Oclacitinib, a Janus Kinase Inhibitor, Reduces the Frequency of IL-4- and IL-10-, but Not IFN-γ-, Producing Murine CD4 and CD8 T Cells and Counteracts the Induction of Type 1 Regulatory T Cells.

The purpose of the present study was to broaden the knowledge and understanding of the effects of oclacitinib (OCL), a Janus kinase inhibitor, on T cells in the context of both the immune mechanisms underlying anti-inflammatory and anti-allergic properties of the drug and its safety. The results indicate that beneficial effects of OCL in the treatment of skin allergic diseases may be partially mediated by the inhibition of IL-4 production in CD4 and CD8 T cells. To a certain extent, the antiproliferative effect of OCL on CD8 T cells may also contribute to its therapeutic effect.

Development, Validation, and Application of the LC-MS/MS Method for Determination of 4-Acetamidobenzoic Acid in Pharmacokinetic Pilot Studies in Pigs.

Each drug has pharmacokinetics that must be defined for the substance to be used in humans and animals. Currently, one of the basic analytical tools for pharmacokinetics studies is high-performance liquid chromatography coupled with mass spectrometry. For this analytical method to be fully reliable, it must be properly validated.

Quercetin affects uterine smooth muscle contractile activity in gilts.

Quercetin is a polyphenolic flavonoid occurring in leaves, stems, flowers and fruits of many plants. In traditional Chinese medicine, it is used as a natural therapeutic agent with a broad spectrum of activities (antioxidant, neuroprotective, anti-inflammatory, anticancer, antibacterial and antiviral). Moreover, quercetin affects function of the reproductive tract, however the knowledge of this activity is still fragmentary.

The pharmacokinetics and antiparasitic activity of ivermectin in Hutsul and Toric horses.

The aim of this study was to compare the pharmacokinetics of ivermectin and its antiparasitic activity in two horse breeds. Eight Hutsul and 14 Toric horses were administered ivermectin orally at a dose of 0.2 mg/kg body weight.

Oclacitinib depletes canine CD4 and CD8 T cells in vitro.

Oclacitinib (OCL) is a novel immunosuppressive agent approved for dogs that controls itch and inflammation in allergic disease via the inhibition of the JAK/STAT pathway. This paper investigates the in vitro effect of OCL, a novel Janus kinase inhibitor, on selected canine regulatory (Treg) and effector (Teff) CD4 and CD8 T cells. Exposure of peripheral blood lymphocytes to OCL did not affect the transcription factor Foxp3 (Forkhead Box P3 protein) expression in CD25CD4 and CD25CD8 T cells.

Prostaglandin E2 exerts the proapoptotic and antiproliferative effects on bovine NK cells.

The aim of this research was to determine whether prostaglandin E2 (PGE2) affects bovine NK cells in respect of their counts, apoptosis and proliferation, and if it does, then which of the PGE2 receptor (EP) subtype(s) mediate(s) these effects. We here report that long-term, but not short-term, exposure of bovine peripheral blood mononuclear cells to PGE2 at 10(-5)M, 10(-6)M and 10(-7)M, but not at 10(-8)M, caused a significant increase in the percentage of early apoptotic cells among NK cell subset. Moreover, PGE2 at 10(-5)M and 10(-6)M, but not at 10(-7)M and 10(-8)M, induced a considerable decrease in the absolute count of NK cells.

Involvement of regulatory T cells and selected cytokines in the pathogenesis of bronchial asthma.

Asthma pathogenesis is complex and involves the interplay of many factors and actions. Airway inflammation in allergic asthma is characterized by an exaggerated activation of T helper type 2 cells, IgE production and infiltration and activation of eosinophils. The results of studies conducted in recent years indicate that the deficit of naturally occurring Foxp3+CD25+CD4+ and Foxp3+CD25+CD8+ regulatory T cells and type 1 regulatory T cells plays a pivotal role in the development of this disease.

The influence of prostaglandin E2 on the production of IFN-γ by bovine CD4(+), CD8(+) and WC1(+) T cells.

The aim of these studies was to assess the influence of prostaglandin E2 (PGE2) on the production of interferon-gamma (IFN-γ) by bovine CD4(+), CD8(+), and WC1(+) T cells and furthermore, should this effect exist, to identify the E-prostanoid (EP) receptor subtype(s) responsible for this influence. We here report that exposure of bovine peripheral blood mononuclear cells (PBMCs) to PGE2 significantly and dose-dependently decreased the percentage of IFN-γ-producing CD4(+) and CD8(+) T cells. It was also shown that PGE2 reduced IFN-γ production by WC1(+) T cells, but this effect was not dose dependent.

Comparison of the porcine uterine smooth muscle contractility on days 12-14 of the estrous cycle and pregnancy.

Background: Uterine contractile activity is very important for many reproductive functions including embryo transport, implantation, gestation and parturition. Abnormal contractility leads to implantation failure, spontaneous miscarriage, preterm birth and many other disorders. The objective of the present study was to assess the effects of acetylcholine (ACh), noradrenaline (NA), oxytocin (OT) and prostaglandins F2α (PGF2α) and E2 (PGE2) on the contraction of uterine strips collected from the horns of cyclic gilts (12-14 days of the estrous cycle-group I) and from pregnant (12-14 days after first insemination gilts in which one of the uterine horn was gravid (group IIa) and the second one was non-gravid (group IIb).

IκB kinase β inhibitor, IMD-0354, prevents allergic asthma in a mouse model through inhibition of CD4(+) effector T cell responses in the lung-draining mediastinal lymph nodes.

IκB kinase (IKK) is important for nuclear factor (NF)-κB activation under inflammatory conditions. It has been demonstrated that IMD-0354, i.e.

Pharmacokinetics of oxytetracycline in broiler chickens following different routes of administration.

The aim of this study was to determine the pharmacokinetics of oxytetracycline (OTC) in broiler chickens following intravenous (IV), intramuscular (IM), subcutaneous (SC) and oral (PO) administrations at a dose of 15 mg/kg bodyweight. Plasma concentrations of OTC were determined using liquid chromatography-tandem mass spectrometry and non-compartmental pharmacokinetic analysis was then conducted. The absorption half-life time was 1.

Relationship between drug structure and minimal inhibitory concentration value used for acceptable daily intake analysis.

The minimal inhibitory concentration (MIC) of an antimicrobial agent for a microbial population (MIC(50, obs) and MIC(90, obs)) is an interpolated value determined for antibacterial drugs by in vitro methods. Many studies have tried to determine the correlation between the MIC(50, obs) or MIC(90, obs) value and the physicochemical parameters to allow quantitaive structure activity relationship (QSAR) predictions of efficacy. A rigorous evaluation of approaches to this problem is presented here.

Correlation of elimination fraction area under the curve with total body clearance.

This study attempted to determine the area under the curve ([Formula: see text]), which corresponds to the sum of all elimination processes correlated with the total clearance value. The study attempted to determine the [Formula: see text] based on the coordinates known from classic non-compartmental pharmacokinetics for a single administration of the drug. 318 pharmacokinetics profiles were used for the analysis, obtained from 220 healthy subjects over ten studies.

Prostaglandin E₂ down-regulates the expression of CD25 on bovine T cells, and this effect is mediated through the EP4 receptor.

A crucial event in the initiation of an immune response is the activation of T cells, which requires IL-2 binding to its high-affinity IL-2 receptor for optimal signaling. The IL-2 receptor α-chain (CD25) is needed for the high affinity binding of IL-2 to effector cells and is potently induced after T cell activation. The aim of this research has been to determine whether prostaglandin E2 (PGE2) affects the CD25 expression on bovine T cells, and if it does, then which of the PGE2 receptor (EP) subtype(s) mediate(s) this effect.

Evaluation of sampling spacing in pharmacokinetic studies using six sigma method.

Key elements of pharmacokinetics (PK) studies include both, the number of sampling points (NSP) as well as the spacing between the sampling points (SSP). Optimization of the SSP is discussed in guidelines of all key regulatory agencies (RA). Those however, provide only very general rules on how to properly distribute the NSPs in proposed PK studies.

Influence of oral co-administration of a preparation containing calcium and magnesium and food on enrofloxacin pharmacokinetics.

The objective of this study has been to determine the influence of food and ions on the pharmacokinetics of enrofloxacin (ENRO) in turkeys, administered per os at a dose of 10 mg/kg of body weight (b.w.).

Method of variability optimization in pharmacokinetic data analysis.

For many drugs administered per os, high variability in the concentration-time (C-T) values from first sampling to the phase of distribution may cause difficulty in pharmacokinetic analysis. Therefore, the aim of this study was to propose a method of transformation of C-T data, which would allow significantly reducing the standard deviation (SD) value of observed concentrations, without a statistically significant influence on the value of the mean for each sampling point in group. In the presented study, the lowest value of relative standard deviation of concentrations observed in the elimination phase and the value of precision of the used analytical method, were used to optimize the arithmetic, geometric means, median, and the value of SD obtained after single oral administration of itraconazole in human subjects.

In vitro effects of meloxicam on the number, Foxp3 expression, production of selected cytokines, and apoptosis of bovine CD25+CD4+ and CD25-CD4+ cells.

The purpose of this study was to evaluate the effect of meloxicam (MEL) on selected immune parameters of bovine CD25(high)CD4+, CD25(low)CD4+, and CD25-CD4+ cells. Peripheral blood mononuclear cells (PBMCs) collected from 12-month-old heifers were treated with MEL at a concentration corresponding to the serum level of this medication following administration at the recommended dose (MEL 5 × 10(⁻6) M) and at a concentration 10 times lower (MEL 5 × 10(⁻7) M). After 12 and 24 h of incubation with the drug, the percentage of CD25(high)CD4+ cells decreased; however, this disturbance was quickly reversed.

Effects of dexamethasone and meloxicam on bovine CD25+ CD8+ and CD25- CD8+ T cells--in vitro study.

The aim of undertaken research was an in vitro evaluation of the effects of dexamethasone and meloxicam on selected bovine CD8(+) T lymphocyte subpopulations. Dexamethasone induced a fast-occurring and lasting depletion of CD25(-)CD8(+) cells. This was primarily the result of the proapoptotic effect of dexamethasone, but the antiproliferative effect of the drug was clearly responsible for the deepening of this disturbance.

In vitro studies on the influence of dexamethasone and meloxicam on bovine WC1+ γδ T cells.

In view of the lack of data on the effect of meloxicam (non-steroidal anti-inflammatory drug) on bovine γδ T cells (WC1(+) cells) and very poorly recognized effects of dexamethasone (steroidal anti-inflammatory drug) on these cells, the purpose of the present study has been to determine the in vitro influence of these drugs on CD25(high)WC1(+), CD25(low)WC1(+) and CD25(-)WC1(+) lymphocytes of the peripheral blood of cattle. Peripheral blood mononuclear cells were treated with the drugs in concentrations reflecting their plasma levels achieved in vivo at therapeutic doses (dexamethasone 10(-7)M; meloxicam 5×10(-6)M) and at ten-fold lower concentrations. It was found out that percentages and absolute counts of CD25(high)WC1(+) and CD25(low)WC1(+) cells increased in the presence of dexamethasone, and this effect was at least partly attributable to lower mortality of these cells, whose apoptosis was depressed by exposure to dexamethasone.

Foxp3 expression in bovine CD8+ T cells is associated with the intensity of CD25 expression.

The aim of the undertaken research was to determine whether Foxp3(+)CD25(+)CD8(+) cells exist in cattle and whether Foxp3 expression in CD8(+) T cells is correlated with the intensity of CD25 expression. It has been found that 0.66 and 2.

Comparison of bioequivalence study regulatory requirements for human and veterinary drugs.

Guidelines published by the European Union Regulatory Authority, regarding the planning of bioequivalence studies, are the primary source of knowledge about the study design optimization. The goal of this paper is to compare the key elements (27 points) of bioequivalence study optimization based on a comparison of the two European Medicines Agency guidelines relating to medicines used for humans (HB) and to veterinary drugs (AB). In case of the latter, one can get the impression that the issues of species differences in relation to the physiology and anatomy have been completely ignored.

C (max) and t (max) verification using Fibonacci sequence and absorption rate.

The aim of this study was to verify the values of maximal observed concentration (C max,obs) and the time, at which maximum concentration is observed (t max,obs) using the analysis of the absorption rate constant (k ab). It focused on the changes in concentration over time (C-T) for drugs, for which several peaks of concentration occur. In addition, the attempt was made to use Fibonacci sequence to facilitate the visual analysis of the dynamics in changes of concentration on C-T graphs.

Harmonization of rules in GLP and pharmacokinetic analysis: regulatory view.

This article is an attempt to present issues associated with the principles of GLP system harmonization, particularly in relation to pharmacokinetic (PK) studies at a global scale. Complete harmonization of GLP principles requires unification at several levels: inside registration authorities, between key registration authorities, within the framework of procedures regulating preclinical and clinical phases of the drug-development process and within the framework of procedures regarding GLP principles used in PK analyses and analyses of residuals of veterinary drugs. This large number of discrepancies indicates that total harmonization of rules on this issue will be very difficult and will require close cooperation between institutions responsible for legislative processes and control of GLP principles during PK analysis.

In vitro effects of dexamethasone on bovine CD25+CD4+ and CD25-CD4+ cells.

This paper investigates the in vitro effect of dexamethasone on bovine CD25highCD4+, CD25lowCD4+ and CD25-CD4+ T cells. Only a small percentage of bovine CD25highCD4+ (2-4%) and CD25lowCD4+ (1-2%) cells expressed Foxp3. Dexamethasone caused considerable loss of CD25-CD4+ cells, but it increased the relative and absolute numbers of CD25highCD4+ and CD25lowCD4+ lymphocytes, while at the same time reducing the percentage of Foxp3+ cells within the latter subpopulations.