Molecular Mechanisms of Muscle Tone Impairment under Conditions of Real and Simulated Space Flight.

Kozlovskaya et al. [1] and Grigoriev et al. [2] showed that enormous loss of muscle stiffness (atonia) develops in humans under true (space flight) and simulated microgravity conditions as early as after the first days of exposure. This phenomenon is attributed to the inactivation of slow motor units and called reflectory atonia. However, a lot of evidence indicating that even isolated muscle or a single fiber possesses substantial stiffness was published at the end of the 20th century. This intrinsic stiffness is determined by the active component, i.e. the ability to form actin-myosin cross-bridges during muscle stretch and contraction, as well as by cytoskeletal and extracellular matrix proteins, capable of resisting muscle stretch. The main facts on intrinsic muscle stiffness under conditions of gravitational unloading are considered in this review. The data obtained in studies of humans under dry immersion and rodent hindlimb suspension is analyzed. The results and hypotheses regarding reduced probability of cross-bridge formation in an atrophying muscle due to increased interfilament spacing are described. The evidence of cytoskeletal protein (titin, nebulin, etc.) degradation during gravitational unloading is also discussed. The possible mechanisms underlying structural changes in skeletal muscle collagen and its role in reducing intrinsic muscle stiffness are presented. The molecular mechanisms of changes in intrinsic stiffness during space flight and simulated microgravity are reviewed.

Early Deсline in Rat Soleus Passive Tension with Hindlimb Unloading: Inactivation of Cross-bridges or Activation of Calpains?

The study was aimed at testing the hypotheses about the role of cross-bridges and calpains in reduction of rat soleus passive tension under conditions of hindlimb unloading. For this purpose, we used an inhibitor of µ-calpain PD 150606 as well as a blocker of actomyosin interaction (blebbistatin). It was found for the first time that a decrease in passive tension of rat soleus after 3-day hindlimb unloading is associated with the activity of µ-calpain and does not depend on the processes of cross-bridges formation.

ULTRASTRUCTURAL CHANGES OF WOUND MACROPHAGES UNDER THE INFLUENCE OF INTRAVENOUS OZONE THERAPY IN PATIENTS WITH DIABETES AND INFLAMMATORY PROCESSES OF SOFT TISSUES.

Investigation of ultrastructural peculiarities of morpho-functional changes of macrophages have been studied with the purpose of determining the dynamics and thrust of destructive-necrotic processes in these cells when the ischemic-gangrenous form of diabetic foot syndrome develops show what under the influence of intravenous ozone therapy stimulant effect on functional activity and beneficial effect on elimination, mainly due to genetically programmed cell death (apoptosis), playing a significant role in the regulatory mechanisms of the inflammatory process. The stimulation of macrophages functional activity under the influence of ozone, as well as the presence of destructive changes in such cells without necrotizing lesions, is explained by the inclusion of the mechanism of apoptosis as a positive factor in the regulation of local homeostasis at the completion of the inflammatory (exudative) stage of the wound process.

Pre-treatment condition effects on blood pressure and heart rate variability change in patients with arterial hypertension on therapy.

AIM: To study the relationship of the initial clinical and functional state of patients with arterial hypertension (AH) with the dynamics of daily indices of blood pressure (BP) and sinus rhythm on antihypertensive therapy. MATERIALS AND METHODS: 38 patients were examined (general clinical examination, electrocardiography, echocardiography, daily bifunctional monitoring with the determination of weighted average rhythmogram variations - WARV, clinical and biochemical analysis of blood, glycated hemoglobin, thyroid hormones) and distribyted according to the use of hypotensive drugs of main classes and combined therapy AH. Dynamic monitoring of the effectiveness of treatment was carried out (after 2-4 weeks, then every 1-2 months), clinically and with bifunctional monitoring, correction of therapy. The observation period was 8 months. RESULTS: By the end of the study, 27 patients had target blood pressure, significant decrease in systolic / diastolic blood pressure (10/5 mm Hg and more) occurred in 30 patients. A correlation was found between the effectiveness of antihypertensive treatment and the initial clinical and instrumental parameters of patients: age, heart size (including left ventricular hypertrophy - LVH), thyroid stimulating blood hormone (TSH) level and fasting blood glucose (within normal limits). The level of WARV also correlated with these indicators and was significantly higher in patients who achieved a significant reduction in blood pressure. No significant dynamics of WARV was detected. No relationship between baseline blood pressure with WARV and their changes were identified. The connection of the myocardial mass index with the level of TSH and glycated hemoglobin was demostrated. CONCLUSION: The WARV reflects the severity of organic heart changes associated with age, disease duration, metabolic profile, LVH - heart damage as a target organ in AH, but is not suitable for analyzing its functional changes within one stage of the disease.

Eukaryotic elongation factor 2 kinase activation in M. soleus under 14-day hindlimb unloading of rats.

Functional unloading of m. soleus of male Wistar rats was found to cause a reduction in protein synthesis. The level of phosphorylation of the translation elongation factor 2 (eEF2) and the eEF2 kinase (eEF2k) activity in m. soleus after 14 days of unloading were assessed. Rats were divided into the control group (C) and the group with hindlimb unloading for 14 days (HU14). The level of eEF2 phosphorylation in group HU14 was 80%, whereas in the control is was 40%. The indices of eEF2k expression and protein content in group HU14 increased compared to group C.

NEW METHOD OF TREATMENT OF PYOINFLAMMATORY SOFT TISSUE COMPLICATIONS IN PATIENTS WITH DIABETES MELLITUS.

Our study evaluated the levels of peroxide oxidation of lipids, oxidative modification of proteins, antioxidant protection and dynamic changes in markers of toxicity in patients with diabetes mellitus and purulent-inflammatory complications. In total, 124 patients were enrolled in the study and were divided into two groups according the treatment methods. Study group consisted of 53 patients, who received intravenously ozonized saline in addition to conservative treatment. The control group consisted of 71 patients who received only conventional therapy. The study period was 6-15 days. The results showed that the use of ozone therapy is not accompanied by negative injury responses at the level of hemostasis parameters and blood biochemical characteristics. Furthermore, ozone therapy may have a favorable effect on treatment outcome in patients with purulent-inflammatory complications and daibetes mellitus.

EVALUATION OF THE USE OF OZONE THERAPY IN TREATMENT OF INFLAMMATORY PROCESSES IN DIABETES MELLITUS IN AN EXPERIMENT.

Studying the effect of ozone therapy on the course of pyoinflammatory processes with diabetes mellitus in the experiment, conducted on 30 white 24-30 month rats, weight 300-450 gr with purulent-inflammatory processes, it was found out that diabetes, which was simulated by subcutaneous injection of alloxan, causes mosaic disturbances of hemostasis system in the presence of pyoinflammatory processes. Complicated changes in blood condition were also detected against the background of diabetes mellitus: chronometric hypocoagulation on the intrinsic pathway of blood coagulation in association with chronometric hypercoagulation by the external thrombinogenesis mechanism and fibrinogenesis depression against the background of hypofibrinogenaemia. Thus, the use of ozone therapy in the presence of soft tissues abscesses in old rats with diabetes does not demonstrate significant protective properties with reduced azoalbumin lysis, total non-enzymatic fibrinolytic activity and proteinase activity by Kunitz in blood plasma. Such changes in old rats can be considered as an exacerbation of purulent inflammation, increase in toxicity, reduced protective properties, increase in manifestations of hypercoagulation against the background of chronic course of diabetes, caused by age-related changes.

[EFFECT OF SHORT-TERM DRY IMMERSION ON PROTEOLYTIC SIGNALING IN HUMAN SOLEUS MUSCLE].

The signaling processes initiating proteolytic events in m. soleus of humans during short-term exposure in the non-weight bearing conditions were analyzed. Dry immersion (DI) was used to induce weight deprivation over 3 days. Western blotting was used to define the IRS-1 content, total and phosphorylated neuronal NO-synthase (nNOS), AMP-activated protein kinase (AMPK) that control the anabolic and catabolic pathways, and concentrations of cytoskeletal protein desmin and Ca²âº-activated protease calpin. Already on day-3 of DI calpain-dependent proteolysis manifests itself by reductions in both the total content and level of nNOS phosphorilation. Moreover, AMPK phosphorilation was decreased drastically.

[Changes in the Functional Connectivity of Motor Zones in the Use of Multimodal Exoskeleton Complex "Regent" in the Neurorehabilitation of Post-Stroke Patients].

The article discusses the effect of a course of treatment with the use of multimodal complex exoskeleton (MCE) "Regent" on the reorganization of cortical locomotor zones in 14 patients with post-stroke hemiparesis, mainly atthe chronic stage of the disease. Before the course of treatment, we identified specific areas of activation in the primary sensorimotor and supplementary motor areas and the inferior parietal lobules in both affected and healthy hemispheres by means of functional MRI (fMRI) with the use of special passive sensorimotor paradigms. After the course of treatment with MCE, we observed an improvement of temporal characteristics of walking; it was accompanied by a decrease in the activation zones of inferior parietal lobules, especially in the healthy hemisphere, and by a significant increase in the activation zone of primary sensorimotor and supplementary motor areas. The analysis of the functional connectivity of studied zones before and after the course of treatment with MCE showed significant changes in intra- and interhemispheric interactions.

SENSORIMOTOR REGULATION OF MOVEMENTS: NOVEL STRATEGIES FOR THE RECOVERY OF MOBILITY.

A series of observations have provided important insight into properties of the spinal as well as supraspinal circuitries that control posture and movement. We have demonstrated that spinal rats can regain full weight-bearing standing and stepping over a range of speeds and directions with the aid of electrically enabling motor control (eEmc), pharmacological modulation (fEmc), and training. Also, we have reported that voluntary control movements of individual joints and limbs can be regained after complete paralysis in humans. However, the ability to generate significant levels of voluntary weight-bearing stepping with or without epidural spinal cord stimulation remains limited. Herein we introduce a novel method of painless transcutaneous electrical enabling motor control (pcEmc) and sensory enabling motor control (sEmc) strategy to neuromodulate the physiological state of the spinal cord. We have found that a combination of a novel non-invasive transcutaneous spinal cord stimulation and sensory-motor stimulation of leg mechanoreceptors can modulate the spinal locomotor circuitry to that enables voluntary rhuthmic locomotor movements.

[Evaluation of changes in the cortical gait control in post-stroke patients induced by the use of the "Regent" soft exoskeleton complex (SEC) by navigated transcranial magnetic stimulation].

The mechanisms underlying the locomotion recovery in poststroke patients remain unknown. Navigated transcranial magnetic stimulation (nTMS) is a new method to evaluate the functional state of the motor system. Using of the exoskeleton complex (EC) allow to correct walking pattern significantly. The aim of this study was to evaluate the capability of nTMS to assess changes in gait cortical control using EC in poststroke patients. 14 patients suffered subcortical stroke, mean age was 53.0 years [49, 62], mean duration of a stroke of 14.2 [7.0; 23.0] months were included. All patients trained with EC for 10 times and also received standardized physical therapy. All patients underwent nTMS, as well as clinical assessment using a Fugl-Meyer Scale lower extremity section and 10 m walking test before and after trains. A significant decrease of time to walk 10 meter was observed, while Fugl-Meyer Score remained unchanged. Patients showed the significant reduction of the average latency of motor responses from the affected hemisphere and different patterns of size and localization changes in both legs' cortical motor areas. Navigates TMS may demonstrate individual patterns of changes in cortical representation of leg muscles in post-stroke patients with damage of various motor system elements, while using exoskeleton complex. Thus, navigated TMS may be used not only for verification of neuroplasticity process, but it may also provide its detailed description.

[Mehanisms of Influences of Electrical Spinal Cord Stimulation on Autonomic Functions.]

Recently transcutateous electrical spinal cord stimulation began to be used both for experimental studies of motor functions regulation and for rehabilitation of motor functions in patients with spinal cord injury. The spinal cord is a very important center of vital functions regulation and the spinal cord stimulation directed to the activation of spinal locomotor related networks will affect visceral systems as well. This circumstance is necessary to take into account when this new method will be used for rehabilitation as well as for the studies on healthy subjects. Here the review of publications related to effects of electrical spinal cord stimulation on peripheral and cerebral circulation, on the cardiovascular, respiratory, excretory, and digestive systems of mammals is presented.

[The Effects of Optokinetic Stimulation on Visual-Manual Tracking under Support-Proprioceptive Deprivation.]

To determine the effects of additional visual stimuli (retinal optokinetic stimulation - ROKS) on characteristics of the visual-manual tracking (VMT) without support and with decreased proprioceptive afferentation there was used a horizontal "dry" immersion. Altogether 18 subjects aged from 19 to 31 years participated in the study and they were submerged into the immersion bath from 5 to 7 days. There was evaluated performance of the VMT in tasks to pursue the jerky (saccadically) and smooth (linear, pendular and circular) movement of a point visual stimulus before, during and after immersion. Eye movements were recorded using electrooculography, hand movements - by ajoystick with a biological visual feedback (one of the two visible stimuli on the screen matched the current angle of thejoystick handle). Computerized visual stimulation programs were presented to subject using a virtual reality glasses with and without additional ROKS. We analyzed time, amplitude and velocity characteristics of the visual and manual tracking (VT and MT), including efficiency ratio (e) and gain (g) as ratios of respectively amplitudes and velocities of eyes/hand movements to the stimulus movement. Without ROKS efficiency ratio and gain of both VT and MT were significantly decreased in comparison with baseline during the whole immersion and up to the R + 3 day after. The most pronounced deterioration was observed in parameters of the VT. When using a "threshold" ROKS parameters of the VT and MT weren't changed before immersion, during and after immersion - they improved (on 1-5-7 days during immersion and on R + 3 day after there was a significant improvement of the VT and MT in comparison to same tests without ROKS). The greatest impact of the ROKS was observed in parameters of the VT. Evaluations of the vestibular function (VF) were performed before and after immersion using videooculography approach. We analyzed statical torsional otolith-cervical-ocular reflex (OCOR), dynamical vestibular-cervical-ocular reactions (VCOR) and vestibular reactivity (VR), spontaneous eye movements (SpEM). On R + 1 day after immersion in 28% of subjects there was found a significant decrease of the gain of OCOR (0.12 value in comparison to 0.25 baseline) with simultaneous significant increase of parameters of VCOR/VR. There was found a correlation between parameters of VT and MT, between VF and VT and no correlation between VF and MT. It was found that removal of the support and minimization of the proprioceptive afferentation has a greater impact-upon accuracy of the VT then accuracy of the MT. When using ROKS correlations between the studied parameters were not only preserved, but also intensified. The results obtained indicate the development of sensory deprivation (and afferent deficit) under the immersion exposure and the possibility of its correction with additional ROCKS.

[Comparative Analisys of Efficacy of Countermeasure Provided by Different Modes of Locomotor Training in Space Flight.]

According to the results of the experiment performed on the ISS with participation of 15 Russian cosmonauts was fulfilled the comparative analysis of two models of preventive measures used by the Russian members of the long term space flight: the intense interval training in the aerobic-anaerobic zone power (recommended model) and the continuous low-intensity exercise in the aerobic zone energy power of the muscle activity. The interval trainings in the conditions of the space flight have provided the maintenance of the level of physical performance close to the preflight level; characterized by the maximum running speed, physiological value of work and lactate level after a standard load. The putative mechanisms of counteraction to adaptive remodeling of the propulsion system in zero gravity and enhanced understanding of the laws governing the interaction of the human body with the gravitational field of the Earth are described in the paper. The research results presented in the article show the high preventive efficacy of interval training compared with regular aerobic trainings, what is very important now in the time of searching of the means and methods of prevention of hypogravitation alterations during the interplanetary missions.

[Heat and cardiovascular diseases: A review of epidemiological surveys].

The review summarizes epidemiologic data on the effects of heat on cardiovascular morbidity and mortality. Patients with heart failure and cardiac arrhythmias are most susceptible to negative heat exposure. At the same time, measures aimed at preserving the health of the population lead to a considerable reduction in losses associated with an abnormal rise in air temperature.

Human muscle signaling responses to 3-day head-out dry immersion.

To date little is known about catabolic NO-dependent signaling systems in human skeletal muscle during early stages of gravitational unloading. The goal of the study was to analyze signaling pathways that determine the initial development of proteolytic events in human soleus muscle during short-term gravitational unloading (simulated microgravity). Gravitational unloading was simulated by 3-day head-out dry immersion. Before and after the immersion the samples of soleus muscle were taken under local anesthesia, using biopsy technique. The content of desmin, IRS-1, phospho-AMPK, total and phospho-nNOS in soleus of 6 healthy men was determined using Western-blotting before and after the dry-immersion. Three days of the dry immersion resulted in a significant decrease in desmin, phospho-nNOS and phospho-AMPK as compared to the pre-immersion values. The results of the study suggest that proteolytic processes in human soleus at the early stage of gravitational unloading are associated with inactivation of nNOS. Reduction in AMPK phosphorylation could serve as a trigger event for the development of primary atrophic changes in skeletal muscle.

[Effects of mechanical stimulation of the soles' support zones on H-reflex characteristics under support unloading condition].

The aim of the work was to study the effects of mechanical stimulation of the soles' support zones on state of m. soleus motoneurone pool in man under 7-days support unloading conditions, which was provided by "Dry Immersion" model. Before, during and after immersion exposure the excitability of m. soleus motoneurone pool was estimated by H-reflex amplitude normalized by the maximal amplitude of M-wave. The data registered in two groups of volunteers: "control" in which only immersion exposure was used and "experimental" in which stimulation of support zones of sole was carried out during Dry Immersion were compared. During immersion relative amplitude of H-reflex increased in the control group. These alterations were not revealed in the experimental group with daily application of the support stimulation in natural locomotion regimens during immersion.