No abstract

During Helicobacter pylori (Hp) infections, innate immune cells may be positively or negatively modulated by Hp compounds or by Hp-induced cytokines. We have shown previously that the natural cytotoxic activity of PBMC was lower in Hp-infected [Hp(+)] than Hp-uninfected individuals [Hp(-)]. Here, we asked whether the Hp-modulated cytotoxic amplitude is associated with changes in the number of NK cells, their activation or intracellular cytokine expression. Flow cytometry immunophenotyping of PBMC was performed with regard to the surface receptors CD3, CD56 and CD25, and intracellular cytokine expression of IL-2, IFN-γ and IL-10 after in vitro stimulation with Hp glycine acid extract (GE), Hp LPS or standard Escherichia coli LPS. Hp GE-driven enhancement of lymphocyte cytotoxic activity was associated with the expansion of CD3(-)CD56(+)CD25(+) NK cells and the up-regulation of IFN-γ and/or IL-2 synthesis, up to the higher level in Hp(-) than in Hp(+), while Hp LPS-mediated decrease in lymphocyte cytotoxicity was accompanied by the lack of CD3(-)CD56(+)CD25(+) NK propagation, the inhibition of pro-inflammatory cytokine expression and intense expansion of IL-10-producing NK cells. Thus, the cytotoxic and cytokine activities of NK cells were dependent on the type of antigenic challenge and the Hp status, that is, NK cells could be modulated positively by Hp GE Ags and negatively by Hp LPS.

Helicobacter pylori (H. pylori) bacteria are human pathogens causing symptomatic gastritis, peptic ulcer or gastric cancer. Little is known about the kinetics of immune responses in H. pylori infected patients because the initial moment of infection has not been identified. Various animal models are used to investigate the immune processes related to H. pylori infection. In this study we checked whether H. pylori infection in guinea pigs, mimicking natural H. pylori infection in humans, resulted in the development of specific immune responses to H. pylori antigens by measuring the proliferation of lymphocytes localized in mesenteric lymph nodes, spleen and peripheral blood. The maturity of macrophages and cytokines, delivered by monocyte-macrophage lineage or lymphocytes, were considered as mediators, which might influence the lymphocyte blastogenic response. The obtained results showed the activation of T cells localized in mesenteric lymph nodes by H. pylori antigens in H. pylori infected guinea pigs four weeks postinfection. The blastogenic activity of lymphocytes was shaped by their interaction with antigen presenting cells, which were present in the cell cultures during the whole culture period. Moreover, the balance between cytokines derived from adherent leukocytes including interleukin 8--IL-8 as well as interferon gamma--IFN-γ, and transforming growth factor beta--TGF-β delivered by lymphocytes, was probably important for the successful proliferation of lymphocytes. The H. pylori specific lymphocytes were not propagated in peripheral blood and spleen of H. pylori infected animals. The modulation of immunocompetent cells by H. pylori antigens or their different distribution cannot be excluded.

Abstract:The aim of this work was to synthesize selected thiophene-derived aminophosphonic systems and evaluate the phytotoxicity of newly obtained products according to the OECD 208 Guideline. Seven new thiophene-derived N-substituted dimethyl aminomethylphosphonic acid esters 2a-h were synthesized by the addition of an appropriate phosphite to azomethine bond of starting Schiff bases 1a-h, and NMR spectroscopic properties of aminophosphonates were investigated. These eight compounds were analyzed in regard to their phytotoxicity towards two plants, radish (Raphanus sativus) and oat (Avena sativa). On the basis of the obtained results, it was found that tested aminophosphonates 2a-h showed an ecotoxicological impact against selected plants, albeit to various degrees.

Leukemias are one of most common malignancies worldwide. There is a substantial need for new chemo-33 therapeutic drugs effective against this cancer. Doxorubicin (DOX), used for treatment of leukemias and 34 solid tumors, is poorly efficacious when it is administered systemically at conventional doses. Therefore, 35 several strategies have been developed to reduce the side effects of this anthracycline treatment. In this 36 study we compared the effect of DOX and doxorubicin-transferrin conjugate (DOX-TRF) on human leu-37 kemia cell lines: chronic erythromyeloblastoid leukemia (K562), sensitive and resistant (K562/DOX) to 38 doxorubicin, and acute lymphoblastic leukemia (CCRF-CEM). Experiments were also carried out on nor-39 mal cells, peripheral blood mononuclear cells (PBMC). We analyzed the chemical structure of DOX-TRF 40 conjugate by using mass spectroscopy. The in vitro growth-inhibition assay XTT, indicated that DOX-TRF 41 is more cytotoxic for leukemia cells sensitive and resistant to doxorubicin and significantly less sensitive 42 to normal cells compared to DOX alone. During the assessment of intracellular DOX-TRF accumulation it 43 was confirmed that the tested malignant cells were able to retain the examined conjugate for longer peri-44 ods of time than normal lymphocytes. Comparison of kinetic parameters showed that the rate of DOX-45 TRF efflux was also slower in the tested cells than free DOX. The results presented here should contribute 46 to the understanding of the differences in antitumor activities of the DOX-TRF conjugate and free drug. 47 48 49 60 carried out to improve the chemotherapeutic potency of doxorubi-61 cin and other anthracyclines (Luo et al., 2011; Salvatorelli et al., 62 2012). The goal of anticancer drug development is to identify 63 agents that are effective cancer medicines and yet have minimal 64 systemic side effects. A way to improve the selectivity of cancer 65 therapy is to direct drug activity against therapeutic targets that 66 display altered levels of expression in malignant versus normal 67 cells (Kratz et al., 2008). The use of drug carriers, such as liposomes, 68 dendrimers, nanoparticles, antibodies and others may be part of 69 this approach in allowing increased intracellular concentrations 70 of the cytotoxic agents in cancer cells, therefore helping to over-71 come the chemoresistance of neoplastic cells (Haag and Kratz, 72 2006). 73 Effective and selective anticancer drug carriers are protein con-74 jugates of anthracyclines. Transferrin (TRF) is a plasma protein that 75 can be used as a carrier of anthracyclines because receptors for this 76 protein are overexpressed at the surface of cancer cells, due to the 77 high demand of tumor cells for iron ions, which participate in 78 energy production, heme synthesis, and cell proliferation