The aim of the work was to investigate the nerve grown factor (NGF) level in the blood serum in patients with melancholic depression (MD). The investigated group consists of 23 patients. At admission in the clinic (before any antidepressive treatment) the NGF concentration in patient’s serum was 278.28 ± 43.68 pg/mL that was significantly higher in comparison with controls 239.51 ± 22.15 pg/mL, (p 0.05), respectively. It is supposed, that the increased NGF level in serum of the MD patients can be connected with the impairment of the functioning of the brain-blood barrier and the increase of its permeability for the NGF.
Abstract—The study was aimed at investigating the peculiarities of the conformational changes in serum albumin in patients with anxious and melancholic depression. Albumin conformation was measured by the method of the subnanosecond laser time resolved fluorescence spectroscopy. Anxious depression was accompanied by a significant decrease in the values of the three amplitudes of the serum albumin in comparison with controls. In the melancholic depression, the values of all three amplitudes of serum albumin molecules were significantly elevated in comparison with controls. These results clearly indicate that anxious and melancholic depression are accompanied by oppositely directed changes in serum albumin conformation.
The aim of the study was investigation of the peculiarities of the conformational changes of serum albumin in patients with anxious and melancholic depression. Albumin conformation was measured by the method of the subnanosecond laser time resolved fluorescence spectroscopy. Anxious depression was followed with the significant decrease of the values of the three amplitudes on the serum albumin in comparison with controls. In the melancholic depression the values of all three amplitudes on serum albumin molecules were significantly elevated in comparison with controls. These results are clearly indicated that anxious and melancholic depression are followed by differently directed changes in serum albumin conformation.
The review describes the syndrome of endogenous intoxication in patients with mental disorders. Oxidative stress, middle-mass endotoxic molecules, impaired functional properties of serum albumin and albumin thiol groups, neurotrophic factors, and enzymes, including monoamine oxidase and semicarbazide-sensitive amine oxidase contribute to the development of endogenous intoxication. Possible pathogenetic mechanisms of the endogenous intoxication development in mental disorders and approaches to its treatment are discussed.
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.
Introduction.Approaches to therapy, predicting the dynamics and evaluating the effectiveness of psychopharmacotherapy of mood disorders is an extremely important problem in biological psychiatry.The fluorescence of a tryptophan residue is very sensitive to changes in the structure of its environment in the protein.In human serum albumin (HSA), radiation at wavelengths from 295 to 305 nm absorbs mainly tryptophan (Trp214), which, as an internal probe of albumin molecules, makes it possible to selectively observe the state of the albumin molecule and its possible conformational changes.Objective: to study the kinetics of fluorescence decay of HSA tryptophan in patients with melancholic depression using subnanosecond fluorescence spectroscopy.Material.We examined 14 patients (the main group) diagnosed with ICD-10 melancholic depression (MD), their psychopathological state was assessed as a depressive episode within the framework of bipolar affective disorder (F31.3) or recurrent depressive disorder (F33.1).The control group consisted of 14 volunteers without morbid changes according to the results of express diagnostics of clinical-psychopathological and clinical-biochemical studies.There were no statistically significant differences between the examined groups in terms of age and sex parameters.Methods.Psychometric quantification of the severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HAMD-21, HDRS-21) and Anxiety Rating Scale (HARS).The examination was carried out on the first day of the patient's admission to the hospital before the start of active psychopharmacological treatment.Tryptophan fluorescence decay kinetics were measured on a Laser Emission Diode setup with a pulsed light source.The excitation wavelength was 290±10 nm.Results.Analysis of all parameters of tryptophan fluorescence decay in blood serum samples of the examined groups before the start of therapy showed that the average values of the A1 and A3 amplitudes in the serum of patients with MD of the main group were statistically significantly (p=0.01)lower than in the control group of volunteers (for A1 -378 versus 440, for A3 -285 versus 327, respectively).Conclusion.Based on the results of the study, it was demonstrated that conformational changes in the albumin molecule in patients with mental pathology (melancholic depression) can be detected using subnanosecond fluorescence spectroscopy of fluorescent tryptophan residua, which confirms the scientific novelty, practical significance of the work and the need to continue this direction.
The aim of the study was to investigate the serum albumin conformation in patients with melancholic depression. There were investigated 22 patients with melancholic depression and 54 healthy volunteers. Patients with melancholic depression were investigated in dynamics of the antidepressive therapy (venlafaxine, 75–150 mg/daily): at admission, on 15th and 30 th days. Subnanosecond laser time resolved fluorescence spectroscopy with K-35 fluorescent probe (dimethylaminonaphthalic acid N-carboxyphenylimide, CAPIDAN) was used for the investigation of albumin conformation There were revealed in controls 3 binding site for the probe on albumin molecule with decay times of 1, 3 and 9 nanoseconds (amplitudes A 3 , A 2 , and A 1 , respectively). The mean amplitudes A 3 , A 2 , and A 1 in the serum albumin of patients with melancholic depression were significantly higher than in controls ( p = 0.025). After antidepressive therapy with venlafaxine there was revealed that all three amplitudes significantly decreased and were equal to the amplitudes of controls. We can hypothesize that investigated parameters can serve as potential biomarkers for the evaluation of the efficacy of the psychopharmacotherapy.
The review summarizes the results of our own studies and published data on the biological markers of psychiatric disorders, with special emphasis on the activity of platelet monoamine oxidase. Pharmacotherapy studies in patients with the mixed anxiety-depressive disorder and first episode of schizophrenia have shown that the activity of platelet monoamine oxidase could serve as a potential biomarker of the efficacy of therapeutic interventions in these diseases.
Abstract—The kinetics of fluorescence decay of the K-35 probe and the tryptophan amino acid residue were measured after the addition of sodium hypochlorite in human albumin serum (HSA). The K-35 fluorescent probe (excitation 405 nm, fluorescence 530 nm) binds to drug binding site I of albumin. During the experiment the molar concentration of albumin in the fraction varied from 0.3 to 20 μM. Oxidation of the fraction with hypochlorite was recorded by the change in the fluorescence of tryptophan also located in binding site I of albumin (excitation 290 nm, fluorescence 350 nm). It was shown that, at serum albumin concentration of about 30 μM, HSA has antioxidant activity which maintains its ability to bind ligands even after exposure to relatively large amounts of hypochlorite (up to 50 oxidizing molecules per protein molecule). HSA retains its ability to bind ligands because the properties of the K-35 probe during oxidation remained almost unchanged and we observed only insignificant changes in binding characteristics. The added hypochlorite is, predominantly, used to oxidize albumin amino acids, including Trp oxidation as observed in the experiment. For 14 sera of donors, we showed significant differences in the fluorescence of oxidized and native tryptophan.
Исследование динамики содержания цилиарного нейротрофического фактора в
Uzbekov M*1, Babushkina T2, Klimova T2, Peregudov A2, Syrejshchikova T3, Smolina N1, Brilliantova V1, Dobretsov G4 and Shikhov S1 Author Affiliations 1Professor, Moscow Research Institute of Psychiatry, Russia 2Senior Researcher, A N Nesmeyanov Institute of Elementoorganic Compounds, Russia 3Senior Researcher, Lebedev Physical Institute, Russia 4Professor, Research and Clinical Center of Physic-Chemical Medicine, Russia Received: February 07, 2019 | Published: March 01, 2019 Corresponding author: Uzbekov MG, Laboratory of Brain Pathology, Moscow Research Institute of Psychiatry, Moscow, Russia DOI: 10.26717/BJSTR.2019.15.002695
We studied the effect of the neuroprotective dipeptide drug noopept on the level of biogenic amines in the retina during the thrombosis of its vessels in experiments with male chinchilla rabbits. Ischemic lesion of the retina was modeled by intravenous administration of rose bengal at a dose of 40 mg/kg body weight followed by 10-min transpupillary focal illumination of the temporal vascular arcade with white light. Noopept was injected intravenously immediately after the thrombosis modeling at a dose of 0.5 mg/kg body weight; then, throughout the entire experiment (up to 14 days) it was administered per os three times a day at a dose of 10 mg/kg body weight. It has been demonstrated that ischemia causes the following disturbances in the neurotransmitter balance in the retina: an increase in the aspartate and GABA levels, a decrease in the dopamine and taurine levels, and a decrease followed by an increase in the glycine level. Noopept administration led to the normalization of the GABA, glycine, and aspartate levels and an increase in the dopamine content.
Ciliary neurotrophic factor (CNTF) is a 22-kDa cytokine belonging to the interleukin-6 family and is mainly expressed in glial cells of the central and peripheral nervous systems [1]. Ciliary neurotrophic factor is a neurotrophin which could act as a neuroprotective agent [2]. CNTF plays an important role in the regulation of neuronal development, neuroprotection and may also influence cognitive processes [3]. However, the physiological relevance of circulating CNTF still needs to establish. Depression is one of the most prevalent mental disorders and one of the main causes of disability worldwide.
Abstract—The goal of this work was to search for blood serum parameters that would be associated with the state of patients with mental disorders. Such indicators are needed for an objective assessment of this state versus the prevailing subjective evaluation methodologies. The kinetics of tryptophan fluorescence decay in the serum albumin fraction was compared in patients with melancholic depression (before treatment) and in healthy volunteers. Albumin fluorescence is mainly due to the tryptophan 214 residue, which is located in the immediate vicinity of the first drug-binding center of the molecule. The decay kinetics were described as a sum of three exponential functions with lifetimes τi (in the 6.5, 2.8 and 1.0 ns region) and the amplitudes Ai. The τi values were similar in both groups of individuals. In contrast, there was a significant difference between patients and controls in the A1/A3 amplitude ratio. It is suggested that the A1/A3 value can be considered as a potential marker indicating the presence or absence of melancholic depression in patients before treatment.
We studied the influence of the neuroprotective dipeptide drug noopept on the state of the retina during thrombosis of its vessels in an experiment with male chinchilla rabbits. The pathology was modeled by intravenous injection of rose Bengal at a dose of 40 mg/kg followed by transpupillary focal illumination with white light of the temporal vascular arcade for 10 min. Noopept was administered intravenously immediately after modeling thrombosis at a dose of 0.5 mg/kg, and then three times per day per os at a dose of 10 mg/kg throughout the experiment. It was found that noopept improves the functional state of the retinal neurons according to electroretinography. At the 5–7th and 14th days, noopept reduced the glutamate content in the retina by 86.8% and 84.1% compared to the control animals (p < 0.05), decreased the concentration of products of reaction with thiobarbituric acid by 17.3% and 14.9% on the 3rd and 7th days (p < 0.05), and increased the activity of glutathione-S-transferase by 34.5% on the 1st day (p < 0.05).
Background: Pathogenetic mechanisms of attention deficit hyperactivity disorder (ADHD) or hyperkinetic syndrome (HKS) are not clear.The aim was to identify possible clinical and biochemical (monoaminergic) correlates of ADHD/HKS. Methods:The levels of monoamines, their metabolites and kynurenine metabolite in urine samples were estimated using fluorometric and chromatographic methods.Results: It was found that ADHD/HKS is followed by activation of dopaminergic and inhibition of noradrenergic systems.3 weeks of psychostimulant -sydnocarb treatment had improved children's clinical status that was followed by decrease of dopaminergic and serotonergic system activities.Sydnocarb therapy has revealed reciprocal relationship between serotonergic and kynurenine systems. Conclusion:Symptom improvement in ADHD/HKS children is followed by an activation of the kynurenine system.We propose a hypothesis that the kynurenine system plays significant role in the pathogenetic mechanisms of ADHD/HKS.We want to draw attention that these results were received using sample size of 42 patients.Thus, it is necessary to perform such kind investigations on the more representative and larger samples.
РЕЗЮМЕЦелью работы явилась попытка обобщения имеющихся собственных и литературных данных по поиску биологических маркеров психических и неврологических заболеваний.С точки зрения потенциального биомаркера рассматривается моноаминоксидаза (МАО) тромбоцитов.Исследование первого эпизода шизофрении и тревожной депрессии показало, что МАО тромбоцитов может служить потенциальным биомаркером эффективности фармакотерапии этих расстройств.Повышение активности МАО в остром периоде (4-5 дней) после инсульта рассматривается как компенсаторная реакция, направленная на восстановление неврологических функций, тогда как повышение активности