Effect of anorexigenic peptide obestatin on platelet aggregation and osmotic resistance of erythrocytes.

We studied the effects of the anorexigenic peptide obestatin on the coagulation system and blood rheology (by the parameters of platelet aggregation and osmotic resistance of erythrocytes) in vitro and in vivo. Obestatin inhibited in vitro platelet aggregation in the entire dose range and reduced osmotic resistance of erythrocytes in all doses except 300 nmol/kg (obestatin in a dose of 300 nmol/kg had no effect on this parameter). Similar to the results of in vitro experiments, intranasal, intraperitoneal, and subcutaneous administration of obestatin in a dose of 300 nmol/kg inhibited platelet aggregation and had no effect on the osmotic resistance of erythrocytes.

Effects of GSM-Frequency Electromagnetic Radiation on Some Physiological and Biochemical Parameters in Rats.

Single exposure of white outbred rats to electromagnetic radiation with a frequency 905 MHz (GSM frequency) for 2 h increased anxiety, reduced locomotor, orientation, and exploration activities in females and orientation and exploration activities in males. Glucocorticoid levels and antioxidant system activity increased in both males and females. In addition to acute effects, delayed effects of radiation were observed in both males and females 1 day after the exposure. These results demonstrated significant effect of GSM-range radiation on the behavior and activity of stress-realizing and stress-limiting systems of the body.

Consequences of the α-ketoglutarate dehydrogenase inhibition for neuronal metabolism and survival: implications for neurodegenerative diseases.

Neurodegenerative diseases are accompanied by reduced activity of mitochondrial α-ketoglutarate dehydrogenase multienzyme complex (KGDHC). We present a new cellular model to study molecular mechanisms of this association. By application of the highly specific and efficient inhibitor of KGDHC, succinyl phosphonate (SP), to cultured neurons, we characterized the concentration- and time-dependent consequences of decreased KGDHC activity for neuronal metabolism and viability. Metabolic profiling of SP-treated neurons established accumulation of α-ketoglutarate and pyruvate as indicators of the KGDHC inhibition and ensuing impairment of pyruvate oxidation in the tricarboxylic acid cycle. Concomitant increases in alanine, glutamate and γ-aminobutyrate indicated a scavenging of the accumulated pyruvate and α-ketoglutarate by transamination and further decarboxylation of glutamate. Changes among other amino acids were in accordance with their potential to react with α-ketoglutarate or products of its transamination and serve as fuel compensating for the KGDHC block. Disturbances in neuronal amino acid pool were accompanied by changed polyamines, decreased total protein and increased thymine, suggesting increased catabolism of amino acids to decrease translation and affect DNA turnover/repair. The ensuing ATP salvage was observed as the paradoxical increase in neuronal ATP by mitochondrial inhibitor SP. Extensive exposure of neurons to SP reduced viability, as revealed by both the ATP- and NAD(P)H-dependent viability tests. Thus, we provide experimental evidence on the KGDHC impairment as a cause of neurodegeneration and decipher underlying molecular mechanisms, exposing the key regulatory complex of the tricarboxylic acid cycle as a promising target for directed regulation of neuronal function and survival.

[Transgenerational consequences of acute antenatal stress in pregnant rats].

The aim of the present study was to investigate the effects of acute hypobaric hypoxia in early organogenesis on three following generations including pregnant females (FO) and two generations of their posterity (F1 and F2). Animals of all generations mentioned above demonstrated marked changes in motor and exploratory activity as well as in anxiety level while the litter of F1 and F2 generations showed also changes in learning ability. Besides, acute hypobaric hypoxia interfered in maternal behavior of females of the FO and F1 generations. The revealed changes kept till pubertal period. Possible mechanisms of gestational stress influence are discussed.

[Changes of glucocorticoid level in plasma and adrenal glands of pregnant rats and their offspring after antenatal stress of different etiology].

We investigated the glucocorticoid level in plasma and adrenal glands of pregnant rats in the period of early organogenesis. Tests were performed 24 hours after stress of different etiology (acute hypobaric hypoxia, intermittent normobaric hypoxia, and immobilization) and then repeated in the adult offspring. There was a significant decrease in the glucocorticoid level in pregnant rats 24 hours after hypoxic stress. Various changes of the basal glucocorticoid level were found in the offspring after antenatal stress. Changes were mostly found in female offspring.

Comparative analysis of the effects of various stress factors at the stage of early organogenesis on heart rate variability in pregnant female rats and their offspring.

We studied changes in the autonomic balance of heart regulation (by the parameters of heart rate variability) in non-pregnant female rats and rats on the days 10-11 of pregnancy on the next day after stress provoked by acute hypobaric hypoxia, intermittent normobaric hypoxia, or immobilization. The same parameters were assessed in 36-day-old offspring. In non-pregnant rats, the intermittent hypoxia resulted in a shift of the autonomic balance of heart regulation towards activation of the parasympathetic nervous system; in pregnant females, immobilization led to a shift of the autonomic balance towards the sympathetic nervous system. In the offspring, the changes also depended on the type of stress.

Behavioral impact of the regulation of the brain 2-oxoglutarate dehydrogenase complex by synthetic phosphonate analog of 2-oxoglutarate: implications into the role of the complex in neurodegenerative diseases.

Decreased activity of the mitochondrial 2-oxoglutarate dehydrogenase complex (OGDHC) in brain accompanies neurodegenerative diseases. To reveal molecular mechanisms of this association, we treated rats with a specific inhibitor of OGDHC, succinyl phosphonate, or exposed them to hypoxic stress. In males treated with succinyl phosphonate and in pregnancy-sensitized females experiencing acute hypobaric hypoxia, we revealed upregulation of brain OGDHC (within 24 hours), with the activity increase presumably representing the compensatory response of brain to the OGDHC inhibition. This up-regulation of brain OGDHC was accompanied by an increase in exploratory activity and a decrease in anxiety of the experimental animals. Remarkably, the hypoxia-induced elevation of brain OGDHC and most of the associated behavioral changes were abrogated by succinyl phosphonate. The antagonistic action of hypoxia and succinyl phosphonate demonstrates potential therapeutic significance of the OGDHC regulation by the phosphonate analogs of 2-oxoglutarate.

[Influence of antenatal intermittent normobaric hypoxia during early organogenesis on the development of white rats].

The influence of antenatal intermittent normobaric hypoxia during early organogenesis (days 9-10 of intrauterine development) on the physical development, vegetative balance, and antioxidant defense system of 60-day-old rats was studied. Antenatal exposure to intermittent hypoxia resulted in the impaired physical development of all offspring during the early 15-day postnatal period and caused changes in the vegetative balance of heart regulation, which were differently directed in males and females. Moreover, females that survived antenatal hypoxia had a decreased superoxide dismutase activity in the brain, compared to that in the control rats.

Transgeneration effects of antenatal acute hypoxia during early organogenesis.

We studied the effect of acute hypobaric hypoxia in early organogenesis on physiological and behavioral parameters of second-generation albino rats. Antenatal acute hypoxia was followed by physical and sexual retardation, increase in the mortality rate, and behavioral changes in second-generation animals (hypoactivity of males and females on day 22 of life and hyperactivity of males on day 57 of life). Second-generation animals exhibited no gender differences in body weight and horizontal and vertical locomotor activity.

Effect of antenatal hypoxia on age-specific dynamics of ECG parameters and content of biogenic amines in the central nervous system.

We studied the effect of acute antenatal hypoxia during the stages of progestation and early organogenesis on some ECG parameters and level of biogenic amines in brain structures in rats. The effect of acute hypoxic exposure during the organogenesis period on the studied parameters was more pronounced than the effect of acute hypoxic exposure during the progestation period. The shift of the autonomic balance towards the sympathetic regulation of cardiac activity is linked with increased content of biogenic amines in the brain stem and cortical structures.

[Modern methods of neuro-visualization of brain pathology in central form of Recklinghausen's disease]. / Sovremennye metody neirovizualizatsii patologii golovnogo mozga pri tsentral'noi forme bolezni Reklingkhauzena.

The paper reviews the data available in the literature on the diagnosis of brain lesions in the central form of Recklinghausen's disease (neurofibromatosis) by magnetic resonance imaging. The results of a clinical observation of 10 children suffering trom neurofibromatosis and the data of electroencephalography, computed tomography and MRI are given and analyzed. Conclusions are made on the magnitude of and the most common site of MRI changes. It is suggested that MRI shows a higher sensitivity in detecting brain lesions in Recklinghausen's disease than other diagnostic techniques.

[Mortality and disablement as criteria in the evaluation of ecological situation]. / Smertnost' i invalidizatsiia naseleniia kak kriterii otsenki ékologicheskoi situatsii.

A uniform study analyzed criteria for evaluation of ecologic jeopardy of some territories. Mortality and disablement appeared to be inadequate for that evaluation. The authors suggest specific parameters for cities neighbouring to major chemical enterprises.

[Disease characteristics of the population on the territory of the city of Kirovo-Chepetsk]. / Kharakteristika zabolivaemosti naseleniia na territorii g. Kirovo- Chepetska.

Medical and ecologic evaluation of ecologic situation in Kirovo-Tchepetsk (Kirov region) included study of morbidity in the town and referent territories. Levels and dynamics of morbidity, prevalence, number of pathologic processes in children and other parameters could characterize the town as an ecologically unfavorable territory.

Event-related neuronal responses in the human strio-pallido-thalamic system. II. Cognitive functions.

Multiunit activity was recorded from the strio-pallido-thalamic system in the same parkinsonian patients (as described in the previous paper) who bore gold electrodes for diagnosis and therapy. The patients voluntarily participated in various tasks designed to study neuronal correlates of cognitive functions: "odd-omissions," "short-term memory," "cued bimodal," "assessment," and "dual-stage delayed response" tasks. Preparatory-related activities were found in multiunits reacting to sensory cues. In a few multiunits these activities depended upon the specific features of the stimuli that were anticipated for evaluation. The most striking characteristic of stimulus-related activity was the suppression of the multiunit responses when the stimuli become behaviourally meaningless. The hypothesis of action programming is discussed: the loop, including the cortex, neostriatum, pallidum and appropriate parts of the thalamus, is involved in the selection of actions, thus providing the organization of sequential behaviour.

Changes associated with the organization of motor acts in the on-going frequency of the discharges of neurons of subcortical structures of the human brain.

The impulse activity of subcortical structures was recorded in 16 parkinsonian patients (six women) using deep electrodes implanted in the strio-pallido-thalamic system on the basis of treatment and diagnostic indications. The patients voluntarily participated in four psychological tests. Two groups of pallidal and thalamic neuronal populations (neuronal populations associated with the response and associated with the stimulus, containing 25% each out of the total number of neuronal populations recorded) were classified on the basis of evoked changes in on-going frequency in the motoric version of the odd ball test. Some of the neuronal populations associated with the response reacted primarily during counting, some during the naming of the stimulus, and some during button pressing.

[The subcortical neuronal correlates of human assessment actions]. / Podkorkovye neironnye korreliaty otsenochnykh deistvii u cheloveka.

In patients with parkinsonism to whom in accordance with medical-diagnostic indices electrodes were implanted into the nuclei of thalamus and striopallidal system, impulse activity of neurones was recorded in tests with presentation of visual and acoustic stimuli. It has been shown that neurones of these structures, reacting by a change of discharges frequency in carrying out the assessing actions by man constitute a special class of neurones, spatially separated from those, connected with the organization of motor acts. The typical feature of neuronal reactions is a high degree of their value dependence on the level of attention. Neurones of the above structures reacts also during preparation of the assessing actions and fixation of their results in the short-term memory.

[Changes in the flux frequency of the neuronal discharges of human subcortical brain structures related to the organization of motor acts]. / Izmeneniia tekushchei chastoty razriadov neironov podkorkovykh struktur mozga cheloveka, sviazannye s organizatsiei dvigatel'nykh aktov.

16 Parkinsonian patients (6 females) with depth electrodes within striopallido-thalamic system implanted for diagnostic and therapeutic purposes, voluntarily participated in four psychological tests. Two groups of the pallidal and thalamic neuronal populations (response- and stimulus-related neuronal populations) were distinguished on the basis of evoked responses in the motor odd ball test. Response-related neurons were in turn separated into several subgroups according to their reactions in the delayed-response tasks. Some of these neuronal populations reacted preferentially to counting, some--to naming, some--to pressing button.