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Biomedical subjects

J Wójcicki

Publications and source records attributed to J Wójcicki.

At least 19 recordsLinked to original sources
PubMed1997

N-acetylation and hydroxylation polymorphisms in type II diabetics with microvascular disturbances.

The N-acetylation and hydroxylation (CYP2D6) genetic polymorphisms were assessed in 43 healthy subjects and in 84 type II (non-insulin-dependent) diabetics. The proportions of slow and fast acetylators as well as poor and extensive metabolisers in a group of diabetics suffering from microvascular disturbances (nephropathy, retinopathy and neuropathy) were compared with the control group and with diabetics without such complications. Sulphadimidine was used as a probe for polymorphic acetylation and debrisoquine for CYP2D6. Debrisoquine and its 4-OH metabolite were assayed by means of HPLC, and sulphadimidine using a modified Bratton-Marshall procedure. The frequency of the slow phenotype (63%) was significantly higher in diabetics with microvascular disturbances than in patients without diabetic complications (P < 0.005). In patients with type II diabetes (84), only the extensive phenotype of hydroxylation was observed.

Acetylation↗
PubMed1996

Comparative pharmacokinetics of theophylline in rabbits and in humans with hyperlipidemia.

UNLABELLED: The study was carried out on male rabbits divided into two groups: a control and an experimental one, fed on a high-fat diet. Humans were also ascribed into two groups: control and those affected with primary, mixed form of hyperlipidemia. The animals and humans were given theophylline intravenously as a single dose. Blood was sampled after 5, 10, 15, 30 and 45 min and 1, 2, 4, 6, 8, 12 and 24 h following theophylline administration. FPIA method was used to determine blood serum concentrations of theophylline. Considerable alterations of theophylline pharmacokinetics in humans suffering from mixed form of hyperlipidemia were observed. Marked decrease in area under the concentration-time curve (AUC), diminished volume of distribution, increased total body clearance, and shortened elimination half-life were observed. On the contrary, in rabbits with alimentary induced lipid metabolism disturbances t1/2 of theophylline was practically unchanged and AUC only slightly increased. IN CONCLUSION: (1) hyperlipidemia affects the pharmacokinetics of theophylline in human beings, (2) rabbit model with dietetary induced lipid metabolic disturbances is not a suitable subject for estimation of pharmacokinetics of xanthine derivatives.

Adult↗
PubMed1996

Pharmacokinetics of phenazone (antipyrine) in rabbits with experimental common bile duct obstruction.

1. An altered functional state of liver due to experimental cholestasis could result in a change in the biotransformation of drugs. The aim of this study was to evaluate an influence of obstructive cholestasis on the pharmacokinetics of phenazone (antipyrine). 2. The investigation was carried out on male rabbits, randomly allocated into two groups: shamoperated and animals with biliary ducts ligation. Phenazone was administered intragastrically as a probe of drug metabolism. 3. Measurements, i.e. laboratory and pharmacodynamic tests, as well as pharmacokinetic assays, were performed before the operation as well as 10-12 days after the bile duct ligation. At the end of the study livers were examined macro- and microscopically and biochemical analysis of the liver microsomes was performed. 4. The measured pharmacokinetic parameters suggested an impaired biotransformation of phenazone in animals with obstructive cholestasis, leading to a slower drug elimination.

Animals↗
PubMed1996

[Effect of mestranol on pharmacokinetics of phenazone in the rabbit].

There was studied the influence of mestranol on the pharmacokinetics parameters of phenazone. There was proved the decrease AUC abridgement the period of semi duration for elimination phase and increase total clearance. On the base of these experiments there was able to make a conclusion that estrogens influence on the phenazone's pharmacokinetic probably by induction of microsomal enzymes of liver.

Animals↗
PubMed1995

Extractum Fagopyri reduces atherosclerosis in high-fat diet fed rabbits.

A group of 30 male mongrel rabbits was divided into 3 subgroups: controls, animals receiving a high-fat diet (HFD) containing cholesterol and coconut oil, HFD + Extr. Fagopyri (EF) were treated for 12 weeks. Surface areas of lipid deposites after 12 weeks of treatment measured planimetrically in the intima of the aorta, averaged 86.5% in HFD-fed animals, but 68.6% in EF treated rabbits. The positive effect of EF was confirmed histopathologically. The finding of this study is that the EF administration results in the reduction of atherosclerotic plaque formation.

Animals↗
PubMed1994

The pharmacokinetics of phenytoin in rabbits with hyperlipidemia induced by high-fat diet.

The study was aimed at the evaluation of changes in phenytoin pharmacokinetics during dietary induced hyperlipidemia in rabbits. It was carried out in 17 New Zealand, male rabbits, 3-month old, randomly assigned to two groups: control maintained on standard diet and experimental one fed on a high-fat diet for 2 months. Pharmacokinetic assays were performed in all animals after 2 months of the experiment. Phenytoin was given intragastrically as a single dose 10 mg/kg. Blood for assays was sampled within 48 hours after phenytoin administration. The two compartment open model for extravascular administration was used for calculations. It was demonstrated that the administration of phenytoin in the group of animals with experimental hyperlipidemia was followed by a decrease of the drug concentration in the blood serum, a drop in area under the plasma concentration-time curve, a shorter elimination half-time as well as an increase in total body clearance. All revealed changes suggest that the dietary induced hyperlipidemic state alters the pharmacokinetics of phenytoin, leading to a faster drug elimination from the body.

Animals↗
PubMed1994

Effect of mestranol on pharmacokinetics of paracetamol.

The aim of this study was to investigate the effect of mestranol on pharmacokinetics of paracetamol. The study was carried out on 20 female rabbits. Paracetamol was administered to rabbits intragastrically at a dose of 50 mg/kg b.w. One group of animals was given mestranol intragastrically 0.1 mg once daily during 2 months. The method of Routh A. et al. was used to paracetamol concentration assay. Blood for the assays was collected within 24 hours after drug administration, prior to the study as well as 1 month and 2 months after continuous mestranol administration. The two compartment open model was used for calculations. The study revealed an increase in AUC and paracetamol half-life as well as decrease in the total body clearance. We conclude that there is an interaction between mestranol and paracetamol leading to a decrease in total body paracetamol clearance.

Acetaminophen↗
PubMed1994

Effect of experimental hyperlipidemia on the pharmacokinetics of digoxin.

The study was carried out on 18 male rabbits randomaly ascribed into two groups: control one on standard diet and experimental one on high-fat diet for 2 months. Pharmacokinetic assays were performed in all animals after 2 months of the experiment. Blood was sampled within 24 hours after intragastrical administration of digoxin at a dose 0.02 mg/kg. The two compartment open model for extravascular administration was used for calculations. Marked increase in plasma drug concentration, as well as decrease in total clearance were noted. The study revealed the influence of experimental hyperlipidemia on digoxin pharmacokinetics leading to a slower drug elimination.

Animals↗
PubMed1993

Pharmacokinetics of multiple-dose administered gentamicin to unilaterally nephrectomized rabbits.

The aim of this study was to investigate the effect of unilateral nephrectomy on the pharmacokinetics of gentamicin. The study was carried out on 19 male rabbits. Gentamicin was injected i.v. at a dose of 3.5 mg/kg twice daily during 5 days, before operation and after 2 weeks as well as 3 months from nephrectomy. Blood for the assays was collected within 6 hours after the drug administration on the 5th day of each study stage. The immunofluorescence polarization method was employed for determination of gentamicin concentration. The one-compartment open model was used for calculations. It was shown that in unilaterally nephrectomized rabbits the elimination of gentamicin can be significantly impaired during the whole study period.

Animals↗
PubMed1993

[Pharmacokinetics of paracetamol after removal of ovaries in rabbits].

The study was aimed at the determination of the effect of estrogens on paracetamol pharmacokinetics in female rabbits subjected to bilateral ovariectomy. Eighteen female rabbits divided into two groups, control and experimental, subjected to ovariectomy, were used in the study. Pharmacokinetic experiments were carried out in all the animals before the operation, 1 month after, and 2 months after ovariectomy. Samples of blood were taken periodically during 24 hours after intragastric administration of paracetamol at a dose of 50 mg/kg of body weight. An open two-compartment model was used for the description of concentration changes. A decrease in the area under the curve of changes of paracetamol concentration and in the half-time of the elimination phase, as well as an increase in the total clearance of the drug, have been observed. The results of the study indicate that the rate of elimination of paracetamol is higher in ovariectomized animals.

Acetaminophen↗
PubMed1993

[Pharmacokinetics of acetaminophen in individuals occupationally exposed to polyvinyl chloride modified with plasticizers].

The aim of this study was to evaluate the health state of a random group of subjects occupationally exposed to polyvinyl chloride. The emphasis was put on the hepatic functional tests in comparison with acetaminophen pharmacokinetics. Forty two males were assigned to two groups: the control group free from occupational exposure and the group exposed to polyvinyl chloride. The latter one was divided into two subgroups according to the length of exposure. The following examinations were carried out in all subjects: subjective and physical examinations, basic laboratory and functional hepatic tests, radioisotope examinations of the liver and spleen, and acetaminophen pharmacokinetics was analysed as well. Acetaminophen was administered intragastrically in a single dose of 1.0 g. Blood was collected within 24 hrs after drug administration. The method of Routh et al. was used for determination of paracetamol concentration. A two-compartment open model for extravascular administration was used for calculation of pharmacokinetic parameters. The results suggest that polyvinyl chloride leads to an accelerated acetaminophen biotransformation, regardless of the length of occupational exposure. There was no correlation between changes in paracetamol metabolism and standard functional hepatic tests. The acetaminophen test can be useful in detecting alterations in the activity of hepatic microsomal enzymes, a symptom of early occupational exposure to chemical compounds with potential hepatoxic properties.

Acetaminophen↗
PubMed1992

Essential phospholipids modify immunological functions and reduce experimental atherosclerosis in rabbits.

Atherosclerosis was induced in male mongrel rabbits with a high-fat diet and the influence of essential phospholipids (EPL) on plaque formation, parameters of lipid metabolism and immunological functions was studied. When EPL were added to the high-fat diet there was a significant reduction in the area of atherosclerotic involvement of the aorta. The serum concentration of lipids decreased, often to normal values, and cholesterol esterified with polyunsaturated fatty acids appeared. Normalization of the malonyldialdehyde level in plasma was accompanied by a decrease in the concentration of ascorbate free radicals in blood and liver. The high-fat diet caused a depression of both non-specific and specific immune functions studied. With EPL in the diet the tests showed near normal or normal values. It is inferred from these results that a normal state of the immune system is important for preventing the progress of atherosclerotic changes. This is discussed with reference to the role of some immune cells in the metabolism of lipids and to participation of essential phospholipids in plasma membrane functions.

Animals↗
PubMed1992

Caffeine reduces the hepatotoxicity of paracetamol in mice.

Paracetamol causes extensive liver damage when taken in overdose quantities; however, it is less hepatotoxic when administered in combination with caffeine. The present work in mice was undertaken to study the effect of caffeine on mortality rates and biochemical and histological parameters of liver damage after administration of toxic doses of paracetamol. It was found that caffeine markedly increased the survival rate after administration of a dose of paracetamol that was lethal to 50% and 100% of mice, reduced liver damage as assessed by serum glutamic pyruvic and glutamic oxaloacetic transaminase activities, partially prevented the depletion of reduced glutathione and reduced histological changes to the liver accompanying paracetamol intoxication. The results support the possibility that caffeine might be useful for the treatment of paracetamol intoxication in humans.

Acetaminophen↗
PubMed1992

[Pharmacokinetics of phenazone after bilateral ovariectomy in female rabbits].

The aim of this study was to evaluate the influence of female sex hormones on phenazone pharmacokinetics using as an experimental model female rabbits after a bilateral ovariectomy. Eighteen female rabbits divided into two groups: control animals and experimental rabbits, that underwent ovariectomy, were used in the study. Pharmacokinetic assays were performed in all animals: prior to the study, after 1 month and after 2 months. Blood was sampled within 24 hours after intragastric administration of phenazone at a dose 50 mg/kg b.w. Two compartment open model was used for calculations. Significant increase in AUC and prolongation of phenazone halflife as well as a decrease in the total body clearance were noted. The study demonstrated the possible inhibition of the microsomal mixed-function oxidase system by oestrogens.

Animals↗
PubMed1992

Padma 28 modifies immunological functions in experimental atherosclerosis in rabbits.

The effect of Padma 28 on selected parameters of humoral and cellular immune reactions in rabbits subjected to experimental atherosclerosis was studied. The drug significantly reduced the size of atherosclerotic plaques in the aorta and restored to a varying extent the immune functions studied. The possible mechanism by which Padma 28 may exert its anti-atherosclerotic action is discussed in the scope of the immunological theory of atherosclerosis.

Animals↗
PubMed1991

Effect of selenium and vitamin E on the development of experimental atherosclerosis in rabbits.

Male mongrel rabbits, divided into 5 groups (1) controls, (2) animals receiving a high-fat diet (HFD) containing cholesterol and coconut oil, (3) HFD + selenium, (4) HFD + vitamin E, (5) HFD + selenium + vitamin E, were treated for 12 weeks. In the groups receiving selenium and/or vitamin E, the elevation of serum total lipids, beta-lipoproteins, total cholesterol and triglyceride was markedly suppressed. HDL cholesterol in these groups of animals was increased. The cytochrome P-450 content in liver microsomes was increased, and the concentration of malondialdehyde in the blood plasma of rabbits was significantly decreased, while thyroid hormones (T4, T3), cortisol and insulin level were increased. Surface area of the lipid deposits at 12 weeks measured planimetrically averaged 76% in HFD-fed animals but only 28% in selenium + vitamin E treated rabbits. The important finding of this study is that combination of selenium and vitamin E, results in an intensified effect on the improvement of metabolic processes and on the reduction of atherosclerotic plaque formation.

Animals↗
PubMed1991

Hepatoprotective effect of selenium and vitamin E in rabbits fed a high-fat diet.

The high-fat diet consisted of cholesterol, hydrogenated coconut oil, and cholic acid. In the blood serum and in liver homogenate lipid content, cholesterol, and triglycerides were assayed. Cytochrome P-450 concentration in liver microsomes was also estimated. In animals receiving selenium and vitamin E, the content of lipid fractions in the blood serum and liver homogenate fell, while the cytochrome P-450 content in the liver microsomes was markedly elevated. The intensified protective effect of vitamin E and selenium applied in combination against changes induced in the liver of animals receiving a HFD was confirmed by macroscopic and microscopic examination of the organ.

Alanine Transaminase↗