[The sanitary constitution and somatic status of students on territory of the Privolzhye Federal Okrug].

The features of sanitary constitution of students of the Nizhniy Novgorod region related to gradation of intra-group somatologic characteristics are presented. The results of anthropometric screening of 10 400 students of the Nizhniy Novgorod Oblast (boys/girls 5100/5300) aged 7-17 years were analyzed; body types were evaluated according to the Darskaya S. S. methodology; biological age - according to the Maximova T. M. methodology; physical development groups - according to the Baranov A. A. and Kuchma V. R. methodology. The typology was considered in formation of age and gender groups. They intra-group statistical analysis was implemented. The patterns of somatotyping were established. In boys/girls main types were thoracic type 58.9/67.3%, muscular - 21.6/17.4%, asthenoid - 9.1/8.2%, digestive - 7.3/8.3% and indefinite - 3.1/3.2%. The age factor significantly (p < 0.05) modifies dynamics of distributions of somatic types. The significant (p < 0.01) heterogeneity on the factor of biological maturation level was demonstrated in 66.0/68.6% of biological age corresponded to passport age, lag in 19.7/15.3%, advance in 14.3/16.1%. The decelerating ones in 30.9% of cases demonstrated thoracic somatotype with a single occurrence of asthenoid body type. In pre- and post-puberty individuals with thoracic somatotype in 57.0% had passport age that corresponded to biological age. For children with advanced type thoracic and muscular body types are specific and the digestive somatotype is specific only to advanced type (p = 0.01). The body typologies in combination with levels of biological development individualize characteristics of growing organism. The rate of maturation decreases its informative significance in post-puberty period. The individuals with different somatotypes are characterized by intra-group morphofunctional features.

Identification of Neurophysiological Markers of Verbal Information Processing Using Cognitive Evoked Potentials for Studying Schizophrenia Spectrum Disorders.

The aim of the study is to identify neurophysiological markers of information processing sensitive to verbal thinking impairment in persons with schizotypal personality organization using the method of cognitive evoked potentials. Materials and Methods: Cognitive evoked potentials were studied in 40 students of higher school with high and low (control) scores obtained on the Schizotypal Personality Questionnaire (SPQ) in response to the presentation of visual verbal information in the form of agreed word-combinations. In the first series of presentations, it was necessary to refer the attribute to one of the categories and to read the noun silently (non-target condition). In the second series, the attribute should be read silently, and then the following noun has to be categorized (target condition). There has been performed a cluster analysis of the evoked potential curves obtained in response to the noun presentation in the target and non-target conditions in the groups of participants with high and low scores gained on SPQ. Results: Processing of the verbal stimulus under passive reading conditions and under the conditions of word categorization within the frameworks of a simple context has shown that in the group with low scores on the schizotypal questionnaire, lateralization of the N150 component to the left side was observed in contrast to the group with high scores. In this group, increase of the N400 component amplitude was found in response to the words presented for their passive reading in comparison with the categorization condition. On the contrary, in the group with high schizotypy scores, the N400 component appeared to be insensitive to the type of the task, i.e. neurophysiological differences were not expressed between reading and performing stimuli categorization task. These persons were found to have the decreased amplitude of the late positive component as compared to the control group under the condition of passive reading of the words. Increase of the late negative wave amplitude was registered in response to the target words subjected to categorization in comparison with reading in both groups of participants. Insufficiency of language lateralization and deficit connected with the language networks being activated automatically at the initial stage of word recognition are observed in the examined persons with schizotypy. Additionally, processing of the information in these persons at the stage of lexical-semantic processes is weakly modulated by the task imposing different requirements on the level of mental activity control. Some reduction of mnestic process activation is also possible, which is manifested during passive reading of the words, but not in the conditions of their categorization. Conclusion: The research conducted may serve as a starting point for a more detailed and long-term study of the fundamental mechanisms of impairment in information processing in the course of clinically evident pathology formation. In the applied aspect, the work may be considered as a contribution to the ongoing search for neurophysiological markers for early diagnosis of schizophrenia spectrum disorders.

A Method for Recording the Bioelectrical Activity of Neural Axons upon Stimulation with Short Pulses of Infrared Laser Radiation.

The aim of the study was to develop a method for long-term non-invasive recording of the bioelectrical activity induced in isolated neuronal axons irradiated with short infrared (IR) pulses and to study the effect of radiation on the occurrence of action potentials in axons of a neuron culture in vitro. MATERIALS AND METHODS: Hippocampal cells of mouse embryos (E18) were cultured in microfluidic chips made of polydimethylsiloxane and containing microchannels for axonal growth at a distance of up to 800 µm. We studied the electrophysiological activity of a neuronal culture induced by pulses of focused laser radiation in the IR range (1907 and 2095 nm). The electrophysiological activity of the neuronal culture was recorded using a multichannel recording system (Multi Channel Systems, Germany). RESULTS: The developed microfluidic chip and the optical stimulation system combined with the multichannel registration system made it possible to non-invasively record the action potentials caused by pulsed IR radiation in isolated neuronal axons in vitro. The propagation of action potentials in axons was detected using extracellular microelectrodes when the cells were irradiated with a laser at a wavelength of 1907 nm with a radiation power of 0.2-0.5 W for pulses with a duration of 6 ms and 0.5 W for pulses with a duration of 10 ms. It was shown that the radiation power positively correlated with the occurrence rate of axonal response. Moreover, the probability of a response evoked by optical stimulation increased at short optical pulses. In addition, we found that more responses could be evoked by irradiating the neuronal cell culture itself rather than the axon-containing microchannels. CONCLUSION: The developed method makes it possible to isolate the axons growing from cultured neurons into a microfluidic chip, stimulate the neurons with infrared radiation, and non-invasively record the axonal spiking. The proposed approach allowed us to study the characteristics of neuronal responses in cell cultures over a long (weeks) period of time. The method can be used both in fundamental research into the brain signaling system and in the development of a non-invasive neuro-interface.

Prognostic Value of Investigating Neuron-Specific Enolase in Patients with Ischemic Stroke.

The aim of the study was to assess the prognostic value of the plasma neuron-specific enolase (NSE) level as a predictor of functional outcome and motor function recovery in the acute period of ischemic stroke (IS). Materials and Methods: Fifty patients with IS have been examined. On admission to the hospital and at 12-14 days after stroke onset, a clinical and neurological examination have been carried out with the supplementary quantitative assessment of neurological deficit severity according to the National Institutes of Health Stroke Scale (NIHSS), functional outcome according to the Modified Rankin Scale, and Rivermead Mobility Index. Enzyme immunoassay was used to determine NSE concentration in blood plasma in the acute period of the disease. Results: The NSE level in patients' blood plasma in the first 48 h after stroke onset positively correlates with the ischemic focus volume (r=0.49; p=0.003) and the severity of neurological symptoms (according to NIHSS) (r=0.33; p=0.02). NSE less than 2 ng/ml in the acute disease period is a predictor of good functional outcome 12-14 days after stroke onset (OR=12.4; р=0.006). The NSE level >2.6 ng/ml is associated with a high likelihood of lethal outcome.Neurological deficit below 15 according to NIHSS as well as the NSE level <2 ng/ml in the acute IS period are estimated as prognostic factors of significant recovery of motor function at 2 weeks after disease onset (OR=5.8; р=0.02). Conclusion: Determination of NSE in blood plasma makes it possible to predict functional outcome of the disease development and the recovery of motor function in patients with IS.

Choosing the Optimal Rat Stock as a Model for Research into Pharmacological Correction of Male Sexual Dysfunction.

The aim of the study is to identify the mechanisms mediating differences in sexual behavior between Sprague Dawley and Wistar rats, in order to choose the optimal stock for research into pharmacological correction of male sexual dysfunction. Materials and Methods: The experiments were carried out on sexually mature male rats of two stocks (Sprague Dawley and Wistar) weighing 350-450 g and aged 3 to 6 months. The comparative study of animal behavior was performed using standard tests for social interaction, locomotor activity, and anxiety level, as well as male mating behavior patterns. In order to determine the role of hypothalamic glycine receptors in the male sexual behavior, pharmacological manipulations of glycine receptor activity during mating with receptive females were conducted via bilateral intracerebral microcannulas implanted in the medial preoptic area (mPOA) of the male rat anterior hypothalamus. Results: The obtained results revealed statistically significant inter-stock differences in sexual behavior at the final consummatory stage of both intact animals and those after pharmacological activation of glycine receptors in the mPOA. The number of anxiety-related grooming patterns in the Open Field test significantly differed between the stocks for both intact animals and those after pharmacological activation of glycine receptors; the observed differences disappeared after the mPOA glycine receptors were blocked. In the Crowley test of social interaction, no significant difference was found between the stocks.Thus, the revealed difference in sexual behavior between Sprague Dawley and Wistar male rats is likely due to the difference in the level of anxiety, which, in turn, may be associated with difference in the mechanisms of glycinergic neurotransmission in the hypothalamic mPOAs of these rats. Conclusion: To study the relationship between the level of anxiety and sexual behavior, the choice of the Wistar rat stock is optimal since the male sexual behavior in this stock is more sensitive to stress than that in Sprague Dawley rats. However, to model male sexual dysfunction not associated with anxiety, the use of Sprague Dawley male rats should be preferred as these animals show more stable sexual behavior, which is less dependent on the level of anxiety.

Effect of Mechanical Stretching of the Right Atrium of Isolated Rat Heart on Dispersion of Repolarization before Fibrillation.

The multi-electrode mapping method was used to analyze electrical activity of isolated rat heart under conditions of standard perfusion, pharmacological stimulation of fibrillation, and mechanical stretching of the right atrium both under normal conditions and before cardiac fibrillation. It was shown that stretching of the right atrium prevented the increase of repolarization dispersion and latency of the electrical signal in the myocardium that were observed before cardiac fibrillation.

Effects of Glycine Receptors of the Medial Preoptic Nucleus on Sexual Behavior of Male Wistar Rats.

We studied the effect of bilateral microinjections of selective pharmacological agents modulating glycine receptor activity into the medial preoptic nucleus on sexual behavior of male Wistar rats. Application of the glycine receptor blocker strychnine (20 µM, 2 µl) led to a significant inhibition of both appetitive and consummatory components of sexual behavior, whereas stimulation with glycine (1 mM and 50 µM, 2 µl) had no significant effect.

A New Cofilin-Dependent Mechanism for the Regulation of Brain Mitochondria Biogenesis and Degradation.

The aim Was to study the role of post-translational modifications of cofilin in the regulation of respiration and autophagy in murine brain mitochondria. MATERIALS AND METHODS: The experiments were performed with C57BL/6 mice. To obtain cytoplasmic and mitochondrial fractions of the brain tissue, differential centrifugation was used. Expressions of cofilin, phospho-cofilin, K48- and K63-associated chains of ubiquitin, and the autophagy marker LC3B were determined using electrophoresis, immunoprecipitation and Western blot methods. To study the processes of ubiquitination, we used PR619 - the inhibitor of deubiquitinating enzymes. Respiratory activity of brain mitochondria was evaluated using high-resolution fluorespirometry. RESULTS: Modification of cofilin by non-canonical K63 multiubiquitin chains in the cytoplasm and mitochondria from murine brain was demonstrated. Different levels of phospho-cofilin, cofilin, and its ubiquitinated proteoforms were found. PR619, the inhibitor of deubiquitinating enzymes, affects the expression of phosphorylated and ubiquitinated forms of cofilin in the mitochondria and cytoplasm, at the same time it changes the activity of tissue respiration and mitophagy. CONCLUSION: The sensitivity of cofilin to the inhibitor of deubiquitinating enzymes indicates the existence of a new non-catabolic mechanism of cofilin modification, which may be involved in the regulation of mitochondrial functions, specifically, the mitochondrial respiration and autophagy. The data help understand the molecular mechanisms of mitochondrial function in normal and pathological conditions, which may be useful in developing novel methods for the treatment of diseases of the nervous system.

Formation of Neural Networks in 3D Scaffolds Fabricated by Means of Laser Microstereolithography.

We developed and tested new 3D scaffolds for neurotransplantation. Scaffolds of predetermined architectonic were prepared using microstereolithography technique. Scaffolds were highly biocompatible with the nervous tissue cells. In vitro studies showed that the material of fabricated scaffolds is not toxic for dissociated brain cells and promotes the formation of functional neural networks in the matrix. These results demonstrate the possibility of fabrication of tissue-engineering constructs for neurotransplantation based on created scaffolds.

Antihypoxic and Neuroprotective Effects of Glial Cell-Derived Neurotrophic Factor (GDNF) in Cultures of Dissociated Hippocampal Cells under Conditions of Experimental Hypoxia.

We analyzed the effect of glial cell derived neurotrophic factor (GDNF) on changes in functional bioelectric and calcium activity in dissociated hippocampal cell cultures under conditions of modeled acute normobaric hypoxia in vitro. GDNF (1 ng/ml) partially neutralized the negative effects of hypoxia on cell survival and parameters of functional network activity. GDNF exhibited a pronounced anti-hypoxic effect.

[Compatibility of cells of the nervous system with structured biodegradable chitosan-based hydrogel matrices].

Hydrogel matrices for cell cultivation have been generated by two-photon laser polymerization of unsaturated chitosan derivatives and methacrylated hyaluronic acid. The adhesive and toxic properties of the matrices have been assessed, and the matrices have been shown to have a good compatibility with primary hippocampal cell cultures. The formation of morphologically normal neural networks by cells of the nervous system cultured on the surface of hydrogel matrices has been observed. The metabolic status of dissociated hippocampal cells cultured on the matrices was similar to that of the control cultures, as shown by the results of MTT reductase activity assay. Thus, matrices based on unsaturated polysaccharide derivatives crosslinked by laser irradiation showed good compatibility with differentiated cells of the nervous system and considerable potential for use in neurotransplantation.

Effect of N-arachidonoyl dopamine on activity of neuronal network in primary hippocampus culture upon hypoxia modelling.

We studied the effect of endocannabinoid N-arachidonoyl dopamine on spontaneous bioelectric activity of cultured hippocampal neurons in a model of hypoxia/reoxygenation. Incubation under hypoxic conditions induced irreversible decrease in spontaneous bioelectric activity of neurons and their death. Application of N-arachidonoyl dopamine during hypoxia and in the post-hypoxic period preserved bioelectric activity and viability of neurons. The protective effect of N-arachidonoyl dopamine was primarily mediated by type I cannabinoid receptors.

[Relative bioavailability of glucosamine after oral, intramuscular and transdermal administration of hondroxid maximum preparation in experiment].

A comparison of the relative bioavailability and intensity of penetration of glucosamine sulfate in oral, injection and topical administration of the dosage form Hondroxid Maximum as a cream containing micellar system for transdermal delivery of glucosamine in the experiment by Sprague-Dawley rats was carried out. On the base on the pharmacokinetic profiles data of glucosamine in rat blood plasma with daily administration in 3 times a day for 1 week by cream Hondroxid Maximum 400 mg/kg and the single injection solution of 4% Glucosamine sulfate 400 mg/kg was found that the relative bioavailability was 61.6%. Calculated penetration rate of glucosamine in the plasma through the rats skin in 4 hours, equal to 26.9 µg/cm2 x h, and the penetration of glucosamine through the skin into the plasma after a single dose of cream in 4 hours was 4.12%. Comparative analysis of literature and experimental data and calculations based on them suggest that medicine Hondroxid Maximum, cream with transdermal glucosamine complex in the treatment in accordance with the instructions can provide an average concentration of glucosamine in the synovial fluid of an inflamed joint in the range (0.7 - 1.5) µg/ml, much higher than the concentration of endogenous glucosamine human synovial joint fluid (0.02 - 0.07 µg/ml). By theoretical calculations taking into account experimental data it is shown that the medicine Hondroxid Maximum can reach the bioavailability level of the modern injection forms and exceed the bioavailability level of modern oral forms of glucosamine up to 2 times.

[Atrial natriuratic peptide and experimental vasorenal hypertension in rats].

Vasorenal hypertension in rats resulted in increase of arterial pressure, the plasma concentration of creatinine and potassium. By EM immunocytochemistry we have demonstrated that atrial natriuretic peptide (ANP) was kept in the granules of secretory cardiomyocytes of the right atrium. It has shown that cardiomyocytes released ANP by means of diffusion. The increased secretion of atrial natriuretic peptide has been detected in blood. However the physiological effects this peptide probably was impaired due to the reducing of the density of natriuretic peptide receptors.

[Contralateral ultrastructural changes of the perifocal zone of the local ischemia caused by photoinduced thrombosis of the rat prefrontal brain cortex].

Perifocal ischemia zone ultrastructural changes caused by unilateral photoinduced thrombosis of the rat prefrontal brain and reciprocal changes in an opposite hemisphere of a brain in 1 and 24 hours after an ischemia are investigated. Reactive changes of microcirculation, astrocytes, neurons in the perifocal zone of the ischemia, and also in the contralateral site of the intact hemisphere as increase in hematoencephalic barrier permeability, numbers of degraded neurons, astrocyte transport injury and glucose metabolic imbalance are revealed. The degree of reactive changes of neurons and glia in the contralateral hemisphere is less expressed, than in a right hemisphere and has other temporal dynamics.

[Radio wave influence upon the local processes of free radicals oxidation intensity in oral cavity operational field in laboratory animals].

Experimental study of free radicals oxidation intensity processes in the tissues of oral cavity operational field in case of the use of the traditional surgical scalpel and radio wave device. The status of the primary and final products of lipid peroxidation and local antioxidation activity was assessed. Appropriate peculiarities of the studied processes in experimental animals wounds were detected. During all periods of the study there was no negative dynamics of the local antioxidation activity of the studied substrate that testified to compensation and controllability of the running processes and softer local processes flow of free radicals oxidation in operational field in experiment especially when radio wave surgery method was used.

[The effect of ozonated physiological solution on the postreperfused lipid composition and the level of carbohydrate metabolism substrates].

The effect of ozonated physiological solution on lipid composition, lipid peroxidation and level of carbohydrate metabolism substrates were investigated in the early reperfusion period. The total ischemia/reperfusion model was used. This study shows that injection of ozonated physiological solution in the early reperfusion period did not prevent cardiac myocyte membrane delipidization, activation of lipid peroxidation due to antioxidation exhaustion. Treatment with ozonated physiological solution promotes normalization in the lysophosphatidylholine and lysophosphatidylserine content, activation of hydrolytic degradation of neutral lipids, the decrease in membrane lipid microviscosity, activation of the aerobic glucose utilization and prevents lactic acidosis in the heart.

Effect of electromagnetic radiation modulated by biostructures on the course of alloxan-induced diabetes mellitus in rats.

Exposure of rats with experimental diabetes mellitus to wide-band electromagnetic radiation generated by He-Ne laser and modulated by the pancreas and spleen is informing and phenomenological method prolonging animal life span, normalizing blood glucose level, and promoting regeneration of the pancreas.

[The influence of ceruloplasmin on the rat neocortical ultrastructure in circulatory hypoxia].

Diffuse cerebral ischemia and circulatory hypoxia were modeled by carotid arteries occlusion in 40 white Wistar male rats. The changes of microcirculation bed and neurons of the sensomotor cortical area in hypoxia, preventive and therapeutic regimes of ceruloplasmin injections were compared to the neocortex state of intact rats. The changes of the neocortical ultrastructure established by electron microscopy were characteristic of hypoxic lesions described earlier in the literature. As a result of prolonged administration of ceruloplasmin there was a significant decrease of sensomotor neocortical hypostasis and improvement of microcirculation that suggested its neuroprotective properties.