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EN
Recently, we found that dexamethasone caused a depletion of CD25⁻ CD4⁺ T cells, but it increased the number of CD25highCD4⁺ and CD25lowCD4⁺ T cells. We also determined meloxicam-induced increase in the number of CD25highCD4⁺ T cells. In view of this, and taking into consideration the latest reports indicating that meloxicam shows an anti-proliferative effect on bovine peripheral blood mononuclear cells, it was considered purposeful to determine the effect of both drugs on proliferation of bovine CD25highCD4⁺, CD25lowCD4⁺ and CD25⁻ CD4⁺ T cells. Flow cytometry analysis and 5-bromo-2’-deoxyuridine incorporation assay were applied to detect the cell proliferation. It was demonstrated that dexamethasone, but not meloxicam, significantly reduced cell proliferation within all three evaluated CD4⁺ T cell subpopulations. Thus, the depletion of CD25⁻ CD4⁺ T cells by treatment with dexamethasone can partly be the effect of the anti-proliferative action of the drug, however, dexamethasone-induced increase in the number of CD25highCD4⁺ and CD25lowCD4⁺ T cells cannot be the result of enhanced proliferation of these cells.
EN
Fluoroquinolones are a group of antimicrobial agents which are widely used in human and veterinary medicine. These drugs may cause interactions with other compounds. The paper describes the latest views concerning interactions between fluoroquinolones and metal cations. Simultaneous administration of fluoroquinolones with 2- and 3-valent cations causes a significant decrease in the bioavailability of these drugs due to the effect of chelating cations by carboxylate and the carbonyl group of fluoroquinolone. These interactions may result in an inefficient antimicrobial therapy and, in order to prevent this occurring, spaced dosing of fluoroquinolones and a formulation containing metal cations is recommended.
EN
This study analysed the relaxant properties of salbutamol (β₂₋adrenoceptors agonist) and BRL 37344 (β₃₋adrenoceptors agonist) regarding the contractility of porcine myometrium on days 10-14 of the oestrous cycle (cyclic group; n = 10) and on days 3-5 of pregnancy (early pregnant group; n = 6). The activity of myometrial strips (tension, frequency and amplitude) was recorded under isometric conditions using force transducers. The contractility was assessed further following the administration of increasing concentrations of the agonists (10⁻⁹-10⁻⁴ M), both with and without β-adrenoceptor antagonists (butaxamine – a selective β₂₋ adrenoceptor antagonist, propranolol- a non-selective β₁₋and β₂₋adrenoceptor antagonist and bupranolol – a non-selective β₁₋, β₂₋ and β₃₋adrenoceptor antagonist) at a concentration of 10⁻⁴ M. Although neither salbutamol nor BRL 37344 caused changes in the tension, at the highest concentrations they decreased the frequency and amplitude of contractions. These changes were more evident after salbutamol treatment and in the early pregnant group. Antagonists given alone did not cause changes in the parameters examined but changed some activity of the agonists. Butoxamine reduced the decrease in frequency and amplitude induced by salbutamol and produced a decrease in the tension after BRL 37344 treatment in the early pregnant group. Propranolol reduced the decrease in frequency and amplitude induced by salbutamol in both examined groups and did not cause significant changes in BRL 37344 activity. The administration of bupranolol before salbutamol treatment caused an increase in the tension and reduced the decrease in the frequency in the cyclic group. Moreover, bupranolol eliminated a decrease in frequency and induced an increase in amplitude caused by BRL 37344 in both groups and these changes were more evident in the early pregnant group. The data indicates that both β₂₋ and β₃₋adenoreceptors are involved in the regulation of the contractility in both groups, but the changes after agonists and antagonists treatment are more evident in the early pregnant myometrium.
EN
Quinolone-induced arthropathy has been observed after a single very large dose, or after several moderately large doses in juvenile animals of multiple species. The purpose of the present study was to determine whether long-term treatment with therapeutic doses of enrofloxacin has a detrimental effect on chicken articular cartilage. 21-day-old broiler chickens were treated orally with 10 mg/kg/day of enrofloxacin for 10, 20 and 35 days. 24 hours after the last dose, the animals were killed and the femoral head with condyles and tibial condyles were subjected to a gross and histopathological investigation. The necropsy did not reveal macroscopic visible pathological changes in the articular cartilage surface, as well as in soft tissues surrounding joints in any of the animals from this study. Also, light microscopy evaluation did not show significant histopathological changes in any of the specimens from either experimental and control animals. In conclusion, our results indicate that treatment with a therapeutic dose of enrofloxacin for a period exceeding the recommended duration of therapy does not cause arthropathy in growing chickens. Moreover, the results obtained seem to indicate that chondrotoxicity of quinolones does not have a cumulative nature.
EN
Tigecycline (TIG), a novel glycylcycline antibiotic, plays an important role in the management of complicated skin and intra-abdominal infections. The available data lack any description of a method for determination of TIG in avian plasma. In our study, a selective, accurate and reversed-phase high performance liquid chromatography-tandem mass spectrometry method was developed for the determination of TIG in turkey plasma. Sample preparation was based on protein precipitation and liquid-liquid extraction using 1,2-dichloroethane. Chromatographic separation of TIG and minocycline (internal standard, IS) was achieved on an Atlantis T3 column (150 mm x 3.0 mm, 3.0 μm) using gradient elution. The selected reaction monitoring transitions were performed at 293.60 m/z → 257.10 m/z for TIG and 458.00 m/z → 441.20 m/z for IS. The developed method was validated in terms of specificity, selectivity, linearity, lowest limit of quantification, limit of detection, precision, accuracy, matrix effect, carry-over effect, extraction recovery and stability. All parameters of the method submitted to validation met the acceptance criteria. The assay was linear over the concentration range of 0.01-100 μg/ml. This validated method was successfully applied to a TIG pharmacokinetic study in turkey after intravenous and oral administration at a dose of 10 mg/kg at various time-points.
EN
Although prostaglandin E₂ (PGE₂) is a pro-inflammatory mediator, it also produces some effect which is anti-inflammatory in character. It is suggested that one of the mechanisms responsible for the latter effect is the increased synthesis of IL-10. The aim of this study has been to determine the influence of PGE₂ on IL-10 production by bovine CD⁴⁺ and CD⁸⁺ T cells and NK cells. With this aim, peripheral blood mononuclear cells collected from 12-month-old heifers (n = 10) were treated without or with PGE₂ (10⁻⁶ M). Flow cytometric analysis showed that PGE₂ caused a reduction in the percentage of IL-10 producing CD⁴⁺ T cells (P < 0.001), while leaving the secretion of this cytokine by CD⁸⁺ T cells and NK cells unaffected. This seems to indicate that PGE₂ in cattle does not produce an anti-inflammatory effect by increasing the synthesis of IL-10; contrary to this, it may aggravate an inflammatory response by inhibiting the secretion of this cytokine by CD⁴⁺ T cells.
EN
The aim of the study was to determine whether treatment with recommended doses of meloxicam or flunixin had an effect on the apoptosis of peripheral blood T lymphocytes in calves. The study was carried out on 4-5 months old calves (n = 24, 8 per group). Experimental animals were injected subcutaneously with a single dose of 0.5 mg . kg-1 of meloxicam or intravenously with 3 doses of 2.2 mg . kg-1 day-1 of flunixin. The non-treatment animals served as control. Blood samples were taken at day 0 and at days 1, 2, 3, 5, 7 and 14 after the first NSAIDs injection. Apoptosis was determined by flow cytometry using Annexin V-PE/7-AAD staining. The kinetic analysis of apoptosis in the total lymphocyte population, as well as in the CD4+ and CD8+ subsets did not reveal significant differences in the frequency of early apoptotic cells between control and experimental groups throughout the period studied. Although, 24 h after administration of the first dose of NSAIDs, late-stage apoptosis/necrosis was significantly increased in the total lymphocyte population (the meloxicam group), as well as in the CD4+ (the meloxicam group and the flunixin group) and CD8+ (the flunixin group) subsets of T cells. However, this disturbance was transient, relatively poorly expressed and, thus, unlikely to be of clinical significance. Our results indicate that the use of meloxicam or flunixin in accordance with the recommended dosage regimen in cattle do not have a clinically significant influence on apoptosis of peripheral blood T cells.
14
Content available Pharmacological characteristics of metamizole
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EN
Metamizole (dipyrone) is a popular analgetic, non-opioid drug, commonly used in human and veterinary medicine. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug (NSAID). Metamizole is a pro-drug, which spontaneously breaks down after oral administration to structurally related pyrazolone compounds. Apart from its analgesic effect, the medication is an antipyretic and spasmolytic agent. The mechanism responsible for the analgesic effect is a complex one, and most probably rests on the inhibition of a central cyclooxygenase-3 and activation of the opioidergic system and cannabinoid system. Metamizole can block both PG-dependent and PG-independent pathways of fever induced by LPS, which suggests that this drug has a profile of antipyretic action distinctly different from that of NSAIDs. The mechanism responsible for the spasmolytic effect of metamizole is associated with the inhibited release of intracellular Ca²⁺ as a result of the reduced synthesis of inositol phosphate. Metamizole is predominantly applied in the therapy of pain of different etiology, of spastic conditions, especially affecting the digestive tract, and of fever refractory to other treatments. Co-administration of morphine and metamizole produces superadditive, antinociceptive effects. Metamizole is a relatively safe pharmaceutical preparation although it is not completely free from undesirable effects. Among these side-effects, the most serious one that raises most controversy is the myelotoxic effect. It seems that in the past the risk of metamizole- induced agranulocytosis was exaggerated. Despite the evidence showing no risk of teratogenic and embryotoxic effects, the drug must not be administered to pregnant women, although it is allowed to be given to pregnant and lactating animals. This paper seeks to describe the characteristics of metamizole in the light of current knowledge.
EN
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.
EN
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.
EN
The objective of the present study was to determine the influence of nonsteroidal anti-inflammatory drugs (NSAIDs) representing different chemical groups on progesterone (P₄) production by cultured bovine steroidogenic luteal cells. The cells were enzymatically isolated from corpora lutea collected on days 8-12 of the estrous cycle. After 24 h preincubation they were incubated for 24 h with medium only (control) or stimulated with bovine luteinizing hormone – LH (100 ng/ml; positive control) or increasing concentrations (10⁻⁸ to 10⁻⁴ M) of acetylsalicylic acid, indomethacin, ibuprofen, naproxen, piroxicam, phenylbutazone, dipyrone or nimesulide. Concentartions of P₄ in the culture media were determined by enzyme immunoassay. LH significantly increased P₄ secretion, while acetylsalicylic acid and indomethacin did not affect the production of this hormone. A significant increase in P₄ secretion was observed after administration of dipyrone at all concentrations, piroxicam at concentrations of 10⁻⁸, 10⁻⁷ and 10⁻⁵ M, phenylbutazone and naproxen at concentrations of 10⁻⁷ and 10⁻⁶ M and ibuprofen at concentrations of 10⁻⁵ and 10⁻⁴ M. Nimesulide did not affect P₄ production at concentrations of 10⁻⁸ – 10⁻⁵ M, while at a concentration of 10⁻⁴ M it inhibited P₄ secretion. The results obtained indicate that NSAIDs may change the production of P₄ in bovine luteal cells, however, these changes are dependent on the substance used.
EN
Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolones that is widely used to treat bacterial infections in animals. Fluoroquinolones cause severe lesions in articular-epiphyseal cartilage complexes of growing mammals. The aim of the present study was to determine whether enrofloxacin has chondrotoxic, dose- and time-dependent effects on avian articular cartilage. 21-day-old male broiler chickens were treated orally with a single or five doses of 10, 50, 100, 300 and 600 mg/kg/day of enrofloxacin. 24 hours after the last dose the animals were killed and femoral head with condyles and tibial condyles were subject to a gross and histopathological investigation. The lesion scoring system was used to determine the progression of lesions. The mean score in birds treated with a single dose of 300 and 600 mg/kg of enrofloxacin was significantly increased when compared to the control group, while the administration of one dose of 10, 50 and 100 mg/kg of the drug did not cause substantial changes in the examined articular cartilages. The mean score was significantly greater in birds dosed for 5 days with 50, 100, 300 or 600 mg/kg/day of enrofloxacin when compared to the control group. Histologic changes included, among others, occurrence of chondrocytes with shrunken cytoplasm and pyknotic nuclei, spindle-shaped cells, clusters of chondrocytes and loss of proteoglycan. In conclusions, our results indicate that the use of enrofloxacin in growing chickens at recommended dosage is safe from the point of view of possibility of chondrotoxic effect. Only very high dosage of enrofloxacin, significantly exceeding the therapeutically applied doses, can induce toxic effects in articular cartilage and intensity of chondrotoxicity is dose- and time-dependent. Moreover, our findings suggest that quinolone-induced arthropathy is considerably less expressed in birds than in mammals.
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