Matrix Metalloproteinases MMP-1 and MMP-9 and Their Inhibitor TIMP-1 as Markers of Dilated Cardiomyopathy in Patients of Different Age.

We studied the expression of MMP-2, MMP-9, and inhibitor TIMP-1 in myocardial autopsy samples from subjects of different age and in cardiomyocyte cultures in the norm and in dilated cardiomyopathy. In autopsy samples of normal myocardium and in cardiomyocyte cultures, expression of molecules involved in extracellular matrix remodeling did not change during aging. In dilation cardiomyopathy, expression of MMP-2, MMP-9, and TIMP-1 and their ratios in autopsy material and in cultures was elevated by 1.5-9 times. Remodeling of extracellular matrix plays an important role in the pathogenesis of dilated cardiomyopathy. MMP-2, MMP-9, and their inhibitor TIMP-1 and the MMP/TIMP ratios can be regarded as promising predictors of dilated cardiomyopathy and used for evaluation of the effectiveness of treatment of this conditions in patients of different ages.

[Aging of the myocardium and dilated cardiomyopathy: morphological and molecular aspects].

The review considers various aspects of myocardium aging in normal and dilated cardiomyopathy (DC). There is a partial fibrosis of the heart tissue due to accumulation of collagen type 1, and accumulation of amyloid during normal aging. Men myocardial aging is accompanied by loss of cardiomyocytes and increased volume of the remaining cells, whereas in women this effect is absent. There is an expression of nuclear proteins decrease (lamin A and C), the accumulation of lipofuscin, increased content of reactive oxygen species, reduction of protein synthesis Sirt1 in cardiomyocytes with aging. Sirt1 has a cardioprotective effect, supports the balance of lipid metabolism, inhibits the development of inflammation and the formation of atherosclerotic plaques. Reduction of its expression not only indicates the accelerated pace of myocardial aging, but can be a predictor of the development of DC. In DC occurs stretching of the heart cavities and systolic dysfunction, predominantly in the left ventricle. DC is characterized by the development of inflammation in the myocardium. Its markers is increased expression of ICAM-1 adhesion molecule, MMP-2, MMP-9 matrix metalloproteinases, TIMP-1 tissue inhibitor of matrix metalloproteinases and decreased expression of MMP-1 matrix metalloproteinase.

[Molecular phylogenetic analysis of the ant genus Formica L. (Hymenoptera: Formicidae) from Palearctic region].

Sixty-five sequences of the mitochondrial DNA cytochrome b gene fragment (759 bp) and 23 sequences of the NADH dehydrogenase subunit 6 gene fragment (224 bp) were compared in ants of the genus Formica L. from different regions of the Palearctic and in Polyergus rufescens Latr. as outgroup. In total, 28 species of the genus Formica were examined. As a result, dated trees with a molecular clock were constructed showing the phylogenetic relationships of Formica ants. The topology of the obtained tree based on the Cyt-b sequences was found to be not consistent with the generally accepted opinion on the Formica rufa and F. rufibarbis groups. New data on the formation history of the present-day fauna of Formica ants of the Palearctic were obtained. It was demonstrated that a considerable fraction of the examined species (about a third) were formed in the Quaternary Period.

[THE COGNITIVE STATUS DYNAMIC OF CARDIOSURGICAL PATIENTS AND THE PREDICTORS OF ITS DISTURBANCE].

UNLABELLED: AIM OF RESEARCH: To estimate the cognitive status dynamics ofpatients during the early postoperative period after cardiac interventions and to reveal predictors of cognitive functions deterioration at this category of patients. MATERIALS AND METHODS: 118 cardiac patients were tested of neurocognitive functions one days before operation, and then for the 2-3rd days after operation by means of the MMSE test, the FAB test, Shulte's test, a questionnaire of a depression of CES-D, the BATTERY OF FRONTAL DYSFUNCTION TEST. Data of the perioperation's period was analyzed. RESULTS: Deterioration of results in the 2nd and more tests were registered at 61% of patients. The main distinctions between patients with postoperative deterioration of testing results and without it were: parameters of mehanical ventilation (tidal volume/ideal body weight, airways pressure), initial condition and existence of signs of initial deficit of blood circulation (decrease in the cardiac index and O2 delivery, increase of level of a lactate), decrease in cerebral oksimetry, existence of respiratory alkalosis dekompensation during CPB. Administration of the Dopamine before CPB and use of Desfluran demonstrated the positive influence to the cognitive status. CONCLUSIONS: 1) Neurocognitive dysfunction during the early postoperative period after cardiac surgery is tipical for 30-70% of patients. 2) The most significant predictors of deterioration of neurocognitive function in the postoperative period are the excessive depth of anesthesia and significant intraoperative decrease in the cerebral oxygenation. 3) Influence of the mehanical ventilation parameters on postoperative neurocognitive function is revealed, use of the large tidal volumes is especially negative. 4) Existence of the blood circulation deficit and decrease in oxygen delivery without timely intraoperative correction, and also an intraoperative hyperglycemia worsen a neurocognitive function in the postoperative period. 5) Desfluran administration has positive impact on the neurocognitive function.

Thermo-induced modifications and selective accumulation of glucose-conjugated magnetic nanoparticles in vivo in rats - increasing the effectiveness of magnetic-assisted therapy - pilot study.

Ferro-Magnetic nanoparticles (Fe-MNP) have gained a lot of attention in biomedical and industrial applications due to their biocompatibility, ease of surface modification and paramagnetic properties. The basic idea of our study is whether it is possible to use glucose-conjugate Fe-MNP (Glc-Fe-MNP) for targeting and more accurate focusing in order to increase the effect of high-frequency electromagnetic fields induced hyperthermia in solid tumors. Tumors demonstrate high metabolic activity for glucose in comparison with other somatic cells.Increasing of accumulation of glucose conjugated (Glc)-Fe-MNP on tumor site and precision of radio frequency electro-magnetic field (RF-EMF) energy absorption in solid tumors, precede RF-EMF induced hyperthermia. Rat model for monitoring the early development of breast cancer. Twenty female Wistar rats (MU-line-6171) were divided into two groups of 10 rats that were either treated with N-methyl-N-nitrosourea to induce breast cancer and 10 with carrageenan to induce inflammation (control). Glc-Fe-MNP can offer a solution to increase hyperthermia effect to the desired areas in the body by accumulation and increasing local concentration due to high tissue metabolic assimilation. In this condition, it is considered that the magnetization of the nanoparticles is a single-giant magnetic moment, the sum of all the individual magnetic moments and is proportional to the concentration of Glc-Fe-MNP.

[PHARMACOLOGICAL NEUROPROTECTION IN CARDIOSURGERY (Part 1): DRUGS FOR GENERAL ANESTHESIA].

This literature review is devoted to modern condition of pharmacological neuroprotection. Aeuroprotection as a complex method of brain protection and reduction of neurological complications is a relevant trend in practical anesthesia and intensive care. The following data represents frequency of neurological complications in different types of surgery and its main classifications. In the first part of the review potential neuroprotectional abilities of modern anesthesia medications are discussed Mechanisms of neuronal destruction and possible ways of impact on the pathophysiological processes via pharmacological agents are observed. The most promising drugs with neuroprotectional effects are selected. In the second part of the review we are going to examine neuroprotection effects of non-anesthetic drugs.

[POSSIBILITIES OF PHARMACOLOGICAL NEUROPROTECTION IN CARDIAC PATIENTS DRUGS NOT INTENDED FOR GENERAL ANESTHESIA].

The following paper is the second part of pubished review which reveals today state of pharmacology in neuroprotection issue. In the first part of the review we discussed neuroprotective possibilities of anesthesia medicine, but there is also another trend in pharmacological neuroprotection which is on high demand today: medicine that are not general anaesthesia drugs. This paper surveys medicines from different pharmacological groups and possible neuroprotective properties of these medicine are widely discussed in medical media. Unlike anesthetic medicine, most drugs mentioned in the second part of the review, can be used both for primary and secondary neuroprotection. The survey presents data from experimental and clinical studies of medicines neuroprotective properties.

Effect of adrenoblockers on slow (LF) waves in rabbit heart rate.

Propranolol and atenolol were used to examine the role of the adrenergic system in the genesis of slow HR variations (waves) in rabbits, the animals characterized by pronounced sympathetic influences. The control experiments were performed with physiological solution and long-term records in intact rabbits. The harmonic (spectrum) analysis was performed with fast Fourier transform. The adrenoblockers produced no decrease in the power of slow waves. The study did not found the sympathetic genesis of slow variations in rabbit HR.

Application of Barophoresis in Chronic Generalized Periodontitis: a Mathematical Substantiation.

The aim of the study was to evaluate the use of barophoresis for the delivery of liquid-air drug substances to the gums using a mathematical model of the interaction of the drug mixture with periodontal tissues. Materials and Methods: The solution to the problem was preceded by generation of a geometric CAD model of the device and nozzle for barophoresis, including the nozzle and injector geometry. The Ansys SpaceClaim software package was used to generate the CAD geometry. Results: When solving the problem of finding the optimal distance from the nozzle to the gum surface, the numerical modeling showed that at a distance of 5 mm, the volume fraction of liquid in the mixture is 18-20%. The mixture actually breaks through the gum, filling 0.8 mm of the gum thickness and spreading symmetrically to the sides at a distance of up to 3 cm, forming a cavity. At a distance of 10 mm from the nozzle to the gum surface, the liquid volume fraction in the mixture close to the gum lies in a narrow range of values of 5 to 7%. The mixture touches the surface of the gums, penetrating slightly - at a distance of 0.30-0.45 mm. At a distance of 15 mm from the nozzle to the gum surface, the volume fraction of liquid in the mixture near the gum lies in the range of 2-5%. The mixture slightly touches the gum surface, getting inside at a distance of up to 0.2 mm, having practically no effect on the gum. Conclusion: The developed mathematical model confirmed the feasibility of application of barophoresis in the treatment of chronic generalized periodontitis. The optimal distance from the nozzle to the surface should be considered to be 10-15 mm. This distance is safe and allows the drug delivery to a depth of 0.45 mm.

[Which of algorithms of warfarin dosing based on results of pharmacogenetic testing is suitable for patients in Russia].

Aim of the work was selection of optimal for patients in Russia algorithm of warfarin dosing based on results of pharmacogenomic testing. We analyzed data from 78 patients aged 63.4+/-9.4 years with known CYP29 and VKORC1 genotypes who had participated in an earlier retrospective study in which they received warfarin according to traditional scheme with starting dose of 5 mg/day. We used 5 known algorithms of determination of initial warfarin dose based on results of pharmacogenomic testing and correlated calculated doses with those which had been actually selected in our patients. Correlation was closest for doses obtained with algorithm of Gage et al (www.warfarindosing.org) (r=0.887, p<0.0001). Therefore we consider this algorithm most suitable for patients in Russia.

[Anticoagulant action and safety of warfarin dosing based on pharmacogenetic testing: results of the first Russian prospective pilot study].

Aim of the study was to compare numbers of episodes of excess hypocoagulation and bleeding with warfarin dosing based on pharmacogenetic testing and traditional method in patients with high risk of thromboembolic complications. In 76 patients (43 men and 33 women aged 60.3 +/- 12.3 years) warfarin was administered starting with the dose calculated according to the gage algorithm with consideration of results of pharmacogenomic testing (genotyping of CYP2C9 and VKORC1). Control group comprised 78 patients aged 63.4 +/- 9.4 years who had participated in an earlier retrospective study in which they received warfarin according to traditional scheme with starting dose of 5 mg/day. In both groups we analyzed data obtained during 6 months after start of drug administration. Genotyping was carried out by polymerase chain reaction. Episodes of excess hypocoagulation (international normalized ratio above therapeutic range) and bleeding accurred more rarely with the use of pharmacogenetic approach to dosing of warfarin compared with standard method (17.1 vs 56.4%, p = 4.1 x10(-7), and 4 vs 18%, p = 0.009 respectively).

Geometrically nonlinear dynamic model for a hexagonal lattice.

It is shown that angular stiffness in the hexagonal lattice model plays a significant role in the geometrical nonlinear terms in the equations of the continuum limit. A geometrically nonlinear discrete model is formulated for the hexagonal lattice by considering the interaction of two sublattices. An asymptotic procedure is developed in order to obtain the nonlinear coupled equations of motion in the continuum limit of the discrete model. An interaction of longitudinal and shear plane strain waves is studied by using the solutions of the obtained equations.

The contribution of activity-dependent synaptic plasticity to classical conditioning in Aplysia.

Plasticity at central synapses has long been thought to be the most likely mechanism for learning and memory, but testing that idea experimentally has proven to be difficult. For this reason, we have developed a simplified preparation of the Aplysia siphon withdrawal reflex that allows one to examine behavioral learning and memory while simultaneously monitoring synaptic connections between individual identified neurons in the CNS. We previously found that monosynaptic connections from LE siphon sensory neurons to LFS siphon motor neurons make a substantial contribution to the reflex in the siphon withdrawal preparation (Antonov et al., 1999a). We have now used that preparation to assess the contribution of various cellular mechanisms to classical conditioning of the reflex with a siphon tap conditioned stimulus (CS) and tail shock unconditioned stimulus (US). We find that, compared with unpaired training, paired training with the CS and US produces greater enhancement of siphon withdrawal and evoked firing of LFS neurons, greater facilitation of the complex PSP elicited in an LFS neuron by the siphon tap, and greater facilitation of the monosynaptic PSP elicited by stimulation of a single LE neuron. Moreover, the enhanced facilitation of monosynaptic LE-LFS PSPs is greater for LE neurons that fire during the siphon tap and correlates significantly with the enhancement of siphon withdrawal and evoked firing of the LFS neurons. These results provide the most direct evidence to date that activity-dependent plasticity at specific central synapses contributes to behavioral conditioning and support the idea that synaptic plasticity is a mechanism of learning and memory more generally.

Recombinant models of lipoproteins. Apolipoprotein A-I/phosphatidylcholine/cholesterol complexes formed in a 2-chloroethanol-water mixture.

Apolipoprotein A-I can spontaneously associate with phosphatidylcholine and cholesterol in 2-chloroethanol-water mixture. It was demonstrated, using a spin label technique, that dissolved molecules participate in complex formation. The apolipoprotein A-I/phosphatidylcholine/cholesterol complexes were isolated by gel chromatography. Complexes of three types were prepared and characterized: type A, large heterogeneous aggregates with molecular weight 600 000, sedimentation coefficient 10 S and the following molar composition - protein/phosphatidylcholine/cholesterol, 1:(70-100):(10-12); types B and C, with weight average molecular weights 140 000 and 110 000, average sedimentation coefficients 3.6 S and 1.7 S, respectively. Both types have the same molar composition - protein/phosphatidylcholine/cholesterol, 1:25:8. The dissimilar sedimentation coefficients between complexes B and C may be explained by the difference in the monomer/tetramer ratio (monomer molecular weight 50 000). The spin label sn-1-O-stearoyl-2-O-9'-spiro(4'',4''-dimethyloxazolidine-3''-oxyl) heptadecanoylglycero-3-phosphocholine introduced into the complexes A and B showed different thermal properties of these complexes, which may be due to differences in the lipid-protein interactions.

Distribution of neurotransmitter secretion in growing axons.

Neurotransmitter secretion from the nerve terminal is mediated by the fusion of synaptic vesicles with the plasma membrane. It is generally believed that neurotransmitter release in mature synapses is localized to the presynaptic nerve terminals. To probe the topology of neurotransmitter secretion along developing axons in culture, we recorded membrane currents from myocytes manipulated into contact with axons. At the early stages of growth, exocytotic events were detected along the axon as well as at the growth cone. At the later stages of growth, neurotransmitter secretion adopted the form of a smooth proximodistal gradient, with the highest level of activity at the growth cone region. Our results reveal the existence of a previously undetected early stage of axonal growth and suggest developmental regulation in the pattern of neurotransmitter secretion along the growing nerve processes.

Does a HDL injection reduce the development of serum hyperlipidemia and progression of fatty streaks in cholesterol fed rabbits?

The influences of homologous (rabbit) or heterologous (human) high density lipoprotein (HDL) on the development of serum hyperlipidemia and progression of fatty streaks were studied in cholesterol fed rabbits. Three groups of New Zealand rabbits were fed a 0.5% cholesterol rich diet for 8 weeks. Additionally into these animals the following solutions were injected intravenously two times per week: group 1 (control): saline; group 2: human HDL dissolved in saline; group 3: rabbit HDL dissolved in saline. The animals of group 2 had lower serum cholesterol levels during the dietary period than rabbits of group 1 (p < 0.05) but the surface of intima covered with fatty streaks was the same as in group 1. On the other hand, the serum cholesterol level in rabbits of group 3 was the same as in group 1 during the whole experimental period, but the surface of aorta covered with fatty streaks was significantly lower (p < 0.05) in group 3 than in group 1. The results of this study support the hypothesis of an antiatherogenic action of HDL, which seems to be independent of the influence of HDL on the serum lipids but depends on the source of HDL.

Effect of He-Ne laser treatment on the level of lipid peroxidation products in experimental cataract of rabbit eyes.

The effect of low-intensity laser irradiation on the processes of lipid peroxidation in lens homogenate and aqueous humor during experimental diquat-induced cataract of rabbit eyes was studied. The levels of primary and secondary products of lipid peroxidation (LPO), conjugated dienes and thiobarbituric acid reactive substances (TBARS), were evaluated. We found that the experimental cataract model leads to a significant increase in the content of conjugated dienes and in the content of TBARS both in lens homogenate and in aqueous humor. The data obtained support the important role of oxidative stress in the development of the diquat-induced cataract model. Low-intensity laser treatment does not provoke a significant decrease in conjugated dienes or in TBARS in either lens homogenate or aqueous humor. Although our therapeutic scheme led to a slightly decreased level of LPO products, we conclude that the effect of low-intensity laser-irradiation may depend on the dose applied, individual tissues and other factors.

[Metabolism of phosphatidylcholine in model lipoproteins. Use of phospholipid micelles immobilized on apoHDL-Sepharose]. / Obmen fosfatidilkholina v model'nykh lipoproteinakh. Ispol'zovanie fosfolipidnykh mitsell, immobilizovannykh na apo-LVP-Sefarose.

A phosphatidyl choline (PC) exchange between apoHDL/PC micellar complexes in solution and the same complexes immobilized on Sepharose was studied. The PC exchange in buffer was represented in terms of pseudo first order reversible process. The first order constants for the unidirectional efflux of PC from apoHDL/PC-Sepharose (k1) and for the unidirectional efflux of PC from apoHDL/PC complexes (k2) were equal to (0.45 +/- 0.2) x 10(-3) and (1.35 +/- 0.2) x 10(-3) min-1, respectively. The k1 values showed the Arrhenius dependence on the temperature within range 278-323 K. Plasma serum proteins facilitated the PC efflux from apoHDL/PC-Sepharose being additional acceptors of PC. These data allow use of apoHDL/PC-Sepharose for correcting lipid plasma composition in vitro.

[Immobilization of phospholipid micelles on modified apoHDL-Sepharose]. / Immobilizatsiia fosfolipidnykh mitsell na modifitsirovannoi apoLVP- Sefarose.

There was developed a procedure for immobilization of phosphatidyl cholines (Egg yolk phosphatidyl choline and polyunsaturated soya beams phosphatidyl choline) on the modified apoHDL-Sepharose. The formation of phospholipid micelles was proved by linear dependence of the content of the sorbed phosphatidyl choline versus, the content of apoHDL bound to Sepharose. Incubation of apoHDL/PC-Sepharose with human plasma was shown to change the plasma lipid composition. The apoHDL/PC-Sepharose might be used for correction of the plasma lipid composition on vitro experiments.