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H. Ziółkowski, J.J. Jaroszewski, N. Ziółkowska and A. Jasiecka

Abstract

A significant number of cases of clinical canine epilepsy remain difficult to control in spite of the applied treatment. At the same time, the range of antiepileptic drugs is increasingly wide, which allows efficient treatment. In the present paper we describe the pharmacodynamics and pharmacokinetics of the newer antiepileptic drugs which were licensed after 1990 but are still not widely used in veterinary medicine. The pharmacokinetic profiles of six of these drugs were tested on dogs. The results of experimental studies suggest that second generation antiepileptic drugs may be applied in mono- as well as in poli- treatment of canine epilepsy because of the larger safety margin and more advantageous pharmacokinetic parameters. Knowledge of the drugs’ pharmacokinetics allows its proper clinical appliance, which, in turn, gives the chance to improve the efficiency of pharmacotherapy of canine epilepsy.

Open access

T. Maślanka, J. Jaroszewski, W. Markiewicz, H. Ziółkowski and D. Barski

The presence of CD25 on bovine WC1+ γδ T cells is positively correlated with their production of IL-10 and TGF-β, but not IFN-γ

WC1+ cells in cattle exhibit both regulatory and effector activities. However, it has not been elucidated whether they are so plastic that both activities co-exist in one cell or there are separate subpopulations of effector and regulatory cells. Since the production of IFN-γ and IL-10 seems to be related to WC1+ cells' effector and regulatory function, respectively, the main aim of this study was to determine whether those cytokines are produced by separate subpopulations of WC1+, or are co-produced by the same cells. Due to increasingly frequent emphasised role of consumption of IL-2 in the mechanism of suppressor action of mouse CD25+CD4+ T regulatory cells, expression of the receptor's α chain for interleukin 2 (CD25) on WC1+ lymphocytes has been evaluated. An average of 5.21% of WC1+ cells obtained from PBMCs of 12-month-old heifers show constitutive expression of the CD25 molecule, with CD25highWC1+ and CD25lowWC1+ cells accounting for 1.05% and 4.10% of WC1+ lymphocytes, respectively. For detection of intracellular cytokine production, PBMCs were stimulated with concanavalin A. Both IFN-γ- and IL-10-producing cells within the CD25-WC1+ and CD25+WC1+ subpopulations were mainly separate subpopulations. The average percentage of IFN-γ+IL-10-, IFN-γ-IL-10+ and IFN-γ+IL-10+ cells among CD25-WC1+ lymphocytes was 4.03%, 2.67% and 0.51%, respectively. A positive correlation was observed between the presence of the CD25 molecule on WC1+ lymphocytes and production of IL-10 and TGF-β, because the average percentage of IFN-γ-IL-10+ and IFN-γ+IL-10+ among CD25+WC1+ lymphocytes was 3 and 4.5 times higher as compared to the corresponding cells in the CD25-WC1+ subpopulation, whereas the percentage of IFN-γ+IL-10- cells in both the subpopulations was not significantly different. The percentage of TGF-β+ cells within the CD25+WC1+ subpopulation was 2.72 times as high as that of CD25-WC1+ lymphocytes. Therefore, with respect to the production of IFN-γ, IL-10 and TGF-β, CD25+WC1+ lymphocytes turn out to have a more suppressor profile than CD25-WC1+.

Open access

A. Spodniewska, D. Barski and H. Ziółkowski

Abstract

The study was undertaken to examine the effect of single and combined administration of dimethoate (an OP insecticide) and pyrantel embonate (an anthelmintic agent) on the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx) and glutathione reductase (GR) in rats. Dimethoate (Group I) was administered to rats at a dose of 1/10 LD50 for 5 consecutive days and pyrantel embonate (Group II) at a dose of 1/5 LD50 for 3 consecutive days. The animals of group III were given both of the mentioned above compounds in the same manner as group I and II, but pyrantel embonate was applied on day 3, 4, and 5 from the beginning of dimethoate intoxication. Material from 6 rats randomly selected from each group was obtained after 3, 6 and 12 hours and 2, 7 and 14 days following the last applied dose of the compounds under study. It was found that application of pyrantel embonate caused only slight changes in the analysed parameters i.e. GSH, GPx and GR. Dimethoate administration caused disturbances in the antioxidative system manifested as a decrease in GSH concentration in the liver (max. - 37.7% after 6 hours) and an increase of GPx and GR activities in erythrocytes (max. - 21.7% and 29.6% after 3 hours, respectively), compared to the control group. The profile of changes after combined intoxication was similar, but their intensity was higher compared to the group of animals exposed to dimethoate only. Based on current studies, it was concluded that both dimethoate and pyrantel embonate at the applied doses showed a pro-oxidative activity.

Open access

A. Jasiecka, T. Grabowski, T. Maślanka, H. Ziółkowski and J.J. Jaroszewski

Abstract

The aim of the present study was to determine the pharmacokinetics of simvastatin (SIM) administered orally in 6-week-old turkeys at a single dose of 2 mg/kg b.w. The SIM concentrations in plasma were determined by validated HPLC-MS/MS method. Mean (± SD; n = 10) values of pharmacokinetic parameters evaluated were as follows: Cmax = 0.49 ± 0.21 ng/ml, tmax = 1.6 ± 1.1 h, AUC(0-∞) = 1.08 ± 0.57 h×ng/ml, t1/2kel = 2.14 ± 1.3 h and MRT = 3.08 ± 1.52 h. The results indicate that the SIM is absorbed from the gastrointestinal tract of turkeys; however, achieved plasma level is lower compared to those observed in mammals.

Open access

M. Zuśka-Prot, H. Ziółkowski, J.J. Jaroszewski and T. Maślanka

Abstract

The present study describes the distribution of CD4+CD8+ double-positive (DP) T cells in various immune compartments of mice with ovalbumin (OVA)-induced allergic asthma. It was found that the absolute number of DP T cells was considerably increased in the mediastinal lymph nodes and lungs of asthmatic mice as compared with that determined in the healthy subjects. On the contrary, the absolute counts of DP T cells was significantly decreased in the head and neck lymph nodes, and in peripheral blood of OVA-immunized mice. These results suggest that DP T cells may be involved in the pathogenesis of allergic asthma.

Open access

R. Sokół, M. Raś-Noryńska, M. Michalczyk, A. Jasiecka, H. Ziółkowski and J. Jaroszewski

Abstract

The aim of the present study was to determine the efficacy of ivermectin against Cyathostominae infections and to describe the drug’s pharmacokinetic parameters during two seasonal deworming treatments in horses. The study was performed on warm-blooded mares aged 3-12 years weighing 450-550 kg. A single bolus of an oral paste formulation of ivermectin was administered at a dose of 0.2 mg/kg BW in spring and autumn. Fecal samples were tested before treatment and 1, 2, 3, 4, 6, 10, 20, 30, 40, 50, 60, 75 days after treatment. Ivermectin concentrations in blood samples collected before treatment, 0.5, 1, 2, 3, 4, 6, 12, 24, 36 and 48 hours after treatment, and 3, 4, 6, 8, 10, 15, 20, 25, 30, 40, 50, 60 and 75 days after drug administration were determined by high pressure liquid chromatography. Drug absorption was significantly (p<0.05) slower (tmax: 21.89±11.43 h) in autumn than in spring (tmax: 9.78±8.97 h). Maximum concentrations (Cmax) of ivermectin in the blood plasma of individual horses (8.40-43.08 ng/ml) were observed 2-24 h after drug administration during the spring treatment and 2-36 h (6.43-24.86 ng/ml) after administration during the autumn treatment. Significantly higher (p<0.05) ivermectin concentrations were found during the first 4 hours after administration in spring in comparison with those determined after the autumn treatment.

The administration of the recommended dose of ivermectin resulted in 100% elimination of parasitic eggs from feces in spring and autumn treatment.