Drug abuse situation in the republic of Belarus in the period 2009 — 2013

The situation with the prevalence of drug abuse in the Republic of Belarus and its regions was investigated for the period 2009-2013 using the official data of the Ministry of Health Narcological Service. Over that years the number of registered drug abusers raised by 42% in Belarus. The majority of them were injecting drug users (IDU’s), and the persons who abuse opium-based drugs, cannabinoides, and inhalants. In 2013 there was a sudden increase in detecting of the persons who were poisoned by the Spice type smoking mixtures. The number of registered drug abusers varied depending on a region. The data obtained indicate necessity of regional studies on drug abuse prevalence, and might be useful for working up preventive measures to combat the spread of drug addiction.Исследована ситуация с распространением наркопотребления в Республике Беларусь и ее регионах в 2009-2013 гг. на основе анализа официальных данных наркологической службы Министерства здравоохранения. За указанный период численность зарегистрированных потребителей психоактивных веществ (ПАВ) в Беларуси увеличилась на 42%. В структуре учтенного контингента преобладали потребители инъекционных и опийных наркотиков, каннабиноидов и ингалянтов. В 2013 г. значительно выросло выявление случаев употребления курительных смесей типа «Спайс». Установлены различия в распространенности наркопотребления по регионам Беларуси. Представленные данные свидетельствуют о необходимости учета региональных особенностей при разработке профилактических мер противодействия распространению наркоманий

Ocena rozpowszechnienia uzywania substancji psychoaktywnych wsrod ludnosci na Biatorusi

psychoactive substances, drug abusers, Narcological Register, population, BelarusAim. To evaluate the prevalence of psychoactive substance abuse among the population of Belarus. Material and methods. The data on registered drug abusers, who were recorded in the Narcological Register in health care institutions between 1998 and 201 2, were analyzed. Results. During that period the significant growth (by 3.5 times) in the number of recorded drug abusers was observed, mainly of those who abuse cannabinoides and opiates. Conclusion. It was assumed that the total number of drug abusers in Belarus may be about 6-10 times greater than the number of detected persons. The common trends and patterns of drug abuse in Belarus, Russia and Ukraine were highlighted with the least manifestation of this phenomenon in Belarus

CONTRIBUTION OF VIOLATIONS OF NEUROMEDIATION IN THE BRAIN AND METABOLISM OF GLUCOSE IN THE LIVER AND MUSCLES OF RATS TO MECHANISMS OF FORMATION OF MORPHINE INTOXICATION

Background. The introduction of morphine to the body is followed by numerous metabolic violations. They are both shifts in the functioning of key neuromediator systems of the brain and visceral pathologies. Complex assessment of these violations will enable to create a complete idea of mechanisms of the formation of morphine intoxication with its subsequent metabolic correction. Purpose. Assessment of contribution of the central and peripheral metabolic violations to the formation of morphine intoxication. Material and methods. The complex research of components of the main neuromediator systems in various departments of the brain as well as indicators of glycolysis and a pentose phosphate pathway in the liver and muscles of rats in the main manifestations of morphine intoxication (acute, chronic) and a morphine withdrawal was conducted. Results. The signs of violation of catecholamine neuromediation in thalamic area and midbrain which manifest in three-four weeks after intoxication are revealed. In acute morphine intoxication the activation of glycolysis in the liver and skeletal muscles is noted. In chronic intoxication and withdrawal the effects of morphine manifest in the form of inhibited metabolism of glucose in the studied tissues. Conclusions. There are central and peripheral metabolic mechanisms of formation of morphine intoxication. The received data have important practical value and contribute significantly to understanding biological mechanisms of formation of this disease. These results can be theoretical justification for elaboration of methods of effective diagnostics and treatment of morphine addiction

THE STATE OF NEUROMEDIA IN RAT BRAIN STRUCTURES CAUSED BY CHRONIC AND INTERRUPTED ALCOHOL INTOXICATION

Background. The results of the literature review show that functional state violations of the brain neurotransmitter systems play a key role in the formation of alcohol intoxication signs and the development of addiction syndrome. Purpose of study. To study the influence of chronic (ChAI) and interrupted (IAI) alcohol intoxication with different intervals of ethanol administration on the state of neurotransmitter systems and the level of neurotransmitter amino acids in brain structure of rats. Material and methods. 30 white outbred rats weighing 180-220 g. The content of free amino acids and biogenic amines was determined by HPLC. Results. IAI was not accompanied by changes in the neurotransmitters concentrations in the cortex and the cerebellum. In the striatum IAI-1caused the increase in tyrosine and tryptophan concentration, whereas IAI-4 increased the content of noradrenalin. Conclusions. СhAI and PAI are characterized by the development of neurotransmitter disorders in the studied regions of the brain, with the development of the most pronounced shifts in the striatum

Neurotransmitter Systems of Some Brain Regions of Rats Subjected to Chronic Morphine Intoxication

morphine, brain, dopamine, noradrenaline, serotonin, GABAThe content of neurotransmitters and their metabolites was investigated in brain cortex hemispheres, thalamus and brainstem of rats subjected to chronic morphine intoxication (7-21 days). Morphine administration for 7-14 days was accompanied by changes of the catecholamine system functioning, which was the most pronounced in the thalamus and the brainstem. These changes included increased secretion of dopamine and noradrenaline, their decrease in the brain tissue, and an increased content of their metabolites. The changes in serotonin and GABA content were less pronounced and included a decrease of serotonin level and the increase of the GABA content in different periods of opiate administration

The Effects of Discontinuous Morphine Intoxication on the Pools of Neuroactive Amino Acids and Biogenic Amines in Brain Regions

discontinuous morphine intoxication, biogenic amines, free amino acids,We developed a model of discontinuous morphine intoxication, which is based on 1, 2, and 3 cycles of intraperitoneal morphine administration to rats. During cycle 1, morphine was injected at a dose of 30 mg/kg twice a day for 4 days; a dose of 40 mg/kg was used in cycles 2 and 3. These periods were alternated with drag-free periods. We studied the effects of intermittent morphine administration on the levels of biogenic amines, including serotonin, dopamine, and norepinephrine, and their metabolites and several neuroactive amino acids in the cerebral cortex and midbrain of rats. The alterations in the indices of the serotonergic neurotransmitter system and the pool of free amino acids in brain regions varied depending on the duration of discontinuous morphine administration. Discontinuous morphine intoxication for 14 days was accompanied by the accumulation of serotonin and its metabolites in both brain regions that were studied. This effect became less expressed after more prolonged morphine administration. The metabolic effects of 21-daylong discontinuous morphine intoxication were reflected in the lower content of amino acids and pools of aromatic, neurotransmitter, and excitatory amino acids. Under these conditions, the levels of bio¬genic amines and their metabolites changed insignificantl

Zebra Finch Glucokinase Containing Two Homologous Halves Is an In Silico Chimera

Chimerical nature of the gene annotated as Zebra finch (Taeniopygia guttata) glucokinase (hexokinase IV) has been proved in this study. N-half of the protein encoded by that gene shows similarity with glucokinase from other vertebrates, while its C-half shows similarity with C-halves of hexokinases II. We mapped 7 new exons coding for N-half of hexokinase II and 4 new exons coding for glucokinase of Zebra finch. Finally, we reconstructed normal genes coding for Zebra finch glucokinase and hexokinase II which are situated in "head-to-tail" orientation on the chromosome 22. Because of the error in gene annotation, exons encoding N-half of normal glucokinase have been fused with exons encoding C-half of normal hexokinase II, even though they are separated from each other by the sequence 98066 nucleotides in length

Ethanol binding sites on proteins

Ethanol Hydrogen bonds Binding site Beta strand Alpha helix 3/10 helix Secondary structureThis study is on the analysis of ethanol binding sites on 3D structures of nonredundant proteins from the Protein Data Bank. The only one amino acid residue that is significantly overrepresented around ethanol molecules is Tyr. There are usually two or more Tyr residues in the same ethanol binding site, while residues of Thr, Asp and Gln are underrepresented around them. Residues of Ala and Pro are significantly underrepresented in ethanol binding surfaces. Several residues (Phe, Val, Pro, Ala, Arg, His, Ser, Asp) bind ethanol significantly more frequent if they are not included in beta strands. Residues of Ala, Ile and Arg preferably bind ethanol when they are included in an alpha helix. Ethanol molecules often make hydrogen bonds with oxygen and nitrogen atoms from the main chain of a protein. Because of this reason, the binding of ethanol may be associated with the decrease of the length of alpha helices and the disappearance of 3/10 helices. Obtained data should be useful for studies on new targets of the direct action of ethanol on enzymes, receptors, and transcription factors

Inhibition of Rat Muscle and Liver Phosphofructokinases by High Doses of Ethanol

Activities of both rat muscle and liver phosphofructokinases are significantly inhibited after a single ethanol intake in the dose of 2.5 g per kg of body weight. This inhibitory effect is indirect, since ethanol in concentration (50 mM) close to that established after 2.5 g per kg of body weight intake cannot decrease their activities in vitro. Inhibition of liver phosphofruclokinase activity after the 5.0 g per kg ethanol intake may be direct, since liver phosphofructokinase activity decreases in vitro when ethanol is added to supernatants of rat liver tissue in 100 mM concentration. According to the results of molecular docking, ethanol at high concentrations can be bound by adenine-binding pocket of the allosteric ADP-binding site of liver phosphofructokinase (Asp543, Phe308, Phe538, and Phe671) and its activation by ADP can be blocked by C2H5OH molecule. Direct inhibition of muscle phosphofructokinase activity, probably due to the binding of ethanol to the similar ADP-binding site, is possible when the concentration of ethanol (500 mM) is much higher than the level which can be established in living cells. So, inhibition of muscle phosphofructokinase activity after a single 5.0 g per kg intake is indirect and probably linked with the inhibition of the enzyme by elevated citrate and phosphoenolpyruvate levels

The Influence of Ethanol on Pyruvate Kinases Activity in Vivo, in Vitro, in Silico

Ethanol, Muscle pyruvate kinase, Liver pyruvate kinase, Acute alcohol intoxication, Chronic ethanol intoxication, Ligand dockingThe influence of ethanol on enzymatic activities of muscle and liver pyruvate kinases has been studied in rats in series of in vivo and in vitro experiments accompanied by in silico study. Activity of muscle pyruvate kinase significantly decreased in experiments on acute alcohol intoxication (5.0g/kg of body weight), during chronic alcohol consumption (3.5g/kg of body weight 2 times a day for 14 and 28 days) and during the abstinence after the period of alcohol consumption (5.0g/kg of body weight 2 times a day for 5 days). Activity of liver pyruvate kinase was not decreased in rats after the period of alcohol consumption (5.0g/kg of body weight 2 times a day for 5 days) and during chronic alcohol consumption (3.5g/kg of body weight 2 times a day for 28 days). It even became significantly higher during the chronic alcohol consumption (3.5g/kg of body weight 2 times a day) lasting for 14 days. Inhibitory effect of alcohol bolus on activities of both pyruvate kinases should be linked with certain indirect mechanisms, since direct inhibitory effect was seen in vitro only after the addition of 500 mM ethanol to the rat muscle and liver supernatants. Since lactate dehydrogenase is used in a coupled assay for pyruvate kinase activity estimation we approved that 500mM ethanol did not inhibit lactate dehydrogenase activity in human plasma. Direct inhibition of pyruvate kinases activities should be due to the ability of ethanol to bind amino acid residues from the known allosteric site for alanine binding on muscle and liver pyruvate kinases shown by us with the help of molecular docking. Indirect activation of liver pyruvate kinase can be explained by the increase of glucose blood levels in rats during alcohol consumption promoting dephosphorylation of the enzyme as well as expression of the gene coding for it, and the decrease of alanine concentration in liver