[The link of platelet cytochrome C-oxidase activity with some clinical parameters of depression in elderly patients]. / Svyaz' aktivnosti trombotsitarnoi tsitokhrom s s-oksidazy s otdel'nymi klinicheskimi parametrami depressii u bol'nykh pozhilogo vozrasta.

OBJECTIVE: To search for correlations between platelet cytochrome c-oxidase (COX) activity and the quality of therapeutic outcomes and other clinical parameters of depression in elderly patients. MATERIAL AND METHODS: Twenty elderly women, aged 55-78 years, with depressive episodes in recurrent depressive disorder (RDD) or bipolar affective disorder (BD) were studied. COX activity and severity of depression were evaluated twice: before the beginning of antidepressant treatment and at the 28-th day of the therapy, using the Hamilton Depression Rating Scale (HAMD-17) and the Hamilton Anxiety Rating Scale (HAM-A). RESULTS: Significant correlations were revealed between platelet COX activity and some clinical parameters of the disease and the severity of depression in patients after treatment. The baseline level of the platelet COX activity was correlated with the age of disease onset (R= -0.63, p=0.003) and its duration (R=0.55, p=0.010). Significant negative correlations were also found between the baseline level of COX activity and depression severity (HAMD-17 total score) (R= -0.48, p=0.032) and the severity of anxiety (HARSHAM-A total score) (R= -0.54, p=0.010) after 28-day treatment. CONCLUSION: This pilot study has revealed a link between platelet COX activity and the severity of depression and anxiety after a 28-day antidepressant therapy. The results indicate the prospects for further study of COX as a biomarker of therapeutic outcomes in elderly patients with depression.

[Augmentation with carnicetine for late depression]. / Augmentatsiia karnitsetinom terapii pozdnikh depressii.

AIM: Comparative evaluation of the efficacy and safety of antidepressant monotherapy and complex antidepressant therapy in combination with carnicetine in the treatment of depression in elderly patients in a psychiatric hospital. MATERIAL AND METHODS: Two groups of hospitalized patients, aged from 60 to 79 years, with mild or moderate depression (according to ICD-10), comparable in basic demographic and clinical characteristics, received mono- or complex (in combination with carnicetine) antidepressant therapy for 8 weeks. Treatment efficacy was assessed with HAM-D, HARS, CGI-S and CGI-I; the level of cognitive activity was assessed with MMSE, the 10-word memory test and clock drawing test. RESULTS: It has been established that the use of complex antidepressants therapy with the inclusion of carnicetine allows to achieve a more rapid and pronounced therapeutic response compared to antidepressant monotherapy. This is confirmed by the earlier (by the 4th week) and significant reduction of depressive and anxiety symptoms (p<0.01), a greater number of responders and better quality of depressive outcomes to the end of treatment and a more rapid improvement in cognitive functioning. CONCLUSION: The results allow us to recommend the inclusion of carnicetine for the augmentation of antidepressant therapy in elderly patients of the psychiatric hospital to achieve a more rapid and complete therapeutic response and reduce the duration of hospitalization.

[Optimization of the efficacy and safety of antidepressant therapy in patients of a geriatric psychiatric unit].

AIM: A comparative evaluation of the efficacy and safety of monotherapy with one of the modern antidepressants (venlafaxine, agomelatine, or fluvoxamine) and combination treatment of one of the above mentioned antidepressants with acetyl-L-carnitine (ALС, carnicetine) in the geriatric psychiatric unit. MATERIAL AND METHODS: Two groups of elderly patients (aged 60-79 years) with mild or moderate depression, randomized according to a number of demographic and clinical characteristics, were treated with antidepressants in monotherapy or combined therapy (antidepressant/carnicetine) within 8 weeks. RESULTS: Combination therapy with the neurotrophic agent carnicetine proved to be more effective compared to monotherapy. At the end of treatment, the more rapid clinical response has been shown for depression, anxiety, apathy, and cognitive dysfunction. Furthermore, combination therapy provides less adverse effects. CONCLUSION: Antidepressant/carnicetine combination therapy may be recommended for treatment of depression in elderly patients.

[Experience of the antidepressive therapy with valdoxan (agomelatine) in a psychogeriatric unit of the psychiatric hospital].

OBJECTIVE: To assess therapeutic efficacy, tolerability and safety of valdoxan (agomelatine) in the treatment of depression in elderly inpatients of the psychiatric hospital. MATERIAL AND METHODS: The study included 20 patients, aged 60 years and older, with depression of varying severity. Patients received valdoxan in standard doses 25-50 mg/day during 42 days. RESULTS: Valdoxan showed a good balanced profile (in terms of indicators of depression, anxiety and anhedonia) of therapeutic response and tolerability in inpatients with mild to moderate depression. The use of valdoxan led to a significant reduction of depressive disorders and anxiety already in the early period of treatment. The severity of anhedonia decreased to the 14th day of treatment. A significant improvement in cognitive functioning of patients was noted to the end of treatment. CONCLUSION: Valdoxan can be recommended for treatment of mild and moderate depression in inpatients of psychiatric hospitals.

[The changes of EEG correlation synchrony at depressive disorder of psychogenic type].

In this work we use the alternative method of assessing the EEG-synchrony which previously has proved its high sensitivity to the differentiation of psychopathological and functional states. The original recording of EEG had been performed in the state of quiet wakefulness with eyes closed for two groups of examinees/patients at the age of 49-82 years: a group of normal subjects (n = 29) and the group of subjects with depressive deviations of F43.21 category according to ICD-10 (n = 51). As a result of research it is received the comprehensive picture of significant topographical, interhemispheric and regional differences between groups of norm and depression. One of basic features of the obtained integrated picture is existence at a depression of the extended zones of reduced EEG-synchrony covering the entire premedial region in the frontal-occiptal direction, including intrahemispheric connections as well as lateral frontal-temporal connections in both hemispheres. It testifies to the deep deprivation with depression frontal-occipital and interhemispheric interaction. As a compensatory reaction during depression the increase of synchrony in axial aimed intrahemispheric pairs of derivations. It is noted the similarity of changes in EEG-synchrony topography of depression to those observed in schizophrenia. The used method has provided close to 100% reliability of the classification of the EEG norms and depressive deviations, which makes possible and promising its use as an auxiliary quantitative differential indicator.

[Neurophysiological characteristics of treatment efficacy in late onset depression].

To reveal neurophysiological correlates of treatment efficacy of late onset depression, EEG spectral power, peak latencies of the "late" components of auditory cognitive evoked potentials, and sensorimotor reaction time have been analyzed in two groups of elderly patients, aged 53-72 years, with prolonged psychogenic depressive reaction (F43.21 by ICD-10) and with endogenous depression (F33.1 and F31.3 by ICD-10) during the treatment with antidepressants. Baseline depression severity has been associated with the EEG signs of the decreased functional state of anterior areas of the left hemisphere, and of the increased activation of the right hemisphere (especially, of its temporal regions). The pronounced improvement of clinical condition of patients after psychopharmacotherapy with antidepressants led to the decrease of peak latencies of the "late" components (Р2, N2 и Р3) of auditory cognitive evoked potentials, and to the acceleration of sensorimotor reaction time that have been associated with the EEG signs of the improvement of the functional state of posterior brain areas, and of the facilitation of inhibitory processes in the right hemisphere (especially, in its frontal, central and temporal regions), and of the more pronounced activation of frontal areas of the left hemisphere. The results are in line with the views on systemic character of brain functioning impairment in depression, as well as on the preferential role of the left hemisphere in the control of positive emotions, and of the right hemisphere role in the control of negative emotions as well as in the pathogenesis of depression.

[Neuropsychophysiological correlates of reactive depression].

With the aim of justifying of neurophysiological correlates of depressive disorders spectral parameters of EEG, and peak latencies of the "late" components of auditory cognitive evoked potentials, and latencies of sensorimotor reactions have been analysed in middle age and elderly patients (age 53-72) during the therapy of prolonged psychogenuously provoked depressive reaction (F43.21 by ICD-10). Background depression severity has been associated with the EEG signs of decreased functional state of anterior areas of the left hemisphere, and of increased activation of the right hemisphere (especially, of its temporal regions). Pronounced improvement of clinical condition resulted from psychopharmacotherapy led to acceleration ofsensorimotor reactions, and to decrease of peak latencies of the "late" components (P2, N2 P3) of auditory cognitive evoked potentials, that have been associated with the EEG signs of improvement of functional state of posterior brain areas, of facilitation of inhibitory processes in the right hemisphere (especially, in its frontal, central and temporal regions), and of more pronounced activation of frontal areas of the left hemisphere. The data obtained are in good concordance with the views on systemic character of impairments of brain functioning in depression, as well as on preferential role of the left hemisphere in control of positive emotions, and of the right hemisphere role in control of negative emotions.

[Effect of cholesterol on the bond ordering in hydrated unsaturated lipid bilayers].

Molecular dynamics computer simulations of hydrated bilayers of unsaturated phosphatidylcholines in which double bonds are in the states: 18:0/18:1(n-9)cis (PC), 18:0/18:2(n-6)cis (PC), 18:0/18:3(n-3)cis (PC), 18:0/20:4(n-6)cis (PC), and 18:0/22:6(n-3)cis in the presence of cholesterol (40 mol%) and its absence have been performed. The simulation have been performed at 303 K and 1 atm, under the conditions corresponding to the experimentally observed liquid-crystalline state of the bilayer from phosphatidylcholine. The C-C and C-H bond order parameter profiles with respect to the bilayer normal and the C-C bond orientation distribution functions have been calculated. The widths of the functions and positions of their maxima have been determined. The dependence of these characteristics on the type of the bond, the degree of unsaturation of the chain, the presence of cholesterol in the bilayer, and the bond order parameters have been analyzed.

[Effect of cholesterol on the structure and dynamic properties of unsaturated phospholipid bilayers].

Molecular dynamics (MD) computer simulations of five different hydrated unsaturated phosphatidylcholine lipid bilayers built up by 18:0/18:1(n-9)cis PC, 18:0/18:2(n-6)cis PC, 18:0/18:3(n-3)cis PC, 18:0/20:4(n-6)cis PC, and 18:0/22:6(n-3)cis PC molecules with 40 mol% cholesterol, and the same five pure phosphatidylcholine bilayers have been performed at 303 K. The simulation box of a lipid bilayer contained 96 phosphatidylcholines, 64 cholesterols, and 3840 water molecules (48 phosphatidylcholine molecules and 32 cholesterols per layer and 24 water molecules per phospholipid or cholesterol in each case). The lateral self-diffusion coefficients of the lipids in these systems and mass density profiles with respect to the bilayer normal have been analyzed. It has been found that the lateral diffusion coefficients of phosphatidylcholine molecules increase with increasing number of double bonds in one of the lipid chains, both in pure bilayers and in bilayers with cholesterol. It has been found as well that the lateral diffusion coefficient of phosphatidylcholine molecules of a lipid bilayer with 40 mol% cholesterol is smaller than that for the corresponding pure phosphatidylcholine bilayer.

[Viscumin modulates neutrophil respiratory burst, caused by a chemotactic peptide]. / Viskumin moduliruet respiratornyi vzryv v neitrofilakh, vyzvannyi khemotaksicheskim peptidom.

The ability of viscum at different concentrations to modulate the respiratory burst in neutrophils, induced by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine was studied. This does not exclude the possibility that viscum can interact with the receptor of this peptide. The analysis of the primary structure of viscum revealed elements structurally analogous to the chemotactic peptide. It is assumed that viscum can exhibit the properties an antagonist of the receptor of N-formyl-methionyl-leucyl-phenylalanine, and the mechanism of action of viscum depends on its concentration.

[Features of the modulating effect of complexes of ribosome-inactivating proteins type II with sugars on respiratory burst of neturophils, caused by a chemotactic peptide]. / Osobennosti moduliruiushchego deistviia kompleksov ribosom-inaktiviruiushchikh belkov II tipa s sakharami na respiratornyi vzryv neitrofilov, vyzvannyi khemotaksicheskim peptidom.

It was shown that agents inducing phagocytosis (zymosan, lectins) cause changes in the number of receptors responsible for fast neutrophil reaction (chemotaxis or respiratory burst) or inhibit the binding of the agonist to its receptor. Among lectins are ribosome-inactivating proteins of type II ricin and agglutinin ricin, which penetrate the cell by binding to mannose and galactose receptors. It was shown that ribosome-inactivating proteins of type II can exhibit the properties of the antagonist of the receptor N-formylmethionylleucylphenylalanine. Ricin is more effective in modulating the respiratory burst induced by the chemotactic peptide than agglutinin ricin. The modulating effect of ribosome-inactivating proteins of type II on neutrophils is likely to be mediated by their interaction with galactose rather than mannose receptors. Presumably, the affinity of ribosome-inactivating proteins to galactose receptors increases with increasing amount of saccharides bound to the protein molecule. The modulating effect of ribosome-inactivating proteins of type II on the respiratory burst of neutrophils induced the chemotactic peptide is due to the structural peculiarities of these proteins.

[Symmetry-regulated dynamics of multi-enzyme complexes. A model of a pyruvate dehydrogenase complex from Escherichia coli]. / Upravliaemaia simmetriei dinamika mul'tifermentnykh kompleksov. Model' piruvatdegidrogenaznogo kompleksa iz Escherichia coli.

A dynamic model for quaternary structure of a multienzyme complex is considered. The model is based on the supposition of simultaneously existing similar subunits in a number of different conformational states in the "core" of the multienzyme complex. It is supposed that cyclic conformational transitions of the "core" subunits conserve the symmetry of the entire complex. Such transitions drive the core dynamics as well as the suprastructural multienzyme dynamics. The dynamic model is constructed for the pyruvate dehydrogenase complex from E. coli in a supposition of three different conformers existing in its "core" which correspond to the three steps of the cyclic catalytic process. The model is in accordance with the data from the literature.

[Symmetry of multienzyme complexes]. / O simmetrii polifermentnykh kompleksov.

A model for studying the symmetry of stable states arising from polyenzymic complex conformations is proposed. A formal scheme of submolecular structure self-assembly, on which the model is based, enables it not only to limit the class of conformations but in some cases to determine the structure of a complex in an unambigous manner. The model is shown in its application to polyenzymic complexes of dehydrogenases of alpha-keto acids.