Polymorphisms and allele frequencies of glutathione S-transferases A1 and P1 genes in the Polish population.

Glutathione S-transferases (GST) A1 and P1 are crucial enzymes involved in the biotransformation of drugs, carcinogens, and toxins, and their activity may influence drug response, susceptibility to diseases, and carcinogenesis. The genes encoding these enzymes, GSTA1 and GSTP1, have been examined in many studies because of their genetic variability, which may affect enzymatic activity. The goal of this study was to determine the distribution of the alleles GSTA1*A/*B and GSTP1*A, *B, and *C in the Polish population. A total of 160 subjects from the Polish population were genotyped for 2 polymorphisms (I105V and A114V) in the GSTP1 gene using pyrosequencing. The promoter region of the GSTA1 gene was screened using sequencing. The detected variants were subjected to haplotype analysis. We found that the distribution of the alleles GSTA1*A/*B and GSTP1*A, *B, and *C in the Polish population correspond to the results of studies in Caucasians. Furthermore, we identified additional single nucleotide polymorphisms, excluding 3 well-known changes (G-52A, C-69T, T-567G), which are linked to alleles GSTA1*A/*B, that affect enzyme activity. A total of 4 haplotypes were identified in 160 Polish individuals.

[Clinical evaluation of hemofiltration in perioperative medicine]. / Ocena kliniczna hemofiltracji w medycynie okolooperacyjnej.

Haemofiltration (HF) in perioperative period is used in order to improve the function of circulatory system by means of: elimination of cytokines in patients with increased inflammatory cascade activation; improvement of gas exchange conditions by decreasing the amount of lungs extravascular fluid; reduction of high levels of metabolism products; compensation of electrolyte disequilibrium and decreasing of right ventricle afterload as well as right and left ventricles preload. The aim of the study was clinical evaluation of usefulness of continuous vein-to-vein haemofiltration (CVVH) technique used in multiprofile adults intensive care. The analysis included 20 patients aged 24-73 (mean age 48.5), treated with HF in 1998-1999. HF was introduced in the following clinical conditions: multiorgan trauma with ARDS, acute pancreatitis with multiple organ dysfunction syndrome (MODS), peritonitis, status after laparotomy and chronic circulatory failure in patients qualified to heart transplantation. In six patients (30%), significant improvement of general state and stabilisation of haemodynamic and ventilation parameters were obtained. In fourteen patients (70%), despite CVVH, no improvement of circulatory and respiratory systems state was obtained. HF is very useful technique employed in perioperative medicine. It enables improvement of gas exchange conditions by decreasing the amount of lungs extravascular fluid in patients with ARDS in the course of MODS. HF simplyfies preparation the patient with chronic circulatory failure for diagnostic and therapeutic cardiosurgical procedures. In the course of sepsis and septic shock, HF creates better prospects to nutritional therapy and replaces haemodialysis or is its continuation.

The impact of genetic factors on response to anaesthetics.

In recent years, exceptional progress has been observed in pharmacogenetics, i.e. investigations of inherited conditioning of the organism's response to drugs or xenobiotics. On the other hand, modern molecular biology techniques have been implemented, making it possible to perform studies determining the involvement of genetic factors in differing responses to agents employed in general anaesthesia. Unexpected and incorrect response of the organism to the administration of specific anaesthetics is most commonly associated with a genetic defect of the metabolic pathway of a given agent or its receptor. The majority of agents used in anaesthesia are metabolised in the liver by the cytochrome P450 superfamily enzymes (CYPs) and phase II drug-metabolising enzymes: glutathione S-transferases (GSTs), sulphotransferases (SULTs), UDP-glucuronosyltransferases (UGTs) and NAD(P)H:quinone oxidoreductase (NQO1). Propofol is presently widely used for gastrointestinal (GI) and several other procedures. Among genes associated with metabolism of the most commonly applied anaesthetics such as propofol and sevoflurane, the following ones can be mentioned: CYP2E1, CYP2B6, CYP2C9, GSTP1, UGT1A9, SULT1A1 and NQO1. Moreover, the basic mechanism of propofol action involves its interaction with an ionotropic receptor GABAA inhibiting transfer of nerve impulses. Molecular studies have shown that polymorphic changes in GABRG2 receptor gene turn out to be important in the propofol anaesthesia. Planning of optimal anaesthesia can be considerably assisted by the determination of genetic factors of prognostic value taking advantage of genotyping and making it possible to select anaesthetics and reduce risk of side effects as well as undesirable actions.