Study of the microcirculation level in bone with osteoporosis and osteoporotic fractures during therapy with recombinant erythropoietin, rosuvastatin and their combinations

The experiment was carried out in female white Wistar rats. The effects of recombinant erythropoietin, rosuvastatin and their combination were investigated based on the blood supply to the bone after a modelled experimental osteoporosis. It was found that the studied drugs prevent decrease of bone microcirculation in cases of osteoporosis and in callus tissue in experimental osteoporotic fractures, positively influencing the course of reparative regeneration of bone tissu

A regulatory motif in nonmuscle myosin II-B regulates its role in migratory front-back polarity

In this study, we show that the role of nonmuscle myosin II (NMII)-B in front–back migratory cell polarity is controlled by a short stretch of amino acids containing five serines (1935–1941). This motif resides near the junction between the C terminus helical and nonhelical tail domains. Removal of this motif inhibited NMII-B assembly, whereas its insertion into NMII-A endowed an NMII-B–like ability to generate large actomyosin bundles that determine the rear of the cell. Phosphomimetic mutation of the five serines also inhibited NMII-B assembly, rendering it unable to support front–back polarization. Mass spectrometric analysis showed that several of these serines are phosphorylated in live cells. Single-site mutagenesis showed that serine 1935 is a major regulatory site of NMII-B function. These data reveal a novel regulatory mechanism of NMII in polarized migrating cells by identifying a key molecular determinant that confers NMII isoform functional specificityThis work is supported by grants SAF2011-24953 from MINECO, FP7 Marie Curie CIG-293719 from the EU, CIVP16A1831 from the Ramon Areces Foundation (M. Vicente-Manzanares), GM 23244 (A.R. Horwitz), GM037537 (D.F. Hunt), and the Cell Migration Consortium U54 GM64346 (A.R. Horwitz and D.F. Hunt). M. Vicente-Manzanares is an investigator from the Ramón y Cajal Program (RYC-2010-06094)

The study of osteoprotective properties of nanoparticulated forms of resveratrol and losartan

The study demonstrated that endothelial dysfunction of bone microvasculature and deterioration of regional blood flow in bone developed eight weeks after ovariectomy in female white Wistar rats thus raising the risk of generalized osteoporosis. Nanoparticulated forms of losartan and resveratrol possessing endothelioprotective action effectively prevented reduction of regional microcirculation in bone tissue through keeping it at the same level as intact rats ha

Pharmacological correction of experimental osteoporosis and fractures related to it by means of rosuvastatin, L-norvaline and their combination

Osteoporosis (OP) is a multifactorial disease which is based on a dynamic decrease in bone mass and, as a result, disruption of bone structure, leading to higher chances of skeletal fractures. Endothelial dysfunction is a key cause of impaired blood supply to the bone, resulting in a decreased perfusion, disrupted osteogenesis and, as a consequence, osteoporotic changes. According to modern literature and available research, L-norvaline and rosuvastatin have a powerful endotheliotropic effect. However, there is no information that the osteoprotective properties of these drugs used as a monotherapy and as their combination have ever been studie

Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency

In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)–related diseases. Three patients presented with EBV-associated Hodgkin’s lymphoma and hypogammaglobulinemia; one also had severe varicella infection. The fourth had viral encephalitis during infancy. Homozygous frameshift or in-frame deletions in CD70 in these patients abolished either CD70 surface expression or binding to its cognate receptor CD27. Blood lymphocyte numbers were normal, but the proportions of memory B cells and EBV-specific effector memory CD8+ T cells were reduced. Furthermore, although T cell proliferation was normal, in vitro–generated EBV-specific cytotoxic T cell activity was reduced because of CD70 deficiency. This reflected impaired activation by, rather than effects during killing of, EBV-transformed B cells. Notably, expression of 2B4 and NKG2D, receptors implicated in controlling EBV infection, on memory CD8+ T cells from CD70-deficient individuals was reduced, consistent with their impaired killing of EBV-infected cells. Thus, autosomal recessive CD70 deficiency is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of inherited CD27 deficiency. Overall, human CD70–CD27 interactions therefore play a nonredundant role in T and B cell–mediated immunity, especially for protection against EBV and humoral immunity

Test-system for estimation of activity of GSK-3 inhibitors as antihypoxants and differentiation of endothelial progenitors in vitro

A model test-system was developed for validation in vitro of antihypoxic and endothelio-differentiating activity of newly created glycogen synthase kinase-3 inhibitors in comparison with the reference drug β4-thymosi

Study of the influence of L-norvaline, rosuvastatin and their combination on the level of microcirculation in bone tissue in experimental osteoporosis and fractures on its background

The experiment was carried out in female white Wistar rats to investigate the effect of L-norvaline, rosuvastatin and their combination on parameters of blood supply to the bone tissue on models of experimental osteoporosis and osteoporotic fracture

STUDY OF ANTI-OSTEOPOROTIC ACTION OF DRUGS FROM THE GROUP OF STATINS

In an experiment on female Wistar white rats, the osteoprotective effect of atorvastatin, simvastatin and rosuvastatin was studied in a model of experimental osteoporosis caused by bilateral ovariectomy. It was found that after ovariectomy in female rats develops endothelial dysfunction, including the vessels of the microcirculatory of the bone, leading to a deterioration of blood supply to bone tissue and the occurrence of osteoporosis. It was found that atorvastatin, simvastatin and rosuvastatin, possessing endothelioprotective activity, prevent deterioration of blood supply to bone tissue and thinning of bone trabeculae, thus having anti-osteoporotic activity. Key words: osteoporosis, endothelial dysfunction, statins, atorvastatin, simvastatin, rosuvastatin, strontium ranelate

The research of abnormal toxicity and local irritant effect in the Draize test of the drug furacilin, concentrate for the preparation of a solution for local and externaluse

The research of abnormal toxicity and locally irritating effect of the drug Furacilin, concentrate for the preparation of a solution for local and external use in comparison with the drug Furacilin, tablets for the preparation of the solution, was carried ou