[Bile and serum biochemical parameters in chronic opisthorchiasis].

Bile biochemical composition and serum hepatic samples were studied in patients with opisthorchiasis and non-parasitic diseases of the biliary tract. Opisthorchiasis was found to cause a much more significant reduction in the concentration of bile acid in the gallbladder. The specific features of the invasive disease manifested themselves in the maximum blood level of cholesterol with its less considerable increase in the cystic bile and with the least concentration of bilirubin in the gallbladder. Analysis in each group of the patients being examined reveals specific correlations between the values of biochemical composition of bile and blood. The findings suggest that biliary tract dysfunction in the absence of a parasitic burden is insufficient to have a noticeable impact on the state of the pancreas and that the composition of cystic bile is predominately affected by impaired biliary excretion in patients with nonparasitic diseases and by the altered concentration function of the gallbladder in those with chronic opisthorchiasis. Thus, comparison of the biochemical composition of bile and serum permits identification of the specific features of the invasive disease and induces to pay attention to the immunopathogenetic mechanisms responsible for hepatic synthetic dysfunction and to the specific features of gallbladder concentration function in opisthorchiasis.

[Biochemical parameters of hepatobiliary system functions in viral hepatitis or ixodes tick-borne borreliosis concurrent with chronic opisthorchiasis].

The biochemical parameters of hepatobiliary system functions were studied in patients with opisthorchiasis and concomitant diseases, such as chronic viral hepatitis concurrent with chronic opisthorchiasis, as well as Ixodes tick-borne borreliosis in the presence of the same invasion. Although the magnitude ofbiochemical changes is not great in chronic opisthorchiasis or chronic viral hepatitis, the concomitance of these two diseases were ascertained to result in pronounced abnormalities, by demonstrating the exhaustion of spare capacities of the hepatobiliary system in parasitic invasion (or viral infection). When opisthorchiasis was concurrent with Ixodes tickborne borreliosis, some parameters under study differed from those in the groups of patients with monoinfections. Variance analysis showed that chronic opisthorchiasis had a great impact on carbohydrate and lipid metabolisms (glucose and cholesterol levels). The findings suggest that the formation of stable host-parasite relationships in chronic opisthorchiasis alters human metabolic processes and their compensatory capabilities.

[Dynamic changes of brain serotonergic and dopaminergic activities during development of anxious depression: experimental study]. / Dinamicheskue izmeneniia serotonergicheskoi i dofaminergicheskoi aktivnosti mozga v protsesse razvitiia trevozhnoi depressii: éksperimental'noe issledovanie.

Chronic psychoemotional stress of social defeats produces development of experimental anxious depression in male mice similar to this disorder in humans. 5-HT and 5-HIAA levels, TPH and MAO A activities, 5-HT1A-receptors in different brain areas were investigated at different stages of development of experimental disorder. It has been shown that initial stage (3 days of social stress) is accompanied by increase of 5-HT level in some brain areas. Decreased 5-HIAA levels in the hippocampus, amygdala and nucleus accumbens were discovered at the stage of forming depression (10 days of social stress). Pharmacological desensitisation and decreased number of 5-HT1A-receptors were shown in frontal cortex and amygdala. At the stage of pronounced depression (20 days of stress), there were no differences in 5-HT and 5-HIAA levels in all brain areas (excluding hypothalamus) of depressive animals. However increased number of 5-HT1A-receptors and decreased affinity in amygdala and decreased TPH and MAOA activities in hippocampus were found in depressive mice. Hypofunction of serotonergic system is suggested at the stage of pronounced depression state in animals. Similar processes had place in brain dopaminergic systems. It is concluded that dynamic changes of brain monoaminergic activities accompany the development of anxious depression in animals. Various parameters of monoaminergic systems are differently changed depending on brain area, mediator system and stage of disorder.

[Changes in the expression of monoaminergic genes under the influence of repeated experience of agonistic interactions: from behavior to gene]. / Izmeneie ékspressii monoaminergicheskikh genov pod vliianiem povtornogo opyta agonisticheskikh vzaimodeistvii: ot povedeniia k genu.

The role of genetic and environmental factors as well as brain neurochemistry in regulating aggressive and submissive behaviors in animals are considered. We present a review of data on changes in brain monoaminergic activity (synthesis, catabolism, receptors) and on the expression of monoaminergetic genes under repeated daily agonistic confrontations in male mice. A repeated experience of aggression was shown to result in the total activation of the dopaminergic system and the inhibition of the serotonergic one. This was accompanied by a decrease in the mRNA level of the catechol-O-methyltransferase gene in the midbrain and an increase of the mRNA level of the dopamine transporter and tyrosine hydroxylase genes in the ventral tegmental area of aggressive male mice. Repeated experience of social defeats produced dynamic changes in the serotonergic system of some brain areas and an increase of the mRNA level of the serotonin transporter and monoamine oxidase A genes in the midbrain raphe nuclei. Theoretical and methodological possibilities of the proposed ethological approach for studying molecular mechanisms of agonistic behavior are discussed in the context of the fundamental problem of investigating the ways of regulation from behavior to gene.

[Impact of anthelminthic therapy for opisthorchiasis on the biochemical parameters of hepatic function]. / Effekt terapii na biokhimicheskie pokazateli funktsii pecheni pri opistorkhoze.

A response of a complex of biochemical parameters of hepatic function to therapeutic exposures was studied at different stages of development of Opisthorchis invasion. The activity of AST, ALT, GGT, GGT, AP, AM, and CE and the concentration of bilirubin, cholesterol, and glucose in the sera from 232 patients with acute or chronic opisthorchiasis were studied. Their study was conducted in several steps: before treatment, after a course of pathogenetic therapy, 1-3 days after antihelminthic therapy with bilthricide and azinox, in early (following 1-3 months) and late (following more than 6 months) residual periods. Pathogenetic therapy was found to alleviate an acute inflammatory process in the liver, but without eliminating cholestasis completely. Antihelminthic therapy improved the results of hepatic tests in different periods after treatment for acute or chronic opisthorchiasis in relation to the rate of compensation of structural lesions. By and large, after pathogenetic and antihelminthic therapy for opisthorchiasis the parameters characterizing the cytolytic syndrome became more rapidly than those that reflect the biliary system. However, there was no complete recovery of impaired hepatic and pancreatic functions throughout the follow-up.

[Biochemical characteristics of hepatic functions in different clinical forms of chronic opisthorchiasis]. / Biokhimicheskaia kharakteristika funktsii pecheni pri razlichnykh klinicheskikh formakh khronicheskogo opistorkhoza.

The main biochemical indices of hepatic functions (the activities of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, alpha-amylase, choline esterase and the concentrations of total bilirubin, cholesterol, and glucose) were studied in the sera of 256 patients with chronic opisthorchiasis. It was found that with diseases manifested in different clinical forms (cholangitis, cholecystitis, cholangiocholecystitis, cholangiohepatitis, cholecystitis in combination with pancreatitis), most study indices are within the normal ranges, but significantly differ from the means in a group of apparently healthy individuals. The findings suggest that such clinical forms of opisthorchiais as cholangiocholecystitis and cholangiohepatitis are characterized by manifestations of cytolysis and cholestasis, as cholecystitis is manifested by cytolysis, as cholecystitis in combination with pancreatitis, by cholestasis, and as cholangitis, by cholestasis and hepatic cell insufficiency. It is possible that further studies will provide evidence for how to correct detected disorders during pathogenetic therapy.

[The effect of the repeated experience of aggression in daily confrontations on the individual and social behavior of male mice]. / Vliianie povtornogo opyta agressii v ezhednevnykh konfrontatsiiakh na individual'noe i sotsial'noe povedenie samtsov myshei.

The influence of repeated experience of aggression in daily intermale confrontations on individual and social behaviour was studied in male mice of C57BL/6J (C57) and CBA/Lac (CBA) strains. Repeated experience of aggression led to a decrease of emotionality in males of highly emotional CBA strain and increase in exploratory activity in the open field and exploratory activity tests, decrease of immobility time in Porsolt's test and pain sensitivity estimated by the "hot plate" test. Low emotional C57 males did not change their individual behaviour in different situations under the influence of repeated experience of aggression. However, aggressive C57 mice demonstrated anxiety-like behaviour estimated in the plus-maze test. In the partition test aggressive mice of both strains showed an increase in communicative level (as a reaction to a familiar male) in comparison with their behaviour before aggressive confrontations. Behavioural reaction to a receptive female under unfamiliar conditions decreased which testified to a decrease in sexual motivation. It is concluded that formation of the aggressive type of social behaviour is accompanied by changes in the individual and social behaviour of male mice. Characteristics of these changes are genetically determined and depend on the duration of confrontations.

[The effect of the repeated experience of victories and defeats in social conflicts on the function of the brain serotoninergic system in male mice]. / Vliianie povtornogo opyta pobed i porazhenii v sotsial'nykh konfliktakh na sostoianie serotoninergicheskoi sistemy golovnogo mozga samtsov myshei.

Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels, tryptophan hydroxylase (TPH) activity, and 5-HT1A receptor binding were studied in brain areas of male mice after repeated experience of victories (winners) and defeats (losers) in daily male confrontations. A decrease in the TPH activity in midbrain and its decrease in hypothalamus were shown in winners in comparison with controls. The victory experiences were accompanied by a pronounced increase of Bmax of 5-HT1A receptors in the frontal cortex and decrease of Kd in the hypothalamus. Repeated defeats in social confrontations were accompanied by an increase in 5-HT level in the amygdala and increase of 5-HIAA/5-HT index in the hippocampus in comparison with controls. A decrease of Bmax in the hypothalamus and of Kd of 5-HT1A receptors both in the frontal cortex and hypothalamus was shown in losers as compared to controls. An increase in TPH activity under the influence of repeated defeats was shown in striatum and hypothalamus. The obtained evidence point to specific changes in serotonergic activity which characterize aggressive or submissive types of social behaviour, and unspecific changes which are similar in winners and losers and are likely to be induced by social stress.

[Changes in the activity of gamma-glutamyltransferase and cholinesterase in the blood of patients with opisthorchiasis at different phases of the disease]. / Izmeneniia aktivnosti gamma-glutamiltransferzay i kholinésterazy v krovi bol'nykh opistorkhozom v razlichnykh fazakh zabolevaniia.

The plasma activity of gamma-glutamyl transferase (GGT) and cholinesterase (CE) was assayed in 79 patients with opisthorchiasis in its active and chronic periods, as well in different periods after anthelminthic therapy with biltricide and azinox. The mean values of CE activity did not significantly differ between the groups of the examinees. The probability of decreased CE synthesis in the residual period was significantly greater in the treatment of chronic than acute opisthorchiasis. The maximum activity of GGT was found in acute opisthorchiasis, its values were also significantly higher than the control ones and remained unchanged within a year after anthelminthic therapy. Possible causes of delayed normalization of enzymatic activity following the treatment of chronic versus acute opisthorchiasis are discussed in the paper.

[The myeloperoxidase of the polymorphonuclear leukocytes as a marker of the stage of Opisthorchis invasion and as an indicator of the efficacy of chemotherapy]. / Mieloperoksidaza polimorfno-iadernykh leikotsitov kak marker stadii opistorkhoznoi invazii i indikator éffektivnosti khimioterapii.

A total of 152 patients with Opisthorchis infection at the acute and chronic stage of the diseases, as well as 1-3 days and 1-2 months after therapy with biltricide in a dose of 60 mg/kg body weight. Intracellular myeloperoxidase was spectrophotometrically determined. Its activity was demonstrated to be significantly varying at the different opisthorchiasis stage. At the acute stage there was a 6-fold increase in the activity of the enzyme as compared with that at the chronic stage. The therapy resulted in the drop of myeloperoxidase levels, at the same time the authors interpret the heterodirectional changes in the activity of myeloperoxidase in the early post-therapeutic period as a fact of individual anthelmintic intolerance the normalization of the parameter studied 1 month after the therapy only in 42.1% of the cases as a fact residual Opisthorchis antigen persistence.

[Experimental model of depression: neurochemical changes and the effects of imipramine and citalopram]. / Eksperimental'naia model' depresii: neirokhimicheskie izmeneniia, éffekty imipramina i tsitaloprama.

A study was made of the influence of the antidepressants imipramine and citalopram (10 mg/kg, chronic administration, i.p.) on the depression-like condition in submissive male rats. The above condition developed under the effect of chronic emotional stress because of successive experience of defeat in social confrontations (Kudryavtseva, Bakshtanovskaya, 1988). Imipramine rather than citalopram exerted a remarkable antidepressive effect recorded by the Porsolt's test. Measurements of the content of serotonin, dopamine and noradrenaline in brain structures have demonstrated changes in the serotoninergic and catecholaminergic systems in males with the depressive symptomatology in relation to intact animals. It should be mentioned that at different stages of pathological process formation, the role of certain structures and mediator systems underwent definite changes.

[The neurochemical control of aggression and submission]. / Neirokhimicheskii kontrol' agressii i podchineniia.

Neurochemical mechanisms of agonistic behaviour in different models of aggression are discussed. The effects of aggression and submission experience in 10 mice intermale confrontations under conditions of sensory contact on the levels of brain neurotransmitters and their metabolites were investigated in 7 brain areas. The values obtained in aggressive and control, or submissive and control, animals were compared. In this comparison neurochemical alterations specific for aggressive or submissive behaviours, or nonspecific became apparent. The long experience of victories leads to activation of dopaminergic system through DA catabolism which leads to DOPAC formation. The long experience of defeats increases the 5HT metabolism and decreases NA level in some brain areas. The dopaminergic system of Nucleus accumbens and midbrain are nonspecifically activated in both aggressive and submissive animals. The investigation of values obtained in animals with conversion of behavioural type (after defeat of previously aggressive animals and/or display of aggressive reaction by previously submissive mice) allowed to find many significant differences between aggressive, submissive and "converted" males; in particular the amygdala is the site of opposite changes in 5HT system during inversion of aggressive or submissive behaviours. The above data evidence for the specific role of transmitter systems and brain structures in maintaining or inversion of different types of agonistic behaviour.

[The strategy of submissive behavior in male mice: the effect of the genotype and the experience of preceding agonistic encounters]. / Strategiia submissivnogo povedeniia samtsov myshei: vliianie genotipa i opyta predshestvuiushchikh agonisticheskikh stolknovenii.

The male mice of two strains with experience of 2 or 10 defeats in intermale agonistic confrontations significantly differ in pattern of submissive behavior (balance of upright and sideways defensive postures, withdrawal, freezing, "on the back" posture). In mice with experience of 20 defeats genetic differences have not been found. The acquisition of consequent experience of defeats does not change the pattern of CBA mice submissive behavior, but significantly increases the share of immobile submissive postures in behavior of C57BL mice. Among submissive males of C57BL strain animals with more active strategy of behavior keep capability for aggressive response to weaker partner. The influence of genotype and previous social contact experience on formation of adaptive in experimental situation strategy of submissive behavior is discussed.

[The effect of the animals' emotional state on ethanol consumption under free-choice conditions]. / Vliianie émotsional'nogo sostoianiia zhivotnykh na potreblenie étanola v usloviiakh svobodnogo vybora.

Voluntary ethanol consumption (20% solution) in mice of C57BL/6J strain with different experience in social agonistic confrontations was studied. It has been shown, that aggressive males daily winning other individuals did not change the level of ethanol consumption, while the submissive mice with daily experience of defeat in intermale encounters dramatically increased that level. Ethanol enhanced the behavioural reactivity of submissive animals to other individuals. It was supposed that emotionally positive or negative states differentiate the ethanol motivations in mice.

[The development of pathological forms of behavior in submissive male C57BL/6J mice during agonistic zoosocial interactions. A possible model of depression?]. / Razvitie patologicheskikh form povedeniia u submissivnykh samtsov myshei linii C57BL/J v protsesse agonisticheskikh zoosotsial'nykh vzaimodeistvii. Vozmozhnaia model' depresii?

It is shown that a long experience of defeats in daily zoosocial collisions (ZC) elicits changes in the structure of submissive behaviour. Male mice of C57BL/6J line after 20 defeats demonstrated poses of passive subordination instead of active defence and run away which they manifested in the first ZC. Moreover, new immobile poses appeared which were rare in the first ZC. Submissive animals (CA) demonstrated a decrease of travels in the open field test and an increase of immobility time in the Porsolt test. Chronic administration of imipramine (10 mg/kg, i.p., twice a day during two weeks against the background of repeated ZC) prevented an increase of depressivity, estimated in Porsolt test. Changes were noted in the content of serotonin and 5-HIAA in some brain structures of subordinated mice in comparison to control animals (five days of isolation). The data are discussed from a position of the development of depression in SA of C57BL/6J line as a result of a long nonavoided zoosocial stress.

[Effect of gamma-aminobutyric acid on the development of catatonia-like states in mice]. / Vliianie gamma-aminomaslianoi kisloty na razvitie katatonopodobnykh sostoianii u myshei.

Catatony-like states including periods of tonic immobility and locomotor paroxysms were induced in mice by a single pinch at the scruff of the neck. GABA-positive drugs (aminooxyacetic acid 20 mg/kg, muscimol 0.5 mg/kg) increased the duration of periods of immobility as compared with control. GABA-negative drugs (thiosemicarbazide 5 mg/kg, bicuculline 3 mg/kg in combination with aminooxyacetic acid) increased only the number and duration of locomotor paroxysms.

[Catatonia as an element of submissive behavior in mice during interspecies agonistic interactions]. / Katatoniia kak élement submissivnogo povedeniia u myshei pri vnutrividovykh agonisticheskikh vzaimodeistviiakh.

A catatonia-like state was elicited in male mice with different experience of social interactions, by pinch of scruff of the neck in a suspended state. In submissive males with long experience of defeat the total time of catatonia reaction during test is considerably greater than in aggressive individuals with a long experience of victories. The change of the social status of the individuals resulting from agonistic interactions leads to a change of the catatonia reaction: manifestation of submissive behaviour is accompanied by an increase of total time of catatonia reaction in the test, the aggressive behaviour is accompanied by its decrease.