Simulation of the effect of microgravity on the human body by its prolonged rotation about the horizontal located long axis.
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Biomedical subjects
Publications and source records attributed to V M Okudzhava.
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A study was made of metabolism of the new antiepileptic drug halonal in guinea-pigs. It was established that on oral administration halonal was not absorbed from the intestinal tract and only its metabolite, phenobarbital, was detectable in blood serum. It is assumed that halonal produces a therapeutic action only thanks to phenobarbital, its pharmacologically active metabolite.
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Inversion of the early component of IPSPs in neurons of the sensorimotor cortex by artificial hyperpolarization of the membrane was demonstrated in cats immobilized by myorelaxants in acute experiments. The late component of IPSP was not inverted. Amplitudes of the early component of IPSPs were decreased by the membrane depolarization while the late component was completely reduced. The input resistance of the membrane which decreased during the early component of IPSPs was restored to the initial level during the late component.
In cats the hypothalamus proved capable of the primary epileptogenesis. It suggests the principal feasibility of diencephalic (hypothalamic) epilepsy.
In acute experiments on immobilized cats intracellular injection of Ca+ decreased of IPSP and postburst hyperpolarization amplitudes in pyramidal neurons of the sensorimotor cortex. Intracellular injection of ethylene glycol tetraacetic acid had almost the same effect. This substance also reduced the late part of spike afterhyperpolarization, while the early part remained practically unchanged. It is concluded that Ca2+-dependent K+-conductance might play an important role in the genesis of IPSP, postburst and spike afterhyperpolarization in the membrane of pyramidal neurons of the cat sensorimotor cortex.
Major pharmacokinetic parameters of the Soviet anticonvulsive drug benzobarbital used with different regimens of administration (single and prolonged) are described. The authors have studied the interrelationship between benzobarbital and carbamazepine when these drugs are used in combination and drawn a conclusion as to their weak pharmacokinetic synergism. On the basis of the established pharmacokinetic parameters a number of practical inferences pertaining to the mode of benzobarbital administration have been made.
One of the metabolites of the anticonvulsant drug Benzonal (BZL) has been isolated and its chemical structure studied. High-performance liquid chromatography (HPLC) was utilized for isolation of the metabolite from the blood plasma in patients after a single oral BZL dose of 100 mg. Using this technique and ultraviolet, infrared and mass spectrometries BZL was found to be partially metabolized into phenobarbital by human organism.
In 14 epileptic patients the authors determined concentrations of carbamazepine, its total and relative clearance, the period of half-elimination and the elimination constant. Blood levels of carbamazepine were assayed by gas liquid chromatography. The pharmacokinetic parameters have been found to be important for specifying the causes of dissociation between the level of blood anticonvulsant and the therapeutic effect when the attacks cannot be controlled or there were signs of intoxication. The mean diagrams of fluctuations of blood concentrations of the drug in the interval between single doses indicate the dependence of the clinical effect on the amplitude of fluctuations and create the prerequisites for the optimization of anticonvulsive therapy.
Intracellular correlates of evoked rhythmic cortical "spike-and-wave" potentials produced in sensorimotor cortex during 3/s stimulation of the thalamic relay nucleus (VPL) and of self-sustained "spike-and-wave" afterdischarges following 8-14/s stimulation of the same nucleus were studied in acute experiments on cats immobilized by myorelaxants. Intracellular recordings of pyramidal tract neurons revealed that different components of evoked "spike-and-wave" potentials, i. e. the spike-like negative wave and the long lasting negative wave, are postsynaptic in origin: the first is due to EPSPs with spike discharges, and the latter--to IPSPs of cortical neurons. Components of "spike-and-wave" afterdischarge mostly reflect the paroxysmal depolarizing shifts of the membrane potential of cortical neurons. After cessation of sustained "spike-and-wave" activity the long-lasting hyperpolarization accompanied by inhibition of spike discharges and subsequent recovery was observed in cortical neurons. It is presumed that the negative wave of the evoked "spike-and-wave" potential as well as slow negative potentials of direct cortical and primary responses reflect IPSPs of deeper parts of pyramidal tract neurons, while the waves of the sustained "spike-and-wave" afterdischarges are due to paroxysmal depolarizing shifts in cortical neurons.
The intracellular activity of pyramidal tract neurons during electrical stimulation of ventro-lateral and ventro-postero-lateral nuclei of thalamus was studied in acute experiments on cats immobilized by myorelaxants. Both somatic and presumably dendritic spikes (d-spikes) were observed. The latter were characterized by relatively low and variable (5-60 mV) amplitude; d-spikes occurred both spontaneously and in response to single shock and tetanic (8-14/s) stimulation of the thalamus. They were also induced by intracellular depolarizing current pulses and thalamic stimulation following iontophoretic application of strychnine. Simultaneously generated somatic and d-spikes revealed no collision between each other. Intracellular hyperpolarizing current pulses abolished only somatic spikes, while d-spikes were not affected. Dendritic origin with multiple generation zones of these variable spikes is suggested. Possible functional role of d-spike is discussed.
Inversion of the early component of IPSPs in pyramidal neurons of the sensorimotor cortex by intracellular injection of chloride ions was demonstrated in cats immobilized by myorelaxants in acute experiments under moderate composed anesthesia (40 mg/kg nembutal and 20 mg/kg chloralose intraperitoneally). The late component of IPSPs as well as the post-burst hyperpolarization in pyramidal neurons were not inverted. It is concluded that during the early component of IPSPs of both pyramidal and nonpyramidal neurons the membrane permeability is increased for chloride ions, while both the late component of IPSPs and the post-burst hyperpolarization in pyramidal neurons are less dependent on the chloride permeability.
In acute unanesthetized immobilized cats a sequence of fast hyperpolarization and long-lasting depolarization was found in pyramidal tract neurons of the sensorimotor cortex during tetanic stimulation (8-14/s for 10 s) of the ventro-postero-lateral nucleus of the thalamus. During long-lasting depolarization after cessation of stimulation self-sustained rhythmic paroxysmal depolarizing membrane potential shifts appeared which were terminated by long-lasting hyperpolarization. In glial cells only depolarization was observed during stimulation as well as during self-sustained "spike-and-wave" rhythmic activity. Hyperpolarization in glial cells appeared only after its termination in neurons. It is suggested that the long-lasting changes in the membrane potential of cortical elements may play a particular role in formation and cessation of "spike-and-wave" rhythmical activity.
The possibility of cortical "kindling" organization in short time interval (2-3 hours) was shown in acute experiment on cats. The middle area of g. suprasilvius was stimulated by square current pulses (20 per s, 1 ms duration for 5 s with interstimulus intervals of 3 min). As a result of stimulation after the projection discharge in the mirror focus the convulsive activity generalization and formation of independent secondary focuses were observed. In the process of formation of cortical "kindling" the activity of spindle waves could be recorded in all ECoG traces. The frequency of spindle emergence grew according to the epileptization of the animal. The spindle activity transformation into the multiple spike-wave activity was also recorded. The results obtained proved the participation of subcortical structures in the formation of cortical "kindling".
In acute experiments on cats under light nembutal anaesthesia, immobilized by myorelaxants, superficial application of strychnine was shown to suppress the slow negative potentials (arising during direct and primary cortical responses) and IPSPs of the pyramidal neurons corresponding to the slow negative potentials. Iontophoretic application of strychnine blocks predominantly the early component of IPSP during which the input resistance is significantly less than that of the late component indicating their different genesis. It is concluded that individual components of evoked potentials have a common genesis, the slow negative potential is the reflection of the IPSP of pyramidal neurons whose early component seems to be generated by axo-somatic synapses while the late one by axo-dendritic inhibitory synapses. Neurotransmitters in these inhibitory synapses may be different.
In acute experiments on immobilized cats, potentials evoked by stimulation of the ventrolateral and intralaminar thalamic nuclei, of the surface of the sensorimotor cortex and pyramidal pathways as well as the corresponding postsynaptic responses of pyramidal neurons, were studied. A negative shift of potential in response to tetanic stimulation of the cortical surface or thalamic nucleus occurred on the cortical surface. Concominantly, intracellular recording of the glial-cell activity was performed. Superficial application of strychnine induced the suppression of the slow-negative potential arising during direct cortical and primary responses and the corresponding slow potentials of IPSP. The effects of iontophoretic application of strychnine on IPSP of pyramidal neurons and cortical glial-cell response were also studied. Both ways of application appeared to block mainly the early component of IPSP during which the input resistance was significantly lesser than that of the late component, pointing to the difference in their genesis. The findings indicate that slow-negative potentials reflect hyperpolarization of pyramidal neurons, while the separate components of responses have common genesis.
Using gas liquid chromatography, the authors studied phenobarbital levels in the blood and cerebrospinal fluid of 41 epileptic patients following the administration of this anticonvulsant alone. The data obtained showed variations in the concentration of blood phenobarbital at various time intervals after the intake of the drug and a certain correlation between its level and the therapeutic effect. The ratio of phenobarbital level in the cerebrospinal fluid to that in the blood indicates that phenobarbital penetrates the blood-brain barrier. Fluctuations in the blood phenobarbital content from one administration to another is important for selecting its optimal dosage and the interval between intakes.
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