[Neuroprotective effect of N-acylethanolamines in chronic morphine dependence. III. Influence on the content of neurotransmitters in the rat brain].

The effect of the mixture of saturated and unsaturated N-acylethanolamines (NAEs) on the functional activity of catecholamine- and serotoninergic systems of the rat brain with experimental morphine dependence was investigated. A significant decrease of dopamine levels was found in the hypothalamus, midbrain and cortex of rats with morphine dependence. The administration of NAEs to rats with morphine dependence in time course dose of 35 mg/kg markedly increased the levels of dopamine in the hypothalamus, middle brain and cortex. Simultaneously the significant decrease of serotonine content was observed in the midbrain and cortex. The results obtained suggest that one of the important aspects of neuroprotective action of NAEs under morphine dependence is the restoration of dopamine content in the brain.

[Excretion of catecholamines in development of the opium and alcohol abstinence syndrome and in post-abstinence period]. / Ekskretsiia katekholaminiv pid chas rozvytku opiinoho i alkohol'noho abstynentnoho syndromu ta v pisliaabstynentnomu periodi zakhvoriuvannia.

Excretion of catecholamines has been studied in patients with opium narcotic and alcoholic dependence in developmental dynamics of the opium and alcoholic abstinence syndrome and in the postabstinence period. It has been revealed that 8-10 h after cessation of the psychoactive substances (the preabstinence period) the level of excretion of adrenaline [A], dioxyphenylalanine [DOPA], dopamine [DA] and, to the greatest extent, of noradrenaline [NA] especially in patients with alcoholic dependence decreases in comparison with the control variant. As compared to the control variant the acute form of abstinence syndrome (1-3 days after cessation of the psychoactive substances is characterized by the higher level of the A and DA excretion and the lower level of the NA excretion (especially in patients with opium narcotic dependence). As compared to the preabstinence period under conditions of the acute abstinence syndrome there is an essential increase in the level of the A, NA, DOPA and DA excretion. As compared to the control variant the postabstinence period (10-20 days after cessation) is characterized by the lower level of the NA excretion, especially in patients with alcoholic dependence, and of DOPA. The level of DA decreases in patients with alcoholic dependence. As compared to the acute abstienence syndrome the postabstinence period differs by the lower level of the A, NA (especially in patients with alcoholic dependence), DOPA (only inpatients with alcoholic dependence) and of DA excretion.

[Effect of glutaminic acid on the activity of the sympatho-adrenal system and the concentration of calcium in urine under conditions of development of the alcohol abstinence syndrome]. / Vplyv hlutaminovoï kysloty na aktyvnist' sympatyko-adrenalovoï systemy i vmist kal'tsiiu v sechi dynamitsi formuvannia alkohol'noho abstynentnoho syndromu.

The paper deals with the influence of glutaminic acid on the functional activity of the sympatho-adrenal system and the concentration of calcium in urine under conditions of the alcoholic abstinence syndrome development. Changes in the functional activity of sympatho-adrenal system and in the concentration of calcium in the process of the abstinence syndrome development are shown to be of the phase character. It is established that in the period of the developed abstinence syndrome glutaminic acid produces a normalizing action on the excretion of adrenaline and dopamine and also facilitates a decrease in the level of calcium in urine.

[Comparative analysis of the effects of alcoholism and opium addiction on liver function]. / Porivnial'nyi analiz vplyvu alkohol'noï ta opiinoï intoksykatsiï na funktsional'nyi stan pechinky.

Groups of patients suffering alcoholism and narcomania were examined for the effect of intoxication on the blood serum enzymes of mainly liver origin: alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), as well as on thymol test. It has been shown that in patients with the first stage of alcoholism one could observe only functional disturbances in the liver: the increase of ADH activity which evidences for the induction of its synthesis. In patients with the first stage of opium narcomania one can record total hyperenzymenia, decrease of de-Rimis coefficient at the expense of more considerable increase of ALT activity than that of AST, as well as the sharp increase of thymol test--these are the signs of destructive and metabolic disturbances in the liver. In patients with the second stage of alcoholism one can observe the decrease of ALDH activity under the increase of ADH, AST, ALT activity and high thymol test-these are the signs of toxical hepatitis. Destructive and metabolic changes increase in the liver in the patients with the second stage of narcomania.

[Aldehyde dehydrogenase activity and level of dopamine in certain sections of the brain of rats preferring and refusing ethanol]. / Al'degiddegidrogenaznaia aktivnost' i soderzhanie dofamina v nekotorykh otdelakh mozga krys, predpochitaiushchikh i otvergaiushchikh étanol.

Aldehyde dehydrogenase activity (KF 1.2.1.3) of cytosol fractions of brain structures (hypothalamus, midbrain and new cortex) as well as dophamine content in these structures were studied in comparative aspect in rats preferring and rejection ethanol. It has been shown that there were two isoforms of aldehyde dehydrogenases (aldehyde dehydrogenase 1 and aldehyde dehydrogenase 2) in cytosol fractions of all investigated brain structures of animals preferring ethanol while only aldehyde dehydrogenase 2 has been found in the new cotex of rats rejecting ethanol. Thus, aldehyde-dehydrogenase activity is higher in the animals preferring ethanol than in those ones rejecting ethanol. Content of dophamine in the rats preferring ethanol is higher than in those ones rejecting ethanol both in the hypothalamus and new cortex. Differences between the studied groups of animals can underlie the pathologic attraction to alcohol.

[The effect of medikhronal on the psychophysiological and metabolic processes in alcoholism]. / Vplyv medykhronalu na psykhofiziolohichni ta metabolichni protsesy pry alkoholizmi.

Pathopsychological examination, biochemical analysis of blood and urine as well as electroencephalogram (REG) were made in patients of the second (II) stage of alcoholism. The state of higher nervous activity (HNA) before and after treatment with antialcoholic drug medichronal was also analyzed. It has been shown that the course of treatment with medichronal applied to patients with alcoholism results in the removal of the inclination to alcohol, to improvement of functional state of the central nervous system, as well as ethanol (E), acetaldehyde (AcA) and catecholamines (CA) exchange, the disturbances in their metabolism (and first of all AcA) apparently being the basis of pathogenetic mechanisms of alcoholism.

[Role of opiate system in mechanisms of formation of alcohol-dependence]. / Rol' opioidnoi sistemi v mekhanizmakh formuvannia alkogol'noi zalezhnosti.

Effect of naloxon on the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the blood serum and content of catecholamines (CA) in the brain structures (hypothalamus, midbrain, new cortex) and blood of rats under alcoholic dependence were studied. Participation of opiate structures of receptors in formation of alcoholic dependence is shown.

[The effect of medikhronal on the biogenic amine level in the brain structures and blood of animals with alcohol dependence]. / Vplyv medykhronalu na vmist biohennykh aminiv u strukturakh mozku ta krovi tvaryn z alkohol'noiu zalezhnistiu.

Peculiarities of changes in the content of biogenic amines in the brain structures (hypothalamus, midbrain and new cortex) and blood of rats under alcohol intoxication and formation of alcohol dependence were investigated, and the effect of medichronal and its components on the mentioned processes was found out. It has been established that accumulation of acetaldehide plays a considerable role in the mechanism of formation of alcohol dependence. Changes in the level of ethanol (E) and AcA in blood after the arrival of exogenic E to the organism evokes phase dynamics of content of biogenic amines in the blood and brain sections. Medichronal components, binding and inactivating AcA, as well as taking the mutually supplementing effect on synthesis of biogenic amines, promote normalization of the mentioned processes and elimination of alcohol dependence.

[The characteristics of the metabolic and psychophysiological disorders in patients in different stages of chronic alcoholism]. / Osoblyvosti metabolichnykh i psykhofiziolohichnykh zrushen' u khvorykh na riznykh stadiiakh khronichnoho alkoholizmu.

The content of endogenic ethanol (EE) and acetaldehyde (AcA) in blood, excretion of catecholamines (CA) with urine and their content in blood, functional activity of vegetative nerve system and central nerve system were studied in patients with chronic alcoholism in the period of short-term remission. It is shown that the formation and development of chronic alcoholism is accompanied by the shift of the relation AcA/EE towards the progressive accumulation of AcA, disturbances in CA metabolism, shifts in the activity of vegetative nerve system and CNS. Data obtained in the work evidence for the important role of disturbances in metabolic processes (especially E metabolism, as well as CA) in pathogenesis of alcohol dependence.

[The physiological and biochemical indices of the disposition of rats to alcohol use]. / Deiaki fiziolohichni ta biokhimichni pokaznyky skhyl'nosti shchuriv do vzhyvannia alkoholiu.

Activity of aldehide dehydrogenase (ALDH), alcohol dehydrogenase (ADH) in cytoplasmic fractions of brain structures (hypothalamus, midbrain, new cortex) and in blood serum as well as the content of noradreneline (NA) and dofamin (DA) in the mentioned structures and blood of rats preferring ethanol (PE) and rejecting ethanol (RE) has been investigated. ALDH isoforms have been revealed in rats preferring ethanol (PE) and these rejecting it (RE). The activity of the revealed forms of ALDH is higher in PE rats that in RE rats. PE and RE rats do not differ from one another as to ADH activity. It is shown that the NA content is decreased in PE rats and the DA level is increased in a number of brain structures and in blood as compared to RE rats.

[Disturbances in catecholamine metabolism during formation and development of chronic alcoholism]. / Porushennia obminu katekholaminiv pry formuvanni ta rozvytku khronichnoho alkoholizmu.

There has been carried out an investigation dealing with catecholamines metabolism in the patients suffering from alcoholism in the first, second and third stage at the short-term remission. The first developed alcoholism stage was determined as a typical one for increasing the excretion with urine of DOPA, dopamine (DA), noradrenaline (NA) and adrenaline (A), as well as the blood levels of DA, NA and A. DA/NA rate evidences about an increased synthesis of NA with DA. The marked second alcoholism stage is characterized by an acute decrease of excreting with urine and blood levels of NA. Alongside with the latter. DA excretion with urine and its blood levels remained high. DA/NA rate indicates to the considerably low relative activity of NA with DA synthesis, both in relation to the control and to the developed first alcoholism stage. In the third alcoholism stage NA excretion with urine and its blood levels become lower relatively to the marked second stage. Simultaneously DA excretion with urine and its blood levels are lower than in the developed second stage, hower exceed the control values. DA/NA rate testifies the slight activation of NA and DA synthesis. The results obtained in the work indicate to the significant role of CA metabolism disturbances in the alcoholic dependence formation.

[Effect of acetaldehyde on the formation of alcohol dependence in animal experiments]. / Vliianie atsetal'degida na formirovanie alkogol'noi zavisimosti v éksperimentakh na zhivotnykh.

As a result of the experiment on the laboratory animals under the continuous administration of acetaldehyde there has been revealed the latter as inducing the aldehyde dehydrogenase activity in the cytosol fraction of the cerebral structures/hypothalamus, mid-brain and new cerebrum cortex/as well as in the levels of biogenic amines/noradrenaline and 5-hydroxytryptamine/in the same structures while forming experimentally in the laboratory animals the alcoholic dependence under acetaldehyde alcoholic dependence. The work displays some changes of alcohol dehydrogenase and action.

[Dopamine content in blood and activity of alcohol-transforming enzymes in alcoholism]. / Vmist dofaminu v krovi ta aktivnist' systemi alkogol'peretvoriuiuchikh fermentiv za alkogolizmu

An increase of alcohol dehydrogenase activity is observed in patients with chronic alcoholism at the first stage of the disease under normal indices of activity of aldehyde dehydrogenase, aspartate- and alanine aminotransferase and thymol sample that evidences for the induction of alcohol dehydrogenase synthesis in the liver. At the second stage of alcoholism the activity of alcohol dehydrogenase, aspartate- and alanine aminotransferase, the index of thymol sample increase while activity of aldehyde dehydrogenase decreases that indicates to organic destructive changes in the liver. At the third stage of alcoholism one can observe the decrease in activity of alcohol dehydrogenase, aldehyde dehydrogenase and alanine aminotransferase relative to activity of these enzymes at the second stage, that can evidence for the increase of the possibility of the processes of synthesis of the liver. The correlation of alcohol dehydrogenase activity to that of aldehyde dehydrogenase in the process of formation and development of alcoholism is shifted towards the progressive accumulation of acetaldehyde. Parallel increase of dopamine concentration in blood creates conditions for formation of morphine-like alcaloides--products of condensation of acetaldehide with dopamine.

[Biochemical characteristics of various adaptation mechanisms in acute alcoholic intoxication]. / Biokhimicheskaia kharakteristika nekotorykh adaptatsionnykh mekhanizmov pri ostroi alkogol'noi intoksikatsii.

Phase character of metabolic shifts (ethanol, acetaldehyde, catecholamines content, alcohol dehydrogenase and aldehyde dehydrogenase activity) has been revealed in the experiments on white non-inbred rats after a single administration of a sub-narcotic dose of ethanol. Some adaptation-adjustment mechanisms have been established which promote the decrease of the toxic effect of alcohol (induction of activity of alcohol-metabolising enzymes and condensation of acetaldehyde with catecholamines).

[The role of acetaldehyde in the pathogenetic mechanisms of the development of chronic alcoholism]. / Rol' atsetal'degida v patogeneticheskikh mekhanizmakh razvitiia khronicheskogo alkogolizma.

Experiments on white rats were carried out to confirm an important role of acetaldehyde in pathogeny of alcoholism. It is evidenced by results of experiments when animals were given acetaldehyde and medichronal (a drug which combines acetaldehyde) and by data obtained in the course of studies of changes in the content of endogenic ethanol and acetaldehyde, activity of alcohol dehydrogenase and aldehyde dehydrogenase, concentration of biogenic amines (catecholamines and serotonin) in the blood and brain structures.

[Aldehyde dehydrogenase activity of blood serum exposed to different concentrations of acetaldehyde]. / Al'degiddegridrogenaznaia aktivnost' syvorotki krovi pri raznykh kontsentratsiiakh atsetal'degida.

Aldehyde-dehydrogenase activity of blood serum of practically healthy people, patients with chronic alcoholism (stage II) and in the experiment with intact animals (white rats) were studied in comparative aspect. Optimal conditions have been chosen to reveal aldehyde-dehydrogenase activity. It has been shown that aldehyde dehydrogenase of blood serum in healthy people manifests activity at very low (0.012 mM; aldehyde dehydrogenase 1), low (0.060 mM; aldehyde dehydrogenase 2) and high (1 mM; aldehyde dehydrogenase 3) concentrations of acetaldehyde. Activity of aldehyde dehydrogenase 1 is not revealed in patients with chronic alcoholism, while the values of activity of aldehyde dehydrogenase 2 and aldehyde dehydrogenase 3 are decreased. Aldehyde dehydrogenase 2 and aldehyde dehydrogenase 3 have been revealed in the rat blood serum. The apparent values Km and V have been calculated for aldehyde dehydrogenase 1 in people and aldehyde dehydrogenase 2 in rats when using acetaldehyde and NAD as the reaction substrates.

[Norepinephrine content in various brain structures and activity of alcohol dehydrogenase and aldehyde dehydrogenase in blood serum of rats with varying predisposition to ethanol consumption]. / Soderzhanie noradrenalina v nekotorykh strukturakh mozga i aktivnost' alkogol'degidrogenazy i al'degiddegidrogenazy syvorotki krovi krys s razlichnoi predraspolozhennost'iu k potrebleniiu étanola.

Noradrenaline content in hypothalamus, midbrain and new cortex as well as the activity of alcohol- and aldehyde dehydrogenase in the blood serum of rats with different alcohol motivation were studied. It is shown that rats, which prefer ethanol, are characterized by the lower content of noradrenaline in hypothalamus, midbrain and new cortex as compared to animals which prefer water. It is found out that alcohol motivation in rats correlates with high activity of blood serum aldehyde dehydrogenase. No reliable relation between ethanol preferring and activity of blood alcohol dehydrogenase was revealed.

[Toxico-pharmacologic and genetic study of a novel cryopreserving solution for bone marrow cells]. / Toksiko-farmakologicheskie i geneticheskie issledovaniia novogo kriokonserviruiushchego rastvora dlia kletok kostnogo mozga.

Physico-chemical, biological and genetic properties of a cryopreserving solution for myelokaryocytes were studied. It was shown that the solution is harmless for the body, stable during storage, it produces no teratogenic or mutagenic effects, it should not be washed out before bone marrow cell administration to the recipient.

[The enzyme activity and thymol test of the blood serum in chronic alcoholics]. / Aktivnost' fermentov i timolovaia proba syvorotki krovi bol'nykh khronicheskim alkogolizmom.

The authors evaluated the enzymatic activity and thymol test of the blood serum in patients suffering of alcoholism. It was established that the spectra and degree of increase of the examined values in the blood serum differ in the first, second and third stages of the disease and, apparently, to a large extent are caused by functional or organic changes in the liver.