PubMed Health⌕ Search

Biomedical subjects

J Skretkowicz

Publications and source records attributed to J Skretkowicz.

13 recordsLinked to original sources
PubMed2004

Lack of association between arylamine N-acetyltransferase 2 (NAT2) polymorphism and systemic sclerosis.

OBJECTIVES: It has been shown that exposure to some environmental toxins may induce scleroderma-like illness in predisposed individuals, but the etiopathogenesis of the idiopathic form of systemic sclerosis (SSc) remains obscure. The genetic background of this illness has been confirmed in multiple studies. We investigated whether patients with SSc differ from healthy subjects with regard to the enzymatic activity of polymorphic N-acetyltransferase 2 (NAT2). METHODS: The study was carried out in 39 patients with SSc; 15 fulfilled the criteria of diffuse SSc (dSSc) and 24 of limited SSc (lSSc); an ethnically matched control group consisted of 100 healthy volunteers. Acetylation phenotype was estimated using the isoniazid as a model drug. The most common mutations in the Caucasian population at positions 481T, 803G, 590A and 857A on the NAT2 gene were determined using the polymerase chain reaction-restriction fragment length polymorphism method with deoxyribonucleic acid (DNA) extracted from peripheral blood. RESULTS: In the group of patients with SSc, the frequency of fast acetylator genotypes was 38.5% (95% CI 23.4-55.4), while that for the genotypes coding slow acetylator status was 51.3% (95% CI 34.8-67.6). There was a strong correlation between NAT2 phenotype and NAT2 genotype with a concordance of 97%. We did not observe a preponderance of slow acetylators among patients with SSc and in two subsets of SSc. With the sample size analyzed in the present study, there is a 90% probability of detecting significant differences in distribution of slow, fast, and intermediate phenotypes between patients with SSc and controls, there is a difference of at least 30.3, 28.7 and 21.9% in the distribution of these phenotypes in the general population, respectively. CONCLUSION: Acetylator status does not seem to be the significant factor in the development of SSc in patients with both subsets of this autoimmune disease, but further studies are required to confirm this conclusion.

Acetylation↗
PubMed1998

Genotyping of the arylamine N-acetyltransferase polymorphism in the prediction of idiosyncratic reactions to trimethoprim-sulfamethoxazole in infants.

The pathogenesis of hypersensitivity to trimethoprim-sulfamethoxazole (TMP-SMX) is supposed to be associated with the slow acetylation phenotype. This pharmacogenetic defect is associated with the mutations of the arylamine N-acetyltransferase (NAT2) encoding gene. The aim of the study was to compare the usefulness of the acetylation phenotype and NAT2 coding genotype in the prediction of idiosyncratic reaction to Cotrimoxazole in infants. The study was carried out in the group of 20 infants, aged 2-12 months (mean age 6.3 months) treated with Cotrimoxazole, administered at 100 mg/kg b.w./24 h doses. In seven children (35%) no adverse effects of the treatment have been observed, whereas in 13 (65%) children various adverse effects occurred as a result of the therapy, such as rash (4 children), granulocytopenia with anemization (5 children) or liver impairment (4 children). The acetylation phenotype of each child was determined on the basis of urine of N-acetyl isoniazid/isoniazid ratio, after ingestion of isoniazid as a model drug. Furthermore we used polymerase chain reaction (PCR) followed by the analysis of restriction fragments length polymorphism (RFLP) technique to identify the known mutant alleles of the NAT2 gene. It has been presumed that the genotype determining fast acetylation contains at least one of wild-type allele. No correlation has been found between the observed adverse effects of Cotrimoxazole and age, gender and acetylation phenotype. However, it has been demonstrated that the risk of adverse effects of Cotrimoxazole is considerably higher in children with mutations of the NAT2 encoding gene. The comparison of the results from PCR-RFLP genotyping with phenotyping suggested that in infants, the NAT2 genotype rather than phenotype provides the basis for the detection of hypersensitivity to TMP-SMX.

Acetylation↗
PubMedDate not supplied

Effect of some anticancer drugs and combined chemotherapy on renal toxicity.

The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.

Animals↗
PubMedDate not supplied

Investigations of central interaction of ethanol and clonidine.

The combined effect of ethanol and clonidine on rabbit EEG, and the effect of clonidine on ethanol sleep in mice, as well as on acute ethanol toxicity were investigated. Moreover, the effect of clonidine on ethanol level in rabbit blood and in mouse brain and the combined effect of ethanol and clonidine on rabbit arterial blood pressure were evaluated. It has been found that clonidine intensifies the effect of ethanol in EEG and prolongs ethanol sleep. Clonidine does not change acute ethanol toxicity and does not affect ethanol level in blood and the brain. Ethanol prevents the decrease of arterial blood pressure after an intravenous or intracerebroventricular administration of clonidine.

Animals↗
PubMedDate not supplied

Effect of some anti-cancer drugs and combined chemotherapy on the pharmacokinetics of antipyrine in the rat.

The effect of anti-cancer drugs on the metabolic efficiency of the liver was evaluated by means of phenazone (antipyrine) kinetics individually in each rat. Chlormethine (nitrogranulogen, NG), methotrexate (MTX), floxuridine (fluorouracil, 5-fluorouracil, 5-FU), cyclophosphamide (CY, endoxan), and three cytostatics applied jointly (MTX + 5-FU + CY) were administered ip to the rats, while antipyrine was given intravenously. The anti-cancer drugs: NG, MTX, 5-FU, CY and MTX + 5-FU + CY delayed the elimination of antipyrine. Statistically significant prolongation of the half-life, decrease in the elimination rate constant and the clearance of antipyrine have been found in the rats receiving anti-cancer drugs, as compared to the controls. After the administration of MTX, 5-FU, CY and the joint administration of MTX + 5-FU + CY the volume of distribution did not change, while the volume of distribution of antipyrine decreased after the administration of NG. The activity of the investigated enzymes, i.e., alanine aminotransferase (ALAT), aspartic aminotransferase (AspAT), gamma-glutamyltransferase (GGT), alkaline phosphatase (AP), which are the indicators of various liver dysfunctions, did not change after the administration of NG, MTX, 5-FU, CY and MTX + 5-FU + CY. The administered antineoplastic drugs in mono and polytherapy changed the activity of oxidase mixed function responsible for the metabolism of antipyrine. CY administered to rats in polytherapy had less influence on liver metabolic efficiency than in monotherapy.

Animals↗