Time filter

Source Type

Babizhayev M.A.,Innovative Research Inc. | Savel'yeva E.L.,Moscow State University | Moskvina S.N.,Institute of Physicochemical Medicine | Yegorov Y.E.,RAS Engelhardt Institute of Molecular Biology
American Journal of Therapeutics | Year: 2011

Globally, tobacco use is associated with 5 million deaths per annum and is regarded as one of the leading causes of premature death. Major chronic disorders associated with smoking include cardiovascular diseases, several types of cancer, and chronic obstructive pulmonary disease (lung problems). Cigarette smoking (CS) generates a cumulative oxidative stress, which may contribute to the pathogenesis of chronic diseases. Mainstream and side stream gas-phase smoke each have about the same concentration of reactive free radical species, about 1 × 10 radicals per cigarette (or 5 × 10 per puff). This effect is critical in understanding the biologic effects of smoke. Several lines of evidence suggest that cigarette smoke constituents can directly activate vascular reactive oxygen species production. In this work we present multiple evidence that CS provide the important risk factors in many age-related diseases, and is associated with increased cumulative and systemic oxidative stress and inflammation. The cited processes are marked by increased white blood cell (leucocytes, WBCs) turnover. The data suggest an alteration of the circulating WBCs by CS, resulting in increased adherence to endothelial cells. Telomeres are complex DNA-protein structures located at the end of eukaryotic chromosomes. Telomere length shortens with biologic age in all replicating somatic cells. It has been shown that tobacco smoking enhances telomere shortening in circulating human WBCs. Telomere attrition (expressed in WBCs) can serve as a biomarker of the cumulative oxidative stress and inflammation induced by smoking and, consequently, show the pace of biologic aging. We originally propose that patented specific oral formulations of nonhydrolized carnosine and carcinine provide a powerful tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection of telomere attrition associated with smoking. The longitudinal studies of the clinical population groups described in this study including elderly support the hypothesis that telomere length is a predictor of survival and therapeutic treatment requirement associated with smoking behavior. © 2011 Lippincott Williams & Wilkins.


Pozmogova G.E.,Russian Academy of Sciences | Zaitseva M.A.,Institute of Physicochemical Medicine | Smirnov I.P.,Moscow State University | Shvachko A.G.,Institute of Physicochemical Medicine | And 2 more authors.
Bulletin of Experimental Biology and Medicine | Year: 2010

In order to create effective therapeutically signifi cant oligonucleotide structures, a series of analogs of thrombin-binding aptamer d(GGTTGGTGTGGTTGG) containing thiophosphoryl substitutions were synthesized. The anticoagulation effects of the resultant thrombin-binding aptamer analogs were evaluated and the effects of local thiomodifications on their structure and function were studied, including the effects on stability in blood plasma and resistance to DNA nucleases. A promising modified oligonucleotide (LL11) was found with the structure modified only in TT loops. It retains antithrombin properties of thrombin-binding aptamer, but is more resistant to biodegradation. © 2010 Springer Science+Business Media, Inc.


Dobretsov G.E.,Institute of Physicochemical Medicine | Syreishchikova T.I.,RAS Lebedev Physical Institute | Smolina N.V.,Institute of Physicochemical Medicine
Biophysics | Year: 2011

The molecular mobility of the fluorescent probe, N-(carboxymethyl)imide of 4-(dimethylamino)naphthalic acid (K-35), in three types of binding site on a human serum albumin (HSA) molecule has been studied. Study of the time-resolved decay of K-35 polarized fluorescence in HSA has shown that probe molecules bound to different sites have different fluorescence decay times, which poses problems in interpreting the polarization curves. However, it has been found that, in the case of rather slow thermal rotation of the probe, the decay of the vertical and the horizontal components of polarized fluorescence can each be approximated with three exponentials corresponding to three types of binding site. The mobility of the probe in different sites was estimated. The mobility was different but in all cases hindered by tens of times relative to the rotation of K-35 in water. The slowest motion occurred in the sites of the first type localized in the region of the well known drug site I: there the rotational correlation time was at least 72 ns. In the sites of the second type, this time was about 40 ns, and in the sites of the third type, about 10 ns. The faster was the rotation, the higher was the fluorescence quenching rate. Probably, it is this motion that is responsible for different fluorescence decay times in different HSA sites. © 2011 Pleiades Publishing, Ltd.


Koshurnikov D.S.,Institute of Physicochemical Medicine | Petraikin A.V.,Institute of Physicochemical Medicine | Martynov A.K.,Institute of Physicochemical Medicine | Sergienko V.I.,Institute of Physicochemical Medicine
Bulletin of Experimental Biology and Medicine | Year: 2011

Liquor circulation is a directed flow of the liquor from sites of its secretion to sites of resorption. This slow flow is modulated by pulsation caused by heart work. Phase-contrast magnetic resonance imaging is a method for noninvasive measurements of the linear velocity of these pulses in the cerebral aqueduct. A mathematical model reproducing pulsed flow of the liquor in the cerebral aqueduct is proposed and the procedure of evaluation of these parameters is presented. The pliability liquor system can be calculated from the values of liquor flow linear velocity in the cerebral aqueduct, measured by noninvasive method. © 2011 Springer Science+Business Media, Inc.


Dobretsov G.E.,Institute of Physicochemical Medicine | Gryzunov Y.A.,Institute of Physicochemical Medicine | Syreishchikova T.I.,RAS Lebedev Physical Institute | Smolina N.V.,Institute of Physicochemical Medicine | And 2 more authors.
Biophysics (Russian Federation) | Year: 2012

Fluorescent probe N-(carboxyphenyl)imide of 4-(dimethylamino)naphthalic acid, K-35, is used as an indicator of structural changes of human serum albumin molecules in pathology. The probe occupies albumin binding pockets where the probe environment is of very high polarity; probably, the pockets contain protein polar groups and also water molecules. At the same time the rather small Stokes shift of K-35 fluorescence spectrum shows that the polar group motion is one-two orders of magnitude lower than the mobility of polar molecules in polar fluids. K-35 fluorescence decay in HSA can be described as a sum of three exponentials with time constants close to τ1 = 9 ns; τ2 = 3.6 ns and τ3 = 1.0 ns. The difference between excitation maxima of these three decay components shows that the environment of these three species of K-35 molecules has been different before excitation. Different τ values are probably a consequence of nonidentical structure of several binding sites, or the binding site(s) can have variable conformation. © 2012 Pleiades Publishing, Ltd.


Dobretsov G.E.,Institute of Physicochemical Medicine | Syrejshchikova T.I.,RAS Lebedev Physical Institute | Smolina N.V.,Institute of Physicochemical Medicine | Uzbekov M.G.,Institute of Psychiatry
Bulletin of Experimental Biology and Medicine | Year: 2012

Albumin is a carrier of nonesterifi ed long-chain fatty acids and many other ligands. The status of its binding centers was studied for various proportions of nonesterifi ed long-chain fatty acids and albumin as exemplifi ed by palmitic acid. The status of the binding center was tested by recording K-35 probe fl uorescence decay in the subnanosecond band. This method showed the work of three types of centers. Palmitic acid enhanced binding activity of all centers, though to a different degree: If the palmitic acid/albumin proportion increased to 2-3, the probe binding to type 1 centers (located in the drug center I region) increased 1.5 times, while binding to type 3 centers increased more than 3-fold. Modifi cation of these centers by nonesterifi ed long-chain fatty acids was similar in the isolated human albumin preparation and in diluted blood serum. Hence, K-35 probe showed the actual status of various albumin centers, their binding capacity depending to a different measure on the fatty acid charge of albumin. © 2012 Springer Science+Business Media, Inc.


Dobretsov G.E.,Institute of Physicochemical Medicine | Syreishchikova T.I.,RAS Lebedev Physical Institute | Gryzunov Y.A.,Institute of Physicochemical Medicine | Smolina N.V.,Institute of Physicochemical Medicine | Komar A.A.,RAS Lebedev Physical Institute
Biophysics | Year: 2010

A study was made of the binding of a fluorescent probe K-35 (N-(carboxyphenyl)imide of 4-(dimethylamino)naphthalic acid), used as an indicator of albumin structural changes in pathology, to human serum albumin (HSA). Based on the data on the fluorescence decay of the probe, four types of site of K-35 binding to HSA have been recognized, which differ in fluorescence decay time (τ) and binding constant (K). Probe molecules bound to the first type of site have a decay time of 8-10 ns; this value corresponds to a high fluorescence quantum yield of about 0.7. These sites have a maximal binding constant, K1 = 5 · 104 M-1. The τ2 of the second type of site is close to 3.6 ns and K2 = 1 · 104 M-1, which is much lower than K1; however, the number of these sites is several times greater. The number of sites of the third type and the binding constant are close to those of the second type, but the decay time τ3 is 1 ns, which is significantly lower than τ2. The binding of K-35 to sites of the second and the third types is characterized by a positive cooperativity. Their properties are similar but not completely identical. The total number of sites of these three types is about two per one HSA molecule. There are also one-two sites of the fourth type where bound K-35 molecules have a very short decay time τ4 ≪ 1, i. e., are virtually nonfluorescent, and K4 = 1 · 104 M-1. The major contribution to the steady-state fluorescence is made by probe molecules bound to sites of the first and second types. As a rule, the concentration of albumin binding sites in blood is significantly higher than the concentration of metabolites and xenobiotics transferred by albumin. Therefore, the metabolite-or the probe in these experiments-is distributed among different sites in accordance with their Kini values (ni is the number of sites of the i-th type per albumin molecule). The low occupancy of the sites results in an approximately equal number of K-35 molecules bound to different sites of types 1, 2, and 3. The competition of K-35 with phenylbutazone, a marker of the albumin drug-binding site I, allows one to suggest that the K-35 site of the first type is localized exactly in the drug site I region, while the sites of the second and third types are close to it. © 2010 Pleiades Publishing, Ltd.


PubMed | Institute of Physicochemical Medicine
Type: Journal Article | Journal: Bulletin of experimental biology and medicine | Year: 2012

Liquor circulation is a directed flow of the liquor from sites of its secretion to sites of resorption. This slow flow is modulated by pulsation caused by heart work. Phase-contrast magnetic resonance imaging is a method for noninvasive measurements of the linear velocity of these pulses in the cerebral aqueduct. A mathematical model reproducing pulsed flow of the liquor in the cerebral aqueduct is proposed and the procedure of evaluation of these parameters is presented. The pliability liquor system can be calculated from the values of liquor flow linear velocity in the cerebral aqueduct, measured by noninvasive method.


PubMed | Institute of Physicochemical Medicine
Type: Journal Article | Journal: Bulletin of experimental biology and medicine | Year: 2010

The kinetics of thrombin inhibition by irons ions was studied in the thrombin time test with normal plasma. The kinetic and concentration characteristics for recovery of thrombin activity by desferal were evaluated at various periods of thrombin incubation with iron ions. The thrombin time test showed that incubation of thrombin with iron sulfate in a final concentration of 200 microM for 25-35 min is followed by the loss of thrombin activity. Pretreatment of iron-containing incubation system with desferal was shown to decelerate the process of thrombin inactivation. The kinetic characteristics for recovery of thrombin activity by 2 mM desferal were estimated at various periods after addition of iron sulfate in the inhibitory dose. The effect of reversibility was shown to depend on the time of thrombin preincubation with iron. Incomplete recovery of thrombin activity after increasing the time of incubation with iron (more than 30 min) was probably related to oxidative modification of thrombin.

Loading Institute of Physicochemical Medicine collaborators
Loading Institute of Physicochemical Medicine collaborators