Repetitive Transcorneal Alternating Current Stimulation Reduces Brain Idling State After Long-term Vision Loss.

BACKGROUND: Deafferentation of visual system structures following brain or optic nerve injury leaves cortical areas deprived of visual input. Deprived cortical areas have a reduced sensory information processing and are characterized with localized enhanced or synchronized rhythms believed to represent an "idling state". OBJECTIVE/HYPOTHESIS: We hypothesized that cortical idling can be modified with transcorneal alternating current stimulation (tACS) known to modulate cortical oscillations and thus change the functional state of the deafferented areas. METHODS: tACS was applied in rat model of severe optic nerve crush using a protocol similar to our clinical studies (200 µA, 2-8 Hz) for 5 treatment days right after the lesion and at the chronic stage (3 months later). EEG and VEP were recorded over the visual cortices. In vivo confocal neuroimaging of the retina and histology of the optic nerves were performed. RESULTS: Morphological investigations showed massive retinal ganglion cells death and degeneration of the optic nerves after crush. Visual loss was associated with increased EEG spectral power and lower coherence, indicating an "idling state". Stimulation induced a significant decrease of EEG power towards normal values. These effects were especially pronounced in the chronic stage. CONCLUSION: Our results suggest that alternating current injected via the eye is able to modulate visually deprived brain areas and thus reduce cortical idling.

Tissue factor and atherothrombosis.

Tissue factor (TF) is known to be the key element in the initiation of the extrinsic pathway of the coagulation cascade and appears to be a critical determinant of atherosclerotic plaque thrombogenicity. TF is needed to produce thrombin from prothrombin. In the extrinsic pathway, TF activates factor Vll. TF is expressed mainly on subendothelial tissues, but TF expression may be induced on endothelial cells by inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha). Subendothelial TF is responsible for initiating fibrin formation at sites of vascular injury, bloodborne TF may be an important contributor to propagation of the developing thrombus. It has been postulated that the blood-borne TF initiates the thrombogenic stimulus, leading to the formation of larger and more stable thrombus. TF may attach to cellular receptors, which in turn affect the production and release of inflammatory mediators. Baseline plasma TF activity has been demonstrated as an independent predictor for cardiovascular death in patients with acute myocardial infarction. TF is expressed by macrophage-derived foam cells in atherosclerotic plaques. TF levels were higher in atheroma from patients with unstable angina than with stable angina. These results suggest that high levels of TF exposed upon plaque rupture trigger atherothrombosis. Inhibition of TF would be expected to reduce thrombosis associated with a variety of diseases. TF pathway is a potential target for new therapeutic agents that can decrease TF activity, such as active site-inactivated factor VIIa, recombinant TF inhibitor and antibodies against TF or peptides interfering with TF-FVIIa complex activity. Significant clinical forms of atherosclerosis, such as sudden death, myocardial infarction, and stroke have common pathogenesis. The occlusion of the vessel lumen is the result from atherosclerotic plaque rupture/erosion that initiate thrombus formation. This thrombus has complex structure and contains predominantly fibrin in addition to platelets, suggesting an important role for the coagulation cascade in plaque thrombus formation. Tissue factor (TF) is known to be the key element in the initiation of the extrinsic pathway of the coagulation cascade and appears to be a critical determinant of atherosclerotic plaque thrombogenicity.

Age dynamics of evoked brain potentials in involuntary and voluntary attention to a deviant stimulus in schoolchildren from the northern region.

The central mechanisms of involuntary and voluntary regulation of attention in schoolchildren from the northern region were studied using a method based on the P300 wave of evoked brain potentials (the oddball paradigm). Data were compared with results obtained from psychological tests. Differences in the organization of EP were seen in the "passive" and active (counting) perception of deviant stimuli. Three components were identified within the time envelop of the P300 wave, two of which dominated in the frontal and one in the parietal area of the cerebral cortex. The latency of the P300 wave decreased with age in the children, reflecting increased rates of information processing and increases in the volume of operative memory. In passive perception, the statistical relationship characterized by a reduction in P300 latency with age was significant for leads in the central, temporal, parietal, and occipital areas; in active perception, this applied to all areas including the frontal. The most significant changes in P300 parameters were seen in children aged from seven to 12 years, indicating that this period can be regarded as "critical" in the development of learning skills. The roles of the parietal and frontal areas of the cortex in the mechanisms of involuntary and voluntary regulation of attention are discussed, along with the possibility of using the P300 method to identify children with delayed rates of development of voluntary attention in population studies.

Cortical-subcortical interactions and the regulation of the functional state of the brain in acute hypoxia in humans.

The mechanisms regulating the functional state (FS) of the brain were studied in humans in conditions of dosed acute hypoxia (breathing a mixture of 8% oxygen in nitrogen for 15-25 min). The dynamics of the FS of the brain due to changes in the balance of the activities of brain regulatory structures in hypoxia were reflected in rearrangements of EEG spatial relationships (factor and cluster analysis of EEG crosscorrelation matrixes) and the redistribution of intracerebral locations of electrically equivalent dipole sources (EEDS), with increases in EEDS density in the projections of the medial and basal parts of the temporal lobes of the hemispheres (EEDS tomography data). Changes in cortical-subcortical interactions were characterized by a decrease in the tone of the activatory brain system, a decrease in the inhibitory control of subcortical structures by neocortical formations, and activation of limbic system and hypothalamic structures. Switching of the integrative regulatory mechanisms from the cortico-thalamic level to the limbic-diencephalic level may allow release of the energy-consuming nonspecific components of hypoxic stress and more stable regulation of physiological parameters by the major vital systems in conditions of increasing oxygen deficit.

[Cortical-subcortical interactions and the brain functional state regulation under acute hypoxia in man].

Regulation mechanisms of the brain functional state (FS) were studied in man during acute hypoxic conditions (inhalation of 8% O2 hypoxic air for 15-25 minutes). Changes in balance of the brain regulatory structures activities caused by hypoxia determine FS dynamics that is reflected in the reorganization of the EEG spatial interrelations (by data of factor and cluster analysis of EEG cross-correlation matrices), as well as translocation of intracerebral position of electrical equivalent dipole sources (EEDS) coupled with EEDS density rising in medial and basal regions of the cerebral hemisphere temporal lobes (by EEDS-tomography data). Alterations of the cortical-sub-cortical interactions show a decline in the brain activating system tone, a decrease in the neocortical inhibitory control of subcortical processes, and activation of structures of limbic and hypothalamic regions. Switching of integrative regulatory control mechanism from "cortical-thalamic" system level to "limbic-dyencephalic" one could ensure both removal of powerful unspecific components of hypoxic stress and a greater stability of essential physiological parameters of the main vital functions regulation during oxygen deficiency accumulation.

[Developmental changes of auditory event-related potentials under involuntary and voluntary attention towards deviant stimuli in school children from the north region].

The central mechanisms of attention involuntary and voluntary regulation were studied in school children from the North region with the P300 (oddball task) eventrelated potential (ERP) method. ERP measurements were assessed in conjunction with behavioral tests. Our results showed different P300 waveform as well as P300 maturational changes in children in "passive" tone listening and "active" deviant tone counting task. Responses to deviant stimuli consisted of 3 dissociable components in the P300 time range: frontal-central component (Novelty P3), parietal component and an additional anterior component. Age-related reduction of P300 latency coincided with increase in information processing speed and short-time memory capability as indicated by behavioral tests. A significant negative correlation between age and P300 latency was found in central, temporal and posterior cortical areas in passive task, and all over the cortices including frontal leads in active task. The most pronounced P300 changes were found in children aged from 7 to 12. This period is suggested to be "critical" in learning skills development. Role of parietal and frontal cortex is discussed in relation to mechanisms of attention involuntary and voluntary mechanisms, as well as usefulness of P300 diagnostic is considered as to revealing of children with delayed delayed cognitive development.

Characteristics of the formation of systems activity in the brain and autonomic functions in children in conditions of the European North (discussion paper).

Results obtained from complex medical-physiological investigations performed during 10 scientific expeditions in the Arkhangel'sk Region in 2003-2005 are presented. The effects of climatological-geographic, biogeochemical, and social conditions of the conditions obtaining in the Far North region of Russia on sexual maturation, formation of the structural-functional organization of the brain, autonomic functions, and immunological and biochemical status of schoolchildren were studied using state-of-the-art neurophysiological methods (computerized electroencephalography, computerized rheoencephalography, computerized electric dipole origin tomography, etc.), psychophysiological and psychometric methods (assessment of the state of cognitive and memory functions, Wechsler intellectual scale), along with biochemical assay of monoamine oxidase (MAO, the key enzyme in adrenergic neurotransmitter metabolism) and the liver enzyme butyrylcholinesterase (BuChE) and physicochemical analysis of the levels of macroelements and trace elements in the body.

[Characteristics of the brain system activity and vegetative function formation in children under conditions of the European north (a problem study)].

Results of complex medical-physiological research performed during 10 scientific expeditions in Arkhangelsk region in 2003-2005 are presented. Influence of climatic-geographic, biogeochemical and social conditions of North-West region of Russia on sexual maturation, formation of the brain structural-functional organization, vegetative functions, immunological and biochemical status of schoolchildren was studied with the aid of modern neurophysiologic (computer electroencephalography, computer rheoencephalography, computed electric dipole origin tomography, etc.), psychophysiological and psychometric methods (evaluation of cognitive and mnestic functions, Vechsler 1Q estimation), biochemical assessment of monoamine oxidase and butyrylcholinesterase activity, physical-chemical analysis of macro- and microelements in the organism.

[Tuberculosis and HIV infection in the Kaliningrad Region].

The first cases of tuberculosis in the HIV infected were notified in the Kaliningrad Region in 1997. A total of 254 HIV-infected persons fell ill with tuberculosis in 1997-2003. In the HIV infected, the number of new cases of tuberculosis increased by 9.9 times in 2003 as compared with 1997; their proportion among the first detected patients with tuberculosis was 8%. In 2003, the incidence of tuberculosis in the HIV infected was 20.7 times greater than that in the general population. In this year, the rates of death in the HIV infected from tuberculosis were 34.6 times higher than those in the general population. The course and outcomes of tuberculoses were followed up in 165 patients with HIV infection. The diagnostic features of tuberculosis are shown in end-stage HIV infection. The findings showed the low efficiency of treatment for tuberculosis in patients with comorbidity. The early detection and treatment of tuberculosis are of priority in antituberculous work among the HIV-infected persons.

[Functional status of the intima and thrombocytic hemostasis in patients with symptoms of atherosclerosis of the cerebral and peripheral vessels]. / Funktsional'noe sostoianie intimy i trombotsitarnogo gemostaza u bol'nykh s proiavleniiami ateroskleroza mozgovykh i perifericheskikh sosudov.

The indices characterizing the state of lipid metabolism, endothelium of arteries and thrombocytic hemostasis were investigated. It was shown that in the zone of atherosclerotic stenosis of the arteries there were marked transformations of the endothelium followed by a decrease of their anticoagulatory properties. The cause and effect relationship between the disturbed thrombocytic hemostasis and lesions of the endothelium in atherosclerosis was confirmed. It is these factors which are the cause of frequent thromboembolic complications, especially in patients with lesions of the cerebral arteries. It is necessary to include methods of correction of the disturbed thrombocytic hemostasis in the complex treatment of patients with atherosclerosis.

[The use of tactivin for treating patients with IHD]. / Primenenie taktivina dlia lecheniia bol'nykh IBS.

Immunomodulating drug tactivin was used for treatment of 29 IHD patients with low T-suppressor activity and high cell sensitization to apoprotein B-containing lipoproteins and with lipoprotein-antibody immune complex detected in the blood. Tactivin was injected subcutaneously in the dose 10 micrograms (5 injections for 12 days). Tactivin treatment normalized T-suppressor activity, lowered concentration of plasma lipoprotein-antibody immune complex and improved clinical course of IHD. The beneficial effect of tactivin was observed in 70% of patients during 2 months. 30% of patients needed a second course of treatment of recover normal immunological and clinical indices. The treatment with tactivin of IHD patients must be combined with application of routine antianginal drugs.

[Effects of T-activin on the course of ischemic heart disease in cases of the development of sensitization to apoprotein B-containing lipoproteins]. / Vliianie T-aktivina na techenie ishemicheskoi bolezni serdtsa v sluchaiakh razvitiia sensibilizatsii k apoprotein-B-soderzhashchim lipoproteidam.

A comprehensive clinicoimmunological examination was made of 105 male patients aged 35-65 years who suffered from coronary heart disease. The authors identified a group of 33 patients whose unstable course of angina pectoris was associated with pronounced apolipoprotein B sensitization, as well as with the presence of the autoimmune lipoprotein-antibody complex and abnormalities in the cellular link of immunity. All 33 patients received antianginal agents. Out of them, 15 patients took additionally a course of T-activin therapy to modulate immunological shifts. The results of the examination demonstrated that the immunomodulator exerted a beneficial effect both on the course of CHD (reduction in the number of anginal episodes, improvement of left ventricular contractility) and the immune system (recovery of T-suppressor function, disappearance of lipoprotein sensitization, decrease in the patient's blood detection rates of the autoimmune lipoprotein-antibody complexes from 83 to 28%). The highest effect was reached by T-activin 1.5-2 months following termination of the course therapy. Immunomodulating therapy is regarded as an additional approach to the treatment of CHD patients with marked lipoprotein sensitization.

The immune response of the definitive hosts to diphyllobothriid antigens.

It was established that antigens of diphyllobothriids entered the organisms of nestlings of gulls (Larus fuscus) and terns (Sterna hirundo) through the intestine. In terns, the most intensive neutralization of parasite antigens was found in the intestine inducing a weak response of the immune system. In gulls, there was no complete neutralization of the parasite antigens in the intestines. The antigens penetrated into the blood stimulating a response of the immune system. The intensity of the local immunity of terns seems to result from the absence of invasion in adult birds.

[Differences in surface antigens of three diphyllobothriidae species, detected by serologic methods]. / Razlichiia poverkhnostnykh antigenov trekh vidov difillobotriid, vyiavliaemye serologicheskimi metodami.

Immunochemical studies of somatic and surface extracts from D. dendriticum, D. ditremum and D. latum tape-worms demonstrated low specificity of somatic antigens of all three species and serological specificity of D. latum. D. dendriticum and D. ditremum, though serologically close, contained specific components demanding more precise extraction methods.

[Immunoreactivity in ischemic heart disease of atherosclerotic etiology]. / Immunoreaktivnost' pri ishemicheskoi bolezni serdtsa ateroskleroticheskoi étiologii.

Using a combined immunomorphologic and clinico-immunologic approach to the analysis of section and clinical findings, the authors introduce a specific nosological form of coronary heart disease in which there is a cause-and-effect relation implying the development of sensitization to atherogenic lipoproteins, rapid advance of coronary atherosclerosis and the onset of coronary insufficiency.