Non-alcoholic fatty liver disease as a cause and consequence of cardio-metabolic complications. Role of the ursodeoxicholic acid in the pharmacotherapy.

The article presents an update of the role of non-alcoholic fatty liver disease (NAFLD) in cardiometabolic diseases and events: arterial hypertension and components of the metabolic syndrome. A review of NAFLD modern pharmacotherapy has been conducted. Particular attention is paid to the place of ursodeoxycholic acid in the complex treatment of NAFLD.

Coherent combining efficiency in tiled and filled aperture approaches.

Different approaches to qualify coherent beam combining performance in tiled and filled aperture combining experiments are discussed. The dependence of the combining efficiency on different misalignments and the number of combining pulses has been investigated and analytical equations for its evaluation have been obtained. The results provide design guidelines for laser systems based on coherent beam combining and allow comparison of experiments performed in different combining approaches. The analysis shows that there are good prospects to scale achieved peak intensity.

Coherent combining of femtosecond pulses parametrically amplified in BBO crystals.

We report on the first experimental realization of coherent combining of parametrically amplified femtosecond pulses. The proposed and implemented two-loop active stabilization system allows us to achieve 110 as relative timing jitter between combined pulses, which is necessary for efficient coherent beam combining. In each channel of the two-channel laser setup, pulses were parametrically amplified in ß-BaB2O4 (BBO) crystals to 50 µJ energy, compressed to 49 fs duration, and then coherently combined with efficiency as high as 97%. Currently, it is the shortest duration of amplified pulses for which coherent combining is demonstrated.

Nanoplasma resonance condition in the middle-infrared spectral range.

The resonance-absorption condition in the laser-nanoplasma interactions has been considered to follow the wavelength dependence of the critical plasma density. We experimentally demonstrate that this assumption fails in the middle-infrared spectral range, while it is valid for visible and near-infrared wavelengths. A thorough analysis supported by molecular dynamic (MD) simulations indicates that the observed transition in the resonance condition is caused by the reduction of the electron scattering rate and the associated increase of the cluster outer-ionization contribution. An expression for the nanoplasma resonance density is derived based on experimental results and MD simulations. The findings are important for a broad range of plasma experiments and applications, since the extension of the laser-plasma interaction studies to longer wavelengths has become increasingly topical.

[Large-scale fragmentation of dna and the death of tumor cells by the action of the binary system ascorbic acid-metallocomplexes of cobalt in vitro].

High-molecular-weight DNA fragments are the markers of the early stage of apoptosis induced in eukaryotic cells by cytotoxins of different nature. The dynamics of the development of large-scale DNA fragmentation in K-562 leukemia cells by the action of the antitumor drug, the binary system ascorbic acid--cobalt phthalocyanine within 48 h of incubation, which correspond to two periods of the doubling of cell number in growing control cultures, have been studied. It was shown that, within the first hours of incubation, hydrogen peroxide generated by the system induces the formation of DNA fragments from 2200 to 50 kbp long. Later on the cell death accompanied by a decrease in the content of fragmented DNA is observed. Within 24 h of incubation, part of fragmented DNA remains unrepaired; after 48 h of incubation, a delay or a slowed down proliferation of K-562 cells, which differ from control cells also by a high level of death and a higher content of high-molecular-weight DNA fragments, is observed.

Integrative network analysis identifies novel drivers of pathogenesis and progression in newly diagnosed multiple myeloma.

Multiple myeloma (MM) is an incurable malignancy of bone marrow plasma cells characterized by wide clinical and molecular heterogeneity. In this study we applied an integrative network biology approach to molecular and clinical data measured from 450 patients with newly diagnosed MM from the MMRF (Multiple Myeloma Research Foundation) CoMMpass study. A novel network model of myeloma (MMNet) was constructed, revealing complex molecular disease patterns and novel associations between clinical traits and genomic markers. Genomic alterations and groups of coexpressed genes correlate with disease stage, tumor clonality and early progression. We validated CDC42BPA and CLEC11A as novel regulators and candidate therapeutic targets of MMSET-related myeloma. We then used MMNet to discover novel genes associated with high-risk myeloma and identified a novel four-gene prognostic signature. We identified new patient classes defined by network features and enriched for clinically relevant genetic events, pathways and deregulated genes. Finally, we demonstrated the ability of deep sequencing techniques to detect relevant structural rearrangements, providing evidence that encourages wider use of such technologies in clinical practice. An integrative network analysis of CoMMpass data identified new insights into multiple myeloma disease biology and provided improved molecular features for diagnosing and stratifying patients, as well as additional molecular targets for therapeutic alternatives.

High-resolution chromatin immunoprecipitation (ChIP) sequencing reveals novel binding targets and prognostic role for SOX11 in mantle cell lymphoma.

Sex determining region Y-box 11 (SOX11) expression is specific for mantle cell lymphoma (MCL) as compared with other non-Hodgkin's lymphomas. However, the function and direct-binding targets of SOX11 in MCL are largely unknown. We used high-resolution chromatin immunoprecipitation sequencing to identify the direct target genes of SOX11 in a genome-wide, unbiased manner and elucidate its functional significance. Pathway analysis identified WNT, PKA and TGF-beta signaling pathways as significantly enriched by SOX11-target genes. Quantitative chromatin immunoprecipitation sequencing and promoter reporter assays confirmed that SOX11 directly binds to individual genes and modulates their transcription activities in these pathways in MCL. Functional studies using RNA interference demonstrate that SOX11 directly regulates WNT in MCL. We analyzed SOX11 expression in three independent well-annotated tissue microarrays from the University of Wisconsin (UW), Karolinska Institute and British Columbia Cancer Agency. Our findings suggest that high SOX11 expression is associated with improved survival in a subset of MCL patients, particularly those treated with intensive chemotherapy. Transcriptional regulation of WNT and other biological pathways affected by SOX11-target genes may help explain the impact of SOX11 expression on patient outcomes.

Combined vitamins Bl2b and C induce the glutathione depletion and the death of epidermoid human larynx carcinoma cells HEp-2.

The combination of hydroxocobalamin (vitamin B12b) and ascorbic acid (vitamin C) can cause the death of tumor cells at the concentrations of the components at which they are nontoxic when administered separately. This cytotoxic action on epidermoid human larynx carcinoma cells HEp-2 in vitro is shown to be due to the hydrogen peroxide generated by the combination of vitamins B12b and C. The drop in the glutathione level preceding cell death was found to be the result of combined action of the vitamins. It is supposed that the induction of cell death by combined action of vitamins B12b and C is connected to the damage of the cell redox system.

[The role of intracellular pH in regulation of NS/O myeloma cell growth and death]. / Rol' vnutrikletochnogo pH v reguliatsii rosta i gibeli kletok mielomy NS/O.

Measurements of intracellular pH (pHi) were taken in the course of NS/O myeloma cell proliferation, growth arrest and death. Cell proliferation was shown to take place within a wide range of various pHi values (6.8-7.2), in which cell death could also occur. In dense cultures, after ceasing proliferation the apoptosis pathway of cell death was activated practically without pHi changes. Both proliferation and cell death stimulation were noticed in serum-free medium with apoptosis prevalence up to 72 h. Apoptotic death occurred at various intracellular pH values within the range from 6.5 to 7.2. The data obtained provide the ground to suppose that in contrast to normal cells, the pHi value in NS/O myeloma tumor cells was not a regulator of their proliferation and death. The decrease of cell growth and increase of cell death can take place with put pHi alteration.

[DNA degradation and repair in human laryngeal carcinoma HEp-2 cells after combined exposure to vitamin B12b and ascorbic acid]. / Degradatsiia i reparatsiia DNK v kletkakh épidermoidnoi kartsinomy gortani cheloveka HEp-2 pri sovmestnom deistvii vitamina B12b i askorbinovoi kisloty.

The formation and accumulation of DNA fragments containing no more than 23,000 pairs of bases were observed under exposure of human larynx epidermoid carcinoma cells (Hep-2) to "chemical nuclease", oxycobalamin (vitamin B12b) and ascorbic acid (vitamin C). The obtained DNA damages were repaired more slowly than those induced by gamma-irradiation in the dose adequate to the level of DNA damages. DNA reparation was not revealed after washing the cells from vitamin B12b and ascorbic acid, and in the course of cell incubation with ascorbic acid. Vitamin B12b and ascorbic acid separately did not induce degradation of DNA. DNA damages induced by "chemical nuclease" action precede the cell death observed later.

[Mechanism of cell death in myeloma NS(O) in culture]. / Mekhanizm gibeli kletok mielomy NS(O) v kul'ture.

We studied in vitro myeloma cell death in a serum-free medium. Spectrophotometric assessment of DNA fragmentation, flow cytometry, and staining by Hoechst dye and ethidium bromide indicate that by the beginning of the third day cell death largely followed the apoptotic pathway. We studied dynamics of intracellular pH (pHi) during the cell death and the relationship between the pHi and apoptosis induction during cultivation in media with different pH. We have shown that decreasing pHi in the course of cell death is a consequence rather than the cause of myeloma cell death. Apoptosis took place at cultivation in the media with pH 6.3 and 8.1; the corresponding pHi values were 6.5 and 7.2, respectively. In the presence of Ca-ionophore A23187 we observed appearance of the cells with aberrant distribution of chromatin and fragmented nucleus; however calcium binding in the media with 5-10 mM EDTA induced even more pronounced nuclei fragmentation. This may indicate that both increased and decreased concentration of intracellular calcium induce NS(O) myeloma cell apoptosis.

[Growth inhibition and induction of tumor cell death by phospholipase A2 and lipoxygenase inhibitors]. / Podavlenie rosta i induktsiia gibeli opukholevykh kletok ingibitorami fosfolipazy A2 i lipoksigenazy.

We studied the effect of arachidonic acid metabolism inhibitors in a wide concentration range on the proliferation and death of lympholeukemia cells P-388. Proliferation of the cells was estimated by metaphase frequency and the proportion of cells in S phase; cellular death was determined by their lysis, trypan blue staining, damaged nuclei, the proportion of cells with subdiploid DNA content, and DNA fragmentation. Low concentrations of phospholipase A2 and lipoxygenase inhibitors were shown to stimulate cell division, while higher concentrations inhibited it by blocking G1-S transition and inducing apoptotic cellular death. Indomethacin, a cyclooxygenase inhibitor, had no effect on proliferation and induced no cell death at concentrations up to 10 microM. Inhibitors of phospholipase A2 and lipoxygenase also inhibited tumor growth in mice.

[Stimulation of respiration with Piladox in experimental and clinical conditions during administration of drugs for general anesthesia]. / Stimuliatsiia dykhaniia Piladoksom v éksperimente i klinike v usloviiakh primeneniia sredstv dlia obshchei anestezii.

Experimental and clinical studies of the agent Piladox (RGH 2202) were conducted. Experiments on animals (rats, rabbits, mice) demonstrated that Piladox possesses the property of restoring respiration inhibited by narcotic analgesics and some general anesthetics as well as the respiratory-de-priming effect of acute blood loss and is a more effective stimulator of the respiratory center than cordiamine (nikethamide) or corasol. Clinical study of Piladox in 75 patients showed that intravenous infusion of 1 mg/kg of the agent in the awakening period produced a stimulating effect on respiration through increase of its frequency and increase of the respiratory volume. The minute respiratory volume in this case was even greater than the initial values, whereas the CO2 content in the blood and expired air reached the initial level. The hemodynamic values in this period remained generally stable. Piladox does not change the antinociceptive effect of the narcotic analgesics and analgesia in the immediate postoperative period when combined general anesthesia is applied.

Apoptotic death of human lympholeukemia HL-60 cells resultant from combined effect of cobalt octa-4,5-carboxyphthalocyanine propylenglycol ether and ascorbate.

Cobalt octa-4,5-carboxyphthalocyanine propylenglycol ether proposed for antitumor therapy potentiates the cytotoxic effect of ascorbate on HL-60 human leukemia cells. Combination of these substances caused the formation of H2O2 in the medium and initiated apoptotic death of cells. Catalase abolished the cytotoxic effect of this combination. The results indicate that binary catalytic system of this combination can be regarded as a potential antitumor agent.

[The glycolytic status of peripheral blood phagocytes and its therapeutic correction in patients with foot mycoses]. / Glikoliticheskii status fagotsitov perifericheskoi krovi i ego terapevticheskaia korrektsiia u bol'nykh mikozami stop.

Changed glycogen levels in the neutrophils and monocytes is a pathogenetic component contributing to the development of mycoses of the soles and a characteristic feature of nonspecific immune reactivity. The neutrophilic phagocytic activity is depressed in such patients, and the monocytes are functionally inert. Furazolidonum, potassium orotate, and riboflavin are effective stimulants of the cell-mediated defense in such patients.

[The use of laser radiation in the combined treatment of fingernail pathology]. / Primenenie lazernogo izlucheniia v kompleksnom lechenii patologii nogtei.

Clinical trials evidence the efficacy of laser treatment as a component of multiple-modality therapy of nail diseases of various etiology. The coagulating effect of highly intensive laser radiation may be used for nail plate removal, and that of low-intensity lasers for stimulation of the reparative processes in the nail plate.

[Simulation of the dynamics of trichophytosis morbidity]. / Modelirovanie dinamiki zabolevaemosti trikhofitiei.

A mathematical model is presented, intended to help in the solution of some problems related to analysis and prediction of the time course of trichophytosis morbidity. This model has been employed in analysis of the incidence rates of both the anthroponotic and zoonotic forms of trichophytosis and of the ratio between the rates of these two forms in the whole country and in each of the republics, among the urban and rural residents. This model helped predict trichophytosis morbidity.

[A case of congenital epidermolysis (an albopapuloid form)]. / Sluchaí vrozhdennogo épidermoliza (al'bopapuloidnaia forma).

A case of this rare disease is reported; the authors analyze the literature data and describe the clinical features and therapy of their patient.