bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of combined aerobic and resistance training in body composition of obese postmenopausal women
Authors: Rossi Fabrício E. , Buonani Camila , Viezel Juliana , Silva Eduardo P. da , Diniz Tiego A. , Santos Vanessa R. dos , Fernandes Rômulo A. , Freitas Junior Ismael F.
Published: April 2015

The aim of this study was to investigate the effects of a 16-week program of combined aerobic and resistance training on the body composition of postmenopausal women who are obese. The participants were divided into two groups: training group (TG, n = 37) and non-trained control group (CG, n = 18). The trunk fat, fat mass, percentage of fat mass and fat-free mass were estimated using DXA. Three nonconsecutive 24-hour dietary recalls were conducted. The training protocol consisted of 50 minutes of resistance training followed by 30 minutes of aerobic training. After the 16-week training program, differences were observed in trunk fat (CG= 0.064 x TG= -0.571 Kg; p-value = .020), fat mass (CG= -0.088 x TG= -1.037 Kg; p-value = .020) and fat-free mass (CG= -0.388 x TG= 1.049 Kg; p = .001). Therefore, a 16-week program of systematic combined aerobic and resistance training in obese postmenopausal women was effective in improving fat-free mass and decreasing both whole and abdominal adiposity.
Lament for the Left Bank
Authors: Barnes Djuna , Heisler Aaron Yale
Published: April 2015

In 1940 Djuna Barnes, author of the notorious but weak-selling Nightwood (1936), received a commission from Harry A. Bull, editor of the New York-based society magazine Town & Country, to write a short reminiscence of Paris in the 1920s. The Nazi occupation of the erstwhile world capital of the avant-garde gave Town & Country's well-heeled readership reason to be nostalgic for Paris's glamorous recent past. As for Barnes, despite her dwindling book sales, she still had some celebrity—especially among those American readers who remembered her risqué onetime best seller Ryder (1928)—as an artist, journalist, and character of the Paris scene. Struggling with alcoholism and illness, and fiercely private, but desperate for money, she accepted the commission (Herring 242-50). Drawing on material in a notebook she had carried while working as a journalist in the 1920s (Caselli 116), as well as an unpublished 1939 essay, “Farewell Paris,” Barnes took her miniature memoir through several drafts over the course of 1940 and 1941.
Defining Breast Cancer Intrinsic Subtypes by Quantitative Receptor Expression
Authors: Cheang Maggie C.U. , Martin Miguel , Nielsen Torsten O. , Prat Aleix , Voduc David , Rodriguez-Lescure Alvaro , Ruiz Amparo , Chia Stephen , Shepherd Lois , Ruiz-Borrego Manuel , Calvo Lourdes , Alba Emilio , Carrasco Eva , Caballero Rosalia , Tu Dongsheng , Pritchard Kathleen I. , Levine Mark N. , Bramwell Vivien H. , Parker Joel , Bernard Philip S. , Ellis Matthew J. , Perou Charles M. , Di Leo Angelo , Carey Lisa A.
Published: April 2015

Purpose.

To determine intrinsic breast cancer subtypes represented within categories defined by quantitative hormone receptor (HR) and HER2 expression.

Methods.

We merged 1,557 cases from three randomized phase III trials into a single data set. These breast tumors were centrally reviewed in each trial for quantitative ER, PR, and HER2 expression by immunohistochemistry (IHC) stain and by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), with intrinsic subtyping by research-based PAM50 RT-qPCR assay.

Results.

Among 283 HER2-negative tumors with <1% HR expression by IHC, 207 (73%) were basal-like; other subtypes, particularly HER2-enriched (48, 17%), were present. Among the 1,298 HER2-negative tumors, borderline HR (1%–9% staining) was uncommon (n = 39), and these tumors were heterogeneous: 17 (44%) luminal A/B, 12 (31%) HER2-enriched, and only 7 (18%) basal-like. Including them in the definition of triple-negative breast cancer significantly diminished enrichment for basal-like cancer (p < .05). Among 106 HER2-positive tumors with <1% HR expression by IHC, the HER2-enriched subtype was the most frequent (87, 82%), whereas among 127 HER2-positive tumors with strong HR (>10%) expression, only 69 (54%) were HER2-enriched and 55 (43%) were luminal (39 luminal B, 16 luminal A). Quantitative HR expression by RT-qPCR gave similar results. Regardless of methodology, basal-like cases seldom expressed ER/ESR1 or PR/PGR and were associated with the lowest expression level of HER2/ERBB2 relative to other subtypes.

Conclusion.

Significant discordance remains between clinical assay-defined subsets and intrinsic subtype. For identifying basal-like breast cancer, the optimal HR IHC cut point was <1%, matching the American Society of Clinical Oncology and College of American Pathologists guidelines. Tumors with borderline HR staining are molecularly diverse and may require additional assays to clarify underlying biology.
Computer-based substrate specifity prediction for cytochrome P450
Authors: Veselovsky A.V. , Sobolev B.N. , Zharkova M.S. , Archakov A.I.
Published: April 2015

Cytochrome P450 is important class of enzymes metabolizing numerous drugs. The composition and activity of these enzymes are determined the drug distribution in organism, its pharmacological and toxic effect. Thus the prediction of the behaviour of compounds in organism is essential for discovery and development of new drugs in the early stages of this process. The different isoforms of cytochrome P450 can oxidized wide range of chemical compounds and their substrate specifity do not correlate with their taxonomical classification. The main methods of cytochrome P450 substrate specifity prediction is reviewed. These methods divided based on primary informations that used: prediction based on amino acid sequences, ligand-based (pharmacophore and QSAR models) and structure-based (molecular docking, affinity prediction) methods. The common problem of cytochrome P450 substrate prediction and advantage and disadvantages of these methods are discussed.
Effect of complexes of precursors and modulators of coenzyme q biosynthesis on functional state of old rats' heart mitochondria
Authors: Kuchmenko E.B. , Petukhov D.N. , Donchenko G.V. , Mkhitaryan L.S. , Tymoshchuk S.V. , Strutynskaya N.A. , Vavilova G.L. , Sagach V.F.
Published: April 2015

Our research demonstrate that ageing leads to changes in activity of electron-transporting enzyme complexes in myocardial mitochondria of old rats and to increased sensitivity of mitochondrial permeability transition pore to inductors of its opening - Ca2+ and phenylarsine oxide. We also observed activation of lipid and protein free-radical peroxidation processes. Administration of a complex of biologically active substances that included precursors and modulators of coenzyme Q biosynthesis (α-tocopherol acetate, 4-hydroxybenzoic acid, and methionine) we observed the increase in coenzyme Q content, correction of functional activity of mitochondrial electron-transport chain enzyme complexes, the decrease in intensivity of lipid and protein free-radical peroxidation in the heart and the decrease in sensitivity of mitochondrial permeability transition pore to inductors of its opening. This complex may be used to treat mitochondrial dysfunction under numerous pathologies of cardiovascular system, as well as in ageing.
Cathepsin K and matrix metalloproteases activity in bone tissue of OXYS rats with osteoporosis development
Authors: Venediktova A.A. , Falameeva O.V. , Kolosova N.G. , Sadovoj M.A. , Korolenko T.A.
Published: April 2015

The comparative study of аctivity of cysteine protease cathepsin K and matrix metalloproteases (MMPs) in bone tissue of accelerated senescent OXYS rats with early ageing comparatively to Wistar rats of the same age was performed. Early development osteoporosis is a typical feature of OXYS rats. In bone tissue of 3 month old OXYS rats, before appearance of osteoporosis manifestation cathepsin K activity was higher, whereas MMPs activity was lower than in Wistar rats. In Wistar rats (3 and 14 months old) cathepsin K activity of spine was shown to increase, and MMPs activity to decrease. In OXYS rats age-related change of cathepsin K and MMPs activity in bone tissue had the opposite direction. As a result of this there were no differences between Wistar and OXYS rats 14 months old despite the marked osteoporosis in OXYS rats as revealed our early researches. Serum α2-macroglobulin activity was higher in 14 months old OXYS rats. The role of activation of cathepsin K in bone resorption in the development of osteoporosis in early ageing OXYS rats is discussed.
Antioxidant activity of vegetable oils with different omega-6/omega-3 fatty acids ratio
Authors: Guseva D.A. , Prozorovskaya N.N. , Shironin A.V. , Sanzhakov M.A. , Evteeva N.M. , Kasaikina O.T. , Rusina I.F.
Published: April 2015

Antioxidant activity and the oxidative stability were investigated in flax, sesame, silybum oils and oils with different ω-6/ω-3 fatty acid ratio. The content of antioxidants (AO) in crude oils and their reactivity towards peroxyl radicals were studied using kinetic method for addition of oil in a model reaction of cumol oxidation. There were correlations between PUFA/ω-9 and thermal stability (50°C); between γ-tocopherol content and resistantance to oxidative changes after storage at (10±2)°C for 6 months.
Influence of emotional-painful stress on affinity of blood to oxygen, the state antioxidant system and physical properties hepatocyte microsomal membrane
Authors: Maltsev A.N. , Grekova A.A. , Kits E.A.
Published: April 2015

The emotional-painful stress causes a more pronounced decrease in affinity of hemoglobin to oxygen in portal blood compared with mixed blood. This contributes to increased oxygen pressure in hepatocytes and activates free radical processes in liver microsomes. Activation of lipid peroxidation is accompanied by changes in physical properties (microviscosity, polarity) of microsomal membranes. However, the increase in duration of stress treatment changes in the studied parameters become adaptive; this is accompanied by gradual normalization in blood affinity to oxygen, physical properties of membranes and the increase in antioxidant defence. Possible mechanisms of interaction of these systems during adaptation and regulation of free radical oxydation are discussed.
Comparative characterization of oxide-dependent and nitroxide-forming enzymatic systems of macrophages under staphylococcus aureus and listeria monocytogenes infections
Authors: Somova L.M. , Plekhova N.G. , Goncharuk Yu.N. , Drobot E.I.
Published: April 2015

The reactivity of oxide-dependent and nitroxide-forming enzymatic systems of macrophages infected by bacteria, characterized by intraphagosomal (Staphylococcus aureus) and intracytoplasmatic (Listeria monocytogenes) localization in the phagocyte has been investigated. The correlation analysis revealed links between indices of the activity of oxide-dependent and nitroxide-forming enzymatic systems of infected macrophages.
Brutto-law of ozone decomposition in physiologic solutions and a method of evaluation of ozone dose really introduced to paitients together with solution volume
Authors: Razumovskii S.D. , Konstantinova M.L. , Grinevich T.V. , Korovina G.V. , Zaitsev V.Ya.
Published: April 2015

Ozone solutions in water and in NaCl solutions found are widely used in technology and medicine. Some times ozone employment meets difficulties due to instability of ozone in solution. The paper describes the results of study of ozone decomposition prepared using solutions in distilled water, solutions of NaCl in water, including physiologic solutions from different manufacturers. Also it was proposed the reaction mechanisms explained influence of OH- and Cl- ions on the decomposition rate. Experimental follow the monomolecular law and are described by a straight line in lg(Ct/C0) = f(t) coordinates. It can be used as a basis for a new method of evaluation of real ozone doze introduced to patients.
Study "structure-anti-arrhythmic activity" relationship of n-phenil acetamide derivatives and amides of aromatic carbonic acids
Authors: Khairullina V.R. , Tarasov G.P. , Gerchikov A.Ja. , Zarydiy F.S. , Tjurina L.A.
Published: April 2015

Using the computer system SARD-21 (Structure Activity Relationship & Design) structural features of high- and low-effective anti-arrhythmic agents have been recognized and the influence of these features on the anti-arrhythmic properties has been evaluated. This information has been used for generation of the model for prediction of anti-arrhythmic effectiveness of pharmaceutical preparations with the 82%-level of recognition by two methods. The recognized structural parameters may be successfully used for design of new highly effective anti-arrhythmic drugs, and also for modification of structures of known anti-arrhythmic drugs for the increase of effectiveness of their anti-arrhythmic action.
Citrate influence on oxidative status of rats tissues under experimental toxic hepatitis
Authors: Safonova O.A. , Popova T.N. , Saidi L.
Published: April 2015

The effect of citrate free-radical oxidation intensity and aconitate hydratase, superoxide dismutase and catalase activities in liver and blood serum of rats with experimental toxic hepatitis has been investigated. Citrate administration to rats with hepatitis decreased biochemiluminescence parameters and conjugated diene content in rats tissues, increased under conditions of CCl4-induced liver damage. At the same time aconitase activity, decreased at the pathology, increases. The superoxide dismutase and catalase activities increased in at experimental toxic hepatitis, tended towards control values after citrate administration.
Effect of catalase activators and inhibitors on ethanol pharmacokinetic parameteres and ethanol and aldehyde-metabolizing enzyme activities in the rat liver and brain
Authors: Bardina L.R. , Pronko P.S. , Satanovskaya V.I. , Aliyeva Ye.V.
Published: April 2015

The effects of catalase regulators (aminotriazole, lead acetate, taurine, di-2-ethylhexylphthalate) on the preference for ethanol, its pharmacokinetics, and activities of rat liver and brain ethanol and acetaldehyde-metabolizing enzymes were studied.Lead acetate (100 mg/kg, i.p., 7 days), aminotriazole (1 g/kg, i.p., 7 days), and taurine (650 mg/kg, i.g., 14 days) decreased ethanol consumption under conditions of free choice (10% ethanol water), whereas di-2-ethylhexylphthalate (300 mg/kg, i.g., 7 days) did not exert any effect on this parameter.Taurine, lead acetate and di-2-ethylhexylphthalate significantly activated liver ADH, MEOS and catalase peroxidase activity. Aminotriazole also activated ADH and MEOS, but inhibited liver catalase. The activities of liver and brain AlDH as well as catalase were insignificantly changed by this treatment.The 7-day administration of lead acetate, di-2-ethylhexylphthalate and aminotriazole administrations significantly influenced the ethanol (2g/kg., i.p.) pharmacokinetic parameters: the area under the pharmacokinetic curve and the elimination half-life time were significantly reduced, whereas the elimination constant and clearance were increased. This unequivocally indicates accelerated ethanol elimination. The 14-day ingestion of taurine insignificantly changed the parameters of ethanol pharmacokinetics in rats.
Lipid peroxidation, activity of Na+,K+-ATPase and exzymes of antioxidant defence in rats with nephropathy induced by cobalt chloride
Authors: Tedtoeva A.I. , Dzugkoeva F.S. , Mozhaeva I.V. , Dzugkoev S.G.
Published: April 2015

Chronic parenteral administration of cobalt chloride (6 mg/kg) to male rats for 2 weeks or 1 month was accompanied by activation of lipid peroxidation (LPO), a decrease of superoxide dismutase activity and an increase of catalase activity. The membrane toxic action also resulted in a decrease of cortical and medullar Na+,K+-ATPase activity of kidneys, and the decrease in renal functions (glomerular filtration, renal water reabsorption, spontaneous diuresis, electrolyte excretion).
Study of activity of enzymes of antioxidant system of blood at HIV infection
Authors: Kostyushov V.V. , Bokal I.I. , Petrov S.A.
Published: April 2015

HIV infection is accompanied by activation of lipid peroxidation, oxidative modification of lipoprotein complexes, and a decrease in activity of antioxidant enzymes (superoxide dismutase (SOD), catalase and glutathione peroxidase (GP)) in blood serum. A significant increase of glutathione reductase observed under these conditions is considered as a function of the antioxidant defence. These changes were already seen at early (symptomless) stages of this disease, however, at manifested forms they were more pronounced.
Proteins-markers of placental insufficiency
Authors: Pogorelova T.N. , Gunko V.O. , Drukker N.A. , Linde V.A.
Published: April 2015

The proteomic analysis of the amniotic fluids of women with physiological pregnancy and pregnancy, complicated with placental insufficiency has been carried out on the II and III trimesters. The following difference in protein patterns have been recognized: i) appearance of several proteins lacking in physiological pregnancy; ii) absence of several proteins detectable during physiological pregnancy - hippocalcin-like protein 1, CDC37-like protein, NKG2D ligand 2 (II trimester), CDC37-like protein, NKG2D ligand 2 (III trimester). The established differences in the amniotic fluid spectrum, obviously, have the pathogenetic meaning in the placental insufficiency development. The revealed proteins of distinction may serve as markers of this obstetrical pathology.
Molecular modeling of acetylcholinesterase interaction with irreversible and reversible organophosphorous inhibitors
Authors: Tikhonova O.V. , Skvortsov V.S. , Raevsky O.A.
Published: April 2015

Three-dimensional Quantitative Structure-Аctivity Relationship models were designed for irreversible and reversible acetylcholinesterase inhibitors by molecular modeling methods. In case of irreversible inhibitors CoMFA (the comparative analysis of molecular fields) or CoMSIA (the comparative analysis of indexes of molecular similarity) descriptors together with HYBOT 3D fields provide more statistically valid 3D-QSAR models. This indicates importance of donor-acceptor interactions for irreversible acetylcholinesterase inhibition. In case of reversible organophosphorous inhibitors good quality model for structure-activity relationships was developed using CoMFA fields. The obtained models have good predictive power and can be used for estimation of new organophosphorous compounds inhibitor activity that in turn correlates with toxicity of these compounds.
Functional analysis of epstein-barr virus latent membrane proteins (LMP1) in patients with limphoproliferative disorders
Authors: Smirnova K.V. , Diduk S.V. , Gurtsevitch V.E.
Published: April 2015

Latent membrane protein1 (LMP1) encoded by the LMP1 gene of the Epstein-Barr virus (EBV) is a transmembrane protein, which can activate a number of cellular signal cascades and transcriptional factors leading to cell transformation. In the present study the sequencing of full-length LMP1 variants isolated from Russian patients with Hodgkin's lymphoma (HL), non-Hodgkin's lymphomaе (NHL) and infectious mononucleosis (IM) has been carried out. The phylogenetic analysis of obtained sequences revealed dominance of the LMP1 variants belonging to proteins of low-divergent group LMP1-B95.8b characterized by minimal set of mutations. Investigation of biological properties in the Russian representatives of this group revealed that expression of studied LMP1 variants in embryonic kidney 293 cells was accompanied by insignificant increase in transcriptional factor NF-κB activation and had minor influence on activation of transcriptional factor AP-1. It was also detected that all investigated low-divergent LMP1 variants expressed in Rat-1 cells induced activation of inducible NO-synthase (iNOS) and intracellular production of nitric oxide (NO). At the same time the level of NO accumulation was lower than that induced by the low-transforming prototype variant LMP1-B95.8. The data obtained indicate that the LMP1 variants, which are the most common among Russian patients with EBV-associated lymphoproliferative diseases, are characterized by minimum number of mutations and rather low ability to activate basic cellular signaling pathways regardless the nature of pathological process, benign (IM) or malignant (HL, NHL). It is suggested that in addition to the modest activation of NF-κB and iNOS induction by LMP1 other factors are involved in the cell transformation process.
Inhibition of NO-dependent soluble human platelet guanylate cyclase by isatin
Authors: Severina I.S. , Schegolev A.Yu. , Ponomarev G.V. , Medvedev A.E.
Published: April 2015

Isatin (indole-dione-2,3) is an endogenous indole that exhibits a wide spectrum of biological and pharmacological activities. Physiologically relevant concentrations of isatin (ranged from 1 nM to 10 M) did not influence basal activity of soluble human platelet guanylate cyclase (sGC), but caused a bell-shaped inhibition of the NO-activated enzyme. Inhibition of the NO-dependent activation by isatin did not depend on a chemical nature of the NO donors. The inhibitory effects of ODC (a heme-dependent inhibitor of sGC) and isatin were non-additive suggesting that the inhibitory effect of isatin may involve the heme binding domain (possibly heme iron) and experiments with hemin revealed some isatin-dependent changes in its spectrum. Isatin also inhibited sGC activation by the allosteric activator YC-1. It is suggested that the bell shaped inhibition of the NO-dependent activation of sGC by isatin may be attributed to complex interaction of isatin with the heme binding domain and the allosteric YC-1-binding site of sGC.
The influence of vitamin B group on monooxygenase activity of cytochrome P450 3A4: pharmacokinetics and electro analysis of catalytic properties
Authors: Shumyantseva V.V. , Shich E.V. , Machova A.A. , Bulko T.V. , Kukes V.G. , Sizova O.S. , Ramenskaya G.V. , Usanov S.A. , Archakov A.I.
Published: April 2015

It was shown that vitamin B group permit to shorten the longitude of diclofenak therapy and to reduce the daytime dose of this drug. All three schemes of diclofenac treatment - only diclofenac, diclofenac plus 2 tablets of Gitagamp (mixture of vitamin B group), and diclofenac plus 4 tablets of Gitagamp - gave maximum value of diclofenal in blood through 1 hour after treatment. In the case of diclofenak treatment without vitamins Cmax corresponds to 1137.2±82.4 ng/ml, with 2 tablets of Gitagamp - Cmax 1326.7±122.5 ng/ml, and with 4 tablets - Cmax 2200.4±111.3 ng/ml. Positive influence of vitamin B group on the decrease of pain syndrome was shown. Pharmacodynamics and pharmacokinetics data were confirmed in electrochemical experiments with cytochrome P450 3A4. For enzyme immobilization screen printed graphite electrodes modified with gold nanoparticles and synthetic membrane-like compound didodecyldimethylammonium bromide (DDAB/Au) were used. Electrochemical analysis reviled the influence of vitamin B group on metabolism of non steroid anti inflammation drug diclofenac catalyzed by cytochrome P450 3A4. Riboflavin was the most effective inhibitor of diclofenac hydroxylation by cytochrome P450 3A4 as was compared at 300 M concentration of vitamin B group (B1, B2, B6). These data confirmed the opportunity of pharmacokinetic parameters regulation and the level of pharmacodynamic effects by the influence of vitamin B group on the catalytic activity of cytochrome P450 3A4.
Neopterin as a rarameter, reflecting the inflammatory phase of a dermal wound process
Authors: Pustovalova R.A. , Petrova M.B.
Published: April 2015

Effectiveness of the influence of a natural cytokine complex "Superlymph" on a wound process was evaluated in albino rats. The preparation was used right after surgical treatment and then during 5 days. Interrelationship between morphological and immunobiochemical factors on local and organismic levels was studied. During uncomplicated wound process no statistically significant difference in concentration of blood serum neopterin was found. The main changes occured locally. There was correlation between morphological and immunobiochemical factors.
Blood serum phospholipids in patients with tonsillitis under combinated alcohol-bacterial influence
Authors: Makarov V.K. , Starikov S.V.
Published: April 2015

Blood serum phospholipids were investigated in alcohol abusing patients with tonsillitis. Most significant changes in phospholipids spectrum (low relative content of lysophospholipids and higher phosphatidylholine and phosphatidyletanolamin) in alcohol abusing patients with tonsillitis were observed, compared with alcohol abusers. This may be attributed to the prevailing influence of bacterial infection.
The diagnostic value of RNA oncomarkers in evaluation of malignant breast tumors
Authors: Globa A.G. , Alekseev Y.I. , Varlamov D.A. , Vishnevsky A.A.
Published: April 2015

The levels of the RNA oncomarkers, telomerase (hTERT), cytokeratin-19 (CK-19) and mammaglobin (MAM) have been investigated in capillary blood of female patients with mammary ductal carcinoma. The study revealed overexpression of all three factors in patients with this pathology. This overexpression was not found in healthy donors and female patients with mammary fibroadenoma. Levels of the RNA oncomarkers return to the normal level within 10 days after successful tumor resection. These results have been used for the development of diagnostic kits, which may be applicable for differential diagnostics, screening and postoperation monitoring of patients with malignant breast tumors
A new approach to studying the autoxidation of adrenaline: possibility of the determination of superoxide dismutase activity and the antioxidant properties of various preparations by polarography
Authors: Sirota T.V.
Published: April 2015

The reaction of adrenaline autoxidation in an alkaline buffer with the formation of superoxide radicals and the product of its oxidation, adrenochrome, which models the quinoid pathway of adrenaline conversion in the body, is accompanied by oxygen consumption. This reaction is applicable for polarographic determination of the activity of superoxide dismutase and the antioxidant properties of biological and chemical compounds, it is based on evaluation of the latent period and the rate of oxygen consumption, which are measured in the presence of the compounds examined. It was assumed that the neuro- and cardiotoxicity of quinone products of adrenaline oxidation is related not only to their "own" properties and reactive oxygen species formed but also the hypoxia of those regions of the cell and tissue where the quinoid oxidation of adrenaline occurs.
Determination of phenobarbital in human urine and serum usingflow injection chemiluminescence
Authors: Li K. , Nu L.Z. , Khe K.L. , Song K.H.
Published: April 2015

A sensitive chemiluminescence method, based on the enhancive effect of phenobarbital on the chemiluminescence reaction between luminol and dissolved oxygen in a flow injection system, was proposed for the determination of phenobarbital. The chemiluminescence intensity responded to the concentration of phenobarbital linearly ranging from 0.05 to 10 ng⋅ml-1 with the detection limit of 0.02 ng⋅ml-1 (3σ). At a flow rate of 2.0 ml⋅min-1, a complete determination of phenobarbital, including sampling and washing, could be accomplished in 0.5 min, offering the sampling efficiency of 120 h-1 accordingly. The method was applied successfully in an assay of PB for pharmaceutical preparations, human urine and serum without any pretreatment with recovery from 95.7 to 106.7% and RSDs of less than 3.0%.
Erythrocyte lipid composition at different stages of type 1 diabetes in children
Authors: Mityanina V.A. , Kuptzov V.N. , Saveliev S.V. , Shvets V.I. , Selishcheva A.A.
Published: April 2015

Complete profiles of phospholipid and ceramide molecular species from erythrocyte lipid extracts of children without carbohydrate metabolism disorders, and children with type 1 diabetes were compared by means of high performance liquid chromatography/mass spectrometry. For the first time a statistically significant increase (p<0.05) of lysophosphatidylcholine content in two groups of diabetic children with different duration of the disease (less than one year and more than one year) was found. Statistically significant changes in other lipid classes were not observed. The dependence of the content of phosphatidylcholine and phosphatidylethanolamine molecular species containing arachidonic acid residue (20:4) on the duration of the disease was found. The observed shift in lipid metabolism suggests of phospholipase A2 and chronic inflammatory process at different stages of diabetes mellitus, in cells (erythrocytes), which aer not involved in the immune response.
Antimicrobial peptides: mode of action and perspectives of practical application
Authors: Okorochenkov S.A. , Zheltukhina G.A. , Nebol"sin V.E.
Published: April 2015

This review is devoted to antimicrobial peptides (AMP's) that demonstrate activity against bacteria, viruses and fungi. It considers structure and mechanism of AMP interaction with lipid membrane and intracellular targets of pathogens. Special attention is paid to modern state and perspectives of AMP practical application and also to approaches that increase efficacy and reduce toxicity of AMP by chemical modification of their structure.
Particularities of corrective action of polar lipids and bioantioxidants from sea hydrobionts at imbalances of lipid and carbohydrate metabolism
Authors: Krivoshapko O.N. , Popov A.M. , Artyukov A.A. , Kostetsky E.Y.
Published: April 2015

A total mixture of phospho- and glycolipids from sea macrophytes Sargassum pallidum, Ulva fenestrata, Zostera marina was separated and the fatty acid composition was determined. Biological activity of the mixtures of polar lipids and natural antioxidants echinochrome A from flat sea urchin Scaphechinus mirabilis and polyphenolic complex from sea grass Zostera marina was studied in rats with experimental model of atherosclerosis and diabetes. These experiments revealed optimal compositions for mixtures of polar lipids and antioxidants, which possess high medical-corrective activity. Proposed mechanisms of action of the polar lipids (containing different polyunsaturated fatty acids) and antioxidants studied are presented. These compositions may be used for creation of new biologically-active additives and drugs.
Mechanisms of anti-cancer effects of plant polyphenols II. Suppression on tumor growth
Authors: Zinov'eva V.N. , Spasov A.A.
Published: April 2015

Mechanisms of suppression of carcinogenesis promotion/progression by plant polyphenols have been considered. They can decrease cyclins and cycline dependent kinases and activate inhibitor proteins in tumor cells that results in cell cycle arrest. Plant polyphenols can induce apoptosis by modulating anti/proapoptotic proteins and also can inhibit tumor metastasis and angiogenesis. Polyphenols act through the regulation of cell signal transduction and gene expression.
Antioxidant and antiaggregant effects of covalent bienzyme superoxide dismutase - chondroitin sulfate - catalase conjugate in platelet interactions
Authors: Vavaev A.V. , Buryachkovskaya L.I. , Tischenko E.G. , Uchitel I.A. , Maksimenko A.V.
Published: April 2015

A covalent bienzyme superoxide dismutase-chondroitin sulfate-catalase conjugate (SOD-CHS-CAT) demonstrated the dose-dependent inhibitory action on induced aggregation of platelets in the presence of hydrogen peroxide. Antioxidant activity of SOD-CHS-CAT appeared at much lower doses than for other CAT derivatives. We detected the antiaggregation effect of SOD-CHS-CAT for platelet aggregation induced by ADP, serotonin, TRAP (with their different mechanism of action). Novel properties of SOD-CHS-CAT confirmed with its action agains spread-eagle platelets on glass surface. The new characteristics of SOD-CHS-CAT conjugate underline the prospects of its biopharmaceutical development for antioxidant therapy.
Tissue-specific expression of hormonal carcinogenesis target genes in rats treated with polycyclic aromatic hydrocarbons
Authors: Chanyshev M.D. , Pustylnyak V.O. , Gulyaeva L.F.
Published: April 2015

We have investigated the effect of polycyclic aromatic hydrocarbons (PAHs) on estrogen- metabolizing genes CYP1A1, CYP1B1, CYP19 and ERα and cyclin D1 genes, which control of cell division in estrogen-depended tissues. Treatment of rats with benzo(a)pyren (BP) or 3-methylcholantrene (MC) significantly up-regulated CYP1A1, CYP1B1 gene expression in liver, uterus and ovary, whereas alfa-naphthoflavone (α-NF) did not have any effect. The high level of aromatase gene (CYP19) expression was detected in ovary only. Treatment of rats with BP or MC significantly down-regulated expression of this gene (15- and 5,5-fold, respectively), whereas α-NF did not have any effect. BP produced an increase in ERα and cyclin D1 gene expression in rat liver. This effect was not seen with MC and α-NF. ERα and cyclin D1 mRNA levels were unchanged in uterus of rats after PAHs treatment. On the other hand, BP treatment caused an increase of the ERα and cyclin D1 mRNA levels (3,5- and 2,5-fold, respectively) in ovary, whereas MC and α-NF did not have any effects. Thus, our results give evidence for tissue-specific effects of PAHs on expression of genes, which participate in hormonal carcinogenesis. Moreover, the fact that BP and MC treatment affects the expression of estrogen-metabolizing genes and genes, which control of cell division, supports the view that PAHs may be one of the causes of endocrine disorder and consequent hormonal carcinogenesis.
Macroglobulin signaling system
Authors: Zorin N.A. , Zorina V.N.
Published: April 2015

This review will focus on the systematization of knowledge about structure of macroglobulin signaling system, which includes macroglobulin family proteins (alpha-2-macroglobulin, alpha-2-glycoprotein, pregnancy associated plasma protein A), their receptors (LRP, grp78), ligands (proteinases, cytokines, hormones, lipids, et al.) transforming and transcriptional factors for regulation of macroglobulins synthesis. After reviewing the functions of macroglobulin signaling system, and mechanisms of their realization, we discuss the complex and significant role of this system in different physiological and pathological processes.
The effect of estrogens and progestagens on biochemical components of hemostasis, platelets, continuous intravascular coagulation and tolerance to thrombin: correction of their effect of antioxidants
Authors: Solovyev V.G. , Bychevsky A.Sh. , Karpova I.A.
Published: April 2015

Estrogen and progestin (ethinylestradiol and levonorgestrel, respectively) accelerate LPO in platelets, activate them, increase continuous intravascular coagulation and reduce tolerance to thrombin. Antioxidants limit these effects.
Development of non-hormonal regulators of adenylyl cyclase signaling system on the basis of peptides, derivatives of the third intracellular loop of somatostatin receptors
Authors: Shpakov A.O. , Shpakova E.A.
Published: April 2015

In the majority of the serpentine type receptors the third intracellular loop (ICL-3) is responsible for interaction with heterotrimeric G-proteins and for transduction of hormonal signal to the enzymes, generators of the second messengers. It was found that the peptides corresponding to ICL-3 influence functional activity of hormonal signaling systems in the absence of the hormone and, in consequence, can be considered as prototypes for the development of selective regulators of these systems. We have originally synthesized peptides corresponding to C-terminal regions 255-269 and 240-254 of ICL-3 of type 1 and 2 rat somatostatin receptors (Som1R and Som2R). Micromolar concentrations of these peptides activated Gi-proteins and inhibited forskolin-stimulated activity of adenylyl cyclase (AC) in rat brain tissues. The peptide 255-269 of Som1R is a selective antagonist of Som1R, and the peptide 240-254 of Som2R is an agonist of Som1R. So, the peptide 255-269 of Som1R decreased the regulatory effects of somatostatin and selective Som1R-agonist CH-275 realized via the receptor homologous to them, while the peptide 240-254 of Som2R, on the contrary, increased AC inhibitory action of CH-275. Both peptides insignificantly influenced regulatory effects of the Som2R-agonist octreotide. Summing up, the peptides studied by us are selective regulators of somatostatin-sensitive AC system. Using the peptides it was shown that ICL-3 of Som1R and Som2R includes the main molecular determinants that are responsible for activation of Gi-proteins and regulation of AC system by somatostatin and its analogues.
Increased myelopepoxidase activity is a risk factor for ishemic heart disease in patients with diabetes mellitus
Authors: Gorudko I.V. , Kostevich V.A. , Sokolov A.V. , Buko I.V. , Konstantinova E.E. , Tsapaeva N.L. , Mironova E.V. , Zakharova E.T. , Vasilyev V.B. , Cherenkevich S.N. , Panasenko O.M.
Published: April 2015

Using previously developed spectro-photometrical method (Bioorg. Khim. 2009. V. 35. pp. 629-639), a significant increase of myeloperoxidase (MPO) activity was found in blood plasma of patients with type 2 diabetes mellitus (DM2) without of cardiovascular complications, as well as with ischemic heart disease (IHD). Plasma MPO concentration measured by an enzyme-linked immunosorbent assay was significantly higher only in blood plasma of patient with DM2 and IHD. A direct and significant correlation between MPO activity and MPO concentration was observed only in blood plasma samples from healthy donors. Increased MPO activity did not correlate with MPO concentration in blood plasma of patients with DM2 and DM2 with IHD. Taken together, these results highlight the necessity for studying of the MPO role in the development of pathological processes to determine both the amount of enzyme and its peroxidase activity in the blood. The proposed approach gives comprehensive information about the relationship between MPO activity and MPO concentration in patient blood. Since the high concentration of MPO is a diagnostically significant parameter in the prediction of endothelial dysfunction and cardiovascular disease development, the obtained results evidence the contribution of MPO-dependent reactions in cardiovascular complications associated with diabetes. MPO activity may serve as an additional diagnostic criterion for determination of risk of IHD in DM patients.
Functional state of a sphingomyeline cycle and free radical lipid oxidation activity of a rat's liver during different phases of starvation
Authors: Kuzmenko D.I. , Burov P.G. , Serebrov V.Yu. , Fait E.A. , Perevozchikova T.V.
Published: April 2015

The functional state of a sphingomyeline cycle and character of its mutual relations with the processes of free radical lipid oxidation during starvation of animals without any restriction of access to drinking water at 1, 2, 3 day (I phase) and 6 day (II phase of starvation) were studied at the liver of rats. The maximal values of the ceramide/sphingomyeline ratio and activity neutral sphingomyelinase and executive caspase-3 were reached in a liver of animals at the 3rd day of starvation . From the 3rd day of starvation the concentration of the tumour necrosis factor-α which is one of activators neutral sphingomyelinase was increase in rats blood serum. During the extent of large part of the I phase of starvation the intensity of free radical lipid peroxidation in a liver had almost the same level as in control group - that was a result of the high-grade functioning of antioxidant defense system. After transition the I phase of starvation into the II phase (6 day of experiment) the oxidative stress was developed as result of an exhaustion of system antioxidant defense potential in a liver. The results of this data can testify that during I phase of starvation in a liver the conditions was raised for display of the ceramide-mediated proapoptotic signalling. We assume that ceramide-mediated apoptosis is one of mechanisms of optimization of liver cellular population at the frames of metabolic adaptation. The I phase of starvation in a liver proves by the ceramide-mediated proapoptotic signaling developing. During the II phase of starvation the oxidative stress process were prevailed.
Analysis of complex formation of human recombinant hsp70 with tumor-associated peptides
Authors: Chernikov V.A. , Gorokhovets N.V. , Savvateeva L.V. , Severin S.E.
Published: April 2015

Molecular chaperones of HSP70 family assists presentation of exogenous antigenic peptides by antigen-presenting cells (APC). HSP70-peptide complexes are powerful immunotherapeutic agents, which enhance cross-presentation of captured antigen in dendritic cells and macrophages. Several clinical trials have shown that HSP-based cancer vaccines possess good efficacy and safety. However, sometime it is impossible to isolate sufficient amount of vaccine. These make us to pay attention for recombinant HSP70-based vaccines and to optimize in vitro complex formation mechanism. Here we have investigated two human recombinant proteins HSP70HYB and HSC70. Optimal values of ADP concentration, pH, temperature and peptides excess are determined in this work. We have also shown that proposed complex formation method enriches eluted from HSP70-complexes peptide repertoire compared to in vivo assembled ones.
Thermosensitization of tumor cells with inhibitors of chaperone activity and expression
Authors: Kudryavtsev V.A. , Makarova Y.M. , Kabakov A.E.
Published: April 2015

Effects of inhibitors of the heat shock protein 90 (HSP90) chaperone activity and inhibitors of the heat shock protein (HSP) expression on sensitivity of HeLa tumor cells to hyperthermia were studied. It was found that nanomolar concentrations of inhibitors of the HSP90 activity (17AAG or radicicol) slowed down chaperone-dependent reactivation of a thermo-labile reporter (luciferase) in heat-stressed HeLa cells and slightly enhanced their death following incubation for 60 min at 43°C. Herein, the inhibitors of HSP90 activity stimulated de novo induction of additional chaperones (HSP70 and HSP27) that significantly increased the intracellular HSP levels. If the cells were treated with 17AAG or radicicol along with an inhibitor of the HSP induction (e.g. quercetin or triptolid, or NZ28), this fully prevented the increase in intracellular chaperone levels resulting from the inhibition of HSP90 activity and subsequent heating. Importantly, in the case of conjunction of all the three treatments (an inhibitor of the HSP90 activity + an inhibitor of the HSP induction + 43°C for 60 min), the reporter reactivation was retarded yet stronger while the cell death was sharply (2-3-fold) enhanced. Such an enhancement of the cytotoxicity appears to occur owing to the "chaperone deficiency" when prior to heat stress both the functional activity of constitutive HSP90 and the expression of additional (inducible) chaperones are blocked in the cells.
Cell-free DNA fragments increase transcription in human mesenchymal stem cells, activate tlr-dependent signal pathway and supress apoptosis
Authors: Kostyuk S.V. , Malinovskaya E.M. , Ermakov A.V. , Smirnova T.D. , Kameneva L.V. , Chvartatskaya O.V. , Loseva P.A. , Ershova E.S. , Lyubchenko L.N. , Veiko N.N.
Published: April 2015

Human mesenchymal stem cells (MSCs) are now widely adopted in regenerative medicine. However, many questions on the role of different signaling pathways in the regulation of stem cell (SC) functional activity within the organism remain unaswered. In damaged regions the level of cell death increases and DNA fragments from dead cells (cell-free DNA, cfDNA) are accumulated in blood. We showed that in adipose-derived MSCs exposed in vitro to cfDNA fragments the transcription level increased (the total amount of cellular RNA and the rRNA amount rose). GC-rich CfDNA fragments (GC-DNA) activated the TLR9-dependent signal pathway: the expression of TLR9 and of TLR9-signaling pathway adapter - MyD88 - was up-regulated. AT-rich DNA fragments did not increase the TLR9 expression, though, the MyD88 expression level rose. So we suggest that AT-DNA acts via some other receptors that nevertheless activate MyD88-dependent signalling in MSCs. We also showed that cfDNA fragments decreased the activity of caspase, an apoptotic enzyme. So, cfDNA can significantly influence the functional activity of MSC by activating TLR9- and MyD88-dependent signal pathways and lowering the apoptosis level.
The change in the structural and functional organization of the guerin's carcinoma cytochrome part of respiratory chain in tumor carriers in the conditions of preliminary low-level irradiation
Authors: Voloshchuk O.N. , Marchenko M.M. , Mudrak M.C.
Published: April 2015

The effect of low-level irradiation of tumor-bearing rats on the structural and functional organization of the cytochrome part of respiratory chain of mitochondria isolated from Guerin's carcinoma has been investigated.The maximal reduction in the mitochondrial cytochromes a, b and c content was observed at the terminal stage of Guerin's carcinoma. A low-level irradiation during initial stages of oncogenesis produced opposite changes in the mitochondrial cytochrome content.The possible mechanism of mitochondrial haem-containing cytochromes content reduction may be attributed to impairment in their formation caused by inhibition of the key enzyme of haem synthesis, 5-aminolevulinate synthase.The determined changes of the mitochondrial cytochromes quantitative content were accompanied by decreased activity of cytochrome oxidase. The preliminary low-level irradiation of the tumor-bearing animals produced further reduction in the cytochrome oxidase activity observed in all experimental periods.
The antiradical activity of plant extracts and healthful preventive combinations of these exrtacts with the phospholipid complex
Authors: Baranova V.S. , Rusina I.F. , Guseva D.A. , Prozorovskaya N.N. , Ipatova O.M. , Kasaikina O.T.
Published: April 2015

Using the chemiluminescence method, the effective concentration of antioxidants (AO) and its reactivity toward peroxyl radicals (ARA, the k7 constant) have been measured for 13 plant extracts. In fact all extracts demonstrated ARA higher than ionol. Larix dahurica, Hypericum perforatum, Potentilla fruticosa, Aronia melanocarpa and Rhaponticum carthamoides extracts showed the highest values of ARA. The combinations Aronia + Raponticum extracts; Larix + Hibiscus extracts; Schizandra +Aronia extracts were synergistic (the synergism effect β of 38%, 33% and 22%). Apparently this phenomenon is the result of the synergistic interaction between compounds present in plant extracts. The Phospholipid complex - Lipoid S40, lacting any antioxidant effect alone, showed a potent synergistic effect with Aronia extract (β = 60%), Silybum extract (β = 41%). Clinical trials demonstrated, that combinations "Lipoid + Aronia extract", "Lipoid + Larix extract + Hibiscus extract", "Lipoid + Silybum extract", "Lipoid + Q10 + Rosa majalis extract" may be used as an additional component in the medicinal treatment, or as an individual prophylactic agent.
The influence of natural dicarbonils on the antioxidant enzymes activity in vitro and in vivo
Authors: Lankin V.Z. , Konovalova G.G. , Tikhaze A.K. , Nedosugova L.V.
Published: April 2015

Natural dicarbonyls, which may be accumulated during oxidative stress in atherosclerosis (e.g. malondialdehyde) or carbonyl stress in diabetes mellitus (glyoxal and methylglyoxal) effectively inhibited the activities of commercial preparations of antioxidant enzymes: catalase, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and Se-contained glutathione peroxidase from human and bovine erythrocytes and also rat liver glutathione-S-transferase. After incubation of human erythrocytes with 10 mM of each investigated dicarbonyls the decrease of intracellular Cu,Zn-SOD was observed. The decreased activity of erythrocyte Cu,Zn-SOD was also detected in diabetic patients with carbohydrate metabolism disturbance but effective sugar-lowered therapy was accompanied by the increase of this enzyme activity. The increase of erythrocytes activity of Cu,Zn-SOD of diabetic patients theated with metformin (which may utilize methylglyoxal) was higher than in erythrocytase of diabetic patients subjected to traditional therapy.