small areas of atelectasis as well as oedema and transudate accumulation were seen. These changes were less severe after biotinylated curosurf treatment. In electron microscope studies we found surfactant elements in the air-blood barrier and other structures of the alveolar septa. Immunogold studies confirm the presence of biotynylated surfactant in the elements of the air-blood barrier

Localisation of exogenous surfactants in cell membranes in the air-blood barrier : rat model

The use of exogenous surfactants has been introduced into the therapy of patients of different ages. Much better results have been obtained in the treatment of respiratory distress syndrome with surfactants enriched with surfactant proteins. In the following study we used protein-containing surfactants (survanta and curosurf). The aim of the following study was to determine the localisation of artificial surfactants in the lung tissue. Using the Immunogold Technique, biotinylated surfactant proteins were traced in the air-blood barriers. In all lungs the exogenous surfactant was present only in some alveoli. In these parts small areas of atelectasis as well as oedema and transudate accumulation were seen. These changes were less severe after biotinylated curosurf treatment. In electron microscope studies we found surfactant elements in the air-blood barrier and other structures of the alveolar septa. Immunogold studies confirm the presence of biotynylated surfactant in the elements of the air-blood barrier

Application of Solid Phase Microextraction for Quantitation of Polyunsaturated Fatty Acids in Biological Fluids

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Analytical Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/ac502627wDevelopment of a straightforward strategy for simultaneous quantitative analysis of nonesterified fatty acids (NEFA) species in biofluids is a challenging task because of the extreme complexity of fatty acid distribution in biological matrices. In this study, we present a direct immersion solid phase microextraction method coupled to a liquid chromatography–mass spectrometry platform (DI-SPME- HPLC-ESI -MS) for determination of unconjugated fatty acids (FA) in fish and human plasma. The proposed method was fully validated according to bioanalytical method validation guidelines. The LOD and LOQ were in the range of 0.5–2 and 5–12 ng/mL, respectively, with a linear dynamic range of 100 fold for each compound. Absolute and relative matrix effects were comprehensively evaluated and found to be in the acceptable range of 91–116%. The affinity constant (Ka) of individual FAs to protein albumin was determined to be 9.2 × 104 to 4.3 × 105 M–1. The plasma protein binding (PPB%) was calculated and found to be in the range of 98.0–99.7% for different polyunsaturated fatty acids (PUFAs). The PUFAs under study were found at a high concentration range in fish plasma, whereas only a few were within quantification range in control human plasma. The method was successfully applied for monitoring PUFA changes during the operation in plasma samples obtained from patients undergoing cardiac surgery with the use of cardiopulmonary bypass (CPB). The most significant contribution induced by surgery was noticed in the concentration level of α-linolenic acid (18:3, ALA), arachidonic acid (20:4, AA), and docosahexanoic acid (22:6, DHA) soon after administration of CPB in all cases.Natural Sciences and Engineering Research Council of Canada (NSERC) Supelc

Venom allergy treatment practices in Poland in comparison to guidelines : next edition of the national audit

Introduction: Venom immunotherapy treatment (VIT) is the only causal treatment of hymenoptera venom anaphylaxis, which aims to provide long-lasting immunoprotection against severe reactions to subsequent stings. Aim: To reassess the compliance of VIT procedures in the Polish allergy centres with the European guidelines. Material and methods: A structured questionnaire survey conducted in all 33 VIT-centres. The response rate was 94%. Results: The ultrarush initial protocol was the most common protocol (71%, n = 22), usually lasting for 3.5 h (50%, n = 7). The most frequent (36%, n = 11) time interval from the initial to the first maintenance dose (MD) was 14 days, ranging from 7 to 35 days. All centres used an MD of 100 \mug. The most frequent time interval between subsequent MDs was 4 weeks (58%, n = 18). Five years' of VIT was declared by 71% (n = 22). Before the termination of treatment, more than half of the centres (58%, n = 18) performed sIgE and almost half (42%, n = 13) performed skin tests. To confirm VIT efficacy, few centres (26%, n = 8) conducted the sting challenge. About half of centres provided the patients with an adrenalin auto-injector both at the time of initial diagnostics and at the end of treatment. More than half (55%, n = 17) used antihistamines in all patients. Almost half (45%, n = 14) declared to stop treatment with \beta-blockers and almost one fourth (23%, n = 7) discontinued angiotensin-converting-enzyme inhibitors. Conclusions: In the most important procedures, there is a very high compliance with the guidelines. In the areas where the guidelines are not precise, we observed a large spread of results