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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.

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 | 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.

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