[Steadfastly increased level of the ciliary neurotrophic factor in the blood serum within the positive therapeutic dynamics of depression as possible prognostic marker of depressive relapse]. / Ustoichivoe povyshenie urovnya tsiliarnogo neirotroficheskogo faktora v syvorotke krovi pri polozhitel'noi terapevticheskoi dinamike depressii kak veroyatnyi prognosticheskii marker retsidiva depressivnogo epizoda.

OBJECTIVE: To study a role of the ciliary neurotrophic factor (CNTF) in the pathogenesis of depression and its prognostic significance in dynamics of the antidepressant therapy. MATERIAL AND METHODS: CNTF level was investigated in the blood serum of patients with melancholic depression (n=32) before the start of therapy and after 30 days, when improvement was achieved by at least 75% of baseline scores on the Hamilton Depression Rating Scale. RESULTS: Steadfastly increased level of CNTF in the blood serum of patients with melancholic depression compared with the control, remaining practically unchanged with an obvious improvement in the condition - 732.2±126.5 and 679.1±63.1 pg/ml of serum, respectively (p>0.05). CONCLUSION: The initially elevated level of CNTP indicates its probable significance in the pathogenesis of depression; persistently high serum CNTP level, despite clinical improvement during therapy, can serve as a predictor of the stability of the biological mechanisms of recurrent depressive disorder with a continuing risk of another relapse of a depressive episode.

[Monoamine-hormonal interactions in the pathogenesis of anxious depression]. / Monoamino-gormonal'nye sviazi v patogeneze trevozhnoi depressii.

Biochemical aspects of the relationship between monoaminergic and hormonal systems in the pathogenesis of anxious depression are analyzed on the basis of literature and own results published earlier. Significant alterations in biogenic monoamine metabolism and changes in the hormonal status, that reflects homeostasis disturbance in whole, are inherent to anxious depression. The biochemical mechanisms of imbalance between serotonergic and noradrenergic systems and a role of cortisol in this process are discussed.

[Disturbance of serum albumin conformation in patients with melancholic depression]. / Narushenie konformatsii al'bumina syvorotki u bol'nykh melankholicheskoi depressiei.

OBJECTIVE: Conformational protein changes may be an important component of the disturbance of molecular processes in the development of pathological process in the body. We studied conformations of albumin molecule in the blood of patients with depression using biophysical -nanotechnical approach. MATERIAL AND METHODS: We examined 19 patients with depression and 25 healthy controls. Properties of serum albumin were compared in patients with typical melancholic depression and controls using spectroscopy (subnanosecond range) with K-35 fluorescent probe. RESULTS AND CONCLUSION: The properties of albumin binding sites in patients before and after treatment differed from those in controls. The authors suggest that it points to the changes in albumin molecule conformation that may influence the functional state of the protein. It has been suggested that these changes may be considered as biomarkers of pharmacotherapeutic efficacy.

Effects of fatty acids on human serum albumin binding centers.

Albumin is a carrier of nonesterified long-chain fatty acids and many other ligands. The status of its binding centers was studied for various proportions of nonesterified long-chain fatty acids and albumin as exemplified by palmitic acid. The status of the binding center was tested by recording K-35 probe fluorescence decay in the subnanosecond band. This method showed the work of three types of centers. Palmitic acid enhanced binding activity of all centers, though to a different degree: if the palmitic acid/albumin proportion increased to 2-3, the probe binding to type 1 centers (located in the drug center I region) increased 1.5 times, while binding to type 3 centers increased more than 3-fold. Modification of these centers by nonesterified long-chain fatty acids was similar in the isolated human albumin preparation and in diluted blood serum. Hence, K-35 probe showed the actual status of various albumin centers, their binding capacity depending to a different measure on the fatty acid charge of albumin.

Study of high-resolution H1 nuclear magnetic resonance spectra of the serum and its albumin faction in patients with the first schizophrenia episode.

We studied high-resolution (1)H nuclear magnetic resonance spectra of the serum and serum albumin from patients with the first episode of schizophrenia and healthy individuals. A relative increase in signal intensities of CH(2) protons in serum LDL and VLDL in schizophrenia was demonstrated. Higher intensities of CH(2) and CH(3) protons of non-esterified fatty acids were found in (1)H nuclear magnetic resonance spectra of serum albumin. These data attest to an essential role of changes in lipid metabolism and changed ligand load of albumin in schizophrenia.

[Clinical significance of humoral compensatory reactions in the acute period of ischemic stroke].

To determine the clinical significance of humoral nonspecific reactions in the acute period of ischemic hemispheric stroke (IS), some biochemical and biophysical parameters have been studied in 30 patients (mean age 67±10 years). Platelet monoaminooxidase (MAO) activity, levels of middle-sized molecules (MM), malonic dialdehyde (MDA) and parameters of the functional state of serum albumin (the effective concentration and binding reserve of albumin) have been measured. Severity of neurological deficit and functional recovery of patients with IS was assessed with the NIHSS and the Barthel index. The control group included 17 age- and sex-matched healthy people (p<0,1). The significant changes in all biochemical and biophysical parameters were seen in patients compared to the control group (p<0,01). The increase in MAO activity in patients was associated with the enhancement of free-radical reactions MDA/MAO: rs=+0,62, p=0,0001. The elevation of acceptor capacity of albumin related to the enhancement of its detoxicating function was found in patients with the regression of neurological deficit. It has been assumed that some nonspecific humoral reactions play a pathogenetic role in the acute period of ischemic stroke.

[Role of semicarbazide-sensitive amine oxidase in disturbances of endogenic detoxication in ischemic stroke patients].

Oxidative stress is a pathogenetic factor of ischemic stroke. Enhancement in the activity of one of xenobiotic transformation enzymes and biogenic amines (serum semicarbazide-sensitive amine oxidase (SSAO)) leads to the higher production of secondary toxins stimulating oxidative stress. We studied 38 patients (mean age 69,5 +/- 7,2 years) in the early restoration period of ischemic stroke. A control group included 17 age- and sex-matched healthy people. Severity of neurological and functional deficits was assessed with the NIHSS and the Barthel index, respectively. A number of biochemical parameters: serum SSAO activity, concentration of middle-sized molecules (MSM) and malonic dialdehyde (MDA) were measured. The higher concentration of MSM (0,80 +/- 0,22 and 0,5 +/- 0,1 g/l) and MDA (4,5 +/- 1,25 and 3,66 +/- 0,15 mmol/ml), respectively, was found in patients compared to the controls (p < 0,001). The correlative increase in MSM and MDA suggest the formation of chronic oxidative stress in the 4-5 months of disease. The changes in SSAO activity in patients with ischemic stroke that differed from controls were seen in 84% of cases while the increase in SSAO activity was found in 31% of patients. The pathogenetic link between the increase in SSAO activity and severity of neurological deficit was shown. This increase might be one of the pathogenetic links in the disturbance of neuroplasticity.

Change in platelet monoamine oxidase activity in the acutest period of ischemic stroke is associated with the degree of neurological recovery.

We studied monoamine oxidase activity (MAO) in platelets of patients in the acute period of ischemic stroke. Neurological deficit was evaluated by the data of clinical examinations and scales. In 80% patients MAO activity was considerably increased on 3-5 day after stroke. We found a correlation between increased MAO activity on 3-5 day after ischemic stroke and regression of neurological deficit on day 21 after ischemic stroke. The increase in MAO activity during the acute period of ischemic stroke is presumably a compensatory response aimed at stabilization of tissue homeostasis.

[Endogenous intoxication and compensatory reactions in the restoration period of ischemic stroke].

An aim of the study was to assess the severity of the syndrome of nonspecific metabolic endogenous intoxication (EI) and characteristics of compensatory reaction of serum albumin (SA) in patients in the early restoration period (4-5 months) of ischemic stroke (II). We measured levels of middle-sized molecules (MSM) and malonic dialdehyde (MDA) and determined parameters of functional activity of SA in 30 patients (mean age 69 +/- 8 years) after the first II and in 17 age- and sex-matched healthy people. Neurological deficit and functional restoration of patients were assessed with the NIHSS and Barthel index. The increase of MSM and MDA concentrations was found in 98% and 88% patients, respectively, as compared to healthy people (p<0,01). These metabolic disturbances were associated with the formation of EI and caused functional-structural changes of SA molecules. The correlation between changes of effective concentrations of SA and MDA was characteristic of the group of patients with II. The increase of total SA concentration was found in 87% of cases compared to controls (p<0,01) that indicated the manifestation of compensatory reaction of SA in response to EI. The decrease of all SA parameters, including the total concentration, was noted in 13% of patients and was associated with the decompensatory reaction to SA. The rehabilitation of CNS dysfunctions was associated with the undamaged SA compensatory reaction. The functional-structural changes of SA molecules in patients in the restoration period of II may lead to the changes in drug disposition, i.e. pharmacokinetics and pharmacodynamics, thus reducing possibilities of rehabilitation therapy.

[Disturbance of monoaminooxidase activity and indices of endogenous intoxication in patients with the first episode of schizophrenia].

An aim of the paper was to study some biochemical parameters of drug-naïve patients with the first episode of schizophrenia. Activities of platelet monoaminooxidase (MAO) and semicarbazide, a sensitive blood serum aminooxidase (BSA), levels of middle-sized molecules (MSM) and malonic dialdehyde (MDA), parameters of functional state of serum albumin were assessed in 16 patients. Severity of symptoms in patients with the first episode of schizophrenia was assessed as moderate (PANSS scores 73.1+/-12.5) before the treatment. The increase of MAO by 107%, reduction of BSA by 29% and increase of MSM level by 140% was found in patients compared to controls (p<0.01). The study of other biochemical (MDA level) and biophysical (effective albumin concentration) parameters did not yield unequivocal results. It has been suggested that MAO and BSA are integral components of pathogenetic mechanisms in patients with the first episode of schizophrenia.

[Conformational disturbances of serum albumin binding sites in schizophrenia].

The properties of serum albumin binding sites were studied using quenching of fluorescence of the molecular probe CAPIDAN (N-carboxyphenylimide of dimethylaminonaphthalic acid) with the nitrate anion. The samples of serum were obtained from 24 patients with paranoid schizophrenia and 24 healthy volunteers. In the absence of quencher the specific probe fluorescence was 1,4 times higher in patients than in volunteers. Fluorescence quenching constant for the probe bound to albumin was (M+/-m) 2,48+/-0,17 l/mol in patients versus 4,65+/-0,37 l/mol (p<0,01) in volunteers (p<0,01). The fluorescence fraction assessable to quenching was significantly (p<0,01) lower in schizophrenic patients as compared to controls (0,60+/-0,03 and 0,76+/-0,03) respectively). Thus, it is shown that in patients with schizophrenia the conformational state of albumin binding sites is significantly changed as compared to controls that can lead to the changes in the protein-ligand interaction and, thus, contribute to the pathogenesis of the disease and patient's response to treatment.

[Dynamics of biochemical parameters in patients with anxious depression treated with serotonergic antidepressants with different mechanisms of action].

The aim of the study was to compare the dynamics of some biochemical parameters in patients with anxious depression treated with tianeptine (coaxil) - serotonin reuptake enhancer and sertraline (zofort) - selective serotonin reuptake inhibitor. Forty-three patients with ICD-10 diagnosis of anxious depression (F32.1 and F33.1) were included in the study. Comparing to healthy volunteers, the significant increase of platelet monoamine oxidase activity by 95% and concentration of middle molecules (middle-mass endotoxic molecules) by 86% and decrease of serum amine oxidase activity by 43% and functional albumin activity by 38% was found in patients. An analysis of the biochemical profiles revealed the changes in opposite directions of all investigated parameters for antidepressants with different effects on serotonin reuptake though both tianeptine and sertraline were effective in the treatment of anxious depression.

[Some aspects of metabolic dysregulation in patients with ischemic stroke].

To study the mechanisms of formation of an endogenous intoxication syndrome in patients after ischemic stroke, the activity of platelet monoaminooxidase (MAO) and serum aminooxidase, concentration of middle-size molecules and parameters of functional albumin activity have been determined in 27 patients with illness duration 4-5 months and 16 healthy age- and sex-matched controls. The significant dysregulation of biogenic amine metabolism and total homeostasis was observed in patients compared to controls. There were a significant increase of MAO and concentration of middle-size molecules and a decrease of aminooxidase and functional albumin activity (p < 0.01). Such metabolic disturbances suggest a presence of endogenous intoxication. A possible mechanism of formation of an endogenous intoxication syndrome in ischemic stroke is discussed.

[Certain mechanisms of development of types of body tolerance to acute hypobaric hypoxia].

The regulatory mechanisms of individual rat resistance to acute hypobaric hypoxia were studied using the functional indices of the central nervous system (neurochemical and behavioral) and the hematopoietic system. The resistance to hypoxia was evaluated by the time of attitudinal reflex maintenance and recovery after decompression to a simulated altitude of 11200 m. Animals with different types of tolerance to hypoxia demonstrated different metabolic backgrounds of neurochemical processes (which were most balanced in moderately resistant rats). This agrees with the differences in active behavior and adaptive efficiency of these animals exposed to mild open-field stress. High functional activity of erythropoiesis and early leukocytic response were observed in hypoxia-tolerant rats.

Characteristics of albumin molecule binding centers in patients with anxious depression. Study by the fluorescence quenching method.

The state of binding centers in albumin molecule in patients with anxious depression was studied by the method of quenching of fluorescence of molecular probe (dimethyl-aminonaphthaleic acid carboxyphenylimide) with nitrate ions. Serum samples from 24 donors without somatic and mental diseases and 26 patients were analyzed. In the absence of the quenching agent, specific fluorescence of the probe (standardized by albumin concentration) was lower in patients with depression. The fluorescence quenching constant and the percentage of fluorescence available for quenching were also lower in serum samples from patients. These data indicate that the parameters of binding centers in albumin molecule in patients with anxious depression are significantly modified in comparison with normal subjects. The detected changes can play a role in the pathogenesis of depressive disorders.

Effect of prenatal lead exposure on superoxide dismutase activity in the brain and liver of rat fetuses.

Prenatal lead exposure had a damaging effect on Cu/Zn superoxide dismutase activity in the brain and liver of rat fetuses (20 days of gestation). The decrease in Cu/Zn superoxide dismutase activity in the brain and liver of treated fetuses reflects activation of free radical processes and impairment of the antioxidant defense system during prenatal lead exposure.

[The antioxidative defense system in the liver of rat fetuses upon antenatal exposure to lead]. / Sostoianie sistemy antioksidantnoi zashchity v pecheni potomstva krys pri antenatal'nom vozdeistvii svintsa.

The activity of Zn, Cu-containing superoxide dismutase was studied in the liver of 20-day old fetuses of female rats exposed to different concentrations of lead in different periods and during pregnancy. There were significant changes in the enzyme activity depended on a used dose of lead and on the duration of exposure to this compound. Activation of free radical processes and impairment of the antioxidative defense system are likely to be one of the basic mechanisms responsible for hepatic damage during prolonged antenatal lead intoxication.

Some neurotropic effects of low-intensity electromagnetic waves in rats with different typological characteristics of higher nervous activity.

The effects of low-intensity electromagnetic waves (4200 MHz, modulated with quasichaotic signals at 20-20,000 Hz, energy density 15 microW/cm2; specific energy absorption not greater than 15 mJ/kg) on the neurochemical systems of the brain and on behavioral reactions were studied in experimental animals with different typological characteristics of higher nervous activity. These studies showed that electromagnetic waves produced marked changes in the state and activity of the monoaminergic mediator systems which were in general terms concordant with changes at the integrative level (mostly selective inhibitory effects). The nature of these processes depended to a significant extent on the typological characteristics of the animals.

[Modulation by ultralow intensity electromagnetic fields on pharmacologic effects of psychotropic drugs]. / Moduliruiushchee vliianie élektromagnitnykh polei sverkhnizkoi intensivnosti na farmakologicheskie éffekty nekotorykh psikhotropnykh preparatov.

The ultralow-intensity electromagnetic fields (EMF, frequency of 4200, modulated by a quasistochastic signal in the range of 20-20,000 Hz, power density of 15 microW/cm2, specific body absorption rate up to 4.5 mJ/kg) potentiated the hypnogenic effect of hexenal. The exposure to the EMF shortened the time of falling asleep induced by this drug and increased sleep duration in rats. The exposure to the EMF also potentiated haloperidol catalepsy: it decreased the drug threshold dose and increased the catalepsy duration. The EMF influence on the haloperidol effects was of a prolonged character: it was manifest in a selected suppression of the emotional excitation in the open-field test within 24 hours after the exposure.

[The neurotropic effects of low-intensity electromagnetic waves in rats with different typological characteristics of higher nervous activity]. / Nekotorye neirotropnye éffekty élektromagnitnykh voln maloi intensivnosti u krys s raznymi tipologicheskimi osobennostiami vysshei nervnoi deiatel'nosti.

The effects of the ultralow-intensity electromagnetic fields (EMF, frequency of 4200 and 970 MHz, modulated by a quasistochastic signal in the range of 20-20,000 Hz, power density 15 microW/cm2, specific body absorption rate up to 4.5 mJ/kg) on the reactions of the central nervous system (CNS) of rats with different types of behavior were studied. Some neurochemical and behavioral mechanisms of rats' reactions were investigated. It was shown that the EMF produce pronounced changes in the state and activity of monoaminergic brain systems. These changes, on the whole, correspond to the alterations at the integrative level (predominantly, of the inhibitory character).