Agnieszka Jasiecka-Mikołajczyk

Oclacitinib (OCL), a Janus kinase inhibitor, is a novel immunomodulatory/immunosuppressive agent which is an approved as the first-line treatment for atopic dermatitis (AD) in dogs. The aim of the study was to investigate the effects of OCL on CD4+ and CD8+ T cells and their selected subsets under clinical conditions, i.e. in dogs suffering from AD, in terms of both safety and immune mechanisms underlying its therapeutic actions. Eight dogs were treated for 28 days with OCL at the recommended dose. Blood samples were taken at day 0, 7, 14 and 28. The study showed that the mean percentage and absolute count of CD4+ and CD8+ T cells on the 14th and 28th day of the treatment with OCL did not differ from the corresponding baseline values, i.e. those before the treatment. On the 7th day of the treatment, the mean absolute count of CD4+ T cells and the mean percentage and absolute count of CD8+ T cells were significantly increased. The research found that on the 14th day of the treatment, the mean percentage and absolute count of CD25+CD4+ and CD25+CD8+ T cells were significantly decreased; the reduction in the percentage of CD25+CD4+ T cells persisted on 28th day of the treatment. A two-week treatment with OCL resulted in an increase in the mean percentage of Foxp3+CD4+ T cells, and this effect was sustained at the last time point. The treatment with OCL decreased the eosinophil level but does not affect the absolute counts of basophils, monocytes and neutrophils. The findings of the study strongly suggest that: (a) in terms of the impact of OCL on the number of PB CD4+ and CD8+ T cells, monthly treatment with the drug should be considered as a relatively safe; (b) the eosinophil-reducing effect and the down-regulation of the AD up-regulated CD25 expression on CD4+ Teff cells may constitute significant elements of the mechanism of action underlying the therapeutic effects of the drug in the treatment of canine AD; (c) the generation of inducible Foxp3-expressing CD4+ regulatory T cells - resulting in the shift of the CD4+ Treg cell (i.e. Foxp3+CD4+)/activated Teff (i.e. CD25+CD4+) cell balance toward an increased proportion of Treg cells - may be considered as additional mechanism involved in producing the immunomodulatory/immunosuppressive properties of OCL.

The main purpose of the study was to determine the safety of oclacitinib (OCL), a Janus kinase inhibitor, with respect of its effect on CD4+ and CD8+ T cells as well as B cells in the lymphoid tissue. The mice were treated orally with OCL at a dose of 2.7 mg/kg for 14 days and peripheral blood, head and neck lymph nodes (HNLNs), mediastinal lymph nodes (MLNs) and spleen were collected. The study found that OCL induced depletion of CD4+ T cells in the HNLNs and MLNs, while it did not affect the absolute count of CD8+ T cells in these tissues. Also OCL caused a loss of B cells in the HNLNs, although not in the MLNs. Moreover, OCL depleted B cells in the peripheral blood, but did not affect the absolute count of CD4+ and CD8+ T cells. Thus, it can be concluded that OCL may induce a depletive effect on CD4+ and CD8+ T cells as well as B cells in the lymphoid tissue. This effect should be seen as an unfavorable one, especially in patients with infections. Therefore, a clinical implication is that in such patients, the benefit/risk ratio should be thoroughly considered by clinicians. Moreover, OCL reduced the absolute count of eosinophils, basophils, neutrophils and monocytes. However, it is uncertain whether this effect should be considered to be of clinical importance because the levels of these cells were within the physiological range. It is possible that the depletive effect of OCL toward T and B cells, as well as eosinophils and basophils may contribute to the beneficial effects of the drug in the treatment of skin allergic diseases.

In this study, we report on the effectiveness of electrochemical and biological wastewater treatment for artificially prepared industrial wastewater, comprising small amounts of technologically important dyes, namely Acid Mixture composed of Acid Violet 90 (AV90) and Acid Red 357 (AR357) in Na₂SO₄ (ESS—electrolyte supporting solution), as well as their impact on the environment, using Lemna minor as a bioindicator. Our study revealed that among the tested dyes, the raw ones (AM in ESS+OM) and those subjected to electrooxidation with the use of an iron anode and a copper cathode [AM_Fe/Cuox in ESS+OM (OECD medium is a medium recommended by the Organization for Economic Co-operation and Development for Lemna sp. Growth Inhibition Test)] were the most phytotoxic for L. minor. No phytotoxicity was detected for the tested plants in solution after electrooxidation with graphite anode and cathode (AM_Cox in ESS+OM). Quantitative identification of acid mixture removal was carried out by supplementary UPLC/MS-MS (Ultra-Performance Liquid Chromatography/tandem Mass Spectrometry) and UV-VIS (UltraViolet-Visible spectroscopy) instrumental analysis. The final removal after electrochemical and biological treatment of AV90 and AR357 dye components was 98 and over 99%, respectively. The results suggest that it may be a suitable replacement/addition for the generally used wastewater treatment methods.

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. The study found that OCL does not affect the proliferation of CD4⁺ T cells or the number of IFN-γ- and IL-17-producing CD4⁺ and CD8⁺ T cells. Moreover, OCL was found to counteract the induction of type 1 regulatory T (Tr1) cells and to act as a strong inhibitor of IL-10 production in both CD4⁺ and CD8⁺ T cells. Thus, these results indicate that beneficial effects of OCL in the treatment of skin allergic diseases are not mediated through: (a) the abolishment of IFN-γ and IL-17-production in CD4⁺ and CD8⁺ T cells; (b) generation of Tr1 cells; (c) inhibition of CD4⁺ T cell proliferation; (d) induction of IL-10 production in CD4⁺ T cells. The results of this study strongly suggest that, with respect to the evaluated parameters, OCL exerts a suppressive effect on Th2- but not Th1-mediated immunity.

Traditional wastewater purification processes are based on a combination of physical, chemical, and biological methods; however, typical electrochemical techniques for removing pollutants require large amounts of electrical energy. In this study, we report on a process of wastewater purification, through continuous anodic dissolution of iron anode for aerated Cu/Fe galvanic cell in synthetic Na₂SO₄ wastewater solution. Electrochemical experiments were conducted by means of a laboratory size electrolyzer, where electrocoagulation along with electrooxidation phenomena were examined for wastewater containing Acid Mixture dye. The above was visualized through the employment of electrochemical (cyclic voltammetry and ac impedance spectroscopy techniques) along with instrumental spectroscopy analyses.

The main purpose of this study was to investigate whether the blockade of the interaction between the receptor activator of nuclear factor-κB (NF-ĸB) ligand (RANKL) and its receptor RANK as well as the blockade of NF-κB inhibitor kinase (IKK) and of NF-κB translocation have the potential to suppress the pathogenesis of allergic asthma by inhibition and/or enhancement of the production by CD4⁺ and CD8⁺ T cells of important cytokines promoting (i.e., IL-4 and IL-17) and/or inhibiting (i.e., IL-10 and TGF-β), respectively, the development of allergic asthma. Studies using ovalbumin(OVA)-immunized mice have demonstrated that all the tested therapeutic strategies prevented the OVA-induced increase in the absolute number of IL-4- and IL-17-producing CD4⁺ T cells (i.e., Th2 and Th17 cells, respectively) indirectly, i.e., through the inhibition of the clonal expansion of these cells in the mediastinal lymph nodes. Additionally, the blockade of NF-κB translocation and RANKL/RANK interaction, but not IKK, prevented the OVA-induced increase in the percentage of IL-4-, IL-10- and IL-17-producing CD4⁺ T cells. These latter results strongly suggest that both therapeutic strategies can directly decrease IL-4 and IL-17 production by Th2 and Th17 cells, respectively. This action may constitute an important mechanism underlying the anti-asthmatic effect induced by the blockade of NF-κB translocation and of RANKL/RANK interaction. Thus, in this context, both these therapeutic strategies seem to have an advantage over the blockade of IKK. None of the tested therapeutic strategies increased both the absolute number and frequency of IL-10- and TGF-β-producing Treg cells, and hence they lacked the potential to inhibit the development of the disease via this mechanism.

Due to the unrecognized effect of tigecycline (TIG) on CD4(+) and CD8(+) T cells, the present study has been undertaken in order to determine whether the drug can affect these cells in respect of their counts, and the production of IFN-gamma, IL-17 (pro-inflammatory and immune-protective cytokines), IL-4 (anti-inflammatory and immune-protective cytokine), IL-10 and TGF-beta (anti-inflammatory and immune-suppressive cytokines). Murine lymphocytes were treated with TIG for 48 and 96 h at concentrations reflecting its plasma levels obtained in vivo at therapeutic doses, and at 10-fold lower concentrations. It was found that TIG neither affected substantially the percentage and absolute counts of entire CD4(+) and CD8(+) T cell populations nor influenced the Foxp3(+)CD25(+)CD4(+) regulatory/suppressive T cell subset. Furthermore, the percentages of IL-4-, IL-10-, IL-17- and IGF-beta-producing CD4(+) T cells were not altered following the exposure to TIG. Similarly, TIG did not influence IFN-gamma production by CD8(+) T cells. Thus, with respect to the parameters evaluated, 'FIG does not seem to exert immune-suppressive and anti-inflammatory effects.

The aim of this study was to determine the influence of feed on the pharmacokinetics of flumequine (FLU) administered to broiler chickens as follows: directly into the crop (10 mg/kg of BW) of fasted (group I/control) and non-fasted chickens (group II), or administered continuously with drinking water (1 g/L for 72 h) and with unlimited access to feed (group III). Plasma concentration of FLU was determined by high-performance liquid chromatography with fluorescence detection. In group II, a significant decrease in the maximum concentration(C-max = 2.13 +/- 0.7 mu g/mL) and the area under the concentration curve from zero to infinity (AUC(0 ->infinity)= 7.47 +/- 2.41 mu g.h/mL) was noted as compared to the control group (C-max = 4.11 +/- 1.68 mu g/mL and(AUC(0 ->infinity) = 18.17 +/- 6.85 mu g.h/mL, respectively). In group III, the decrease in AUCwas significant only in the first 3 hours (AUC(0 -> 3) = 5.02 +/- 1.34 mu.g.h/mL) as compared to the control group (AUC(0 -> 3) =7.79 +/- 3.29 mu g.h/mL). The results indicate that feed reduced the bioavailability of FLU from the gastrointestinal tract by at least 50% after the administration of a single oral dose. However, continuous administration of FLU with drinking water could compensate for the feed-induced decrease in absorption after single oral dose.