Das durch Addition von Methylvinylketon an Butadien (Molverhältnis wie l : 1,5) bei 140°C dargestellte Acetylcyclohexen (I) (Ausbeute 90%, bezogen auf Methylvinylketon) läßt sich an Ni (auf Kieselgur) oder Ni‐Cr‐Kontakten bei 150°C und 150 at zum Carbinol (II) hydrieren.

Introduction: Valproic acid (VA) is carboxylic acid with a branched chain, which is used as an antiepileptic drug. Valproic acid influence on cells in vivo: VA, which is an antiepileptic drug, is also a teratogen, which causes defects of a neural tube and an axial skeleton, although the mechanisms are not yet fully clear. Valproic acid influence on mesenchymal stem cells (MSC) in vitro: It is shown that valproic acid reduces the intracellular level of oxygen active forms. Valproic acid effect on tumor cells: VA inhibits tumor growth through several mechanisms, including the cell cycle stop, differentiation induction and inhibition of growth of tumor vessels. Valproic acid influence on enzymes: It affects mainly GSK-3. Valproic acid influence on animals’ cells: It is shown that VA can significantly improve an ability to develop in vitro and improve nuclear reprogramming of embryos. Erythropoietin (EPO): Is an hypoxia-induced hormone and a cytokine, which is necessary for normal erythropoiesis. EPO is widely used in in vitro experiments. Conclusion: Thus, the influence of VA and EPO on cells can be used in cell technologies.

The aim of the article is to evaluate Bischofit gel reparative activity in a linear wound model in rats.Materials and Methods. The study was conducted on 36 male Wistar rats weighing from 193 to 218 grams. On the 8th day after modeling a linear wound defect 50±1 mm long, the reparative effect of bischofite, Actovegin and Contractubex in the gel compositions was evaluated. The evaluation was carried out using: the following methods: 1) studying the physicomechanical characteristics of the wound defect (a wound-tearing machine Metrotest REM-0.2-1); 2) morphological examination of the skin graft taken from the wound area (stained with hematoxylin-eosin and Van Gieson‘s solution); 3) determining the ratio of collagen types I and III in a polarizing microscope (the picrosirius was red); 4) cоlorimetric analysis of the hydroxyproline concentration in the wound surface tissues.Results. On the 8th day, the wound defects sampled from the bischofite treated animals, were characterized by the most pronounced strength (the average force at the rupture moment was 13.70 N), which was significantly higher (p<0.01) than in the control group (11.76 N). Actovegin showed less influence on this parameter (12.60 N), and the use of Contractubex led to its decrease (8.10 N). The effect of the drugs on the morphological state of the skin tissue was similar. The hydroxyproline concentration in the studied groups’ samples was: Bischofit 13.23±1.68; Actovegin 15.89±1.37; Contractubex 17.61 ± 0.67; the Control was 16.59±1.08. According to the impact on the ratio of collagen in types I and III, the studied drugs were arranged in the following sequence: Bishofit (0.73±0.023) > Actovegin (0.67±0.017) > Control (0.56±0.012) > Contractubex (0.38 ±0.020).Conclusion. The carried out study showed that Bischofit has a pronounced ability to stimulate the regeneration of the skin wound defect. Hereby, the reference drug Actovegin showed less activity, and Contractubex worsened wound healing.

The therapeutic effect of multipotent mesenchymal stem cells has been proven on various disease models. One of the mechanisms is the paracrine effect of the cells on the surrounding tissues.The aim. To investigate the secretome effectiveness of the multipotent mesenchymal stem cells in the treatment of adjuvant arthritis and contact-allergic dermatitis in Wistar rats.Materials and methods. Adjuvant arthritis was simulated in 26 female rats by the administration of Freund's complete adjuvant and then treated with the administration of 100 µl of multipotent mesenchymal stem cell secretome or saline. Contact-allergic dermatitis was modeled on 30 female rats by applying 200 μl of an oil solution of dinitrofluorobenzene to the skin on days 1, 5 and 6. Then the rats were treated with fluocinolone ointment (a positive control), baby cream (a negative control), baby cream with a secretome of native multipotent mesenchymal stem cells or from the cells processed with dexamethasone.Results. Judging by the indicators of the longitudinal and transverse dimensions of the paws in rats and a histological examination, the secretome did not have any anti-inflammatory effect on adjuvant arthritis. A cream with a secret from multipotent mesenchymal stem cells processed with dexamethasone, was the most effective on the model of contact-allergic dermatitis: the clinical improvement occurred on the 2nd day. The secretome from native multipotent mesenchymal stem cells and fluocinolone had a therapeutic effect on the 3rd day of application, the negative control - on the 4th day. The lymphocytic infiltration coefficient was significantly lower (p <0.05) in all the cases compared to the negative control (2.8 ± 0.1). However, the lowest infiltration was observed when the cream with secretome from native (1.75 ± 0,1) and dexamethasone-stimulated (1.76 ± 0.1) multipotent mesenchymal stem cells was being used.Conclusion. The cream with the secretome of multipotent mesenchymal stem cells suppresses lymphocytic infiltration more strongly than the highly active topical glucocorticosteroid - fluocinolone - on the model of contact-allergic dermatitis, which is a classic local delayed-type hypersensitivity reaction. However, a further study of the therapeutic effect of the secretome on models of systemic inflammatory diseases is required after its preliminary purification from large-molecular proteins.

The aim of this study was to evaluate the effect of treatment with valproic acid, erythropoietin, and dexamethasone on the anti-inflammatory and immunosuppressive activity of the secretome of adipose-derived multipotent mesenchymal stromal cells (MMSCs) in an in vitro experiment.Materials and methods. MMSCs were isolated from the fat of 6 healthy donors. The cells were grown in the culture up to passage 4. Then they were treated with valproic acid, erythropoietin or dexamethasone for 3 hours, washed from preparations, and incubated in a serum-free medium for 48 hours. Some of the cells were not treated with preparations. Supernatants from the cell cultures were concentrated by ultrafiltration, and protein standardization was performed using a nanophotometer. Then the supernatants were sterilized and added to mononuclear cells from peripheral blood of 8 healthy donors. The mononuclear cells were isolated by Ficoll density gradient centrifugation according to the standard protocol. Concentrations of TNFα, IL-2, IL-4, IL-6, IL-10, and IFNγ cytokines in 24-hour cultures and IL-9, IL-10, IL-17A, and IL-21 cytokines in 48-hour cultures were determined using multiplex analysis.Results. The production of IL-2, IL-6, TNFα, and IL-10 was reduced by the secretome of MMSCs treated with valproic acid. The production of IL-2, IL-6, and TNFα decreased during incubation of the mononuclear cells with the secretome of MMSCs treated with erythropoietin. The secretome of dexamethasone-treated MMSCs suppressed the production of IFNγ, IL-1β, IL-1ra, IL-2, IL-6, IL-9, IL-10, and IL-17A. No statistically significant differences were revealed in the production of IL-4, IL-5, IL-9, and IL-21.Conclusion. Among the studied inducers, dexamethasone enhanced the anti-inflammatory and immunosuppressive activity of MMSCs the most, which was manifested through the effect of their supernatants on peripheral blood mononuclear cells.

Die Addition der Ketone (II) an Butadien (I) bei l40‐150°C (Zusatz von Hydrochinon) liefert die Acetylcyclohexene (III) (Ausbeute 40‐95%).