[A strategy for increasing the efficiency of psychopharmacological treatment of hyperkinetic behavior disorder with pantogam]. / Strategiia povysheniia éffektivnosti psikhofarmakologicheskogo lecheniia giperkineticheskogo rasstroistva povedeniia s primeneniem pantogama.

AIM: To assess short-term efficiency of hopantenic acid (pantogam) in the treatment of children with hyperkinetic behavior disorder, in whom the previous treatment with atomoxetine was not efficient. MATERIAL AND METHODS: Twenty-four children (16 boys and 8 girls), aged 6-11 years, diagnosed with hyperkinetic behavior disorder (ICD-10 item F90.1) were enrolled in this open non-randomized study. RESULTS AND CONCLUSION: A short-term positive therapeutic dynamics was observed when introducing hopantenic acid (pantogam) augmentation strategy to existing atomoxetine therapy. Qualitative improvements in children's state were found not only in the ability to control symptoms but also in their social functioning levels and quality of life. The proposed therapeutic strategy can help to improve treatment outcomes for children with certain clinical forms of hyperkinetic behavior disorder.

[Pantogam augmentation in hyperkinetic behavior disorder treatment]. / Povyshenie effektivnosti lecheniya giperkineticheskikh rasstroistv s primeneniem pantogama.

A clinical case of a child with hyperkinetic conduct disorder is presented, with symptoms of hyperkinetic disorder itself closely intertwining with symptoms of conduct disorder. The qualitative changes in the child's condition are noted, including not only achieved control over the symptoms, but also improved social functioning level, achieved by means of Pantogam (neuroprotective drug) addition to atomoxetine therapy. The proposed strategy can contribute to improvement of treatment results for children with certain clinical types of hyperkinetic conduct disorder.

[The influence of premorbid functioning on the efficacy of psychosocial therapy in adolescents with schizophrenia spectrum disorders]. / Vliianie urovnia premorbidnogo funktsionirovaniia na éffektivnost' gruppovoĭ psikhosotsial'noĭ terapii u podrostkov s rasstroĭstvami shizofrenicheskogo spektra.

AIM: To explore an effect of premorbid functioning level on the efficacy of psychosocial therapy in adolescents with schizophrenia spectrum disorders in order to determine a differential approach to its performance. MATERIAL AND METHODS: A study included 53 adolescents with schizophrenia spectrum disorders at the early stage of remission achievement (PANSS scores <65). An impact of premorbid functioning was assessed with the DD-CGAS and the efficacy of psychosocial therapy with CGAS and PedsQL at baseline and after 3, 6 and 12 months. RESULTS AND CONCLUSION: We described the most relevant differences in characteristics of treatment effect (dc) between three groups with different levels of premorbid functioning. To increase the efficacy of psychosocial interventions, we suggest a differential approach of psychosocial therapy in each group.

[An influence of mental disorder in the child on the parents in the context of differentiated approaches to psychosocial interventions on childhood psychiatry].

OBJECTIVE: To specify parent reaction to a mental disorder in the child and to develop differential approaches to psychosocial family interventions. MATERIAL AND METHODS: Authors studied parents (mostly mothers) of 140 children with schizophrenia spectrum disorders, 100 children with autistic disorders and 85 children with mental retardation. Along with psychiatric examination of the parents, it was used psychometric scales ECI and CGSQ. RESULTS: Authors specified emotional and behavioral characteristics of the parents' reaction as common for all diseases studied as well peculiar for separated forms of mental diseases in children. The factors (cognitive, emotional and behavioral) determining the targets of differentiated therapeutic interventions were singled out. CONCLUSION: The stress coping strategies for parents are formulated.

Cellugyrin is a marker for a distinct population of intracellular Glut4-containing vesicles.

Although Glut4 traffic is routinely described as translocation from an "intracellular storage pool" to the plasma membrane, it has been long realized that Glut4 travels through at least two functionally distinct intracellular membrane compartments on the way to and from the cell surface. Biochemical separation and systematic studies of the individual Glut4-containing compartments have been limited by the lack of appropriate reagents. We have prepared a monoclonal antibody against a novel component protein of Glut4 vesicles and have identified this protein as cellugyrin, a ubiquitously expressed homologue of a major synaptic vesicle protein, synaptogyrin. By means of sucrose gradient centrifugation, immunoadsorption, and confocal microscopy, we have shown that virtually all cellugyrin is co-localized with Glut4 in the same vesicles. However, unlike Glut4, cellugyrin is not re-distributed to the plasma membrane in response to insulin stimulation, and at least 40-50% of the total population of Glut4 vesicles do not contain this protein. We suggest that cellugyrin represents a specific marker of a functionally distinct population of Glut4 vesicles that permanently maintains its intracellular localization and is not recruited to the plasma membrane by insulin.

Glucose transporter Glut3 is targeted to secretory vesicles in neurons and PC12 cells.

In rat brain and cultured neuroendocrine PC12 cells, Glut3 is localized at the cell surface and, also, in a distinct population of homogenous synaptic-like vesicles. Glut3-containing vesicles co-purify with "classical" synaptic vesicles, but can be separated from the latter by sucrose gradient centrifugation. Unlike classical synaptic vesicles, Glut3-containing vesicles possess a high level of aminopeptidase activity, which has been identified as aminopeptidase B. This enzyme has recently been shown to be a marker of the secretory pathway in PC12 cells (Balogh, A., Cadel, S., Foulon, T., Picart, R., Der Garabedian, A., Rousselet, A., Tougard, C., and Cohen, P. (1998) J. Cell Sci. 111, 161-169). We, therefore, conclude that Glut3 is targeted to secretory vesicles in both neurons and PC12 cells.

Akt-2 binds to Glut4-containing vesicles and phosphorylates their component proteins in response to insulin.

Glut4-containing vesicles immunoadsorbed from primary rat adipocytes possess endogenous protein kinase activity and phosphorylation substrates. Phosphorylation of several vesicle proteins including Glut4 itself is rapidly activated by insulin. Wortmannin blocks the effect of insulin when added to cells in vivo prior to insulin administration. By means of MonoQ chromatography and Western blot analysis, vesicle-associated protein kinase is identified as Akt-2, a lipid-binding protein kinase involved in insulin signaling. Akt-2 is found to be recruited to Glut4-containing vesicles in response to insulin.

Block copolymers of ethylene oxide and propylene oxide (pluronics) as immunomodulators and antitumour agents.

Block copolymers of ethylene oxide and propylene oxide (pluronics) are nontoxic water-soluble membranotropic surfactants available as polymers with various compositions, molecular masses, number, and arrangement of blocks. In vivo experiments are reported which demonstrate that these polymers and their functional derivatives stimulate the production of anti-sheep-erythrocyte antibodies in mice. The introduction of reactive (hydroperoxide) groups into the polymers by chemical modification or by solubilization of low-molecular-mass hydroperoxides alters the properties of these immunostimulators. In vitro experiments revealed that these modified polymers enhance the activity of natural killer cells without reducing their viability. It is proposed that the immunomodulatory properties of pluronics and their derivatives play an important role in the antitumour activity of these substances in vivo.

Down-regulation of LAK cell-mediated cytotoxicity: cancer and ageing.

A comparative study was made of the generation of lymphokine-activated killer (LAK) cells in patients with melanoma and healthy donors of different age groups. Significant reduction of effector cell cytotoxicity in patients following 72 h culture with 1,000 U/ml or recombinant IL-2 (rIL-2) as well as a decreased ability to generate LAK cells in elderly individuals were shown to be correlated with suppressor cell activation in rIL-2 stimulated cell population. Suppressor effect depends on monocytes and T-lymphocytes: partial abolition of suppression in LAK cells was observed following removal of adherent cells or treatment with OKT8 monoclonal antibodies and complement.

Proliferative activity, lectin-dependent and natural cytotoxicity in blood, lymph node and spleen from patients with Hodgkin's disease.

Mononuclear cells and T-lymphocytes of the blood, spleen and lymph nodes from 48 patients with Hodgkin disease (HD) and blood donors were tested in assays for lectin-dependent (LD) and natural killer (NK) cytotoxic activity. On average, peripheral blood T cell lectin-dependent cytotoxicity differs from that of the donors. However, cytotoxic activity appears to be dependent on the stage of disease; in the IY stage LD cytotoxicity was decreased 2-fold. The lectin-dependent cytotoxicity was also dependent on the histological type of disease and the lowest level (50% of the control level) was associated with the lymphoid depletion type. The cytotoxic activity of T-lymphocytes from the affected areas of the patients' spleen was more marked than that of the unaffected areas. Spleen cell cytotoxicity showed no other correlations. Cytotoxicity of lymphocytes from the affected lymph nodes was drastically lower than activity of blood and spleen lymphocytes. NK activity of the patients' blood and spleen lymphocytes was twice as low as the control level (healthy donors) and did not correlate with stage and/or histological type of disease. The proliferative activity of lymphocytes from 33 HD patients was tested in vitro using allogeneic mononuclear cells from healthy donors or HD patients and/or PHA as stimulators. The response of patients' lymphocytes to alloantigens appeared to be much less affected than response to polyclonal mitogen. Thus, the results obtained by us demonstrate signs of stimulation of the lymphoid system against a background of general immunosuppression in HD.

Activation of secretion and surface alteration of cytolytic T-lymphocytes interacting with target cells.

Cells obtained in mixed lymphocyte culture (MLC) and memory cells adsorbed on the surface of target cells (TC) were examined using scanning and transmission electron microscopy depending on the time of interaction with TC. Three types of lymphocytes were revealed: type I - cells of spherical shape with a smooth surface or an insignificant amount of microvilli; predominantly small and medium-sized lymphocytes contacting TC with non significant involvement of their surface or by several microvilli; type II - oval or round-shaped lymphocytes evenly covered with microvilli with considerably enlarged region of contact; type III cells - predominantly large lymphocytes and lymphoblasts flattened (spread) on TC, with multiple microvilli, ridge-like projections, and ruffles on their surface. TEM revealed activation of the secretory apparatus in the cytoplasm of such lymphocytes. With increased time of interaction, type III cells increase in number (from 8.6% after 10 min to 90.2% after 60 min of incubation). Memory cells show no morphologic signs of secretion in correlation with the absence of lysis of TC on which they are adsorbed. The surface of the lymphocytes adsorbed on the substrate with poly-L-lysin is not noticeably altered. It is suggested that 3 morphological types of lymphocytes correspond to 3 stages of secretion activation. Lymphocyte contact with TC surface is evidently a specific stimulus for activating secretory apparatus of CTL. SEM can be used for quantitation of activated lymphocytes.