[Neurotransmitter changes in the rat brain under combined intoxication induced by alcohol and morphine]. / Neiromediatornye narusheniia v golovnom mozge krys pri ostroi kompleksnoi intoksikatsii étanolom i morfinom.

We investigated the levels of biogenic monoamines and their metabolites in the rat hypothalamus, midbrain and cerebellum in acute complex intoxication with morphine and alcohol. The distinctive features of neurotransmitter disorders in various parts of the rat brain under a single exposure to ethanol and morphine, as well as the differences between acute morphine-alcohol and alcohol-morphine intoxication were established. Complex intoxication with alcohol and morphine resulted in signs of dopamine consumption only in the hypothalamus, regardless of the order of alcohol and morphine administration. Under conditions of alcohol-morphine intoxication an increase in the level of metabolites of the serotonergic system was noted in the investigated parts of the brain. In the midbrain and cerebellum the manifestation of combined action of ethanol and morphine is mainly determined by the effect of the last of the administered substances. There are features of changes in the indices of the dopaminergic and serotonergic systems in these experimental conditions, confirmed by the processes of dopamine catabolism and a decrease in the norepinephrine and serotonin concentration in the hypothalamus, which are not observed under individual action of ethanol and morphine.

[HOMOCYSTEINE AS A PROGNOSTIC MARKER OF ATRIAL REMODELING AND CLINICAL PICTURE IN PATIENTS WITH PAROXYSMAL AND PERSISTENT FORMS OF ATRIAL FIBRILLATION].

The aim of this work was to study prognostic significance of the relationship between the homocysteine level, structural/functional atrial remodeling, and clinical picture of paroxysmal and persistent forms of atrial fibrillation (AF). The study included 75 patients with AF concomitant with coronary heart disease and hypertensive disease without apparent structural changes in myocardium. Group 1 was comprised of 48 patients with paroxysmal AF, group 2 of 27 patients with persistent AF. 19 patients with coronary heart disease and hypertensive disease without AF served as controls. The structural and functional state of the heart was evaluated based on two-dimensional trans-thoracal echocardiography with the use of the formulas for calculating left ventricular characteristics. Blood homocysteine levels were measured The frequency of AF relapses was determined after an 1 year follow-up. The homocysteine level over 11.2 mcmol/l was related to left ventricle enlargement (over 40 mm), high frequency and relapse rate of AF. It is concluded that the relationship between homocysteine levels, left ventricle size, frequency and relapse rate of AF suggests the influence of homocysteine on atrial remodeling. A rise in the homocysteine level above 11 mcmol/l should be regarded as a prognostic factor of increased AF relapse rate.

[DEVELOPMENT OF THE QUADRIVALENT LIVE ATTENUATED INFLUENZA VACCINE INCLUDING TWO INFLUENZA B LINEAGES--VICTORIA AND YAMAGATA].

This work is devoted to the research of the live attenuated influenza vaccine (LAIV) comprising two reassortant B/USSR/60/69-based vaccine influenza viruses Victoria and Yamagata. The intranasal immunization of the CBA mice with both Victoria and Yamagata strains induced 100% lung protection against the subsequent infection with the wild-type influenza B viruses of any antigen lineage. The quadrivalent LAIV (qLAIV) comprising both reassortant influenza B viruses Victoria and Yamagata were safe and areactogenic in adult volunteers. Following qLAIV administration the immune response was achieved to both Victoria and Yamagata lineages.

[Humoral and cell-mediated immune responses in humans to the A/California/07/ 2009 (H1N1) virus, A(H1N1)pdm2009].

During the twentieth century the world faced four influenza A pandemics: A (H1N1) in 1918, A (H2N2) in 1957, A (H3N2) in 1957 and A (H1N1) recirculation in 1977. In the beginning of 2009 the global spread of A(H1N1)pdm2009 virus was detected. In consideration of clinical evidences and genetic data analysis WHO declared as the novel pandemic of 21th century. However, the fact of exceedingly prolonged previous worldwide circulation of A (H1N1) influenza viruses was not taken into account. Further development showed epidemiological prognosis not to be accurate enough. The present work is an attempt to analyze this question from the immunological standpoint based on our studies of antibody and cellular immunity to A(H1N1)pdm2009 virus in vaccinated and non-vaccinated persons of different ages. The study results allow concluding that A(H1N1)pdm2009 is the drift variant of A (H1N1) viruses antigenically close to A/Swine/1976/1931 (H1N1). It was shown that the significant of persons have cross-reactive B and T cell immunological memory to A(H1N1)pdm2009 strain. This could be a reason of decreased A(H1N1)pdm2009 pandemic severity.

[Effect of infliximab on amino acid content in blood lymphocytes of alcohol-intoxicated rats].

Dose-dependent effects of monoclonal antibodies to tumor necrosis factor alpha (TNFa) in the form of infliximab preparation have been studied in Wistar rats upon with alcohol intoxication for 10 weeks (Lieber- De Carli liquid diet). It is established that the intraperitoneal administration of infliximab within the last 10 days of alcoholization in doses of 1 mg/kg and 10 mg/kg leads to dose-dependent changes in individual indices of the free amino acids pool and the amino acid balance in blood lymphocytes. Infliximab administered on the background of alcohol intoxication increases the pool of free amino acids and activates their metabolism in rat blood lymphocytes, which is probably due to inactivation of TNFalpha and adaptive changes in the amino acid transport system.

[Effect of tritarg on proteinogenic amino acid spectrum in blood serum and lymphocytes].

Single intragastric injection of tritarg leads to different multidirectional changes in the concentration of free proteinogenic amino acids in the blood serum and lymphocytes isolated from the blood and liver. Changes in the amino acid stock of blood and liver lymphocytes were observed 3 and 24 hours after the drug injection. The changes in concentrations of individual free amino acids are more pronounced in liver lymphocytes than in blood lymphocytes. There is a decrease in the content of proteinogenic amino acids in blood serum, which may reflect the supply of these compounds to cells and is indicative of the stimulation of polypeptide and protein synthesis.

[Neuromediator systems in the brain of rats in alcohol abstinence syndrome].

The content of key neuromediators in the brain cortex, brain stem, and thalamus was studied in rats under conditions of alcohol abstinence syndrome. At the peak of the abstinence syndrome manifestation (one day), these parts of the brain were characterized by an increase in the level of dopamine, which was normalized by the end of a one-week period of abstinence. On the third day of abstinence, there was a decrease in the content of noradrenaline in the brain stem on the background of normalization of the neurotransmission processes in the brain cortex and thalamus. Upon a one-week abstinence, the content of noradrenaline in the brain stem and cortex changed in the opposite directions.

[State of neuromediator systems in rat cerebellum and brain stem upon single intake of morphine].

The state of neuromediator systems in the cerebellum and brain stem was studied in rats upon acute morphine intoxication. The drug intake in a single doze of 10 mg/kg is accompanied by a decrease in the levels of dopamine, serotonin, and GABA in the cerebellum. Upon the intake of 20 mg/kg morphine, the contents of dopamine and serotonin in the cerebellum are also lower than in the untreated control, while only the first neuromediator concentration decreases in the brain stem. The administration of morphine in a doze of 40 mg/kg only reduces the level of dopamine in the cerebellum.

[Toxicological evaluation of chronic exposure to dinil].

Experiments on rats were carried out to study the effect of dinil on the animals on chronic intake of the agent in the quantities exceeding the maximum permissible concentrations by many times. Despite few biochemical changes, there was a certain tension of adaptive processes, which appeared as a change mainly in the integral characteristics of the plasma amino acid pool. The observed changes in the levels of neurotransmitters and neuroactive amino acids in the striatum, midbrain, and hypothalamus are characterized by specific characteristics and may underlie the negative effect of dinil on central nervous system functions. Long-term administration of the agent to the animals did not induce pronounced morphological and biochemical disturbances in the tissues of the liver, heart, and kidneys. Changes in the concentrations of serotonin and neuroactive amine acids in the brain regions might have the greatest consequences to the body. Since the detectable changes in a number of metabolites are likely to be functional in the given period (monthly dinil use), an attempt to correct developing disorders with metabolic therapy agents may be recommended.

[Effect of taurine on the pool of central neuroactive compounds during ethanol withdrawal syndrome].

Influence of taurine on the pool of central neuroactive compounds during alcohol withdrawal syndrome has been investigated. Alcohol withdrawal syndrome was accompanied by a pronounced dysbalance in the formation of the pool of neuroactive compounds. The most remarkable changes were found in the levels of markers related to the central serotoninergic system, as well as dopaminergic system. Taurine administration in a dose of 650 mg/kg (i.g.) one hour before decapitation during ethanol withdrawal syndrome alleviates disturbances in the functioning of serotoninergic and (to a lesser extent) dopaminergic systems and improves the ratio of inhibitory and excitatory mediator amino acids.

[GABA metabolism and neuroactive amino acids in the rat brain in morphine withdrawal syndrome].

The changes in the neuroactive amino acid contents, GABA metabolism and TCA reactions have been studied in rat brain regions under experimental morphine withdrawal (MW). MW was developed by means of the cessation of morphine intraperitoneal injections 1 and 36 hours, 3 and 7 days after the course of morphine administration for 7 days. In cortex the significant increase in the contents of glutamate, glutamine, asparagine, and alanine was observed in remote terms of MW. In cerebellum MW led to the decrease in the levels of glutamine and asparagine and increase in glycine level, followed by the GABA-transaminase activation and the succinate dehydrogenase inhibition. In thalamus prolongation of MW caused to the further inhibition of the activities of the GABA-catabolising enzymes. The changes observed in the amino acids levels and the GABA shunt activity are likely to be explained by indirect adaptation of the brain regions differing in the opioid receptors contents to protracted morphine administration.

Metabolic effects of mixture containing branched-chain amino acids and taurine during subchronic poisoning with barbiturates.

We studied the effect of a mixture containing branched-chain amino acids and taurine on the pool of free amino acids and their derivatives during chronic phenobarbital poisoning. Subchronic barbiturate poisoning produced by daily intraperitoneal injection of phenobarbital caused imbalance in the content of some amino acids in blood plasma and liver of rats. Treatment with the mixture of branched-chain amino acids and taurine normalized the content of amino acids in the liver and blood plasma of animals with subchronic phenobarbital poisoning. The mixture of branched-chain amino acids and taurine corrects metabolic processes and normalized the peripheral pool of amino acids. Our findings extend the range for application of amino acids in clinical practice.

[Hepatoprotective effects of amino acids with branched hydrocarbon chains and taurine in experimental subchronic alcohol intoxication and ethanol withdrawal]. / Gepatoprotektivnye éffecty aminokislot s razvetvlennoi uglevodorodnoi tsep'iu i taurina pri éksperimental'noi subkhronicheskoi alkogol'noi intoksikatsii i otmene étanola.

Forced alcoholization of rats according to Majchrowicz led to the development of fatty liver. The subsequent ethanol withdrawal was accompanied by amino acid imbalance in the pool of free sulfur-containing and glycogenic amino acids in liver and blood plasma. Similar changes were observed after prolonged alcohol intoxication. Intragastric administration of the amino acid composition containing branched-chain amino acids and taurine corrected the amino acid imbalance and reduced the development of the steatosis of the liver.

[Effect of the composition of branched chain amino acids, taurine, and tryptophan on the amino acid metabolism in experimental models of alcoholism]. / Vliianie kompozitsii aminokislot s razvetvlennoi uglevodorodnoi tsep'iu, triptofana i taurina na obmen aminokislot v éksperimental'nykh modeliakh alkogolizma.

Ethanol withdrawal after forced alcoholization of rats according to Majchrowicz led to the development of amino acid imbalance in the pool of free amino acids in the liver (increasing levels of alanine, aspartate, glutamate, glutamine and histidine, decreasing levels of glycine, lysine, threonine and taurine) and blood plasma (increasing levels of tyrosine and alanine, decreasing levels of most glycogen aminoacids, branched-chain aminoacids and Lys). Less profound changes were observed after prolonged alcohol intoxication (decreasing levels of alanine, ornitine, citrulline and increasing level of Glu in liver, increasing levels of sulfur-containing compounds, Asp and Lys in blood plasma). Amino acid mixture which contained branched-chain amino acids, taurine and tryptophan administered intragastrically was found to correct levels of sulfur-containing amino acids, threonine, lysine and isoleucine after ethanol withdrawal and to eliminate disorders in urea cycle, exchange of threonine, glycine and phenylalanine after prolonged alcohol intoxication.

[The use of L-tryptophan for correction of disbalance of central neurotransmitters in morphine withdrawal syndrome]. / Primenenie L-triptofana s tsel'iu korrektsii disbalansa tsentral'nykh neiroaktivnykh soedinenii pri sindrome otmeny morfina.

The influence of tryptophan on the content of central neurotransmitters (free amino acids and biogenous amines) in various structures of the rat brain under the conditions of morphine withdrawal has been studied. It is established that the chronic morphine intoxication followed by withdrawal lead to activation of the dopaminergic system and to an increase in the content of exciting amino acids in the rat brain. The morphine withdrawal syndrome is accompanied by inhibition of the serotoninergic activity in all rat brain structures studied. The administration of L-tryptophan (100 mg/kg, i.p.) on the morphine withdrawal syndrome activates the central serotoninergic structures and prevents from further increase in the content of exciting amino acids in the brain.

The effects of melatonin and L-DOPA on the diurnal rhythms of free amino acids content in the rat retina.

The effects of melatonin and dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) intraperitoneal administration on the rhythms of free amino acids content in the retina of rats were studied. The authors found that the levels of those amino acids, which are protein constituents but not neurotransmitters in the rat retina, change diurnally with maximum at 3-6 h after light onset. Diurnal changes of Ala, Arg, Asn, Ile, Met, Ser, Trp, and Val content persisted in the retina of rats maintained at constant darkness. This fact confirms the true circadian nature of these rhythms. Constant lighting abolished diurnal changes of the content of all amino acids with the exception of Trp. Daytime but not nighttime administration of melatonin decreased the levels of Ala, Asn, Gln, Ile, Met, and Ser down to nocturnal values. Diurnal changes of amino acids content vanished in melatonin-injected rats. The effect of melatonin administration disappeared when the protein synthesis was inhibited by cycloheximide. The effect of intraperitoneal administration of L-DOPA on the levels of free amino acids was opposite the effect of melatonin administration. L-DOPA increased nocturnal levels of Gly, Thr, Trp, and Val but had no effect on the daytime amino acids content. As in the case of melatonin administration, significant diurnal changes of amino acid levels disappeared in L-DOPA-injected rats. The authors hypothesize that melatonin and dopamine can serve as zeitgebers-antagonists of amino acids content rhythms in the rat retina.

[The effect of saltwort, Salsola collina, on the phospholipid composition of different sections of the rat brain after ethanol administration and its withdrawal]. / Vliianie solianki kholmovoi na fosfolipidnyi sostav razlichnykh otdelov golovnogo mozga krys posle vvedeniia étanola i ego otmeny.

The authors studied the effect of saltwort alcohol extract (Salsola CK, 200 mg/kg given daily per os for 7 days) on the content of phospholipid fractions in the cerebral hemisphere cortex and brain stem of rats in moderate alcohol intoxication and when the administration of ethanol was stopped (3rd and 7th day). Significant disorders of the phospholipid composition in these brain structures occurred in administration of ethanol and when it was stopped. Administration of CK had no neuroprotective effect on the phospholipid fractions of the cortex of the cerebral hemispheres and brain stem. The possible mechanisms of the discovered changes are discussed.

[Prophylactic effectiveness of a live recombinant influenza type A vaccine in immunizing children aged 3-14 years]. / Profilakticheskaia éffektivnost' zhivoi grippoznoi rekombinantnoi vaktsiny tipa A pri immunizatsii detei 3-14 let.

Children aged 3 to 14 were immunized with live recombinant influenza A vaccine; about 120,000 children were followed up for 6 months. Analysis of the morbidity (excepting ARVI and influenza) of the immunized and control groups permitted a conclusion about the safety of the preparation. The protective index of vaccine efficacy during influenza epidemic caused by A/Taiwan/1/86(H1N1) virus was 1.3 to 1.42. Live recombinant influenza vaccine is recommended for public health to be used for protection of children aged 3 to 14 from influenza.