Stabilizátorok hatékonyságának és mechanizmusának tanulmányozása poliolefinekben különböző körülmények között = Study of the efficiency and mechanism of stabilizers in polyolefins under various conditions

A kutatás során a poliolefinek káros kémiai reakcióit (degradáció), valamint a stabilizátorok viselkedését és hatékonyságát befolyásoló tényezőket tanulmányoztuk. Összefüggéseket állapítottunk meg a polietilén gyártási körülményei, a polimer por jellemzői és a feldolgozott polimer tulajdonságai között. Primer (fenolos) és szekunder (foszfortartalmú) antioxidánsok hatékonyságát és hatásmechanizmusát tanulmányoztuk a polietilén feldolgozási körülményei között. Megállapítottuk, hogy a polietilén degradációját elsősorban a foszforstabilizátor reakciói akadályozzák meg, és meghatároztuk a két antioxidáns szinergetikus hatásának az okát. Modell kísérletekkel feltártuk a foszfortartalmú antioxidánsok reakciómechanizmusát és az azt befolyásoló kémiai jellemzőket. Lezártuk az antioxidánsok hidrolitikus stabilitásának meghatározására korábban elkezdett kutatást. A szintetikus antioxidánsok reakciótermékeinek az emberi szervezetre gyakorolt hatásával kapcsolatban felmerült kérdések miatt kiterjesztettük a kutatást a természetes antioxidánsokra (vitaminok, flavonoidok). Ezek pozitív hatása az emberi szervezetre ismert, de (az alfa-tokoferol kivételével) korábban nem foglalkoztak a viselkedésükkel poliolefinekben. A kezdeti sikeres eredményeket követően jelenleg is folytatjuk a kutatást. | In the frame of the project the effects influencing the degradative chemical reactions of polyolefins, as well as the behavior and efficiency of stabilizers were studied. Relationships were established among the polymerization conditions of polyethylene, the characteristics of the polymer powder, and the properties of the polymer processed. The efficiency and the reaction mechanism of primary (phenolic) and secondary (phosphorous) antioxidants were studied under the processing conditions of polyethylene. It was concluded that the reactions of the phosphorous antioxidant hinder the degradation of polyethylene in the first place, and the synergetic effect of the two antioxidants was explained. The reaction mechanisms of phosphorous antioxidants and the chemical characteristics influencing them were explored by model experiments. The study of the hydrolytic stability of antioxidants started earlier was concluded. Because of the doubts concerning the effects of the reaction products of synthetic antioxidants on the human health, the research was extended to the investigation of natural antioxidants (vitamins, flavonoids). Their positive effects on human health is well known, but (except for alpha-tocopherol) their behavior has not been investigated in polyolefins. After the first successes the research is continued

Stabilizátorok hatékonyságának és mechanizmusának tanulmányozása poliolefinekben különböző körülmények között = Study of the efficiency and mechanism of stabilizers in polyolefins under various conditions

A kutatás során a poliolefinek káros kémiai reakcióit (degradáció), valamint a stabilizátorok viselkedését és hatékonyságát befolyásoló tényezőket tanulmányoztuk. Összefüggéseket állapítottunk meg a polietilén gyártási körülményei, a polimer por jellemzői és a feldolgozott polimer tulajdonságai között. Primer (fenolos) és szekunder (foszfortartalmú) antioxidánsok hatékonyságát és hatásmechanizmusát tanulmányoztuk a polietilén feldolgozási körülményei között. Megállapítottuk, hogy a polietilén degradációját elsősorban a foszforstabilizátor reakciói akadályozzák meg, és meghatároztuk a két antioxidáns szinergetikus hatásának az okát. Modell kísérletekkel feltártuk a foszfortartalmú antioxidánsok reakciómechanizmusát és az azt befolyásoló kémiai jellemzőket. Lezártuk az antioxidánsok hidrolitikus stabilitásának meghatározására korábban elkezdett kutatást. A szintetikus antioxidánsok reakciótermékeinek az emberi szervezetre gyakorolt hatásával kapcsolatban felmerült kérdések miatt kiterjesztettük a kutatást a természetes antioxidánsokra (vitaminok, flavonoidok). Ezek pozitív hatása az emberi szervezetre ismert, de (az alfa-tokoferol kivételével) korábban nem foglalkoztak a viselkedésükkel poliolefinekben. A kezdeti sikeres eredményeket követően jelenleg is folytatjuk a kutatást. | In the frame of the project the effects influencing the degradative chemical reactions of polyolefins, as well as the behavior and efficiency of stabilizers were studied. Relationships were established among the polymerization conditions of polyethylene, the characteristics of the polymer powder, and the properties of the polymer processed. The efficiency and the reaction mechanism of primary (phenolic) and secondary (phosphorous) antioxidants were studied under the processing conditions of polyethylene. It was concluded that the reactions of the phosphorous antioxidant hinder the degradation of polyethylene in the first place, and the synergetic effect of the two antioxidants was explained. The reaction mechanisms of phosphorous antioxidants and the chemical characteristics influencing them were explored by model experiments. The study of the hydrolytic stability of antioxidants started earlier was concluded. Because of the doubts concerning the effects of the reaction products of synthetic antioxidants on the human health, the research was extended to the investigation of natural antioxidants (vitamins, flavonoids). Their positive effects on human health is well known, but (except for alpha-tocopherol) their behavior has not been investigated in polyolefins. After the first successes the research is continued

A regenerative approach to canine osteoarthritis using allogeneic, adipose-derived mesenchymal stem cells. Safety results of a long-term follow-up

Mesenchymal stem cells (MSC) are emerging as an effective therapeutic tool in treating canine osteoarthritis (OA). In this report, we focused on the questions of whether MSC transplantation has long-term beneficial effects for the improvement in motion and also evaluated the safety of MSC injection. Visceral adipose tissue, a surgical waste obtained during routine ovariectomy served as a source of allogeneic MSCs and used to treat OA. Altogether, fifty-eight dogs were transplanted in the study suffering from OA in the elbow (42 animals), hip (5), knee (8), ankle (2), and hock (1). The effect of MSC transplantation was evaluated by the degree of lameness at a 4-5-years follow-up period based on the owners' subjective observations. The results showed that 83% of the OA patients improved or retained improvement in lameness. Clinical safety of the treatment was assessed by evaluating the coincidence of tumors or other diseases and other adverse reactions (such as local inflammation) after MSC cell therapy. Two incidences of local inflammation for <1 week at the site of injection were reported. No other adverse reactions were detected post-treatment. Sixteen dogs died during the study, 4 due to cancer and 12 due to other diseases, diagnosed by veterinarians. Overall, our survey suggests that MSC transplantation has long-term beneficial effects in reducing lameness. Moreover, no enrichment in a specific cause of death was observed in the transplanted animals, compared to reported literature. Our data suggest that MSC treatment could be an effective and safe long-term therapy for canine OA

Licensing by Inflammatory Cytokines Abolishes Heterogeneity of Immunosuppressive Function of Mesenchymal Stem Cell Population

When mesenchymal stem cells (MSCs) are used for therapy of immunological pathologies, they get into an inflammatory environment, altering the effectiveness of the treatment. To establish the impact of environmental inflammatory factors on MSCs' immunofunction in the mirror of intrinsic heterogeneity of mouse MSC population, individual MSC clones were generated and characterized. Adipogenic but not osteogenic differentiation and pro-angiogenic activity of five independent MSC cell lines were similar. Regarding osteogenic differentiation, clones MSC3 and MSC6 exhibited poorer capacity than MSC2, MSC4, and MSC5. To study the immunosuppressive heterogeneity, in vitro and in vivo experiments have been carried out using T-cell proliferation assay and delayed-type hypersensitivity (DTH) response, respectively. A remarkable difference was found between the clones in their ability to inhibit T-cell proliferation in the following order: MSC2MSC5>MSC4>MSC3>>MSC6. Nevertheless, the differences between the immunosuppressive activities of the individual clones disappeared on pretreatment of the cells with pro-inflammatory cytokines, a procedure called licensing. Stimulation of all clones with IFN- and TNF- resulted in elevation of their inhibitory capability to a similar level. Nitric oxide (NO) and prostaglandin E2 (PGE2) were identified as major mediators of immunofunction of the MSC clones. The earlier findings were also supported by in vivo results. Without licensing, MSC2 inhibited DTH response, while MSC6 did not affect DTH response. In contrast, prestimulation of MSC6 with inflammatory cytokines resulted in strong suppression by this clone as well. Here, we have showed that MSC population is functionally heterogeneous in terms of immunosuppressive function; however, this variability is largely reduced under pro-inflammatory conditions

Novel role for galectin-1 in T-cells under physiological and pathological conditions

Secreted, extracellular galectin-1 (exGal-1) but not intracellular Gal-1 (inGal-1) has been described as a strong immunosuppressive protein due to its major activity of inducing apoptosis of activated T-cells. It has previously been reported that T-cells express Gal-1 upon activation, however its participation in T-cell functions has remained largely elusive. To determine function of Gal-1 expressed by activated T-cells we have carried out a series of experiments. We have shown that Gal-1, expressed in Gal-1-transgenic Jurkat cells or in activated T-cells, remained intracellularly indicating that Gal-1-induced T-cell death was not a result of an autocrine effect of the de novo expressed Gal-1. Rather, a particular consequence of the inGal-1 expression was that T-cells became more sensitive to exGal-1 added either as a soluble protein or bound to the surface of a Gal-1-secreting effector cell. This was also verified when the susceptibility of activated T-cells from wild type or Gal-1 knockout mice to Gal-1-induced apoptosis were compared. Murine T-cells expressing Gal-1 were more sensitive to the cytotoxicity of the exGal-1 than their Gal-1 knockout counterparts. We also conducted a study with activated T-cells from patients with systemic lupus erythematosus (SLE), a disease in which dysregulated T-cell apoptosis has been well described. SLE T-cells expressed lower amounts of Gal-1 than healthy T-cells and were less sensitive to exGal-1. These results suggested a novel role of inGal-1 in T-cells as a regulator of T-cell response to exGal-1, and its likely contribution to the mechanism in T-cell apoptosis deficiency in lupus

Characterization and therapeutic application of canine adipose mesenchymal stem cells to treat elbow osteoarthritis

Visceral adipose tissue (AT) obtained from surgical waste during routine ovariectomies was used as a source for isolating canine mesenchymal stem cells (MSCs). As determined by cytofluorimetry, passage 2 cells expressed MSC markers CD44 and CD90 and were negative for lineage-specific markers CD34 and CD45. The cells differentiated toward osteogenic, adipogenic, and chondrogenic directions. With therapeutic aims, 30 dogs (39 joints) suffering from elbow dysplasia (ED) and osteoarthritis (OA) were intra-articularly transplanted with allogeneic MSCs suspended in 0.5% hyaluronic acid (HA). A highly significant improvement was achieved without any medication as demonstrated by the degree of lameness during the follow-up period of 1 y. Control arthroscopy of 1 transplanted dog indicated that the cartilage had regenerated. Histological analysis of the cartilage biopsy confirmed that the regenerated cartilage was of hyaline type. These results demonstrate that transplantation of allogeneic adipose tissue-derived mesenchymal stem cells (AT-MSCs) is a novel, noninvasive, and highly effective therapeutic tool in treating canine elbow dysplasia. © 2017, Canadian Veterinary Medical Association. All rights reserved