THE IMPACT OF DIAMIDE DERIVATIVES OF OXALIC ACID ON FREE RADICAL LIPID OXIDATION IN WHITE RAT BRAIN AND LIVER.

Antioxidants are widely used in medicine due to their ability to bind free radicals - active biomolecules that destroy the genetic apparatus of cells and the structure of their membranes, which makes it possible to reduce the intensity of oxidative processes in the body. In a living organism, free radicals are involved in various processes, but their activity is controlled by antioxidants. The purpose of this work was to conduct a series of studies to identify the antioxidant activity of new synthesized compounds of a series of oxalic acid diamides in the brain and liver tissue of white rats in vivo and in vitro experiments, as well as to determine their potential pharmacological properties. The studies were conducted on outbred white male rats, weighing 180-200 g, kept on a normal diet. After autopsy, the brain and liver were isolated, washed with saline, cleared of blood vessels, and homogenized in Tris-HCl buffer (pH-7.4) (in vitro). The research results showed significant antioxidant activity (AOA) of all compounds with varying effectiveness. The most pronounced activity was demonstrated by compound SV-425 in both brain and liver tissues. Compound SV-427 demonstrated the least activity, with levels in brain tissue and liver tissue. In addition, all physicochemical descriptors of the studied compounds comply with Lipinski's rule of five to identify new molecules for the treatment of oxidative stress. From the data obtained, it can be concluded that the studied compounds have antioxidant properties, helping to protect cells from oxidative stress. This is important for the prevention and treatment of diseases associated with increased levels of free radicals.

Finely-tuned gamma oscillations: Spectral characteristics and links to dyskinesia.

Gamma oscillations comprise a loosely defined, heterogeneous group of functionally different activities between 30 and 100 Hz in the cortical and subcortical local field potential (LFP) of the motor network. Two distinct patterns seem to emerge which are easily conflated: Finely-tuned gamma (FTG) oscillations - a narrowband activity with peaks between 60 and 90 Hz - have been observed in multiple movement disorders and are induced by dopaminergic medication or deep brain stimulation (DBS). FTG has been linked with levodopa or DBS-induced dyskinesias, which makes it a putative biomarker for adaptive DBS. On the other hand, gamma activity can also present as a broad phenomenon (30-100 Hz) in the context of motor activation and dynamic processing. Here, we contrast FTG, either levodopa-induced or DBS-induced, from movement-related broadband gamma synchronisation and further elaborate on the functional role of FTG and its potential implications for adaptive DBS. Given the unclear distinction of FTG and broad gamma in literature, we appeal for more careful separation of the two. To better characterise cortical and subcortical FTG as biomarkers for dyskinesia, their sensitivity and specificity need to be investigated in a large clinical trial.

[Influence of connective tissue differentiation on scar tissue formation in children]. / Vliyanie differentsiatsii soedinitel'noi tkani na formirovanie rubtsovoi tkani v detskom vozraste.

OBJECTIVE: To study the immunohistochemical features of various scar tissues in children without connective tissue pathology and with undifferentiated connective tissue dysplasia syndrome. MATERIAL AND METHODS: Tissue biopsy was performed in 217 children who underwent surgical treatment for various lesions, such as injuries, burns, as well as other procedures. There were 127 boys (58.5%) and 90 (41.5%) girls. The main group consisted of 98 (48.2%) children with scar tissue; group of UCTD syndrome - 65 (30.0%) children; control group - 43 (24.8%) patients without pathological scars. Histological examination of scar tissue and intact skin was carried out during primary or redo reconstructive surgery. Immunohistochemical study of antibodies against CD34, CD105, CD140b, PDGFs, COL types I, III and IV was performed. RESULTS: The study showed a quantitative characteristic of expression of COL type I in hypertrophic scar with predominance in the main group (77.5±5.4%; p<0.05), and decrease in COL type IV. Keloid form was associated with predominance of granulation tissue in all layers of dermis and high levels of all types of collagen. In the group of UCTD, COL type III prevailed in all pathological forms of the scar. We determined quantitative indicators of expression of vascularization factors (CD34; CD105) and fibroblastic activity (CD140b; PDGFs). CONCLUSION: Understanding the process of fibrinogenesis and analysis of stages of triggering mechanisms are essential for development of preventive algorithms. Individualized approach should be considered in the treatment. These studies are especially important in children with UCTD syndrome as high-risk group for pathological scarring. Thus, further research is required.

Subthalamic deep brain stimulation induces finely-tuned gamma oscillations in the absence of levodopa.

Finely-tuned gamma (FTG) oscillations can be recorded from cortex or the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) on dopaminergic medication, and have been associated with dyskinesias. When recorded during deep brain stimulation (DBS) on medication the FTG is entrained to half the stimulation frequency. We investigated whether these characteristics are shared off medication by recording local field potentials (LFP) from the STN from externalised DBS leads in 14 PD patients after overnight withdrawal of medication. FTG was induced de-novo by DBS in the absence of dyskinesias in a third of our cohort. The FTG could outlast stimulation or arise only after DBS ceased. FTG frequencies decreased during and across consecutive DBS blocks, but did not shift with changing stimulation frequency off medication. Together with the sustained after-effects this argues against simple entrainment by DBS in the off medication state. We also found significant coherence between STN-LFP and electroencephalogram (EEG) signals at FTG frequencies. We conclude that FTG is a network phenomenon that behaves differently in the off medication state, when it is neither associated with dyskinesias nor susceptible to entrainment.

Local field potential activity dynamics in response to deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Local field potentials (LFPs) may afford insight into the mechanisms of action of deep brain stimulation (DBS) and potential feedback signals for adaptive DBS. In Parkinson's disease (PD) DBS of the subthalamic nucleus (STN) suppresses spontaneous activity in the beta band and drives evoked resonant neural activity (ERNA). Here, we investigate how STN LFP activities change over time following the onset and offset of DBS. To this end we recorded LFPs from the STN in 14 PD patients during long (mean: 181.2 s) and short (14.2 s) blocks of continuous stimulation at 130 Hz. LFP activities were evaluated in the temporal and spectral domains. During long stimulation blocks, the frequency and amplitude of the ERNA decreased before reaching a steady state after ~70 s. Maximal ERNA amplitudes diminished over repeated stimulation blocks. Upon DBS cessation, the ERNA was revealed as an under-damped oscillation, and was more marked and lasted longer after short duration stimulation blocks. In contrast, activity in the beta band suppressed within 0.5 s of continuous DBS onset and drifted less over time. Spontaneous activity was also suppressed in the low gamma band, suggesting that the effects of high frequency stimulation on spontaneous oscillations may not be selective for pathological beta activity. High frequency oscillations were present in only six STN recordings before stimulation onset and their frequency was depressed by stimulation. The different dynamics of the ERNA and beta activity with stimulation imply different DBS mechanisms and may impact how these activities may be used in adaptive feedback.

[Intraoperative video-angiography in surgery for spinal intramedullary cavernous malformations: first experience of its application at the Burdenko Neurosurgical Center]. / Intraoperatsionnaia videoangiografiia v khirurgii intramedulliarnykh kavernoznykh mal'formatsii spinnogo mozga: pervyi opyt ispol'zovaniia v FGAU 'Natsional'nyi meditsinskii issledovatel'skii tsentr neirokhirurgii im. akad. N.N. Burdenko'.

Spinal intramedullary cavernous malformations are a rare vascular pathology of the central nervous system. They account for 3-5% of spinal cord diseases. The clinical picture in patients with cavernous malformations varies from an asymptomatic course to gross neurological deficit in the case of bleeding from a malformation. Due to the lack of reliable methods for predicting the development of bleeding, the need for surgical treatment of asymptomatic patients remains a relevant and open topic for discussion. The goal of surgical treatment of cavernous malformations is to minimize the risk of repeated hemorrhages and gross neurological deficits in patients. Intraoperative indocyanine green video angiography is a promising technique for intraoperative visualization of the size and adherence area of a cavernous malformation to the spinal cord tissue. This increases the radicality of cavernous malformation resection and minimizes intraoperative risks for the patient.

Localization of beta and high-frequency oscillations within the subthalamic nucleus region.

Parkinsonian bradykinesia and rigidity are typically associated with excessive beta band oscillations in the subthalamic nucleus. Recently another spectral peak has been identified that might be implicated in the pathophysiology of the disease: high-frequency oscillations (HFO) within the 150-400 Hz range. Beta-HFO phase-amplitude coupling (PAC) has been found to correlate with severity of motor impairment. However, the neuronal origin of HFO and its usefulness as a potential target for deep brain stimulation remain to be established. For example, it is unclear whether HFO arise from the same neural populations as beta oscillations. We intraoperatively recorded local field potentials from the subthalamic nucleus while advancing DBS electrodes in 2 mm steps from 4 mm above the surgical target point until 2 mm below, resulting in 4 recording sites. Data from 26 nuclei from 14 patients were analysed. For each trajectory, we identified the recording site with the largest spectral peak in the beta range (13-30 Hz), and the largest peak in the HFO range separately. In addition, we identified the recording site with the largest beta-HFO PAC. Recording sites with largest beta power and largest HFO power coincided in 50% of cases. In the other 50%, HFO was more likely to be detected at a more superior recording site in the target area. PAC followed more closely the site with largest HFO (45%) than beta power (27%). HFO are likely to arise from spatially close, but slightly more superior neural populations than beta oscillations. Further work is necessary to determine whether the different activities can help fine-tune deep brain stimulation targeting.

[Extradural spinal cord hemangioblastoma (a case report and literature review)]. / Ekstradural'naya gemangioblastoma spinnogo mozga (sluchai iz praktiki i obzor literatury).

Hemangioblastoma is a rare CNS vascular tumor that develops sporadically and can also be associated with von Hippel-Lindau disease. Hemangioblastomas account for 2-6% of all spinal cord tumors and are ranked third in the structure of intramedullary space-occupying lesions of the spinal cord. For the first time in our practice, we observed a dumbbell paravertebral hemangioblastoma. The international literature reports only 3 cases of the tumor with this growth type.

[Modern treatments for degenerative disc diseases of the lumbosacral spine. A literature review]. / Sovremennye metody lecheniia degenerativnykh zabolevanii mezhpozvonkovogo diska. Obzor literatury.

Many researchers consider degenerative diseases of the spine as a pandemic of the XXIst century. Herniated intervertebral discs of the lumbosacral spine occur in 61% of patients with degenerative spine diseases. Of these, 15% of patients have herniated discs at the LII-LIII level, 10% of patients at the LIII-LIV level, and 40% of patients at the LIV-LV and LV-SI levels. A high cost of conservative treatment of degenerative spine disease symptoms and its low efficacy in reducing the intensity and duration of pain necessitate the development of new methods of surgical treatment. In this paper, we analyze the literature data on minimally invasive spine surgery and demonstrate the main advantages of percutaneous endoscopic surgical techniques.

ß band stability over time correlates with Parkinsonian rigidity and bradykinesia.

Abnormal oscillatory activity in the basal ganglia is increasingly implicated in the pathophysiology of Parkinson's disease. Such activity is recorded in patients in the form of oscillations in the local field potential (LFP) picked up in the subthalamic nucleus. Previous studies have focused on correlations between features of the time averaged power or amplitude spectrum of the LFP and the clinical state, either off medication or in response to levodopa. However, average spectral densities do not take account of time variant spectral properties and we hypothesised that these dynamic properties of the spectrum of the LFP would contain additional information about clinical state. Here we assess the variability in LFP amplitude over time using the coefficient of variation (CV), evaluating this with regard to clinical state off medication and in response to levodopa in two datasets. The CV of activity in the high beta frequency band was found to be correlated with clinical state off levodopa (rho=-0.59, p<0.001) and this was shown to be complementary, rather than redundant, to spectral amplitude in a multiple regression analysis, selective for rigidity-bradykinesia and highly focal. Similarly, a strong correlation was found between change in clinical scores and change in high beta CV following levodopa (rho=-0.66, p=0.004). This too was selective for rigidity-bradykinesia and non-redundant to spectral power in a multiple regression model. Our results indicate that temporal stability in the beta band is correlated with rigidity-bradykinesia. It is suggested that loss of beta reactivity is deleterious to basal ganglia function over and above any concomitant change in absolute level of beta synchrony. The CV of LFP beta band amplitude may potentially provide an additional index of clinical state suitable for feedback control in closed loop stimulation therapy.

Deep brain stimulation can suppress pathological synchronisation in parkinsonian patients.

BACKGROUND: Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective therapeutic intervention in severe Parkinson's disease, its mechanism of action remains unclear. One possibility is that DBS suppresses local pathologically synchronised oscillatory activity. METHODS: To explore this, the authors recorded from DBS electrodes implanted in the STN of 16 patients with Parkinson's disease during simultaneous stimulation (pulse width 60 µs; frequency 130 Hz) of the same target using a specially designed amplifier. The authors analysed data from 25 sides. RESULTS: The authors found that DBS progressively suppressed peaks in local field potential activity at frequencies between 11 and 30 Hz as voltage was increased beyond a stimulation threshold of 1.5 V. Median peak power had fallen to 54% of baseline values by a stimulation intensity of 3.0 V. CONCLUSION: The findings suggest that DBS can suppress pathological 11-30 Hz activity in the vicinity of stimulation in patients with Parkinson's disease. This suppression occurs at stimulation voltages that are clinically effective.

Parkinsonian impairment correlates with spatially extensive subthalamic oscillatory synchronization.

The local strength of pathological synchronization in the region of the subthalamic nucleus (STN) is emerging as a possible factor in the motor impairment of Parkinson's Disease (PD). In particular, correlations have been repeatedly demonstrated between treatment-induced suppressions of local oscillatory activity in the beta frequency band and improvements in motor performance. However, a mechanistic role for beta activity is brought into question by the difficulty in showing a correlation between such activity at rest and the motor deficit in patients withdrawn from medication. Here we recorded local field potential (LFP) activity from 36 subthalamic regions in 18 patients undergoing functional neurosurgery for the treatment of PD. We recorded directly from the contacts of the deep brain stimulation (DBS) electrodes as they were introduced in successive 2 mm steps, and assessed phase coherence as a measure of spatially extended, rather than local, oscillatory synchronization. We found that phase coherence in the beta frequency band correlated with the severity of Parkinsonian bradykinesia and rigidity, both in the limbs and axial body. Such correlations were frequency and site specific in so far as they were reduced when the lowermost contact of the DBS electrode was above the dorsal STN. Correlations with limb tremor occurred at sub-beta band frequencies and were more lateralized than those between beta activity and limb bradykinesia and rigidity. Phase coherence could account for up to ∼25% of the variance in motor scores between sides and patients. These new data suggest that the strength of spatially extended oscillatory synchronization, as well as the strength of local synchronization, may be worthwhile incorporating into modelling studies designed to inform surgical targeting, post-operative stimulation parameter selection and closed-loop stimulation regimes in PD. In addition, they strengthen the link between pathological synchronization and the different motor features of Parkinsonism.

Influence of unsaturated carbonic acids on hemocompatibility and cytotoxicity of poly-vinylacetate based co-polymers.

The aim of this study was to investigate hemocompatibility and cytotoxicity properties of synthetic polymer coatings containing various unsaturated carbonic acids with vinylacetate. Co-polymers of vinylacetate and crotonic acid (CA), maleic acid (MA), and itaconic acid (IA) were made. The materials were characterized in terms of their adhesion to metal supports (titanium and stainless steel) as well as hemocompatibility (% hemolysis, wettability, erythrocyte aggregation, hemoglobin content, thrombocyte count and lipid peroxidation levels) and cytotoxicity (human endothelial cell activity in vitro and chromosome aberrations, bone marrow proliferation and cell ploidy in rats). Co-polymers of unsaturated carbonic acids with vinylacetate exhibited good hemocompatibility properties, as opposed to vinylacetate homopolymer for which substantial levels of hemolysis were observed. By coating the metal supports with co-polymers the cytotoxic effects associated with the bare metal samples were markedly reduced. MA samples showed excellent hemocompatibility and no cytotoxicity, yet they lacked good adhesion properties to metal substrate, probably due to high water content. CA samples, having the highest density of carboxylic groups among the samples under investigation, showed increased bone marrow proliferation activity and cell ploidy in rats, as compared to controls. The most promising results in the present study were obtained for the samples with IA, which showed good adhesion to metal substrates, good hemocompatibility and low cytotoxicity. Thus, co-polymers of vinylacetate and IA rich in carboxylic groups are promising materials for the design of novel drug-eluting stents.

Suppression of beta oscillations in the subthalamic nucleus following cortical stimulation in humans.

It is unclear how subthalamic nucleus activity is modulated by the cerebral cortex. Here we investigate the effect of transcranial magnetic stimulation (TMS) of the cortex on oscillatory subthalamic local field potential activity in the 8-35 Hz (alpha/beta) band, as exaggerated synchronization in this band is implicated in the pathophysiology of parkinsonism. We studied nine patients with Parkinson's disease (PD) to test whether cortical stimulation can modulate synchronized oscillations in the human subthalamic nucleus. With patients at rest, single-pulse TMS was delivered every 5 s over each primary motor area and supplementary motor area at intensities of 85-115% resting motor threshold. Subthalamic local field potentials were recorded from deep brain stimulation electrodes implanted into this nucleus for the treatment of PD. Motor cortical stimulation suppressed beta activity in the subthalamic nucleus from approximately 0.2 to 0.6 s after TMS (repeated measures anova; main effect of time, P < 0.01; main effect of side, P = 0.03), regardless of intensity. TMS over the supplementary motor area also reduced subthalamic beta activity at 95% (P = 0.05) and 115% resting motor threshold (P = 0.01). The oscillatory activity decreased to 80 +/- 26% of baseline (averaged across sites and stimulation intensities). Suppression with subthreshold stimuli confirmed that these changes were centrally driven and not due to peripheral afference. The results may have implications for mechanisms underlying the reported therapeutic benefits of cortical stimulation.

State of the nonspecific component of the immune system during combination therapy for experimental bile peritonitis.

Combined use of sodium hypochlorite and intravenous laser irradiation of the blood in the postoperation therapy of 24-h bile peritonitis improved recovery of engulfing and digestive activity of neutrophilic granulocytes in the early postoperation period. Enzyme activity of neutrophilic granulocytes in earlier postoperation periods returned to normal after treatment with sodium hypochlorite alone.

Antioxidant status of erythrocytes after acupuncture treatment.

A course of acupuncture therapy in patients with locomotor, peripheral nervous system, gynecological, and bronchopulmonary diseases led to complete or partial normalization of nonspecifically changed MDA content, catalase and glutathione peroxidase activities in erythrocytes. SOD activity increased after therapy and did not differ from the control. Acupuncture stabilized disordered LPO processes and improved the antioxidant status of erythrocytes.

Genetic determination of neurophysiological mechanisms of cortical-subcortical integration of bioelectrical brain activity.

The contribution of genetic factors to the formation of the neurophysiological mechanisms of cortical-subcortical integration was studied in 12 pairs of monozygotic and five pairs of dizygotic twins (aged 18-25 years). Intrapair similarity of the nature of spatial interactions between bioelectrical activity in the cerebral cortex, assessed from different combinations of statistical interactions of EEG from 16 monopolar recordings, was assessed in each pair of twins (and among 544 non-related pairs of subjects in both groups). The results suggest a high level of general population invariance and relatively small inherited and phenotypic variability in the morphofunctional systems making up the major neurophysiological mechanisms of brain integration as a whole. The ontogenetic formation of stem and subcortical regulatory structures, which have a leading role in the systems combination of different parts of the brain into a single formation, appears to occur in all individuals by the same principle, as disturbance can apparently affect the fundamental monomorphic features of the species. In turn, we might expect to find large interindividual variability in the establishment of interregional connections of the neocortex, the role of inherited and environmental factors being different in the processes forming long and relatively short intercortical interactions.

Corticocortical coupling in chronic stroke: its relevance to recovery.

BACKGROUND: The mechanisms behind motor recovery from stroke are not clearly understood. Functional imaging studies have demonstrated task-related brain activation in several motor areas, but few studies have attempted to correlate this with stroke outcome. Moreover, these studies have focused on how motor areas may individually contribute to compensation. Here, the authors investigate whether different cortical areas interact to form dynamic assemblies that may then compensate for disability. METHODS: The authors investigated corticocortical coherence in 16 healthy subjects and 25 patients with chronic stroke involving one cerebral hemisphere and having varying degrees of motor recovery. Scalp EEG was recorded at rest and while right-handed subjects performed a unimanual grip task. The degree of functional recovery after stroke was assessed using a range of outcome measures. RESULTS: Compared with healthy subjects, hand-related asymmetries in task-related EEG-EEG coherence were increased between mesial and lateral frontal regions of the affected hemisphere, over mesial frontal regions, and over lateral frontal areas of the unaffected hemisphere when patients with stroke gripped with their affected hand. Mesial hand-related asymmetries in task-related power and coherence were negatively correlated with recovery. CONCLUSION: Increases in task-related coupling between cortical areas may dynamically compensate for brain damage after stroke. Some of this increased coupling, particularly that over mesial frontal areas, decreases as patients make a functional recovery.

Abnormal corticomuscular and intermuscular coupling in high-frequency rhythmic myoclonus.

Frequency analysis may have some advantages over back-averaging in the neurophysiological assessment of patients with suspected cortical myoclonus in whom myoclonic EMG bursts repeat rhythmically at high frequency. However, the clinical utility of EEG-EMG coherence and related EMG-EMG coherence is not established. Equally, there is an incomplete understanding of the physiology of the systems contributing to the coherence evident between signals in cortical myoclonus. Here we address these issues in an investigation of EEG-EMG and EMG-EMG coupling in proximal and distal muscles of the upper extremities in nine patients with multifocal high frequency rhythmic myoclonus due to non-progressive conditions. We found exaggerated coherence between EEG and contralateral EMG and between pairs of ipsilateral EMG signals. The results of frequency analysis of EMG-EMG mirrored those for EEG-EMG, but the former technique was superior in distinguishing a pathologically exaggerated common drive in distal upper limb muscles. Both techniques were more sensitive than back-averaging. Frequency analysis also revealed important disparities between proximal and distal upper limb muscles. In the latter case, the functional coupling between cortex and muscle was dominated by efferent processes. In contrast, there was considerable inter-individual variation in the extent to which EEG-EMG and EMG-EMG coupling in proximal muscles reflected afferent and efferent loops. Thus, the processes sustaining myoclonic discharges may differ for proximal and distal muscles and between patients.

Fluorescence spectroscopy studies of the association of membrane and soluble forms of chromaffin granule dopamine-beta-monooxygenase to bipolar phospholipid liposomes and micelles.

The association of membrane and soluble forms of dopamine-beta-monooxygenase to liposomes and micelles made from phosphatidylcholine and lysophosphatidylcholine respectively has been studied using the fluorescence spectroscopy technique. As it was shown in our previous study these bipolar phospholipids activate the reaction catalyzed by the enzyme. Effects of pH and ionic strength on the association process were also studied, and efficiency of the association for apo- and holoenzyme was compared. The data obtained demonstrate that electrostatic attraction is involved in the association process. It was also shown that the membrane dopamine-beta-monooxygenase associated with phospholipid liposomes and micelles with higher efficiency than the soluble one did, which might be due to the involvement of the hydrophobic interactions in the association process. The results of the experiments also suggest that this process is specific and depends on the enzyme conformation, particularly on its quaternary structure. The participation of the hydrophobic peptide of the membrane dopamine-beta-monooxygenase in the formation and stabilization of the enzyme-phospholipid complex in vivo is proposed.