[Influence of chronic obstructive pulmonary disease on hospital outcomes of percutaneous coronary interventions in patients with acute coronary syndrome].

AIM: To evaluate the impact of chronic obstructive pulmonary disease (COPD) on hospital outcomes of percutaneous coronary interventions (PCI) in patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: A cohort prospective study of the COPD effect on mortality and coronary microvascular obstruction (CMVO, no-reflow) development after PCI in ACS was carried out. 626 patients admitted in 2019-2020 were included, 418 (67%) - men, 208 (33%) - women. Median age - 63 [56; 70] years. Myocardial infarction with ST elevation identified in 308 patients (49%), CMVO - in 59 (9%) patients (criteria: blood flow <3 grade according to TIMI flow grade; perfusion <2 points according to Myocardial blush grade; ST segment resolution <70%). 13 (2.1%) patients died. Based on the questionnaire "Chronic Airways Diseases, A Guide for Primary Care Physicians, 2005", 2 groups of patients were identified: 197 (31%) with COPD (≥17 points) and 429 (69%) without COPD (<17 points). Groups were compared on unbalanced data (÷2 Pearson, Fisher exact test). The propensity score was calculated, and a two-way logistic regression analysis was performed. The data were balanced by the Kernel "weighting" method, logistic regression analysis was carried out using "weighting" coefficients. Results as odds ratio (OR) and 95% confidence interval. RESULTS: The conducted research allowed us to obtain the following results, depending on the type of analysis: 1) analysis of unbalanced data in patients with COPD: OR death 3.60 (1.16-11.12); p=0.03; OR CMVO 0.65 (0.35-1.22); p=0,18; 2) two-way analysis with propensity score: OR death 3.86 (1.09-13.74); p=0.04; OR CMVO 0.61 (0.31-1.19); p=0.15; 3) regression analysis with "weight" coefficients: OR death 12.49 (2.27-68.84); p=0.004; OR CMVO 0.63 (0.30-1.33); p=0.22. CONCLUSION: The presence of COPD in patients with ACS undergoing PCI increases mortality and does not affect the incidence of CMVO.

[Individual parameters of general low-frequency magnetic therapy as a possibility for improving the clinical efficacy of the combined treatment of patients with essential arterial hypertension].

A new approach is proposed for the choice of low-frequency magnetic therapy on an individual basis using the results of analysis of heart rhythm variability. The clinical efficiency of low-frequency magnetic therapy incorporated in the combined treatment of 65 patients aged between 25 and 45 years with essential arterial hypertension was estimated. The statistically significant positive effects of the treatment included normalization of blood pressure and characteristics of heart rhythm variability as well as resolution of clinical symptoms of vegetative dysregulation.

Calorimetric and Fourier transform infrared spectroscopic study of solid proteins immersed in low water organic solvents.

Calorimetric heat effects and structural rearrangements assessed by means of Fourier transform infrared (FTIR) amide I spectra were followed by immersing dry human serum albumin and bovine pancreatic alpha-chymotrypsin in low water organic solvents and in pure water at 298 K. Enthalpy changes upon immersion of the proteins in different media are in a good linear correlation with the corresponding IR absorbance changes. Based on calorimetric and FTIR data the solvents were divided into two groups. The first group includes carbon tetrachloride, benzene, nitromethane, acetonitrile, 1,4-dioxane, n-butanol, n-propanol and pyridine where no significant heat evolution and structural changes were found during protein immersion. Due to kinetic reasons no significant protein-solvent interactions are expected in such systems. The second group of solvents includes dimethyl sulfoxide, methanol, ethanol, and water. Immersion of proteins in these media results in protein swelling and involves significant exothermic heat evolution and structural changes in the protein. Dividing of different media in the two groups is in a qualitative correlation with the solvent hydrophilicity defined as partial excess molar Gibbs free energy of water at infinite dilution in a given solvent. The first group includes the solvents with hydrophilicity exceeding 2.7 kJ/mol. More hydrophilic second group solvents have this energy values less than 2.3 kJ/mol. The hydrogen bond donating ability of the solvents also assists in protein swelling. Hydrogen bonding between protein and solvent is assumed to be a main factor controlling the swelling of dry solid proteins in the studied solvents.

Self-diffusion and self-association of lysozyme molecules in solution.

Self-diffusion of lysozyme molecules at the process of their self-association were studied by pulsed-field gradient nuclear magnetic resonance (NMR) at different lysozyme concentrations in solution. It was shown that in the intervals of pH from 1.8 to 4.0 and from 6.5 to 9.0, lysozyme self-diffusion coefficients were independent of pH value. In the interval of pH from 4.0 to 6.5, they decreased with increasing pH. Using self-diffusion data, estimations of the equilibrium constant k of the self-association reaction were made. For the model of indefinite self-association, k was found to be 264.5 +/- 0.5 l/M, and for its particular case-dimerization, 143 +/- 0.5 l/M. The dependence of the concentration of monomers and different associates on the total protein concentration was calculated.

Dielectric relaxation, molecular motion and interprotein interactions in myoglobin solution.

The results of the investigation of protein molecule dynamic in solution by Time Domain Dielectric Spectroscopy are presented. The horse myoglobin solutions in wide range of concentration from 0.6% to 54% at 20 degrees C have been investigated. The result of analysis produced in the term of dipole correlation function has shown that the obtained correlation function of macromolecule motion may be presented as sum of three components corresponding to three kinds of protein motions: anisotropic intramolecular motion, anisotropic Brownian tumbling and isotropic slow motion. We suppose that the cause of protein tumbling anisotropy and the possibility to keep slow motion is the interprotein electrostatic interactions. The characteristic time of slow motion depends on the concentration of protein and perhaps is controlled by translational diffusion. The dipole moment of myoglobin calculated by the Onsager-Oncley equation is 200D for solutions less than 10% protein concentration. It is in a good agreement with the theoretical value.

Dynamic structure of proteins in solid state. 1H and 13C NMR relaxation study.

Temperature dependencies of 1H non-selective NMR T1 and T2 relaxation times measured at two resonance frequencies and natural abundance 13C NMR relaxation times T1 and T1r measured at room temperature have been studied in a set of dry and wet solid proteins - Bacterial RNase, lysozyme and Bovine serum albumin (BSA). The proton and carbon data were interpreted in terms of a model supposing three kinds of internal motions in a protein. These are rotation of the methyl protons around the axis of symmetry of the methyl group, and fast and slow oscillations of all atoms. The correlation times of these motions in solid state are found around 10(-11), 10(-9) and 10(-6)s, respectively. All kinds of motion are characterized by the inhomogeneous distribution of the correlation times. The protein dehydration affects only the slow internal motion. The amplitude of the slow motion obtained from the carbon data is substantially less than that obtained from the proton data. This difference can be explained by taking into account different relative inter- and intra- chemical group contributions to the proton and carbon second moments. The comparison of the solid state and solution proton relaxation data showed that the internal protein dynamics in these states is different: the slow motion seems to be few orders of magnitude faster in solution.

Mathematical modelling of electrostatic fluctuations in subtilisin active site.

The intensities of electrostatic fluctuations in subtilisin active site generated by conformational motion of charged side chains, polar side chains and peptide bonds of the main chain are calculated. The comparative analysis of all these fragments reveals that there are few of them which make the main contribution to the total value of the intensity, which has been found to be approximately 10(7) g.cm-1.s-2. These are Ser 125, Thr 220 and peptide bonds of aminoacids 125-126, 218-219. Our present analysis enables us to compare the relative contribution of different fragments but we do not pretend to obtain precise absolute values. The reason for this is the lack of the detailed selective information on the mean-square amplitudes and correlation times of conformational motion of the fragments and on the values of local dielectric constants in the interior of subtilisin. The possibility for electrostatic fluctuations in enzyme active site to be an efficient nonspecific source of substrate activation is discussed.

Overall and internal protein dynamics in solution studied by the nonselective proton relaxation.

A new algorithm for the analysis of nonselective proton relaxation data in protein solution is presented. T1 and T2 of protein protons in lysozyme and RNase solutions were measured at three resonance frequencies--11, 27 and 90 MHz. In addition we measured water T1 dispersions in lysozyme solutions over the frequency range of 10 kHz--10 MHz on a field-cycling installation. It was found that the correlation function of protein Brownian tumbling as a whole is nonexponential: in addition to a component with the usual correlation time tau t it contained also a component with a correlation time exceeding tau t by approximately an order of magnitude and with a small relative amplitude. The experiment shows that the parameters of the slow component of the tumbling correlation function depend both on the concentration and on the pH of the protein solution. To explain the results obtained one must take into account the interprotein electrostatic interactions in solution. All protein molecules in solution experience electrostatic torques from their neighbors and this gives rise to an anisotropy in the protein Brownian tumbling. The lifetime of this anisotropy is controlled by the translational diffusion of proteins.

[The effect of electrostatic intermolecular interactions on Brownian rotation of proteins in solution]. / Vliianie élektrostaticheskikh mezhmolekuliarnykh vzaimodeistvii na Brounovskoe vrashchenie belkov v rastvore.

A qualitative model that takes into account the influence of electrostatic interactions on the form of correlation function of Brownian rotation of a protein as a whole is given. It is supposed that these interactions give rise to anisotropy of Brownian rotation and this leads to the nonexponentiality of the correlation function. To define experimentally the form of the correlation function nonselective measurements of relaxation times T1 and T2 of protein protons at different resonance frequencies in lysozyme solution were carried out. Literature data on frequency dependencies of relaxation time T1 of water in protein solutions were analysed. Analysis of experiments confirms the proposed model. Correlation times, activation energies and parameters of anisotropy were found.

On mechanisms of water nuclear magnetic relaxation in protein solutions.

To describe water nuclear magnetic relaxation in protein solutions a new modification of two-state model has been advanced. It is assumed that the hydration water molecules take part in two type rotation motions: fast anisotropic and slow isotropic ones, each of them can be characterized by a single correlation time. A transition of water molecule from bound state into bulk water is considered as defect arousing and is described by defect diffusion model. The model advanced allows one to describe both frequency and temperature dependences of water spin-lattice relaxation times in protein solutions and to get an information on microdynamic parameters of hydration water molecules such as life time, fraction, hindrance of local motion, etc.

New modification of model-free approach to analysis of nuclear magnetic relaxation data in proteins.

A formal approach to the analysis of 13C magnetic relaxation data in proteins has been developed. It is based on the concepts of one of the authors on the internal motions in solid polymers (Fedotov, V.D., Pulse NMR in bulk polymers, Doctoral dissertation, Kazan, USSR, 1981). According to this approach the intermolecular motions in proteins are considered as anisotropic ones and described in terms of a spectrum of correlation times. To characterize the motions a set of formal microdynamic parameters has been introduced. They are: the anisotropy parameter (a measure of spatial restriction of motion), the most probable correlation time, the parameter of the correlation time distribution width. The analysis of protonated carbon relaxation in globular proteins (bovine pancreatic trypsin inhibitor and ribonuclease S) and polymers has been carried out by the model-free approach. Microdynamic parameters of CH3-, CH2-, aromatic CH-groups have been considered within the framework of the diffusional rotation-oscillation models. To explain the backbone CH-group relaxation the model of the defect diffusion has been applied. The distinctive feature of the results obtained is the broad correlation time distribution for all groups of any type. The causes of nonexponential correlation function of local motion have been discussed. To elucidate the nature of the correlation time the carbon magnetization decays in the wide range of microdynamic parameter values imitating various experimental conditions have been calculated.

[Nuclear magnetic resonance and intramolecular mobility of proteins]. / Iadernyi magnitnyi rezonans i vnutrimolekuliarnaia podvizhnost' belkov.

The quantitative analysis of the data of NMR obtained by different authors in solutions and powders of protein in order to obtain information about the mechanism of intramolecular mobility of macromolecules was. The experiments on selective relaxation 13C and nonselective relaxation 1H in solutions for a number of globular proteins are discussed in detail. Also the experiments on temperature dependences of the broad line spectra of the protons of dry and hydrated proteins are considered. All the experimental data show the absence of the segmental liquid-like motion of the polypeptide chain in the native protein molecule. In the experiments considered only the local anisotropic motions are found which are characteristic of the crystal polymers and related to the torsional vibrations on small angle (15-30 degrees). The only exceptions are the end methyl and methylene groups occupying the periferals of the long side chain, which participate in nearly "free" rotations.