This study was conducted to determine the effect of UGT1A9 98T>C, CYP2B6 516G>T and CYP2C9 430C>T genetic polymorphisms on the pharmacokinetics of propofol in children of different sexes and ages who undergone total intravenous anesthesia (ТIVA) and deep sedation during diagnostic and therapeutic procedures. Patients and Methods: The prospective study included 94 children, ASA I-II status, 1 to 17 years of age, who undergone standard anesthetic protocol for TIVA, which implied the continuous use of propofol. Before the administration of propofol, venous blood was sampled to determine the presence of genetic variations in UGT1A9, CYP2B6 and CYP2C9 gene using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). From each patient included in the study blood samples were taken: 10 mins after the induction of anesthesia, immediately before the discontinuation of the propofol infusion, 10 mins after discontinuation of the propofol infusion and 20 mins after discontinuation of the propofol infusion to determine the pharmacokinetics of the drug in the plasma of the subjects The plasma propofol concentration was determined by HPLC analytical technique. Results: UGT1A9 genotype is an independent predictor of the propofol concentration in children immediately after the end of the continuous infusion and 10 mins afterwards. In the carriers of the polymorphic UGT1A9 C allele, the propofol distribution constant was higher. The carriers of the polymorphic CYP2B6 T allele received a significantly lower overall and initial dose of propofol. Unlike polymorphism of the UGT1A9 gene, the tested CYP2C9 and CYP2B6 gene polymorphisms are not independent predictors of the pharmacokinetics of propofol. Conclusion: Further investigations of UGT1A9, CYP2B6 and CYP2C9 and other genes that participate in propofol metabolism as well as detailed analyses of the general conditions, administered therapies and associated diseases could explain the large interindividual variability of propofol metabolism in children.
Interindividual variability in response to drugs used in anesthesia has long been considered the rule, not the exception. It is important to mention that in anesthesiology, the variability in response to drugs is multifactorial, i.e., genetic and environmental factors interact with each other and thus affect the metabolism, efficacy, and side effects of drugs. Propofol (2,6-diisopropylphenol) is the most common intravenous anesthetic used in modern medicine. Individual differences in genetic factors [single nucleotide polymorphisms (SNPs)] in the genes encoding metabolic enzymes, molecular transporters, and molecular binding sites of propofol can be responsible for susceptibility to propofol effects. The objective of this review (through the analysis of published research) was to systematize the influence of gene polymorphisms on the pharmacokinetics and pharmacodynamics of propofol, to explain whether and to what extent the gene profile has an impact on variations observed in the clinical response to propofol, and to estimate the benefit of genotyping in anesthesiology. Despite the fact that there has been a considerable advance in this type of research in recent years, which has been largely limited to one or a group of genes, interindividual differences in propofol pharmacokinetics and pharmacodynamics may be best explained by the contribution of multiple pathways and need to be further investigated.
This paper presents an innovative method for determining the distribution of the friction generated heat from the contact of a locomotive wheel and rail, as well as the heat partition factor, during wheel slipping of an accelerating locomotive. The new method combines the finite element analysis simulation and experimental determination of the temperature distribution in a downsized model of a wheel and rail. As a result of a virtual experiment by the finite element analysis, an empirical dependence between the temperature distribution and the heat partition factor was established. The determination of the dependence enabled finding of the exact value of the heat partition factor by the optimization procedure based on matching temperatures obtained by the virtual and real experiment.
: Beta-blockers (BBs) have significant side effects that contribute to low adherence and persistence. Therefore, the optimal choice of BB is a vital mode to prevent BB's side effects, leading to an increase in compliance, which can improve the outcomes in BBs' evidence-based indications such as acute myocardial infarction, heart failure, etc. The paper aims to suggest an improved method of reporting contraindications for BBs. We used a search of the following indexing databases: SCOPUS and PubMed, and web search engine Google Scholar to identify guidelines on arterial hypertension (HTN). HTN guidelines published during the last two decades were analyzed (from 2000 to 2020). Some of the contraindications (e.g., bradycardia, acute heart failure) are true for every BB. However, some contraindications do not belong to the whole BB class. For example, propranolol and carvedilol are contraindicated in chronic obstructive lung disease, but nebivolol and bisoprolol are not. To our knowledge, there is a lack of guidelines citing contraindications for individual BBs because they vary a lot within the class of BBs. We suggest that contraindications specific for some BBs (i.e., not for the whole class) ought to be listed with the exact name(s) of the individual BBs. In this way, we may decrease the number of wrong choices among BBs and consequently increase drug adherence (which is currently worse for the class of BBs than for most of the other antihypertensive drugs). It is an approach to improve both primary medical education and guidelines.
Introduction. The arm replantation is extremely rare and challenging procedure. The recognised risk is myoglobinuria and ischemia reperfusion induced renal failure. Case report. Two patients aged 24 and 46-years were admitted after traumatic arm amputation. Ischemia time was two hours and six hours. Postoperative intensive care treatment with assisted ventilation, sedation and obtaining sufficient urine output prevents myoglobin induced renal injury. In case where ischemia time was shorter, there was only one delayed reconstruction of skin defects after fasciotomy, but in the case where ischemia lasted longer, patient had two secondary look procedures with acceptable definitive results. Conclusion. Arm replantation is safe procedure even in cases with longer ischemia time. Postoperative control of urine output and correction of acidosis, preventing myoglobin induced tubular injury is crucial for stable postoperative recovery.
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