Effect of Glycyrrhetic Acid Derivatives on Regulation of Thymocyte Volume.

We studied the effects of glycyrrhetinic acid (bioactive aglycone of glycyrrhizin) and its ester derivatives at positions C-3 and C-30 on the cell volume regulation in rat thymocytes under conditions of hypoosmotic stress. Native glycyrrhetinic acid completely suppressed this process with half-maximal concentration of 12.7±1.4 µM and Hill coefficient of 3.1±0.6. Formation of esters at C-3 (esters with the acetic, cinnamic and methoxi-cinnamic acid) and at C-30 (methyl ester) drastically decreased the inhibitory activity of the molecule, suggesting that intact hydroxyl group at C-3 and carboxyl group at C-30 are structurally important determinants of biological activity of glycyrrhetinic acid towards volume regulation of thymic lymphocytes.

[Criteria for instability of atherosclerotic plaques in carotid arteries]. / Kriterii nestabil'nosti ateroskleroticheskikh bliashek sonnykh arterii.

The purpose of the study was to determine the criteria for instability of atherosclerotic plaques in carotid arteries with the use of improved and new diagnostic techniques. The study enrolled a total of 92 patients examined with the help of instrumental methods of diagnosis, including ultrasound triplex scanning, magnetic resonance imaging and multislice computed tomography. All patients were subjected to the operation of carotid endarterectomy in various standard modifications. The specimens of atherosclerotic plaques taken intraoperatively were examined with the help of morphological, immunofluorescent methods, electron paramagnetic resonance, electron microscopy. A multivariate logistic regression analysis demonstrated that the plaques with an area over 90 mm2 (OR 4.05; 95% CI 1.32-13.2; p=0.006), a volume of more than 0.6 cm3 (OR 2.72; 95% CI 1.05-9.58; p=0.04), and the JBA value of not less than 8 mm2 (OR 2.82; 95% CI 1.22-6.23; p=0.02) were statistically significant independent predictors of histologically verified unstable plaques. The results were compared to the findings of histological methods. In patients with the above mentioned ultrasonographic parameters, unstable plaques were encountered in 94% of cases. Immunofluorescent assay demonstrated a significant increase in the number of inflammatory markers (CD68+, CD36+ cells), as well as CD31+ cells as markers of neovasculogenesis in unstable plaques. According to the findings of electron paramagnetic resonance, bivalent manganese is a marker of plaque instability. Further studies will help reveal the mechanisms of plaque calcification. A decrease in the content of manganese correlated with an increase in the degree of plaque calcification (r =-0.69, p<0.01). This serves as indirect evidence of a destabilizing effect of calcification on plaque stability. It was demonstrated that ultrasound elastography makes it possible to significantly extend the capabilities of standard ultrasound examination in detecting instability of atherosclerotic plaques in carotid arteries.

[Calcification of atherosclerotic plaques and assessment of their stability]. / Kal'tsifikatsiia ateroskleroticheskikh bliashek i otsenka ikh stabil'nosti.

Presented herein is a review of the literature concerning mechanisms of calcification of atherosclerotic plaques (ASP), showing molecular mechanisms of interaction of processes of calcification with the factors inducing instability of ASPs (anti-inflammatory cytokines, neoangiogenesis, increased level of matrix metalloproteinases, etc.), also describing the effect of the value of volume of scope of calcification on stability of ASPs, followed by discussing the problems related to the role of biominerals (hydroxyapatite calcium phosphate) and Mn2+ in calcification of ASPs and their impact upon stability of the plaque.

Pb3+ radiation defects in Ca9Pb(PO4)6(OH)2 hydroxyapatite nanoparticles studied by high-field (W-band) EPR and ENDOR.

W-band pulsed EPR and ENDOR investigations of X-ray irradiated nanoparticles of synthetic hydroxyapatite Ca(9)Pb(PO(4))(6)(OH)(2) are performed. It is shown that in the investigated species lead ions probably replace the Ca(1) position in the hydroxyapatite structure.

Research of the structure and dynamic interactions of particles in the Li0.42K0.58NO3- R (R = α-Al2O3, γ-Al2O3, SiO2) and (LiNO3-LiClO4) - γ-Al2O3 composites in various temperature conditions and phase states.

The paper presents a comprehensive study of the Li0.42K0.58NO3- R (R = α-Al2O3, γ-Al2O3, SiO2) and (LiNO3 - LiClO4) - γ- Al2O3 composite salt systems by vibrational spectroscopy, X-ray diffractometry, and differential scanning calorimetry. According to the results of Raman spectra and XRD analysis, it has been found that in the case of a sufficiently small filler (15 nm-γ-Al2O3 and SiO2), an amorphous phase appears, both for systems based on Li0.42K0.58NO3 and for the nanocomposite based on (LiNO3)0.5-(LiClO4)0.5. In the case of nanocomposites based on the Li0.42K0.58NO3 system, this additionally leads to the formation of the metastable KNO3 (R3m) phase. The temperature changes in the half-widths of the corresponding bands of the Raman spectrum during the transition from a solid-phase to a molten state become less significant as the concentration of the oxide filler increases. At x ≥ 0.7, on the temperature dependences of the half-width of the ν1 (A) band in the vicinity of the melting point, only a small kink characteristic of amorphous systems is noticed. This is confirmed by the results of thermal analysis. It has been found that the solid filler has a different effect on the processes of orientational and vibrational relaxation in the molten phases of the studied NIS, namely, the orientational mobility of NO3- decreases, while the relaxation rate of its vibrational excitation increases.

X-Ray Diffraction and Multifrequency EPR Study of Radiation-Induced Room Temperature Stable Radicals in Octacalcium Phosphate.

Octacalcium phosphate (OCP) {Ca8H2(PO4)6×5H2O] has attracted increasing attention over the last decade as a transient intermediate to the biogenic apatite for bone engineering and in studies involving the processes of pathological calcification. In this work, OCP powders obtained by hydrolysis of dicalcium phosphate dehydrate were subjected to X- and γ-ray irradiation and studied by means of stationary and pulsed electron paramagnetic resonance at 9, 36 and 94 GHz microwave frequencies. Several types of paramagnetic centers were observed in the investigated samples. Their spectroscopic parameters (components of the g and hyperfine tensors) were determined. Based on the extracted parameters, the induced centers were ascribed to H0, CO33-, CO2- and nitrogen-centered (presumably NO32-) radicals. The spectroscopic parameters of the nitrogen-centered stable radical in OCP powders were found to be markedly different from those in hydroxyapatite. According to X-ray diffraction data, γ-ray irradiation allowed the phase composition of calcium phosphates to change; all minor phases with the exception of OCP and hydroxyapatite disappeared, while the OCP crystal lattice parameters changed after irradiation. The obtained results could be used for the tracing of mineralization processes from their initiation to completion of the final product, identification of the OCP phase, and to follow the influence of radiation processes on phase composition of calcium phosphates.

Redox state of adipose tissue for patients with gastric cancer and its connection with the body mass index and distance from the tumor.

Excess body weight has been causally linked to an increased risk of different cancer types, including gastric cancer but the mechanisms underlying this relationship are not well understood. Superoxide generation rate, activity of complex I in electron transport chain of mitochondria, activity of matrix metalloproteinase (MMP-2 and 9) of adipose tissues (AT) of patients with gastric cancer in AT located adjacent to tumor (ATAT) and at a distance of 3 cm (ATD) are measured to follow the connection of the redox state with some of the microenvironment indicators (HIF-1α, CD68, Plin5), body mass index (BMI) and cancer metastasis. Superoxide generation rate in ATAT positively correlates with BMI (r = 0.59, p < 0.05) being 4 times higher than in control (p < 0.05). MMP-2, 9 activities in ATAT positively correlate with BMI (r = 0.67, p < 0.05) being 3.3-4.0 higher than in control (p < 0.05). In ATD a statistically significant increase of MMP-2 activity is found. In ATAT for the group of patients with distant metastasis (M1) the superoxide generation rate, MMP-2, 9 activities are about 2 times higher (p < 0.05) than in the subgroup without distant metastases (M0). M1 is also characterized by the increased values of HIF-1α+ (factor 1.25), CD68+ (factor 1.4) and Plin5+ (factor 2.1) compared to M0 category in tumor tissues (p < 0.05). The results can be used for better understanding the mechanism(s) of symbiosis of tumor and adipose tissues as well as serve as a basis for new therapeutic approaches.

High-field dynamic nuclear polarization in aqueous solutions.

Unexpected high DNP enhancements of more than 10 have been achieved in liquid water samples at room temperature and magnetic fields of 9.2 T (corresponding to 400 MHz (1)H NMR frequency and 260 GHz EPR frequency). The liquid samples were polarized in situ using a double-resonance structure, which allows simultaneous excitation of NMR and EPR transitions and achieves significant DNP enhancements at very low incident microwave power of only 45 mW. These results demonstrate the first important step toward the application of DNP to high-resolution NMR, increasing the sensitivity on biomolecules with small sample volumes and at physiologically low concentrations.

Rectal Cancer: Redox State of Venous Blood and Tissues of Blood Vessels from Electron Paramagnetic Resonance and Its Correlation with the Five-Year Survival.

A role of pro- and antioxidants for reducing rectal cancer (RC) incidence in operative, preoperative, and postoperative treatments is still disputable and controversial. The redox state of venous blood and tissues of blood vessels of 60 patients with RC (T2-4N0-2M0G2) and 20 donors is studied by means of the conventional and spin-trapping electron paramagnetic resonance (EPR). The intensity of the signals from ceruloplasmin (CP), transferrin (TF), and labile iron pool (LIP) at temperature T = 77 K as well as superoxide generation rate and nitric oxide (NO) levels at T = 300 K is measured. The reduced CP and TF activity and decreased NO levels increased LIP levels and superoxide-generating rates are detected in blood species. Correlation analysis for the five-year survival rate as a function of the extracted values is done. The results show that the intensities of the corresponding EPR signals from the "native" and "trapped" paramagnetic centers can be potentially used for the understanding of the molecular mechanisms underlying the RC progression and treatment.

Colorectal Cancer and Mitochondrial Dysfunctions of the Adjunct Adipose Tissues: A Case Study.

Excess body weight has been causally linked to an increased risk of different cancer types, including colorectal cancer (CRC) but the mechanisms underlying this association are practically unknown. We investigate redox state-superoxide (SO) generation rate, activity of complex I in electron transport chain (ETC) of mitochondria and of dinitrosyl iron complexes by electron paramagnetic resonance; activity of matrix metalloproteinase (gelatinase) MMP-2 and MMP-9 by gel zymography of adipose tissues (AT) from 46 patients (64.0 ± 1.6 y.o.) with CRC (II-III stages, pT2-3N0-2M0) in the AT adjacent to tumor (ATAT) and at a distance of 3 cm from the tumor (ATD) to follow the connection of the AT redox state with some of the tumor microenvironment indicators. We have incubated the AT species with the tumor necrosis factor α (TNF-α) to follow its influence on the measured values. As a control, normal AT (NAT) obtained during the liposuction is used. Tumor-induced changes in mitochondrial ETC of ATAT, particularly for Complex I, lead to the enhanced SO generation and consequent oxidative modifications of DNA in ATAT (up to 6.1 times higher than that in NAT and 3.7 times higher than that in ATD, p < 0.05). Gelatinase activity in ATAT is significantly higher than in ATD. A considerable effect of TNF-α on ATAT and ATD (but not on NAT, i.e., only on the tissues where the reprogramming of metabolism has already occurred under the influence of tumor) manifested in increase of cellular hypoxia, gelatinase activity, and SO generation rate is observed. The results can be used for better understanding the mechanism(s) of metabolic symbiosis of tumor and AT as well as serving as a basis for new therapeutic approaches.

EPR study of some rare-earth ions (Dy3+, Tb3+, and Nd3+) in YBa2Cu3O6-compound.

We investigate the low temperature X-band electron paramagnetic resonance (EPR) of YBa(2)Cu(3)O(x) compounds with x congruent with 6.0 doped with Dy(3+), Tb(3+), and Nd(3). The EPR spectra of Dy(3+) and Tb(3+) have been identified. The EPR of Tb(3+) is used also to study the effect of suppression of high T(c) superconductivity by doping with Tb(3+). The EPR of Nd(3+) is probably masked by the intense resonance of Cu(2+). All experimental EPR results compare well with theoretical estimations.

Molecular relaxation processes in the salt systems containing anions of various configurations.

We present in this paper a comparative analysis of the spectral and molecular-relaxation parameters of the ionic salts in the region of solid-liquid phase transition and in the molten state depending on the anion symmetry (thiocyanate (SCN-), a linear rotor, C(infinity v); nitrate (NO3-), a symmetrical top, D3h; and perrhenate (ReO4-), a spherical top, Td), size and charge of the cation, and temperature. We also present new results of the investigations on molecular relaxation in thiocyanate ion in several crown-etheric complexes.

Raman and infrared study of the crystals with molecular anions in the region of a solid-liquid phase transition.

It is presented the Raman and infrared (IR) spectroscopic investigations of the thiocyanates: LiSCN, NaSCN, KSCN, RbSCN, CsSCN; nitrates: Ca(NO3)2, Sr(NO3)2, Ba(NO3)2, Pb(NO3)2; and perrhenates: LiReO4, NaReO4, KReO4 in the region of a solid-liquid phase transition. The differences in a pre-melting behavior of this salts were found which can be attributed to a different geometry of the SCN-, NO3- and ReO4- anions.

[The effect of ionic strength on reversible inhibition of catalytic activity of acetylcholinesterase by thione phosphonates]. / Vliianie ionnoi sily na obratimoe tormozhenie kataliticheskoi aktivnosti atsetilkholinésterazy tionfosfonatami.

The effect of ionic strength was used to analyze the mechanism of reversible acetylcholinesterase inhibition by three alkoxymethylthionphosphonates. The most considerable realization of the hydrophobic interaction with the surroundings of the enzyme esteratic site was marked for n-butyl derivative (compound I). The replacement of piperidine by morpholine (compound II) resulted in a decrease of the anticholinesterase activity by an order due to enhancement of the inhibitor hydrophilicity. An increase of MgCl2 concentration promotes an enhancement of the uncompetitive component contribution for compound III contrast to compound II. Hydrophobicity of the phosphoryl part of the compound I molecule is balanced under hydrophobic interaction of the heterocyclic "cationic head" with the enzyme anionic site. The break of this equilibrium intensifies the allosteric regulation, on the one hand, and lowers the inhibitor efficiency, on the other hand.

[The efficacy of inhaled glucocorticosteroids in different dosage regimens and in combination with theophylline preparations in bronchial asthma patients]. / Effektivnost' ingaliatsionnykh gliukokortikosteroidov pri razlichnom rezhime dozirovaniia i v kombinatsii s preparatami teofillina u bol'nykh bronkhial'noi astmoi.

The authors compare basic body plethysmography and peak flowmetry parameters, quality of life in 37 patients suffering from moderate or severe bronchial asthma. They received for 8 months low-dose glucocorticosteroids (group 1), high-dose glucocorticosteroids (group 2) and combination of low-dose glucocorticosteroids with long-acting theophyllin drugs (group 3). All the parameters assessed, quality of life was better in groups 2 and 3 (p < 0.05). Patients from these groups had also less frequent exacerbations of the disease which appeared less severe. From group 3 patients those who suffered longer and had marked emphysema showed a greater response.

[Spinal segmental myoclonus in multiple sclerosis (case report)]. / Spinal'naia segmentarnaia miokloniia pri rasseiannom skleroze (nabliudenie iz praktiki).

Multiple sclerosis (MS) is a disease with multicentric lesions of central nervous system. These numerous lesions can cause a lot of different symptoms. Sometimes these signs are atypical and make difficulties for MS diagnosing. Hyperkinesis is extremely rare manifestation of MS especially if it concerns spinal myoclonus. Spinal myoclonic jerks can be caused by various focal damages of neuraxis including demyelination lesions. This report describes the case of spinal segmental myoclonus as an unusual manifestation of MS. The patient was diagnosed definite MS according to the McDonald criteria (2010). The nature of movement disorders was defined by careful neurologic and neurophysiologic examination. These movement disorders were reliably caused by demyelinating type lesions in the cervical cord.

The peculiarities of spectral manifestations of high-voltage electric discharge in different phase states of ion systems.

The effects of high-voltage pulsed discharge (HVPD activation) on vibrational spectra of ion salt systems have been studied. The peculiarities of spectral display of HVPD in ion melts and aqueous solutions of electrolytes, in ion-conducting phases of crystalline and glassy salt systems have been investigated. After HVPD a salt system is in non-equilibrium activated state. In the activated state of a salt system, the relaxation time of the vibrational excited states of molecular ions is shorter than in the equilibrium state if the vibrational relaxation rate increases with temperature in the system. For those systems for which the relaxation rate decreases at elevated temperatures, the relaxation time of the vibrational excited states of molecular ions is longer than in the equilibrium state. HVPD activation of a salt system can change the configuration of the electron shell of molecular ions. Therefore, the lifetime values of activated state of salt systems are abnormally large.

Electron paramagnetic resonance study of tumor affected bone marrow.

To study the mechanism of interaction of tumor cells with bone marrow cells continuous wave electron paramagnetic resonance (EPR) experiments at 9 GHz including a spin trapping of superoxide were carried out. The common features of the EPR spectra in healthy and tumor affected tissues of donors and rats as well as their difference are presented and discussed. It is proposed that labile iron pool plays a significant role in mechanisms of tumor invasion. We hope that the observed EPR features could be used to study the mechanisms of invasion and progression of tumor in different organs.