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Biomedical subjects

M I Faktor

Publications and source records attributed to M I Faktor.

At least 19 recordsLinked to original sources

[Levels and molecular heterogeneity of serotonin transporter protein in platelets of patients with different mental diseases: a comparative analysis with the use of monoclonal and polyclonal antibodies].

Polyclonal (PAb) and monoclonal (MAb) antibodies to CT2-epitope of the C-terminal fragment of serotonin transporter (SERT) protein were used to study the levels and molecular heterogeneity of platelet SERT in healthy donors and patients with affective (AD) and somatoform (SD) disorders, schizoaffective disorder (SAD) and schizophrenia. SERT was found to exist as high molecular wight (HMW) and low molecular weight (LMW) forms separated after electrophoresis. The levels of HMW and LMW forms of SERT were significantly, decreased in mentally ill patients as compared to healthy individuals. Unlike PAb, horse radish peroxidase (HRP)-conjugated MAbs were more sensitive and specific to SERT and could detect the LMW form of SERT as a duplet protein form with MW about 40 and 43 kDa. The MAb to CT2 C-terminal fragment of SERT conjugated with HRP is considered to be a new valuable tool for further investigation of SERT expression, properties, and posttranslation modification in the controls and in patients with different psychopathology.

Adult↗

[Specific aspects of thrombocyte system of serotonin in patients with different manifestations of schizoaffective psychosis].

45 women with different manifestations of schizoaffective psychosis (SAP) were examined. The diagnosis corresponded to ICD-10 (F25). According to the classification elaborated in Mental Health Research Centre of Russian Academy of Medical Sciences, groups of patients were identified with different variants of the psychoses course: a nuclear SAP type; a borderline SAP variation with phasic-recurrent course; SAP with progredient variation (schizoaffective variation of schizophrenia). The patients were examined both during the attack and remission. A rate of serotonine uptake (Vmax) in blood platelets, a specific imipramine binding (Bmax) and the level of serotonin in blood platelets were evaluated. It was found that dynamics of both Vmax and the level of serotonin in different SAP types were different, that was related to clinical and biological SAP heterogeneity. A tendency to decreasing of serotonin system functional activity was found in progredient SAP variations, especially during the remission, which was of low quality in these cases. On the contrary, in the borderline variations the indices of the decreased function of serotonin system corresponded well to those of acute psychosis. In nuclear type--a type with the most favourable course of psychosis--any significant changes weren't revealed as compared with the normal parameters.

Acute Disease↗

[The indices of the thrombocyte serotonin system and of the nerve growth factor system in children with hereditary disorders of neuropsychic development].

Indices of both platelet serotoninergic system and the system of nerve growth factor (NGF) were examined in children with neurofibromatosis (15 patients), polygenic oligophrenia (24 patients) and Rett's syndrome (14 ones). There was an increase of both the level of blood serum autoantibodies (aAB) to NGF and the value of specific binding of 3H-imipramine (Bmax) in platelets of patients with oligophrenia. For this group of patients a significant negative correlation exists between the rate of platelet uptake of serotonin (Vmax value) and the degree of mental retardation (r = -0.425, p < 0.03). Decrease of both Vmax and activity of platelet NGF receptors was revealed in patients with neurofibromatosis. In such patients there was positive correlation between sensitivity of platelet NGF receptors to NGF (during their stimulation by test dose of purified NGF) and the degree of mental retardation (r = 0.697, p < 0.04). In patients with Rett's syndrome a significant increase of activity of platelet NGF receptors to NGF was observed. The conclusion was made on the existence of some general mechanism of intellectual defect development. Autoimmune processes considered to be such mechanism.

Adolescent↗

[A clinico-biological study of the thrombocyte serotonin-transport complex in therapeutically resistant patients with endogenous depression undergoing combined treatment].

The platelet parameters of the functional status of the serotonin-reuptake complex were studied in drug-resistant depressive patients given various regimens of complex therapy or selective serotonin re-uptake inhibitors (fluvoxamine and fluoxetine). The most persistent and marked clinical effect was seen in electroconvulsive therapy and it was due to the normalization of the serotonin-reuptake system.

Adult↗

[The thrombocytic serotoninergic markers of the efficacy of electroconvulsive therapy in endogenous depressions].

The changes of main platelet serotonergic parameters (maximal velocity of 3H-serotonin uptake, Vmax; and density of (3)3H-imipramine binding sites, Bmax) were followed up in 25 endogenously depressed patients before and after electroconvulsive therapy (ECT). It was found a marked decrease in the velocity of 3H-serotonin uptake into platelets (Vmax) from patients before ECT (especially in non-responder group) and the significant increase of Vmax- and Bmax-values after the course of ECT in responders but not in resistant patients (non-responders). The increase of Vmax- and Bmax-values in responders was evidence of the rise of the functional activity serotonin system after treatment. The results evidence about the significance of serotonergic-mechanisms in the therapeutic efficacy of ECT.

Adult↗

[Thrombocytic serotoninergic markers in therapy-resistant patients with endogenous depression undergoing alpha-tocopherol treatment].

The main platelet serotoninergic parameters (maximal velosity of 3H-serotonin uptake, Vmax and density of 3H-imipramine binding sites, Bmax) were measured in 17 therapy-resistant endogenously depressed patients before and after combined treatment (antidepressants and alpha-tocopherol). It was found a significant decrease of Vmax-, Vmax/Bmax- values and the increase of Bmax- values in patients before treatment. A beneficial effect of the combined therapy was found in 47% of patients. However, it was not followed by the changes of main platelet serotoninergic parameters in patients after treatment in spite of the obtained clinical improvement. There were not also observed the significant differences of measured biochemical parameters between responders and non-responders. These findings suggest that the beneficial clinical effect of the combined antidepressive therapy with alpha-tocopherol does not involve serotoninergic mechanisms.

Adult↗

[Function of the serotoninergic system of blood platelets in patients with hypertension].

To investigate if there can be alterations in the 5-hydroxytryptamine (5-HT) uptake system in the sensitivity of platelets in patients with essential hypertension, 38 hypertensive patients and 37 normotensive healthy subjects were compared. In patients, the maximal 5-HT uptake velocity was reduced. The density of binding sites for 3H-imipramine was elevated in hypertensive females, but unchanged in males. The sensitivity of 5-HT uptake to trazodone was unchanged in patients. Half-maximal concentrations of 5-HT for inducing a shape change reaction of platelets were positively correlated with diastolic blood pressure in male patients and were reduced in female mild hypertensives. It is suggested that these changes are likely to be involved in the pathogenesis of hypertension.

Blood Flow Velocity↗

[The effect of imipramine and trazodone on the re-uptake of (3H) serotonin by thrombocytes in patients with endogenous depression: changes in antidepressive therapy].

The inhibitory potencies of imipramine (IC50-values for IMI) and trazodone (IC50-values for TRA) on platelet [3H]serotonin uptake were measured in depressed patients. The IC50-values for IMI in patients was shown to be higher (P less than 0.01) than in controls. The IC50-values for TRA in patients were lower (P less than 0.01) than found in platelets from controls. These alterations were not accompanied by the significant decrease of a density of platelet [3H]imipramine binding sites. Drug treatment led to the normalization of the IC50-values for IMI and to the partial increase of the IC50-values for TRA. There was a negative correlation of IC50-values for TRA and severity of depressive symptoms evaluated by the Hamilton Depression Rating Scale. The results support the hypothesis that the mechanisms of the regulation of [3H]serotonin uptake sensitivity to IMI and TRA in patients are different.

Adolescent↗

[Activity of platelet serotonin receptors of patients with endogenous depression before and after treatment with antidepressive agents].

Effective 5-HT concentration eliciting the half-maximal rate of platelet deformation (aggregation) in drug-free bipolar or unipolar depressed women was significantly (p less than 0.001) lower as compared with matched controls (0.13 +/- 0.04 microM and 0.532 +/- 0.1 microM, respectively). After 1-3 months of antidepressant treatment this value increased to 0.47 +/- 0.16 microM and was no longer different from control. Possible mechanisms controlling the activity of serotonin2 platelet receptors are discussed.

Adolescent↗

[Sensitivity of the retrograde uptake of H3-serotonin to imipramine and trazodone in patients with endogenous depression treated with antidepressive drugs].

The potency of imipramine (IMI) and trazodone (TRA) to inhibit (3H)-serotonin intake in unipolar and bipolar endogenous depressed patients (women aged 17 to 57 years) was evaluated before and during the antidepressant treatment. The potency of IMI was lower and that of TRA higher in patients as compared to controls. The both drugs' potencies became normal in patients treated with antidepressants. The significant decrease of imipramine binding sites density (Bmax) was evident after the treatment as against the normal levels. Significant correlation was observed between a severity of the patient's state evaluated using Hamiltone depression rating scale and the TRA potency but not IMI potency or Bmax. The data suggest different mechanisms regulating the serotonin uptake sensitivity to IMI and TRA. These are apparently involved in the pathogenesis of endogenous depression.

Adolescent↗

[Interaction of the anxiolytic agent buspirone with serotonin and other synaptic receptors in the human brain].

Buspirone and Mj 138-05 (up to 0.1 mM) did not displace specifically bound (3H) tryptamine, (3H) strychnine, (3H) flunitrazepam and (3H) imipramine in human cortical and hippocampal membrane preparations. At the same time both compounds displayed similar to serotonin affinity (IC50 in the range of 2-6 microM) for (125I)-LSD specific binding sites in the human cortex and hippocamp. IC50 of serotonin and buspirone and Mj 138-05 for (3H) LSD (2 nM) specific binding sites in the hippocamp was determined as 0.14 microM, 2.3 microM and 6.1 microM, respectively; and for (3H) serotonin specific binding sites in the hippocamp as 0.005 microM, 3.8 microM and 21 microM, respectively. The affinity for human cortex (3H) LSD binding sites was 10-fold lower in case of serotonin and 4-fold lower in case of buspirone and Mj 138-05 than in the hippocamp. However, the affinity for (3H) serotonin binding sites in the cortex was the same as in the hippocamp in case of serotonin and 12-15-fold lower than in the hippocamp in case of buspirone and Mj 138-05. It is concluded that in human brain buspirone and Mj 138-05 interact with micromolar affinity with 5 HT2 and are capable of binding to a subpopulation of 5 HT1 receptors in the hippocamp.

Aged↗

[Development of subsensitivity to imipramine in the system of reverse serotonin uptake by thrombocytes in patients with endogenous depression].

The inhibitory effect of imipramine (IC50) on [3H]serotonin uptake and its kinetic parameter (V400) were measured in platelets of 9 patients with unipolar and 6 with bipolar affective disorder. The IC50 and V400 values in depressed patients were significantly higher (p less than 0.002) than these found in the control group. Treatment with antidepressants significantly decreased the IC50 values. The results support the hypothesis postulating that depression is related to a decreased modulatory capacity of imipramine binding sites and that the clinical effectiveness of these drugs is associated with the said modulatory capacity.

Adolescent↗

[Effect of anxiolytics--buspirone and diazepam--on the prolactin, thyrotropin and cortisol content of the blood in the green monkey].

The influence of two anxiolytics--diazepam and buspirone--on prolactin, thyrotrophin and cortisol levels in green monkey (Cercopithecus aethiops) plasma was studied 30 min following i/m injection. Diazepam at 1 mg/kg decreased prolactin and cortisol levels by 30-50% compared to the control animals. Buspirone at 2.5-10 mg/kg induced a 7-10-fold increase in prolactin level but did not change cortisol and thyrotrophin concentration. Buspirone analog--Mj 138-05 at 10 mg/kg produced a 2-3-fold increase in plasma prolactin content in some animals, while at a dose of 5 mg/kg it exerted no detectable effect. Possible neurochemical mechanisms of the effects observed are discussed.

Animals↗

[Effect of buspirone and diazepam on cGMP level in the rat cerebellum].

Diazepam at a dose of 5 and 10 mg/kg significantly decreases (by 50 and 60%, respectively) cGMP content 30 min following intraperitoneal injection to rats. Buspirone, at a dose of 2.5-25 mg/kg produced a nonsignificant (up to 18%) and at a dose of 50 mg/kg a statistically significant (p less than 0.05) 30% decrease in cerebellum cGMP content. Taking into account the identical anxiolytic effects of diazepam and buspirone, it is suggested that pharmacological effects of buspirone are not linked to the activation of GABA-ergic system.

Animals↗

[Detection of an endogenous inhibitor of benzodiazepine receptor binding].

An original one-stage method for isolating from brain tissue of a water-soluble fraction containing an inhibitor of benzodiazepine specific binding is suggested and the properties of the inhibitor are described. The inhibitor is a thermostable compound with a molecular mass of 2000-10000 dalton. It inhibits diazepam binding depending on the concentration. The IC50 for diazepam binding is approximately ten-fold less than the inhibitor concentration in the brain tissue. The inhibitor is distributed heterogeneously in the rat brain (the maximal content in the cerebellum and cortex) and bovine brain (the maximal content in the thalamus and caudate nucleus).

Animals↗

[Effect of schizophrenic patients' serum immunoglobulins on nerve cell potentials].

With the aid of the microelectrode method, the influence of different protein fractions isolated from the blood serum of schizophrenic patients and normals on an edible snail was studied. The fractions were isolated by means of ion exchange chromatography and contained immunoglobulins (IgG, IgA, IgM). It was established that the fraction of the blood serum in schizophrenic patients, containing IgM is significantly stronger than the respective fraction in normals, depolarizing and inactivating the neuron membrane. It is suggested that there is an increased content of tropic to the nervous tissue antibodies of this class in the blood serum of schizophrenic patients.

Animals↗

[Stimulating effect of schizophrenic patients' plasma on the cellular incorportation of tryptophan in vitro].

A study of 21 schizophrenic patients and 21 normal donors in one experiment, conducted on a pool or erythrocytes in 18 chickens with the use of a double blind method, confirmed the previously obtained data of the stimulant action of plasma in schizophrenic patients on the uptake of tryptophan by chicken erythrocytes. It was demonstrated, that the plasma at the same time evokes an increase of cytoplasmatic enzymes (lactate dehydrogenase and myokynase). The authors studied the correlations between the influence of plasma on the tryptophan uptake and the release of hemoglobin from the erythrocytes and its concentration in the incubation medium. The data also demonstrate the parameters of functions describing the first correlation and that it has a nonmonotonous character. The problem of the connection between the plasma action on the tryptophane uptake and its hemolytic activing is discussed.

Adenylate Kinase↗