[Peculiarities of regenerative processes after the plasty of osteochondral defects with combined cell-tissue grafts on the basis of autologous and allogeneic cell cultures from costal cartilage tissue].

From a position of in vivo regenerative medicine, the efficacy of plasty of osteochondral defects of the articular surface was evaluated in rabbits. The combined cell-tissue grafts were used with the demineralized spongy bone as a biomatrix and autologous or allogeneic cells from the rib cartilage tissue. Morphofunctional characteristics of the cell cultures obtained were studied using morphological, histochemical, immunohistochemical and flow cytometric methods. Cells had features typical to cartilage cell line. While the macroscopic appearance of the plasty area was similar, some differences of histogenesis were observed at the early stages after the placement of transplants containing autologous as well as allogeneic cells, into the osteochondral defect area. In both cases, the complete recovery of subchondral bone and hyaline cartilage took place.

[Substantiation of the program of realization of bases of the state policy of a healthy nutrition of population of the Samara Region for the period till 2020 year].

Substantiate the need for long-term program of sanitation the diet of the population of the Samara Region. A systemic analysis of actual nutrition of different population groups in the region showed an excessive consumption of fats and added sugar--the main risk factors of obesity, cardiovascular diseases and diabetes mellitus. The risks of inadequate consumption of vitamins B, calcium, iron, caused by the irrational combination of the foodstuff use, are revealed.

[Whole body vibration (acceleration) training increases bone mineral density and serum levels of osteocalcin in elderly women].

Hip bone mineral density (BMD) and serum markers of bone turnover during drug (antiresorptic medicaments) and non-drug (acceleration training) therapy in elderly women suffering from postmenopausal osteoporosis has been investigated. The hip BMD measured in elderly women after a 24-week antiresorptic therapy (alendronate) and increased by 2.01%. 24-week acceleration training resulted in 1.56% benefit in hip BMD and also serum levels of osteocalcin (+50%, p < 0.05) significantly increased in postmenopausal women. We have determined that the osteogenic effect of acceleration training is mediated by stimulated bone formation. Our findings suggest that whole body vibration (acceleration) training may be a beneficial technique to prevent and treat osteoporosis.

Down-regulation of the Notch pathway mediated by a gamma-secretase inhibitor induces anti-tumour effects in mouse models of T-cell leukaemia.

BACKGROUND AND PURPOSE: gamma-Secretase inhibitors (GSIs) block NOTCH receptor cleavage and pathway activation and have been under clinical evaluation for the treatment of malignancies such as T-cell acute lymphoblastic leukaemia (T-ALL). The ability of GSIs to decrease T-ALL cell viability in vitro is a slow process requiring >8 days, however, such treatment durations are not well tolerated in vivo. Here we study GSI's effect on tumour and normal cellular processes to optimize dosing regimens for anti-tumour efficacy. EXPERIMENTAL APPROACH: Inhibition of the Notch pathway in mouse intestinal epithelium was used to evaluate the effect of GSIs and guide the design of dosing regimens for xenograft models. Serum Abeta(40) and Notch target gene modulation in tumours were used to evaluate the degree and duration of target inhibition. Pharmacokinetic and pharmacodynamic correlations with biochemical, immunohistochemical and profiling data were used to demonstrate GSI mechanism of action in xenograft tumours. KEY RESULTS: Three days of >70% Notch pathway inhibition was sufficient to provide an anti-tumour effect and was well tolerated. GSI-induced conversion of mouse epithelial cells to a secretory lineage was time- and dose-dependent. Anti-tumour efficacy was associated with cell cycle arrest and apoptosis that was in part due to Notch-dependent regulation of mitochondrial homeostasis. CONCLUSIONS AND IMPLICATIONS: Intermittent but potent inhibition of Notch signalling is sufficient for anti-tumour efficacy in these T-ALL models. These findings provide support for the use of GSI in Notch-dependent malignancies and that clinical benefits may be derived from transient but potent inhibition of Notch.

[Oxidation of sulfur-containing substrates by an association of acidophilic chemolithotrophic microorganisms].

Quantitative and qualitative changes in the content of elements in the solid and liquid phases occurred as the pulp moved through fermenters during biooxidation of an ore flotation concentrate. The association of microorganisms were adapted for utilizing sulfur-containing substrates; however, the rate of their oxidation was insufficient, which led to an increase in the amount of sodium cyanide required for gold recovery. The replacement of one-fourth of the liquid phase of the pulp (density, 13%) with a mineral medium without an energy source, the fractional addition of FeSO4 x 7H2O (1 g/l per day), and the improvement of pulp aeration made it possible to increase the content of SO4(2-) by 80.7, 86.2, and 58.5%, respectively. When one-fourth of the liquid phasa of the pulp (density, 24%) was replaced with a mineral medium without an energy source, the rate of additional oxidation of sulfide minerals increased, which increased the efficiency of gold extraction into solution and gold recovery on charcoal by 3.4 and 3.6%, respectively, and reduced sodium cyanide consumption by 3 kg/ton.

Use of ultrasonic standing wave in biological studies and cell technologies.

In experiments on rat erythrocytes and yeast cells, we studied processes of concentration, separation, and isolation of native cells in suspensions by using standing ultrasonic wave field. Fifteen parameters essential for these processes were determined, and the applications of ultrasonic stratification, concentration, and cell separation methods under experimental conditions were determined.

Ground-state and vibrationally assisted tunneling in the formic acid dimer.

The previously developed instanton theory [G. V. Mil'nikov and H. Nakamura, J. Chem. Phys. 122, 124311 (2005)] is applied to the calculation of vibrationally assisted tunneling splitting of the deuterated formic acid dimer (DCOOH)2 with all the degrees of freedom taken into account. The ground-state tunnel splitting is determined by the density-functional theory combined with coupled cluster level of quantum chemistry to be 0.0038 cm(-1) which is comparable to the experimental value of 0.0029 cm(-1). Further, the tunnel splittings of fundamental excitations are estimated for frequencies below 300 cm(-1). In this energy range it is found that the excitation modes may either enhance or suppress tunneling as compared to the ground state. For the higher-frequency modes a rapid growth of the tunnel splitting is observed. At frequencies above 1000 cm(-1) the semiclassical solution becomes unstable and no reliable tunneling splittings can be obtained. This is in vast contrast to the adiabatic approximation to the instanton theory in which the tunnel splittings can be retrieved up to 3000 cm(-1). We discuss this disparity from the viewpoint of the multidimensional character of tunneling in hydrogen bonds and the adiabatic approximation is concluded to be inaccurate.

[Role of trehalose and glycogen in the survival of aging Saccharomyces cerevisiae cells]. / Rol' tregalozy i glikogena v podderzhanii zhiznesposobnosti stareiushchikh kletok Saccharomyces cerevisiae.

The role of the storage carbohydrates trehalose and glycogen in the survival of aging Saccharomyces cerevisiae cells was studied. Culture aging for one week did not reduce cell viability. During this period, the cells accumulated the storage carbohydrates and raised the activity of the glycolytic enzymes hexokinase and phosphofructokinase. However, further aging led to a drastic drop in cell viability and to a decrease in the cellular content of trehalose and glycogen and in the activity of hexokinase and phosphofructokinase. The possible reasons for these changes are discussed.

[Effect of a low concentration of hydrogen peroxide on metabolism of blood cells]. / Vliianie nizkoi kontsentratsii perekisi vodoroda na metabolizm kletok krovi.

Hydrogen peroxide is known to posses a wide range of physiological effects towards functional activity of cells. We have investigated the influence of H2O2 on the activity of glycolys in the native blood cells. Adding of hydrogen peroxide up to final concentration 50 microM led to decrease of activity some glycolytic enzymes. H2O2 inhibited consumption of glucose by blood cells. Despite the fact that H2O2 is well known as prooxidant, we observed decrease of the level of thiobarbituric acid reactive species in the blood cells after their incubation in the presence of hydrogen peroxide for 2 hours. Based on these data we supposed that effects of hydrogene peroxide occur via signal transduction pathways.

[Arsenite-induced lipid peroxidation in Saccharomyces cerevisiae]. / Arsenit kak induktor processov perekisnogo okisleniia lipidov v kletkakh drozhzhei Saccharomyces cerevisiae.

The ability of sodium arsenite at concentrations of 10(-2), 10(-4), and 10(-6) M to induce lipid peroxidation in Saccharomyces cerevisiae cells was studied. Arsenite at the concentrations 10(-2) and 10(-4) M enhanced lipid peroxidation and inhibited the growth of yeast cells. Enhanced lipid peroxidation likely induced oxidative damage to various cellular structures, which led to suppression of the metabolic activity of cells. Arsenite at the concentration 10(-6) M did not activate lipid peroxidation in cells. All of the tested arsenite concentrations inhibited the activity of alpha-ketoglutarate dehydrogenase and pyruvate dehydrogenase in cells. The inference is made that the toxicity of arsenite may be related to its stimulating effect on intracellular lipid peroxidation.

[T. I. Eroshevskii--founder of the Sarmarsk school of ophthalmology]. / T. I. Eroshevskii--osnovatel' Sarmarskoi shkoly oftal'mologov.

June 26 is the 100 anniversary of Professor T.I. Yeroshevsky--the Hero of socialist Work, the winner of the USSR State Premium, the correspondent of the USSR Academy of Medical Sciences, the Honoured Scientist of the RSFSR, the Honoured Citizen of Kuibyshev (nowdays--Samara) and Gurkovo of the Bulgarian National Republic. His talent sa a innovator in science, a brilliant teacher, a talented clinician and one of the best organizers was shown in the full during the Samara period of his life. The All-Russia conference of ophthalmologists, two Volga region conferences on glaucoma were held in Kuibyshev. T.I. Yeroshevsky took part in the work of international ophthalmologists congresses in Leipzig and Canada, Kabul and Prague, Cairo and Bagdad, Mexico City and Sofia. All this contributed to the popularity and authority of T.I. Yeroshevsky and the unique union of the ophthalmic hospital with a faculty and problem laboratory. It was the first specialised ophthalmic complex in Russian Federation. Being a remarkable teacher, He trained more than a thousand students--the future doctors. More than 70 doctoral and candidate thesis were carried out and defended under his guidance. T.I. Yerosevsky's scientific interests were very diverse. He started his way in science from the research of transplantation of cornea and he devoted to it his doctoral thesis. The study of primary glaucoma was very significant in his research work. His clinic was one of the first in this country to introduce the photocoagulation of retina. At the beginning of the 1980s it introduced the laser surgery and therapy of various eye diseases. Kuibyshev clinic was also one of the first to master cataract cryoextraction and soon it reached the best results in the world in this direction. The regional clinic ophthalmic hospital, the faculty and problem laboratory are scientific centre of this country, it can be proved by 15 digests of scientific works issued under T.I. Yeroshevsky's edition the republic congress and all-Union ophthalmologist conferences held since 1952. This remarkable tradition is kept nowadays.

[The use of gravitation overloading in the treatment of obliterative atherosclerosis of lower extremity arteries]. / Primenenie gravitatsionnykh peregruzok v terapii obliteriruiushchego ateroskleroza arterii nizhnikh konechnostei.

The article sums up results of treatment of 152 patients with obliterating atherosclerosis of the lower extremity arteries which were exposed to 2-3 G gravitation overloading made in a centrifuge of a short radius in direction head--pelvis. The gravitation overloading in the regimen followed were not found to have negative effects of central hemodynamics. Peripheral circulation was noted to considerably improve which is confirmed: 1) by clinical data showing 2-5 times longer distance of painless walking; 2) by the data of ultrasound dopplerography manifested as larger volume rate of blood flow and regional perfusion index; 3) by thermographic explorations evidencing the recovery of the thermoprophile of the legs and feet. Thus, the application of gravitation overloading is a new effective method of conservative treatment of patients with the pathology in question.

Interactions of synthetic estrogens with human estrogen receptors.

Synthetic estrogens have diverse chemical structures and may either positively or negatively affect the estrogenic signaling pathways through interactions with the estrogen receptors (ERs). Modeling studies suggest that 4-(1-adamantyl)phenol (AdP) and 4,4'-(1,3-adamantanediyl)diphenol (AdDP) can bind in the ligand binding site of ERalpha. We used fluorescence polarization (FP) to compare the binding affinities of AdP, AdDP and 2-(1-adamantyl)-4-methylphenol (AdMP) for human ERalpha and ERbeta with the binding affinities of the known ER ligands, diethylstilbestrol (DES) and 4hydroxytamoxifen (4OHT). Competition binding experiments show that AdDP has greater affinity for both ERs than does AdP, while AdMP does not bind the receptor proteins. The relative binding affinities of AdDP and AdP are weaker than the affinity of DES or 4OHT for both ERs with the exception of AdDP, which binds ERbeta with higher affinity than does 4OHT. We also found that AdDP and AdP cause differential conformational changes in ERalpha and ERbeta, which result in altered affinities of the ERs for fluorescein-labeled estrogen response elements (EREs) using a direct binding FP assay. The results show that ERbeta liganded with either AdDP or AdP has greater affinity for human pS2 ERE than the ERbeta-4OHT complex. The data suggest that synthetic molecules like adamantanes may function as biologically active ligands for human ERs. This demonstrates the importance of considering the potential of novel classes of synthetic compounds as selective ER modulators.

Pathomorphological peculiarities of microcirculatory bed in bronchial wall in workers employed in mining and chemical industry.

Morphological alterations of microvessels in bronchial mucosa and blood capillaries of alveolar septa during endobronchitis were examined in workers employed at a plutonium plant and not employed residents (Zheleznogorsk, Krasnoyarsk Region). Alterative, destructive, and dysadaptive changes in pulmonary vessels of workers were paralleled by developing reparative and adaptive processes in neighboring capillaries.

Interactions of dietary estrogens with human estrogen receptors and the effect on estrogen receptor-estrogen response element complex formation.

Epidemiologic and experimental studies support the hypothesis that dietary estrogens from plant sources (phytoestrogens) may play a role in the prevention of breast and prostate cancer. The molecular mechanisms for such chemopreventive effect are still unclear. We investigated the possibility that phytoestrogens may bind differentially to estrogen receptor proteins (ER[alpha] and ERss) and affect the interactions of the ligand-ER complexes with different estrogen response element (ERE) sequences. We used fluorescence polarization to measure the binding affinities of genistein, coumestrol, daidzein, glyceollin, and zearalenone for human ER[alpha] and ERss. Competition binding experiments revealed higher affinity of the phytoestrogens for ERss than for ER[alpha]. Genistein [median inhibitory concentration 12nM] is the most potent and has the same relative binding affinity for ERss as 17ss-estradiol. We also studied the effect of these phytoestrogens on the ability of ER[alpha] and ERss to associate with specific DNA sequences (EREs). The direct binding of human recombinant estrogen receptors to fluorescein-labeled EREs indicates that phytoestrogens can cause conformational changes in both human ERs, which results in altered affinities of the complexes for the ERE from the Xenopus vitellogenin A2 gene and an ERE from the human pS2 gene.