Narcotic Sleep Research Articles

REVERSE INHIBITORY CONNECTIONS THROUGH GABA B-RECEPTORS SYNCHRONIZE INTERICTAL DISCHARGES IN THE CORTEX

Modern experimental data show that interictal discharges consist of a short spike and a slow wave, which is regarded as a prolonged hyperpolarization. On the model of interictal discharges synchronization, a study of reciprocal inhibitory connections was carried out. In rats in light narcotic sleep, after application of GABA A-receptor blockers to the cortex, interictal discharges occurred in neighboring cortical areas independently of each other, and then synchronization occurred. In the experiments in which the interictal discharges occurred simultaneously, the durations of the slow wave (inhibitory phase) were the same. During the registration in these and other experiments, there was an increase in the time delay between the moments of interictal discharges generation. Under conditions of increased synchronization, the duration of the slow wave (inhibitory phase) of interictal discharges increased. Interictal discharges, which occurred first, had a longer duration of inhibition compared to the duration in the neighboring point, because the inhibition from the neighboring networks via feedback inhibitory connections is added to its own inhibition in the neuronal network. When excitation occurred, it was followed by inhibition via feedback, which limited the period of excitation, and thus created a temporary integration window, and this also happened in the neighboring neural networks of the cortex.

Experience in the application of remote anesthesia in Callorhinus ursinus

Marine mammals often become entangled in various objects of anthropogenic origin floating on the surface of the water. Plastic, polyethylene, synthetic packing straps, and fishing gear threaten marine mammals in the water and on land. The study was carried out on 29 specimens of Callorhinus ursinus. We used a combined Zoletil 100 and Medetin 1% for remote sedation of injured Callorhinus ursinus to release foreign objects.Resultsthe first signs of anesthesia were recorded 3‐5 minutes after drug delivery. The difficulty of movement, coordination disorder, weakness were noted. After 5‐15 minutes, the animals lay down but reacted to touch, and their eyes were open. After 15‐20 minutes, the animals lay motionless, practically not reacting to external stimuli. Their eyes were in a half‐closed state. In this state, it is possible to carry out manipulations to remove foreign objects from the animal. The depth of narcotic sleep varied depending on the dose: mild sedation developed at Medetin 1% 0.02‐0.03 mg/kg and Zoletil 100 0.45‐0.65 mg/kg. The animals were lying down, we could approach them, but they reacted to touches and loud sounds. The eyes were open, and it was dangerous to carry out any manipulations with such animals. The seals did not fall into a deep sleep; after 30‐60 minutes without the use of antagonists, they began to move, but there was a slight impairment of coordination of movements for 1‐2 hours. Moderate sedation was observed at a dose of 0.03‐0.05 mg / kg Medetin 1% and 0.5‐0.9 mg / kg Zoletil 100. The animals lay motionless; sometimes, there was a slight twitching of their fins, whiskers, or ears during manipulation of slight pain. Eyes half‐closed. It is possible to carry out small short‐term manipulations with the animal to remove a foreign object without strong painful sensations. After 30‐60 minutes, the seals wiggled their flippers and tried to raise their heads. They began to move independently after 1‐1.5 hours. Slight impairment of coordination was noted 1.5‐2 hours after full awakening. At a dose of 0.05‐0.09 mg/kg Medetin 1% and 0.8‐2.0 mg/kg Zoletil 100, the animals lay motionless and did not react to external stimuli, even during painful manipulations or movement. This sedation is deep, suitable for painful procedures to remove foreign objects with deep skin lesions. Without the use of antagonists, such animals woke up after 1‐1.5 hours. They began to move their flippers, mustache, move around after 2.5‐3 hours. Determining the optimal doses of drugs for remote anesthesia of marine mammals is essential, both for the safe release of foreign objects from the animals and also for the people who perform this work.

Interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication

A sufficient number of facts testifying the importance of liver arginase and nitrogen monoxide in the life processes in the normal and pathological conditions have been accumulated to date. The aim of the study was to determine the significance of the relationship and interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication. In rat experiments using the modern physiological, biochemical research methods and a pharmacological approach, it was found that chronic ethanol intoxication leads to a decrease in the liver arginase activity and the triiodothyronine concentration. At the same time, the increase in the level of “average molecules”, NO3 – /NO2 –, the content of lipid peroxidation products in the plasma, as well as the increase in the blood toxicity degree, the activity of alanine amino transferase, aspartate amino transferase and the narcotic sleep duration were observed. Hyperthyroid rats demonstrated the increased liver arginase activity, the processes of detoxification, lipid peroxidation and body temperature while rats with the experimental hypothyroidism showed the opposite results. The liver arginase depression caused by the injection of Nω-hydroxy-nor-L-arginine (Nor-NOHA), or L-valine into the body prevents the body temperature increase and the development of characteristic changes in the detoxification and lipid peroxidation processes acted upon by exogenous triiodothyronine. Under the conditions of the liver arginase inhibition by Nor-NOHA or L-valine, the ethanol action is accompanied by a more significant inhibition of the liver detoxification function and an increase of NO3 – /NO2 – levels in blood plasma. The preliminary injection of an NG-nitro-L-arginine methyl ester inhibitor of NO-synthase into the animal’s body weakensthe toxic ethanol effect on the liver, as well asthe development of characteristic changes in the liver arginase activity, in the processes of detoxification and lipid peroxidation in rats with chronic ethanol intoxication. Apparently, the activity of liver arginase and L-arginine-NO system determines the severity of detoxification, lipid peroxidation processes and the formation of the thyroid status in the conditions of chronic alcoholization, which is important in the ethanol intoxication pathogenesis.

On the participation of eosinophils in tissue recovery after a local cold injury

The article studies the correlation of the content of peripheral blood and red bone marrow eosinophils with the level of secretion of fibroblast growth factor (FGF-21), insulin-like factor (IGF-1) and vasculoendothelial growth factor (VEGF-C) in blood serum during the formation of dermal collagen after local cold damage. Animals of the experimental group after the onset of narcotic sleep on the depilated skin of the back were simulated contact frostbite of the 3rd degree. On the 3rd, 7th, 14th and 21st day of the experiment, the concentrations of growth factors, % dermal collagen content, and also the content of eosinophils in peripheral blood and red bone marrow were determined in the blood serum. The research results showed that the development of eosinopenia after a local cold injury occurs due to the sequestration of eosinophils in the affected area. The presence of reactive changes after a local cold injury not only in peripheral blood, but also in the red bone marrow may indicate the participation of eosinophils in tissue repair processes after a local cold injury.

CHANGES IN THE CONTENT OF IMMUNE CELLS CONTAINING THE FcR III RECEPTOR IN THE SLEEP AND BRAIN AFTER EXPERIMENTAL TBI

At TBI there are disturbances in activity of immune system, can complicate regenerative and reparative responses in a brain. The aim of the study was to study the content of CD-16 cells in the spleen and brain parenchyma at different times after TBI in rats and in the correction of disorders in their composition by immunomodulatory drug galalite.Methods. Craniocerebral trauma in animals was modeled by dropping a load weighing 100 g from a height of 120 cm on the head of rats that were anesthetized and were in a state of narcotic sleep, which lasted up to 30 minutes. To correct the resulting disorders used immunomodulatory drug galavit at a dose of 2 mg / kg of animal weight in a volume of0.5 ml, which was administered intramuscularly to animals for 2, 3, 4 days after injury. The spleen and the left and right hemispheres of the brain were homogenized in 5.0 ml of medium 199 and suspensions containing 10.0x106 cells per 1 ml of medium 199 microglia were prepared and infiltrated CNS monocytes were prepared by the method of Sedgwick J. in co-authors. Determination of the level of CD-16 cells in suspensions of spleen and microglia was performed on a flow cytometer using monoclonal antibodies against CD-16 receptor company BD Biosciences according to the instructions for antibodies.Results. In mild TBI in rats, the number of CD- 16 cells containing the FcR III receptor decreases in the spleen for 2 to 5 days, and the number of these cells in the fractions of microglial cells increases. Galavit is a drug with immunomodulatory properties, has virtually no effect on low levels of CD-16 cells in the spleen and stimulates their accumulation in the brain for 10 days after TBI.Conclusions. The results indicate the effect of Galavit on the level of CD-16 cells in the spleen and brain, which indicates the immunomodulatory activity of this drug.

Evaluation of knowledge of Polish medical students regarding toxic plants

Abstract Introduction. There are approximately 300 species of poisonous plants in Poland. About 50 of them contain toxic substances which pose threat to health when consumed. Accidental poisonings remain the most common cause, but there were also cases correlated to suicidal or criminal purposes. There are only few toxicological departments in Poland keeping the records of plant poisonings, what makes presented data inaccurate. Aim. The authors decided to evaluate knowledge of Polish medical students regarding toxic plants and symptoms of its intoxication. Material and methods. The number of 734 online responses from students enrolled in medical studies at 16 different Polish universities were collected and analyzed to draw a conclusion. Results. As many as 87.6% of all respondents were in favor of introducing obligatory classes covering the issue of toxic plants. They were also asked to identify plants presented in the pictures. When it comes to 53.1% of students, they were familiar with Datura stramonium L. Over half of the participants were able to recognize the mild symptoms of intoxication, when 25.9% linked the poisoning to narcotic sleep. Taxus baccata L. was identified by 86.6% of the respondents and the majority of them possessed knowledge about the related symptoms. Heracleum sosnowskyi Manden. and Caltha palustris L. were recognized by respectively 94% and 64% of the students. As many as 84.1% of participants knew the effects of Heracleum sosnowskyi Manden intoxication. All correct answers related to this poisoning were chosen by 48.3% respondents. The results revealed that the symptoms of Caltha palustris L. are unknown to the majority. Atropa belladonna L. was successfully identified by 93.6%, Galanthus nivalis L. by 55.4% of the students, with a lower percentage of correct responses related to its intoxication. Conclusions. Such differentiated knowledge can be the result of both educational variances and personal experience. Polish medical universities should consider introducing extra classes that would cover the issue of toxic plant intoxications.

What kind of sleep is narcotic sleep? How different cannabinoids induce changes in the EEG of mice and the mechanism behind it

What kind of sleep is narcotic sleep? How different cannabinoids induce changes in the EEG of mice and the mechanism behind it

Serial electrical stimulations of hypothalamic Orexin-containing neuronal regions lead to elevation of CSF OrexinA concentration, shorten anesthesia time and fasten recovery of normal sleep cycles from deep anesthesia induced sleep

Introduction The aim of the study was to assess the hypothalamic Orexinergic system as the neuronal substrate for speeding up regulation of disturbed sleep homeostasis and recovery of sleep-wakefulness cycle in different behavioral states from some pathological conditions, namely from deep anesthesia induced sleep. Pre-clinical evidence in relation to this question are very sparse and therefore their investigation is highly topical. Materials and methods In white wild rats ( n = 12) after Surgical implantation of recording electrodes and postoperative recovery deep anesthesia was induced by chloralhidrate and/or sodium ethaminal. EEG registration was started immediately and lasted continuously for 48 h. 10 min after administration of anesthetic drugs serial electrical stimulations (8–12 v, 200 c/s, 0.1 ms) of dorsal, lateral, posterior and perifornical hypothalamic Orexin-containing neurons were started. Stimulations lasted for 1 h with the 5 min intervals between subsequent ones applied by turn to the left and right side hypothalamic parts. CSF OrexinA concentration was measured by ELISA method. Statistical processing was made by Students’ t -test. Results Spontaneous recovery of the first fragments of EEG wakefulness from deep anesthesia-induced sleep required 5.0–5.5 h depending on the depth of narcosis. Serial electrical stimulations of dorsal, lateral, posterior and perifornical hypothalamic Orexin-containing neurons significantly speed up wakefulness recovery from both types of narcotic sleep with the first fragments of wakefulness appearing 3.5–4 h after deep anesthesia. The first fragments of wakefulness were rapid (20–30 min) followed by normal deep slow wave sleep episodes. Especially strong influence of serial electrical stimulations of hypothalamic Orexin neuron containing parts was manifested in the recovery of REM sleep. Spontaneous recovery of this behavioral state took 23–24 h after deep anesthesia but under the impact of electrical stimulations of above mentioned hypothalamic parts REM latency became more than two times shorter. Significant elevation was noted in CSF OrexinA concentration in stimulated animals. Conclusion Serial electrical stimulations of hypothalamic Orexin-containing neuronal regions significantly elevate CSF OrexinA concentration and speed up recovery of normal sleep-wakefulness cycle behavioral states from deep anesthesia-induced sleep. Acknowledgements Acknowledgements. Supported by Shota Rustaveli National Science Foundation, Grant #11/04.

Up-regulation of 2-oxoglutarate dehydrogenase as a stress response

2-Oxoglutarate dehydrogenase multienzyme complex (OGDHC) operates at a metabolic cross-road, mediating Ca2+- and ADP-dependent signals in mitochondria. Here, we test our hypothesis that OGDHC plays a major role in the neurotransmitter metabolism and associated stress response. This possibility was assessed using succinyl phosphonate (SP), a highly specific and efficient in vivo inhibitor of OGDHC. Animals exposed to toxicants (SP, ethanol or MnCl2), trauma or acute hypoxia showed intrinsic up-regulation of OGDHC in brain and heart. The known mechanism of the SP action as OGDHC inhibitor pointed to the up-regulation triggered by the enzyme impairment. The animal behavior and skeletal muscle or heart performance were tested to correlate physiology with the OGDHC regulation and associated changes in the glutamate and cellular energy status. The SP-treated animals exhibited interdependent changes in the brain OGDHC activity, glutamate level and cardiac autonomic balance, suggesting the neurotransmitter role of glutamate to be involved in the changed heart performance. Energy insufficiency after OGDHC inhibition was detectable neither in animals up to 25mg/kg SP, nor in cell culture during 24h incubation with 0.1mM SP. However, in animals subjected to acute ethanol intoxication SP did evoke energy deficit, decreasing muscular strength and locomotion and increasing the narcotic sleep duration. This correlated with the SP-induced decrease in NAD(P)H levels of the ethanol-exposed neurons. Thus, we show the existence of natural mechanisms to up-regulate mammalian OGDHC in response to stress, with both the glutamate neurotransmission and energy production potentially involved in the OGDHC impact on physiological performance.This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.

Parameters of Microcirculation in Paired Formations after Single Aspirin Administration: Laser Doppler Flowmetry Data

Laser Doppler flowmetry showed that aspirin can induce blood flow reduction and transitory manifold increase or decrease in vascular tone in rat skin and kidneys. The dynamics is more illustrative when parameters of individual animals are evaluated and depends on the areas of blood flow recording. Deaths and reduction of narcotic sleep duration were noted in concomitant use of nembutal and aspirin.

INHIBITION OF THE BLADDER COOLING REFLEX IN THE AWAKE STATE: AN EXPERIMENTAL STUDY IN THE CAT

We assessed the bladder cooling reflex in the awake cat. The bladder cooling reflex is consistently observed in anesthetized adult cats but not in awake, neurologically normal humans. This discrepancy could indicate a state dependant control of the reflex or a species difference. This study was designed to differentiate between these alternatives, Under ketamine-xylazine 5 animals had an indwelling catheter inserted into the bladder. The cooling reflex was tested by injections of cold saline into the bladder (4C to 8C), lowering its wall temperature to about 30C to 32C. The volume used (5 ml) was subthreshold for the Adelta micturition reflex, as confirmed by control injections of body warm saline. The procedure was repeated with the animals fully awake and it was well tolerated by all of them. Reflex responses were assessed by induced bladder pressures. Typical bladder cooling reflexes with peak pressures greater than 3 kPa were evoked in all cats when in narcotic sleep (group mean +/- CI 7.4 +/- 3.1 kPa). No such reflexes were elicited when the animals were awake (2.0 +/- 1.0 kPa). The difference was significant at the level of individual animals. The bladder cooling reflex is suppressed in adult cats during wakefulness, as in humans. This state dependent control of the bladder cooling reflex adds to its resemblance to the extensor plantar response (Babinski's sign).

Dehydrogenase systems of different rat tissues in experimental alcoholism simulated by inhalation or forced intake of ethanol

It is shown that alcoholization of rats during 1.5 months by the inhalation of ethanol vapors with a long-term subsidence into narcotic sleep results in alcohol dependence and marked shifts in the ratio between the activity of malate and lactate dehydrogenases and a change in the isoenzyme spectrum of the latter. This leads to an enhancement of aerobic processes in the brain and skeletal muscle tissues and of anaerobic processes in the liver and myocardium. Semiforced alcoholization of rats during 11 months, with ethanol solution serving as the only soruce of liquid, moderately lowers the ethanol tolerance and does not affect the dehydrogenase activity in the tissues examined. The effects of ethanol on the activity of functionally associated enzyme systems of malate and lactate dehydrogenases are believed to depend on the method of alcoholization and the type of tissue.

Computer evaluation of cat brain activation by means of striate cortex ecog

We analyzed striate cortex electrocorticograms of 12 cats in the following states: at rest with eyes closed and with eyes open; after light electrical stimulation of the ears; drowsiness; opening of the eyes after drowsiness; narcotic sleep. Spectral and periodometric analyses of the ECOG revealed state-dependent differences in power spectra from cats in two frequency bands (2.8–5.0 and 13.8–20.8 Hz). It is suggested that the ratio of ECOG power spectra in these frequency bands can be used to evaluate brain activation in cats.

Diethylstilbestrol counteracts barbiturate narcosis and hypothermia in male mice.

Treatment with DES one hour prior to pentobarbital injection resulted in diminution of the narcotic sleep and hypothermia usually found after pentobarbital (50 mg/kg 1) injection in male mice. The effect was biphasic: significantly countered relative to saline pretreated controls at low (.001-.10 mg/kg 1) and at high (10-50 mg/kg -1) DES doses only. Giving DES alone did not change core body temperature compared to saline injected controls, at either 25 degrees C or at 33 degrees C. At 33 degrees C, neither PeB narcosis nor body temperature loss was significantly inhibited by DES. Possible cytoplasmic, nonsex differentiated bases for these estrogen effects on barbiturate action in the brain is discussed.

Effect of depth of narcotic sleep on correlations of the electroencephalogram

Effect of depth of narcotic sleep on correlations of the electroencephalogram

Certain characteristics of the onset of narcotic sleep in the frog during inhalation of ether vapor following bilateral severing of the vagosympathetic nerve trunks

In frogs with severed vagosympathetic trunks narcotic sleep during ether vapor inhalation set in earlier, while the excitation phase was earlier and shorter than in frogs with intact lungs. At the same time, the duration of sleep was equal in both, whereas ether expenditure was much larger in the latter.

Associate Professor E. I. Zaitseva (Smolensk). On the significance of functional changes in the liver in the treatment of peptic ulcer disease with sleep

Many aspects of sleep therapy are not yet well understood. Firstly, it cannot be assumed that during the treatment with medication sleep, only conditions that protect the nerve cells are created - at the same time, one or another force shifts in biochemical processes (and, consequently, in the functions) of tissues of all organs and systems. They do not bypass the brain tissue either, and this affects the cortico-visceral relationship. The shifts in the body caused by narcotic sleep are sometimes so significant that they themselves can cause painful manifestations. Secondly, it is quite obvious that not only changes in the central nervous system are to blame for the onset of the disease, and the use of artificial inhibition in all stages and with various manifestations of the disease cannot be considered justified for therapeutic purposes. Thirdly, hypnotic substances make changes during all processes in the body during treatment and thus affect the results of treatment.

Existence and significance of a physiological anticoagulating system.

WHEN moderate doses of tissue thromboplastin are injected into the jugular vein of rats the circulating blood loses its clotting properties, with the result that no intravascular thrombi are, as a rule, produced. This effect of thromboplastin depends upon its capacity for inducing the formation of thrombin in blood from the plasma prothrombin. In most cases intravenous administration of moderate doses of thrombin to healthy animals does not cause thrombosis, for the clotting mechanism becomes disordered almost immediately after the injections. At the same time the thromboplastic activity of blood shows a sharp decrease, while fibrinogen capable of reacting with thrombin disappears and heparin-like substances appear in the blood. This protective reaction, maintaining the blood in a fluid state in the vascular bed when thrombin arises in it, is brought about by the physiological anticoagulating system. Experiments have shown that in narcotic sleep resulting from inhalation of sulphuric ether, as well as from anæsthesia produced by an intramuscular injection of novocaine on both sides of the spinal column, this anticoagulating system ceases to function. It is this effect that accounts for the fact that coagulation of circulating blood and death from thrombosis have been found to occur in anæsthetized test animals (as opposed to controls in a normal physiological condition) after an intravenous administration of certain doses of thrombin (Table 1).

The influence of removal of the cerebral cortex and certain pharmacological substances on the development and course of fever

The influence on the development and course of fever during narcotic sleep in cases of extirpation of the cortex has been studied.