Biomedical subjects

A A Frolov

Publications and source records attributed to A A Frolov.

At least 19 recordsLinked to original sources

PubMed2006

Joint application of independent component analysis and non-stationary fluctuation analysis for studying the mechanisms of the early phase of long-term potentiation in the rat hippocampus.

Interest in studies of synaptic plasticity have led to the development of specific methods for analyzing evoked postsynaptic currents: quantum analysis, component analysis, non-stationary fluctuation analysis, etc. However, the use and interpretation of these methods are not always consistent, which leads to the acquisition of contradictory results from similar experiments. In the present study, simulations were used to analyze the influences of the heterogeneity of the shapes of postsynaptic currents on the results obtained by non-stationary fluctuation analysis. Assessment of postsynaptic channel conductivity was found to depend on the number of synapses involved in generating the response. It is hypothesized that the increase in the assessment of AMPA channel conductivity reported in the literature in conditions of long-term potentiation may be related to changes in the synaptic composition of postsynaptic currents. The hypothesis was tested using a new method for independent component analysis. Studies using the simulation showed that the joint application of this method and non-stationary fluctuation analysis avoids errors of this type. The procedures developed here were applied to data obtained from physiological experiments; the results of this exercise provided general support for the hypothesis.

Animals↗

PubMed2006

[Dynamics of rat hepatocyte histone glycoxidation after general x-ray irradiation].

Dynamics of structural parameters of hepatocyte histone glucoxidative modification 3, 9 and 24 h after general X-ray irradiation of rats at dose 5 Gy was studied. Dynamics of these parameters (content of carbonyl groups, bityrosyl cross-linkings, pentosidines, advanced glycation end products) was compared with alterations in DNA structure (according to agarose gel electrophoresis) and lipid peroxidation extent (by malondialdehyde content). Oxidative stress induced by hepatocyte irradiation results in structural damage of DNA and histones accompanied by an increase of histone bityrosyl cross-linking and carbonyl content. The content of advanced glycation end products in histones corresponds to the extent to DNA damage and malondialdehyde content. The described postradiation modifications of histones may be important for regulation of chromatin function.

Animals↗

PubMed2005

Adjustment of the human arm viscoelastic properties to the direction of reaching.

The viscoelastic properties of the human arm were measured by means of short force perturbations during fast reaching movements in two orthogonal directions. A linear spring model with time delay described the neuromuscular system of the human arm. The obtained viscoelastic parameters ensured movement stability in spite of the time delay of 50 ms. The stiffness and viscosity ellipses appeared to be predominantly orthogonal to the movement direction, which reduced the effect of force perturbation in the direction orthogonal to the reaching movement. Thus, it can be argued that the viscoelastic properties of the neuromuscular system of the human arm are adjusted to the direction of movement according to a "path preserving" strategy, which minimizes the deviation of the movement path from a straight line, when exposed to an unexpected external force.

Adaptation, Physiological↗

PubMed2005

Feedback equilibrium control during human standing.

Equilibrium maintenance during standing in humans was investigated with a 3-joint (ankle, knee and hip) sagittal model of body movement. The experimental paradigm consisted of sudden perturbations of humans in quiet stance by backward displacements of the support platform. Data analysis was performed using eigenvectors of motion equation. The results supported three conclusions. First, independent feedback control of movements along eigenvectors (eigenmovements) can adequately describe human postural responses to stance perturbations. This conclusion is consistent with previous observations (Alexandrov et al., 2001b) that these same eigenmovements are also independently controlled in a feed-forward manner during voluntary upper-trunk bending. Second, independent feedback control of each eigenmovement is sufficient to provide its stability. Third, the feedback loop in each eigenmovement can be modeled as a linear visco-elastic spring with delay. Visco-elastic parameters and time-delay values result from the combined contribution of passive visco-elastic mechanisms and sensory systems of different modalities.

Adult↗

PubMed2004

[Efficacy of cytoprotective agent Mexicor in urgent cardiology].

AIM: To study efficacy of cytoprotector mexicor in patients with unstable angina (UA), acute myocardial infarction (MI), hypertensive crises (HC) in combined therapy with conventional drugs. MATERIAL AND METHODS: An open randomized study included 338 patients with acute forms of ischemic heart disease (IHD) and arterial hypertension running with crises. Combined therapy of 20 patients with UA, 90 patients with MI and 43 patients with HC (study groups) was supplemented with mexicor in a dose 6-9 mg/kg/day. The control matched patients (20, 86 and 79 patients, respectively) received conventional treatment alone. The effects of the treatments were assessed by ultrasound investigation of the heart in M-, B- and Doppler modes, by ECG and arterial pressure 24-h monitoring, by activity of lipid peroxidation (LPO). RESULTS: Adjuvant therapy of urgent cardiological conditions with mexicor diminished oxidant stress, left ventricular dysfunction. In MI patients mexicor promoted reduction of the akinesia zones, recovery of disturbed segmentary contractility. In UA patients mexicor contributed to more pronounced decrease in the frequency, duration and severity of myocardial ischemia, enhanced stabilization of angina. In HC patients mexicor promoted earlier normalization of a 24-h AP profile and variability of cardiac rhythm, recurrence rate of HC decreased 2-fold. CONCLUSION: The addition of mexicor to conventional therapy of UA, MI, HC improves clinical course of these diseases, reduces oxidant stress, accelerates recovery of cardiac contractility and left ventricular diastolic function, normalization of central hemodynamics.

Angina, Unstable↗

PubMed2001

Biomechanical analysis of movement strategies in human forward trunk bending. I. Modeling.

Two behavioral goals are achieved simultaneously during forward trunk bending in humans: the bending movement per se and equilibrium maintenance. The objective of the present study was to understand how the two goals are achieved by using a biomechanical model of this task. Since keeping the center of pressure inside the support area is a crucial condition for equilibrium maintenance during the movement, we decided to model an extreme case, called "optimal bending", in which the movement is performed without any center of pressure displacement at all, as if standing on an extremely narrow support. The "optimal bending" is used as a reference in the analysis of experimental data in a companion paper. The study is based on a three-joint (ankle, knee, and hip) model of the human body and is performed in terms of "eigenmovements", i.e., the movements along eigenvectors of the motion equation. They are termed "ankle", "hip", and "knee" eigenmovements according to the dominant joint that provides the largest contribution to the corresponding eigenmovement. The advantage of the eigenmovement approach is the presentation of the coupled system of dynamic equations in the form of three independent motion equations. Each of these equations is equivalent to the motion equation for an inverted pendulum. Optimal bending is constructed as a superposition of two (hip and ankle) eigenmovements. The hip eigenmovement contributes the most to the movement kinematics, whereas the contributions of both eigenmovements into the movement dynamics are comparable. The ankle eigenmovement moves the center of gravity forward and compensates for the backward center of gravity shift that is provoked by trunk bending as a result of dynamic interactions between body segments. An important characteristic of the optimal bending is the timing of the onset of each eigenmovement: the ankle eigenmovement onset precedes that of the hip eigenmovement. Without an earlier onset of the ankle eigenmovement, forward bending on the extremely narrow support results in falling backward. This modeling approach suggests that during trunk bending, two motion units--the hip and ankle eigenmovements--are responsible for the movement and for equilibrium maintenance, respectively.

Biomechanical Phenomena↗

PubMed2001

Biomechanical analysis of movement strategies in human forward trunk bending. II. Experimental study.

The large mass of the human upper trunk, its elevated position during erect stance, and the small area limited by the size of the feet, stress the importance of equilibrium control during trunk movements. The objective of the present study was to perform a biomechanical analysis of fast forward trunk movements in order to understand the coordination between movement and posture. The analysis is based on a comparison between experimentally observed bending and hypothetical "optimal bending" performed on an infinitely narrow support, as presented in a companion paper. The experimental data were obtained from 16 subjects who performed fast forward bending while standing on a wide platform or on a narrow beam. The analysis is performed by decomposition of the movement into three dynamically independent components, each representing a movement along one of the three eigenvectors of the motion equation. The eigenmovements are termed "hip", "ankle", and "knee" eigenmovements, according to the dominant joint. The experimentally observed movement is characterized mainly by the hip and ankle eigenmovements, whereas the knee eigenmovement is negligible. Similarly to the "optimal bending" the ankle eigenmovement starts earlier and lasts longer than the hip eigenmovement. An early forward acceleration of the center of gravity in the ankle eigenmovement is caused by anticipatory changes in the ankle joint torque. This clarifies the role of the early tibialis anterior burst and/or soleus inhibition usually observed in electromyographic recordings during forward bending. The results suggest that the hip and the ankle eigenmovements can be treated as independently controlled motion units aimed at functionally different behavioral goals: the bending per se and postural adjustment. It is proposed that the central nervous system has to control these motion units sequentially in order to perform the movement and maintain equilibrium. It is also suggested that the hip and ankle eigenmovements can be regarded as a biomechanical background for the hip and ankle strategies introduced by Horak and Nashner (1986) on the basis of electromyographic recordings and kinematic patterns in response to postural perturbations.

Adult↗

PubMed2001

Assessment of the accuracy of a human arm model with seven degrees of freedom.

We are proposing a human arm model that consists of three rigid segments with seven degrees of freedom. The shoulder joint was modeled as a ball-and-socket joint and the elbow and wrist joints were modelled as skew-oblique joints. Optimal parameters for this model were calculated on the base of in vivo recordings with a spatial tracking system. The criterion of optimality was defined as the minimum of the mean-square deviation between the experimentally obtained sensor positions and orientations and their positions and orientations calculated by solving the direct kinematics problem. The minimal value of the direct kinematics error was found to be 0.5-0.6cm for sensor positions and 5-7 degrees for sensor orientations. We are proposing that these values serve as the assessment for the accuracy of the arm model.

Adult↗

PubMed2000

The envelope glycoprotein of simian immunodeficiency virus contains an enterotoxin domain.

By the use of a mouse model, the enteropathic effects of the simian immunodeficiency virus (SIV) surface unit (SU) envelope glycoprotein were explored. Purified SU (0.01-0.45 nmol) was administered intraperitoneally to 6- to 8-day-old mouse pups and induced a dose-dependent diarrheal response. Surgical introduction of SU into adult mouse intestinal loops revealed fluid accumulation without histological alterations and SU-treated unstripped intestinal mucosa induced chloride (Cl(-)) secretory currents in Ussing chambers. Similarly to rotavirus NSP4, the first described viral enterotoxin, SU induced a transient increase in intracellular calcium levels and increased inositol 1,4,5-triphosphate (IP(3)) levels in HT-29 cells. These data indicate the calcium response is mediated by IP(3). The presence of diarrhea and fluid accumulation within intestinal loops in the absence of histological alterations and induction of Cl(-) secretory currents demonstrate that SIV contains an enterotoxic domain localized within SU and is the second viral enterotoxin described.

Animals↗

PubMed2000

On the possibility of linear modelling the human arm neuromuscular apparatus.

It has been widely claimed that linear models of the neuromuscular apparatus give very inaccurate approximations of human arm reaching movements. The present paper examines this claim by quantifying the contributions of the various non-linear effects of muscle force generation on the accuracy of linear approximation. We performed computer simulations of a model of a two-joint arm with six monarticular and biarticular muscles. The global actions of individual muscles resulted in a linear dependence of the joint torques on the joint angles and angular velocities, despite the great nonlinearity of the muscle properties. The effect of time delay in force generation is much more important for model accuracy than all the non-linear effects, while ignoring this time delay in linear approximation results in large errors. Thus, the viscosity coefficients are rather underestimated and some of them can even be paradoxically estimated to be negative. Similarly, our computation showed that ignoring the time delay resulted in large errors in the estimation of the hand equilibrium trajectory. This could explain why experimentally estimated hand equilibrium trajectories may be complex, even during a simple reaching movement. The hand equilibrium trajectory estimated by a linear model becomes simple when the time delay is taken into account, and it is close to that actually used in the non-linear model. The results therefore provide a theoretical basis for estimating the hand equilibrium trajectory during arm reaching movements and hence for estimating the time course of the motor control signals associated with this trajectory, as set out in the equilibrium point hypothesis.

Arm↗

PubMed2000

Kinematics of human arm reconstructed from spatial tracking system recordings.

The kinematics of the human arm in terms of angles of rotations in the joints is reconstructed from the spatial tracking system (Fastrack() Polhemus) recordings. The human arm is modeled by three rigid bodies (the upper arm, the forearm and the hand) with seven degrees of freedom (three in the shoulder, two in the elbow and two in the wrist). Joint geometry parameters (orientations of the axes relative to the arm segments, the angles and the distances between the axes) have been calculated on the basis of passive rotations in the joints. The calculated parameters have been used to solve the direct kinematics problem for the reaching movements in different directions. The difference between calculated and recorded positions and accelerations of the hand has been used to assess the accuracy of the proposed method of kinematics reconstruction. The error analysis showed that spatial tracking system recordings and human arm kinematics reconstruction could reliably be used to accurately analyze multijoint movement in humans.

Adult↗

PubMed1999

Forearm postural control during unloading: anticipatory changes in elbow stiffness.

In this study, the equilibrium-point hypothesis of muscle-torque generation is used to evaluate the changes in central control parameters in the process of postural-maintenance learning. Muscle torque is described by a linear spring equation with modifiable stiffness, viscosity, and equilibrium angle. The stiffness is considered to be the estimation of the central command for antagonist-muscle coactivation and the equilibrium angle to be the estimation of the reciprocal command for a shift of invariant characteristics of the joint. In the experiments, a load applied to the forearm was released. The subjects were instructed to maintain their forearm in the initial horizontal position. Five sessions of approximately twenty trials each were carried out by eight subjects. During two "control" series, the load release was triggered by the experimenter. During three "learning" series, the load supported by one forearm was released by the subject's other hand. The elbow-joint angle, the angular acceleration, and the external load on the postural forearm were recorded. These recordings as well as anthropometric forearm characteristics were used to calculate the elbow-joint torque (which we called "experimental"). Linear regression analysis was performed to evaluate the equilibrium angle, joint stiffness, and viscosity at each trial. The "theoretical" torque was calculated using a linear spring equation with the found parameters. The good agreement observed between experimental and theoretical joint-torque time courses, apart from the very early period following unloading, argues in favor of the idea that the movement was mainly performed under a constant central command presetting the joint stiffness and the equilibrium angle. An overall increase in the stiffness occurred simultaneously with a decrease in the equilibrium angle during the "learning" series in all the subjects. This suggests that subjects learn to compensate for the disturbing effects of unloading by increasing the joint stiffness. The mechanism possibly responsible for the presetting of the central control parameters is discussed.

Cognition↗

PubMed1997

Fatty acid uptake in diabetic rat adipocytes.

The effect of diabetic status and insulin on adipocyte plasma membrane properties and fatty acid uptake was examined. Studies with inhibitors and isolated adipocyte ghost plasma membranes indicated 9Z, 11E, 13E, 15Z-octatetraenoic acid (cis-parinaric acid) uptake was protein mediated. Cis-parinaric acid uptake was inhibited by trypsin treatment or incubation with phloretin, and competed with stearic acid. The initial rate, but not maximal uptake, of cis-parinaric acid uptake was enhanced two-fold in adipocytes from diabetic rats. Concomitantly, the structure and lipid composition of adipocyte ghost membranes was dramatically altered. However, the increased initial rate of cis-parinaric acid uptake in the diabetic adipocytes was not explained by membrane alterations or by a two-fold decrease in cytosolic adipocyte fatty acid binding protein (ALBP), unless ALBP stimulated fatty acid efflux. Thus, diabetic status dramatically altered adipocyte fatty acid uptake, plasma membrane structure, lipid composition, and cytosolic fatty acid binding protein.

Adipocytes↗

PubMed1996

Acyl-CoA binding proteins: multiplicity and function.

The physiological role of long-chain fatty acyl-CoA is thought to be primarily in intermediary metabolism of fatty acids. However, recent data show that nM to microM levels of these lipophilic molecules are potent regulators of cell functions in vitro. Although long-chain fatty acyl-CoA are present at several hundred microM concentration in the cell, very little long-chain fatty acyl-CoA actually exists as free or unbound molecules, but rather is bound with high affinity to membrane lipids and/or proteins. Recently, there is growing awareness that cytosol contains nonenzymatic proteins also capable of binding long-chain fatty acyl-CoA with high affinity. Although the identity of the cytosolic long-chain fatty acyl-CoA binding protein(s) has been the subject of some controversy, there is growing evidence that several diverse nonenzymatic cytosolic proteins will bind long-chain fatty acyl-CoA. Not only does acyl-CoA binding protein specifically bind medium and long-chain fatty acyl-CoA (LCFA-CoA), but ubiquitous proteins with multiple ligand specificities such as the fatty acid binding proteins and sterol carrier protein-2 also bind LCFA-CoA with high affinity. The potential of these acyl-CoA binding proteins to influence the level of free LCFA-CoA and thereby the amount of LCFA-CoA bound to regulatory sites in proteins and enzymes is only now being examined in detail. The purpose of this article is to explore the identity, nature, function, and pathobiology of these fascinating newly discovered long-chain fatty acyl-CoA binding proteins. The relative contributions of these three different protein families to LCFA-CoA utilization and/or regulation of cellular activities are the focus of new directions in this field.

Animals↗

PubMed1996

Recent advances in membrane cholesterol domain dynamics and intracellular cholesterol trafficking.

Cholesterol is distributed nonrandomly in and between biological membranes. Despite over two decades' investigation of these phenomena, the origin, regulation, and function of membrane cholesterol asymmetry are not known. Likewise, although pathways of cellular cholesterol absorption/utilization as well as de novo synthesis have been investigated in depth, parallel progress in elucidating pathways of intracellular cholesterol trafficking and final deposition of cholesterol within membranes remains undefined. Understanding the nature and regulation of these processes is essential to resolving molecular mechanisms of cholesterol uptake, reverse cholesterol transport, steroidogenesis, and modulation of membrane function. Based on the fundamental observation that cholesterol is not distributed uniformly in the cell, three key concepts have contributed to recent advances in this field: First, cholesterol is asymmetrically distributed across the cell surface plasma membrane, wherein it translocates rapidly. Second, cholesterol is distributed within the plane of biomembrane bilayers into dynamic and static domains, with the latter predominating. The exact nature and physiological functions of such cholesterol domains or pools remain an enigma. Third, regulation of the size and kinetics of biomembrane cholesterol domains may be determining factors in intracellular cholesterol trafficking, targeting, and efflux. Contributions of both cytosolic carrier proteins and vesicular processes are recognized.

Animals↗

PubMed1992

The laws of delayed photohaemolysis sensitized by chlorin e6.

The relationships between the rate of post-irradiated photohaemolysis sensitized by chlorin e6 and parameters such as the light fluence (time of irradiation) and sensitizer concentration were studied. On the basis of the single-parametric approach proposed by Valenzeno and Pooler, it was found that the haemolytic rate varies with the square of both the light fluence and the sensitizer concentration. Thus it can be concluded that, in a single erythrocyte lesion, two chlorin e6 molecules participate, each absorbing one photon. The possibility of suppression of post-irradiation haemolysis was also studied using the lipophilic antioxidant, butylated hydroxytoluene (BHT), and scavengers of 1O2, O2.- and HO. radicals. It was found that BHT inhibits, to a considerable extent, the post-irradiation lysis of cells, by about a factor of 2.5 at a BHT concentration of 9 microM. The addition to the medium of NaN3 (a scavenger of 1O2), superoxide dismutase (a scavenger of O2.- radicals), ethanol and D-mannitol (scavengers of HO. radicals), when irradiation was interrupted, did not produce a marked influence on the kinetics of subsequent haemolysis. On the basis of the results obtained, the nature of erythrocyte targets, which are crucial for the photodynamic effect of chlorin e6, is discussed.

Biological Transport↗

PubMed1991

[The physicochemical evaluation of the bile using infrared spectroscopy].

Native bile, inspissated bile, and cholesterol choleliths were examined by infrared spectroscopy. Model compounds spectra were compared with native bile spectra. The spectra were divided into 3 groups: with acid fragments or cholesterol groups predominating and intermediate group. The peak of 3620 cm-1, absent in normal human bile and liable to augment if acid fragment level reduced was detected. The authors suggest a technique of infrared spectroscopy permitting early detection of disordered physicochemical characteristics of the bile in the course of cholesterol cholelithiasis development.

Bile↗

PubMed1990

Chlorin e6-liposome interaction. Investigation by the methods of fluorescence spectroscopy and inductive resonance energy transfer.

On the basis of spectral fluorescence and polarization measurements and results obtained on the luminescence quenching of the membrane fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) by incorporated chlorin e6 (chl e6) molecules, it is shown that the interaction of the water-soluble pigment with smaller unilamellar lipid vesicles occurs by a mechanism of partition between the aqueous and lipid phases (partition coefficient Kp = 6.7 x 10(3) and provides rigid fixing of chl e6 monomers at the boundary between the polar and non-polar parts of the lipid membrane. In terms of inductive resonance electronic excitation energy transfer between DPH and chl e6 (R0 = 36.2 A), we have analysed data on DPH fluorescence quenching under different conditions of chl e6 localization in the lipid bilayer and have concluded that the incorporation of the pigment molecules into the vesicles from the aqueous phase occurs mainly into the external monolayer.

Chlorophyllides↗