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Biomedical subjects

A V Sokolov

Publications and source records attributed to A V Sokolov.

At least 19 recordsLinked to original sources

Interaction of pyridinium bis-retinoid (A2E) with bilayer lipid membranes.

The accumulation of lipofuscin granules within the retinal pigment epithelium (RPE) cells is correlated with the progression of age-related macular degeneration. One of the fluorophores contained in lipofiscin granules is pyridinium bis-retinoid (A2E). To test its membrane-toxic effect, the interaction of A2E with bilayer lipid membranes (BLM) was studied. The incorporation of charged A2E molecules into the membranes has been detected as a change of either zeta-potential of multilayer liposomes or boundary potential of BLM. It was shown that the presence of up to 25mol% of A2E did not destabilize the bilayers made of saturated phosphatidylcholine (PC). However, the destabilizing effect became very significant when BLM contained negatively charged lipids such as cardiolipin or phosphatidylserine. The electrical breakdown measurements revealed that the A2E-induced decrease of BLM stability was primarily associated with the growing probability of lipid pore formation. It was found from the measurements of boundary potential of BLM that exposure of A2E to light initiates its transformation into at least two products. One of them is epoxy-A2E, which, being hydrophilic, moves from the membrane into water solution. The other product is a non-identified hydrophobic substance. Illumination of A2E-containing BLM made from unsaturated PC by visible light caused the membrane damage presumably due to oxidation of these lipids by singlet oxygen generated by excited A2E molecules. However, this effect was very weak compared to the effect of known photosensitizers. The illumination of BLM with A2E also leads to the damage of gramicidin incorporated into the membrane, as was detected by measuring the conductance of channels formed by this peptide.

Electrochemistry↗

Patterns and inventories of radioactive contamination of island sites of the Yenisey River, Russia.

The distribution of radioactive contamination at three island sites downstream from the Krasnoyarsk Mining and Chemical Combine (KMCC) was studied with the objectives of mapping contamination levels, interpreting radionuclide distributions through consideration of alluvial processes and determining radionuclide inventories. Contamination was measured using in situ gamma spectrometry and landforms characterised using topographic surveying methods. Maximum (137)Cs contamination densities (700 kBq m(-2)) were found on low- and middle-level floodplains and low-lying interconnecting areas of Beriozovy Island (16 km from the KMCC). On Mikhin Island (180 km from the KMCC) maximum total (60)Co, (152)Eu and (154)Eu activity concentrations (30-40 kBq m(-2)) occur in low-lying areas inundated during flooding. Maximum (137)Cs and total (60)Co, (152)Eu and (154)Eu contamination densities on Cheriomukhov Island (250 km from the KMCC) were 390 and 50 kBq m(-2), respectively. Estimated (137)Cs inventories were 145, 148 and 16GBq for Beriozovy, Mikhin and Cheriomukhov Islands, respectively.

Cesium Radioisotopes↗

Identification and isolation from breast milk of ceruloplasmin-lactoferrin complex.

The presence of a complex of the copper-containing protein ceruloplasmin (Cp) with lactoferrin (Lf) in breast milk (BM) is shown for the first time. In SDS-free polyacrylamide gel electrophoresis (PAGE), electrophoretic mobility of Cp in BM is lower than that of plasma Cp, coinciding with the mobility of the complex obtained upon mixing purified Cp and Lf. Affinity chromatography of delipidated BM on Cp-Sepharose resulted in retention of Lf. SDS-PAGE of the 0.3 M NaCl eluate revealed a single band with Mr approximately 78,000 that has the N-terminal amino acid sequence of Lf and reacts with antibodies to that protein. Synthetic peptides R-R-R-R (the N-terminal amino acid stretch 2-5 in Lf) and K-R-Y-K-Q-R-V-K-N-K (the C-terminal stretch 29-38 in PACAP 38) caused efficient elution of Lf from Cp-Sepharose. Cp-Lf complex from delipidated BM is not retained on the resins used for isolation of Cp (AE-agarose) and of Lf (CM-Sephadex). Anionic peptides from Cp--(586-597), (721-734), and (905-914)--provide an efficient elution of Cp from AE-agarose, but do not cause dissociation of Cp-Lf complex. When anti-Lf is added to BM flowed through CM-Sephadex, Cp co-precipitates with Lf. Cp-Lf complex can be isolated from BM by chromatography on CM-Sephadex, ethanol precipitation, and affinity chromatography on AE-agarose, yielding 98% pure complex. The resulting complex Cp-Lf (1 : 1) was separated into components by chromatography on heparin-Sepharose. Limited tryptic hydrolysis of Cp obtained from BM and from blood plasma revealed identical proteolytic fragments.

Ceruloplasmin↗

[Effect of blood pressure on the plasma renin-angiotensin system].

The relationship of systolic and diastolic blood pressure (BP) to the peripheral blood renin-angiotensin system (RAS) has been examined. BP has found to be inversely related to the concentration and activity of plasma RAS components. It has been shown that angiotensin-converting enzyme (ACE) affects BP more greatly than do other plasma RAS components. It is suggests that RAS activation or depression is an adjustment to BP elevation or lowering. Altered BP triggers the biochemical mechanisms responsible for regulating vascular tone, cardiac output, and water-salt balance. All RAS components under study show a weak association with BP in some patients. It is concluded that the laboratory plasma RAS test is of low informative value in diagnosing hypertension and hypotension in clinical practice.

Adult↗

Effect of lactoferrin on the ferroxidase activity of ceruloplasmin.

The effects of various forms of lactoferrin (Lf) interacting with ceruloplasmin (Cp, ferro-O2-oxidoreductase, EC 1.16.3.1) on oxidase activity of the latter were studied. Comparing the incorporation of Fe3+ oxidized by Cp into Lf and serum transferrin (Tf) showed that at pH 5.5 apo-Lf binds the oxidized iron seven times and at pH 7.4 four times faster than apo-Tf under the same conditions. Apo-Lf increased the oxidation rate of Fe2+ by Cp 1.25 times when Cp/Lf ratio was 1 : 1. Lf saturated with Fe3+ or Cu2+ increased the oxidation rate of iron 1.6 and 2 times when Cp to holo-Lf ratios were 1 : 1 and 1 : 2, respectively. Upon adding to Cp the excess amounts of apo-Lf (Cp/apo-Lf < 1 : 1) or of holo-Lf (Cp/holo-Lf < 1 : 2) the oxidation rate of iron no longer changed. Complex Cp-Lf demonstrating ferroxidase activity was discovered in breast milk.

Apoproteins↗

[Effects of hyper- and dyslipidemias on activity of angiotensin-converting enzyme (biochemical disturbances in metabolic syndrome)].

AIM: To study influence of lipoprotein complexes on activity of angiotensin-converting enzyme (ACE). Material and methods. Lipoproteins fraction was isolated from the serum of 53 healthy males and females and was studied for lipoproteins action on ACE in vitro. In addition, the examination covered 783 individuals. The data were analysed mathematically for relationships between ACE activity and parameters of lipid metabolism. RESULTS: It was found that blood serum lipoproteins inhibit activity of soluble ACE. Serum ACE activity depends on concentration of total cholesterol (TC) and triglycerides. Maximal activity of ACE is observed in TC 9.41 mM/l and TG concentration 3.05 mM/l. Albumin-related free fatty acids affect ACE activity neither in aqueous solution nor in the presence of lipoprotein complexes. CONCLUSION: . Development of most common atherogenic hyperlipidemias raises 2-fold plasma ACE activity. Elevated ACE activity may be an integral component of biochemical disturbances in metabolic syndrome.

Adult↗

Frequency parameters of feline left ventricular pressure under various experimental conditions.

Cardiac frequency-domain parameters of the left ventricular pressure were studied in acute experiments on cats under conditions of reflex and load stimulation and during maximum inotropic stimulation with epinephrine. A strict correlation was revealed between the upper threshold of the frequency range and the maximum value of pressure first derivative. Without epinephrine infusion, the maximum value of pressure first derivative and the upper threshold of the frequency range attained 9840 mm Hg/sec and 98.4 Hz, correspondingly. During epinephrine infusion, the corresponding values were 12911 mm Hg/sec and 145 Hz. Left ventricular pressure in cats is characterized by high-frequency parameters, which can be measured by special catheter microtransducers and only in some cases by routine pressure gauges.

Animals↗

Nonparametric population modeling of valproate pharmacokinetics in epileptic patients using routine serum monitoring data: implications for dosage.

Therapeutic drug monitoring (TDM) of valproate (VAL) is important in the optimization of its therapy. The aim of the present work was to evaluate the ability of TDM using model-based, goal-oriented Bayesian adaptive control for help in planning, monitoring, and adjusting individualized VAL dosing regimens. USC*PACK software and routine TDM data were used to estimate population and individual pharmacokinetics of two commercially available VAL formulations in epileptic adult and pediatric patients on chronic VAL monotherapy. The population parameter values found were in agreement with values reported earlier. A statistically significant (P < 0.001) difference in median values of the absorption rate constant was found between enteric-coated and sustained-release VAL formulations. In our patients (aged 0.25-53 years), VAL clearance declined with age until adult values were reached at about age 10. Because of the large interindividual variability in PK behavior, the median population parameter values gave poor predictions of the observed VAL serum concentrations. In contrast, the Bayesian individualized models gave good predictions for all subjects in all populations. The Bayesian posterior individualized PK models were based on the population models described here and where most patients had two (a peak and a trough) measured serum concentrations. Repeated consultations and adjusted dosage regimens with some patients allowed us to evaluate any possible influence of dose-dependent VAL clearance on the precision of total VAL concentration predictions based on TDM data and the proposed population models. These nonparametric expectation maximization (NPEM) population models thus provide a useful tool for planning an initial dosage regimen of VAL to achieve desired target peak and trough serum concentration goals, coupled with TDM soon thereafter, as a peak-trough pair of serum concentrations, and Bayesian fitting to individualize the PK model for each patient. The nonparametric PK parameter distributions in these NPEM population models also permit their use by the new method of 'multiple model' dosage design, which allows the target goals to be achieved specifically with maximum precision. Software for both types of Bayesian adaptive control is now available to employ these population models in clinical practice.

Adolescent↗

[Lipoproteins of blood serum and the activity of angiotensin-converting enzyme].

We studied the influence of native lipoproteins on the activity of the angiotensin-converting enzyme (ACE). Lipoproteins of blood serum were inhibiting the activity of soluble ACE. The ACE activity in blood serum was found to depend on a concentration of total cholesterol and of triglycerides. The maximal ACE activity was observed at a concentration of total cholesterol of 9.41 mM/l and at a concentration of triglycerides of 3.05 mM/l. The albumin-linked non-etherified fatty acids affected the ACE activity neither in water solutions nor in presence of lipoprotein complexes. According to the study, the progression of most frequent atherogenic hyperlipidemia results in a 2-fold increase of the ACE activity. It is suggested that an intensified ACE activity in blood plasma can be regarded as an integral component of biochemical disorders in metabolic syndrome.

Algorithms↗

Whether independent regulation of myocardial contractility and diastolic relaxation rate is possible?

In acute experiments on cats neural inotropic and lusitropic reactions of the heart to enhancement of pre- and afterload were assessed by changes in contractility and relaxation indices, which were preliminary chosen for their maximum specificity and sensitivity. The control cardiac responses to increased pre- and afterload were measured after treatment with ganglionic blocker arfonad. The myogenic component of these responses assessed under the action of arfonad was highly pronounced, therefore the neural inotropic and lusitropic reactions were measured as the difference between load-induced changes of indices in experiments with and without arfonad. Increased preload produced similar negative inotropic and lusitropic effects, while increased afterload produced a more pronounced negative inotropic effect, which indicated independent regulation of contractility and diastolic relaxation of the heart.

Animals↗

FAST CARS: engineering a laser spectroscopic technique for rapid identification of bacterial spores.

Airborne contaminants, e.g., bacterial spores, are usually analyzed by time-consuming microscopic, chemical, and biological assays. Current research into real-time laser spectroscopic detectors of such contaminants is based on e.g., resonance fluorescence. The present approach derives from recent experiments in which atoms and molecules are prepared by one (or more) coherent laser(s) and probed by another set of lasers. However, generating and using maximally coherent oscillation in macromolecules having an enormous number of degrees of freedom is challenging. In particular, the short dephasing times and rapid internal conversion rates are major obstacles. However, adiabatic fast passage techniques and the ability to generate combs of phase-coherent femtosecond pulses provide tools for the generation and utilization of maximal quantum coherence in large molecules and biopolymers. We call this technique FAST CARS (femtosecond adaptive spectroscopic techniques for coherent anti-Stokes Raman spectroscopy), and the present article proposes and analyses ways in which it could be used to rapidly identify preselected molecules in real time.

Kinetics↗

Identification and characterization of serum protein in patients with ovarian cancer.

A 36 kDa protein was isolated from the sera of patients with ovarian cancer and rabbit antisera to this protein were prepared. Precipitation test with these antisera detected an antigen with electrophoretic mobility corresponding to alpha-1-globulins and molecular weight of 36 kDa. Direct comparison of precipitating test systems showed that this antigen is not identical to the known carcinoembryonic, placental, and reactive proteins. Serum alpha-1-globulin was not detected in the sera of healthy humans, pregnant women, newborns, and in human adult and fetal visceral tissues at the level of precipitating test system sensitivity 1 mg/liter. It was detected in the sera of patients with ovarian cancer, in ovarian tumor (cancer) tissues, in the contents of ovarian tumor cavities, and in concentrated specimens of amniotic fluid. The antigen was not detected in ascitic fluid of patients with ovarian cancer, but it was present in 75% serum samples from these patients. The antigen was called serum oncoovarian alpha-1-globulin. SDS-PAAG electrophoresis showed that this antigen is an oligomer consisting of subunits (monomers) with molecular weight of 36 kDa. Under denaturing conditions in the presence of 2-mercaptoethanol these monomers dissociate into polypeptide chains with a molecular weight of 18 kDa. The protein is liable to oligomerization. Comparative characteristics of serum oncoovarian alpha-1-globulin and CA-125 antigen are presented.

Adenocarcinoma↗

[Pharmacokinetic aspects of carbamazepine and valproic acid using in reproductive-age women with epilepsy].

Dynamics of carbamazepine and valproic acid concentrations in the middle of follicular and lutein menstrual cycle phases has been studied in women with epilepsy, aged 21-30 years. Nineteen patients were treated with valproic acid (Depakine 900-2000 mg/day), 35--with carbamazepine (500-1200 mg/day). All the patients have been treated during at least 6 months, the remission being observed during the last 3 months. Control group consists of 17 healthy age-matched women with no positive familial history of nervous and endocrine diseases. Carbamazepine and valproic acid concentrations were measured in blood serum using high-performance liquid chromatography. Blood for analysis was donated on an empty stomach in the morning before the next dose (i.e. at the lowest concentration) and two hours after the drug taking. Mean carbamazepine concentrations (4-12 mcg/ml) in the women with epilepsy were adequate when the day dose was more than 10 mg/kg. Carbamazepine concentrations during lutein phase were significantly lower (p < 0.03), comparing to those in the follicular phase. However, in the lutein phase, progesterone, which concentration was ten times higher is follicular one, has an additional effect, acting as anticonvulsive agent. Valproic acid concentrations do not significantly differ in the lutein and follicular phases that allows Depakine using in catamenial epilepsy. Practitioners are not recommended to overestimate the anti-epileptic drug (AED) concentration monitoring because the usage of the lower AED individual therapeutic dose, not achieving even the mean therapeutic drug concentrations, is acceptable. This seems to be of extremely importance for women with potential maternal role function.

Adult↗

[Impact of transrectal microwave hyperthermia on hemodynamics and prostatic cell membranes in chronic prostatitis].

An Aden-Ch apparatus programming complex made in our country was used for transrectal microwave hyperthermia in 75 patients with chronic prostatitis. In addition to its good clinical results achieved in most patients, the complex restored hemodynamics and stabilized the status of prostatic cell membranes. The complex described in the paper may be recommended for the treatment of chronic prostatitis.

Adult↗

Femtosecond light source for phase-controlled multiphoton ionization.

We describe a femtosecond Raman light source with more than an octave of optical bandwidth. We use this source to demonstrate phase control of multiphoton ionization under conditions where ionization requires eleven photons of the lowest frequency of the spectrum or five photons of the highest frequency. The nonlinearity of the photoionization process allows us to characterize the light source. Experiment-to-theory comparison implies generation of a near single-cycle waveform.

Journal Article↗

Effect of intravenous injection of DAGO on neuronal activity in bulbar cardiovascular center.

Effects of intravenous injection of DAGO on impulse neuronal activity of the bulbar cardiovascular center were studied in acute experiments on cats narcotized with Nembutal. DAGO-induced changes in activity of sensory neurons and interneurons were unidirectional and preceded hemodynamic shifts. The antiarrhythmic effect of DAGO is due to its direct action on neurons of the bulbar cardiovascular center.

Analgesics, Opioid↗

Contraction and relaxation indices in the study of neural inotropic and loositropic influences on the heart.

The possibility of using contraction and relaxation indices for evaluation of inotropic and loositropic influences on the heart was studied in experiments on cats. Increased pre- and afterload were used as the stimuli, which are simultaneously loading and reflexogenic. Under conditions of preserved innervation both stimuli elevated the indices selected according to the highest sensitivity/specificity ratio. Ganglionic blocker arfonad potentiated the effects of these stimuli. This attests to a considerable contribution of the myogenic component to the changes in the studied indices in response to increased pre- and afterload and to the existence of negative inotropic and loositropic influences on the heart under conditions of preserved innervation. These conclusions were supported when more specific indices were used: in most cases they decreased during load tests. Thus, when the contraction and relaxation indices are used for evaluation inotropic and loositropic influences on the heart, it seems reasonable either to compare heart responses under conditions of preserved or blocked innervation, or to apply more specific indices. Analysis of changes in most widely used indices (dP/dt)max and t showed that t reliably reflects neural loositropic influences, while the use of (dP/dt)max without proper control can be erroneous.

Animals↗

Comparison of different cardiac relaxation indices.

Sensitivity (response to epinephrine infusion) and specificity (response to changes in pre- and afterload) of some cardiac relaxation indices were compared in acute experiments on cats treated with ganglionic blocker arfonad. Some new indices proposed by us provide better characteristics than widely used relaxation time constant (t) and maximum first derivative of the left ventricular pressure (-dP/dt)max.

Animals↗