Autologous vein grafts used as aortocoronary bypasses are often prone to intimal hyperplasia, which results in stenosis and occlusion of the vein. The aim of this study was to prevent intimal hyperplasia using a newly developed perivascular system with sustained release of sirolimus. This system of controlled drug release consists of a polyester mesh coated with a copolymer of L-lactic acid and ε -caprolactone that releases sirolimus. The mesh is intended for wrapping around the vein graft during surgery. The mesh releasing sirolimus was implanted in periadventitial position onto arteria carotis communis of rabbits, and neointimal hyperplasia was then assessed. We found that implanted sirolimus-releasing meshes reduced intima thickness by 47±10 % compared to a vein graft after 3 weeks. The pure polyester mesh decreased vein intima thickness by 35±9 %. Thus, our periadventitial system for controlled release of sirolimus prevented the develo pment of intimal hyperplasia in autologous vein grafts in vivo in rabbits. A perivascularly applied mesh releasing sirolimus is a promising device for preventing stenosis of autologous vein grafts., I. Skalský ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Depression is a complex disorder related to chronic inflammatory processes, chronic stress changes and a hippocampal response. There is a increasing knowledge about the role of glial cells in nutrient supply to neurons, maintenance of synaptic contacts and tissue homeostasis within the CNS. Glial cells, viewed in the past as passive elements with a limited influence on neuronal function, are becoming recognized as active partners of neurons and are starting to be discussed as a possible therapeutic target. Their role in the pathogenesis of depressive disorders is also being reconsidered. Attention is devoted to studies of the different types of antidepressants and their effects on transmembrane signaling, including levels of α subunits of G proteins in C6 glioma cells in vitro as a model of postsynaptic changes in vivo. These models indicate similarities in antidepressant effects on G proteins of brain cells and effector cells of natural immunity, natural killers and granulocytes. Thus, an antidepressant response can exhibit certain common characteristics in functionally different systems which also participate in disease pathogenesis. There are, however, differences in the astrocyte G-protein responses to antidepressant treatment, indicating that antidepressants differ in their effect on glial signalization. Today mainstream approach to neurobiological basis of depressive disorders and other mood illnesses is linked to abnormalities in transmembrane signal transduction via G-protein coupled receptors. Intracellular signalization cascade modulation results in the activation of transcription factors with subsequent increased production of a wide array of products including growth factors and to changes in cellular activity and reactivity., M. Páv, H. Kovářů, A. Fišerová, E. Havrdová, V. Lisá., and Obsahuje bibliografii a bibliografické odkazy
Matrix metalloproteinases (MMPs) is a family of proteolytic enzymes involved in remodeling of extracellular matrix. Although proteolytic enzymes are produced by many cell types, mast cells seem to be more important than other types in remodeling of pulmonary arteries during hypoxia. Therefore, we tested in vitro production of MMPs and serine proteases in four cell types (mast cells, fibroblasts, vascular smooth muscle cells and endothelial cells) cultivated for 48 h under normoxic or hypoxic (3 % O2) conditions. MMP-13 was visualized by immunohistochemistry, MMP-2 and MMP-9 were detected by zymography in cell lysates. Enzymatic activities (MMPs, tryptase and chymase) were estimated in the cultivation media. Hypoxia had a minimal effect on total MMP activity in the cultivation media of all types of cells, but immunofluorescence revealed higher intensity of MMP-13 in the cells exposed to hypoxia except of fibroblasts. Tryptase activity was three times higher and chymase activity twice higher in mast cells cultivated in hypoxia than in those cultured in normoxia. Among all cell types studied here, mast cells are the most abundant source of proteolytic enzymes under normoxic and hypoxic conditions. Moreover, in these cells hypoxia increases the production of both specific serine proteases tryptase and chymase, which can act as MMPs activators., H. Maxová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The transformed C6 glial cells in cultures were treated with sodium mercaptoborate (Na2B12H11SH, BSH), a carrier of atomic targets (10B) of thermal neutrons for the neutron capture therapy of brain tumors. As shown by light microscopy, the therapeutic dose of BSH (100 µg/ml) did not alter the gross morphology and growth of the population of cells within a 72 h treatment interval. Electron microscopic analysis of these cells revealed activation of nucleoli and, occasionally, enlarged and bifurcated mitochondria. After 200 µg BSH/ml and 72 h treatment, growth of the cell population was inhibited and ultrastructural changes became more profound. They included condensation of chromatin and its allocation to the nuclear envelope which formed deeper invaginations. Mitochondria further increased in size and were characterized by slim or angular cristae. Moreover, in circumscribed segments of some of the slightly swollen mitochondria their cristae disappeared or were reduced to fine pouch-like structures localized near the continuous outer membrane, suggestive for a non-destructive restructuring of the inner mitochondrial membrane. The smooth pinocytotic vesicles near the plasma membrane, lysosomes and heterogeneous dense bodies were more frequent. The revealed subcellular targets of BSH may initiate the development of pharmacological protocols aimed to further improve the tolerance to BSH by the healthy tissues of patients undergoing BNCT of brain tumors, e.g. by intervention into the oxidative stress triggered likely by the altered mitochondria., V. Mareš, D. Krajčí, V. Lisá., and Obsahuje bibliografii