RESUMEN
We compared the efficiency of autologous mononuclear cells and multipotent stromal cells of the bone marrow after their non-selective intracoronary transplantation on day 30 after acute coronary infarction in rats. Improvement of hemodynamic parameters of myocardial contractility (rates of left ventricular pressure rise and drop) in comparison with the initial values and deceleration of postinfarction prolongation of QRS and QT intervals were observed in rats of the experimental group in contrast to controls in 4 weeks after transplantation. These functional changes were more intensive after transplantation of multipotent stromal cells and were accompanied by more pronounced morphological signs of reverse myocardial remodeling: thickening of the scarred left ventricular wall, shrinkage of the scar, and decrease in left ventricular dilatation index.
Asunto(s)
Leucocitos Mononucleares/trasplante , Trasplante de Células Madre Mesenquimatosas/métodos , Contracción Miocárdica/fisiología , Infarto del Miocardio/fisiopatología , Remodelación Ventricular/fisiología , Animales , Cicatriz/fisiopatología , Electrocardiografía , Masculino , Infarto del Miocardio/terapia , Ratas , Estadísticas no Paramétricas , Presión Ventricular/fisiologíaRESUMEN
Previously, we demonstrated that autoantibodies (AAb) in multiple sclerosis (MS) reveal site-specific binding and cleavage toward myelin basic protein (MBP) epitope library. We have found several fragments of MBP immunodominant in terms of AAb binding. Here, we applied these peptides to DA rats with induced protracted relapsing experimental allergic encephalomyelitis (EAE) most closely related to MS. DA rats with EAE induced by syngenic spinal cord homogenate in complete Freund's adjuvant were treated by nasal route with human MBP 46-62, 81-102, 124-139, 147-170, and Copaxone. MBP 124-139 and 147-170 displayed only mild therapeutic effects but MBP 46-62 significantly reduced EAE, reflected by lower clinical scores and shorter EAE duration compared to controls.
Asunto(s)
Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Proteínas del Tejido Nervioso/uso terapéutico , Factores de Transcripción/uso terapéutico , Animales , Anticuerpos Catalíticos/sangre , Anticuerpos Catalíticos/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Autoantígenos/sangre , Autoantígenos/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Acetato de Glatiramer , Humanos , Proteína Básica de Mielina , Proteínas del Tejido Nervioso/inmunología , Péptidos/uso terapéutico , Ratas , Factores de Transcripción/inmunologíaRESUMEN
The synthetic ACTH-like decapeptide H-Val-Lys-Lys-Pro-Gly- Ser-Ser-Val-Lys-Val-OH, corresponding to amino acid residues 11-20 of the variable part of the human IgG1 heavy chain (referred to as immunocortin) was found to have an immunosuppressive effect on cells in vitro: it inhibits blast transformation of mouse thymocytes and reduces spontaneous motility of mouse peritoneal macrophages as well as their bactericidal activity against the virulent bacterial strain Salmonella typhimurium 415. Tritium-labeled immunocortin binds with high affinity to ACTH receptors on thymocytes and macrophages (Kd 2. 1 and 2.5 nM, respectively) and activates adenylate cyclase in these cells. Thus, the interaction of immunocortin with the target cell includes the following main steps: binding to the receptor, activation of adenylate cyclase, and elevation of the intracellular content of cAMP.