[Low doses of quetiapine (Seroquel) as an impulsivity corrector in patients with bipolar affective disorder in remission]. / Nizkie dozy kvetiapina (Serokvelya) v kachestve korrektora impul'sivnosti u patsientov s bipolyarnym affektivnym rasstroistvom v remissii.

OBJECTIVE: To evaluate the effectiveness of low doses (25-75 mg/day) of quetiapine (Seroquel) in patients with bipolar affective disorders in a euthymic state with signs of impaired impulse control. MATERIAL AND METHODS: The main criteria for patients' selection were as follows: both sex, diagnoses of bipolar affective disorders, remission (euthymic state), adult age (from 18 to 60 years old), stable basic therapy. The duration of the study was 6 weeks, a dose of quetiapine (Seroquel) varied from 25 to 75 mg. The examinations were carried out with the Barratt scale, computerized Go-No-Go and Balloon tests. RESULTS: The study group included 32 patients (11 men and 21 women), mean age 31.2±9.7 years (minimum 18, maximum 60 years). The changes in Barratt total score (p=0.000014, Wilcoxon test, effect size 0.48) and Balloon total earnings (p=0.03, Wilcoxon test, effect size 0.22) were statistically significant and reflected clinically significant improvement. The changes of the indices of the Go-No-Go test were not significant. The data of fMRI showed an increase in the connectivity of the cortex of the central and parietal tegmentum of the left hemisphere with other areas of the brain, which correlated with the changes in psychometric and test parameters. CONCLUSION: The results of the study showed that add-on of the low doses of quetiapine (Seroquel) significantly decreases impaired impulse control in remitted patients with bipolar affective disorders both in self-evaluation and in risk-taking experimental test. The drop of high level of impulsivity can improve the quality and stability of remission and reduce behavioral risks due to impaired impulse control.

[Oxidative stress in schizophrenia as a promising target for psychopharmacotherapy]. / Oksidativnyi stress pri shizofrenii kak perspektivnaya mishen' dlya psikhofarmakoterapii.

Until now, only dopamine receptor blockers are used for psychopharmacotherapy of schizophrenia, despite the active search for alternative pharmacological agents and a lot of research. However, most of these studies concerned molecules that somehow affect various neurotransmitter receptors. In addition, various anti-inflammatory drugs have been studied quite actively. At the same time, attempts to correct oxidative stress are given significantly less attention, although the emergence of the latter is facilitated by completely different pathophysiological processes and environmental factors associated with the development of schizophrenia. NMDA receptor blockage, vitamin D deficiency, social isolation, chronic stress in adolescence, inflammation, perinatal infection etc. - all this can ultimately lead to the occurrence of oxidative stress. However, there is a significant difference in the severity of this process depending on the stage of the course of schizophrenia, which probably partially explains the heterogeneity of results of the studies on the oxidative stress biomarkers in this disorder. In order to overcome these methodological problems, it seems promising to conduct double-blind studies of the effectiveness of antioxidants in schizophrenia with the selection of groups of patients taking into account the stage of the disorder and the level of certain biomarkers of oxidative stress (F2-isoprostanes, 8-oxodG, 8-oxoGuo). The optimal pharmacological agents for such studies are N-acetylcysteine due to the positive results of previous studies, and melatonin as an antioxidant with a unique activity profile.

[An effect of cholinesterase blockade on negative symptoms in schizophrenia]. / Vliyanie blokady kholinesterazy na negativnye rasstroistva pri shizofrenii.

Abstruct. OBJECTIVE: To assess the possibilities of influencing the severity of negative disorders in schizophrenic patients with cholinesterase blockade. MATERIAL AND METHODS: The study included stable 26 patients (13 of them women), average age 40.4 (SD 11.7) with paranoid schizophrenia, episodic form according to ICD-10). All patients received antipsychotic therapy, which was not changed at least for 2 months. We used psychometric scales (Positive and Negative Syndrome Assessment Scale (PANSS), Global Functioning Scale (GAF), neurocognitive techniques (Brief Assessment of Cognition in Schizophrenia-BACS), projective psychological techniques (Rorschach test). RESULTS AND CONCLUSION: The results of the study showed that augmentation of maintenance antipsychotic therapy with a cholinesterase blocker (ipidacrine at a dose of 20 mg per day) had positive impact on negative symptoms, decreasing the severity of emotional deficiency. The positive changes of cognitive impairment, measured with BACS, occurred regardless of changes in the severity of negative disorders, measured with PANSS. The Rorschach test showed an improvement in the conventional orientation of the patients' thinking. No exacerbation of psychotic symptoms was registered.

[The efficacy and safety of eculizumab biosimilar in patients with paroxysmal nocturnal hemoglobinuria. Results of a phase III randomized open-label comparative clinical trial].

AIM: To establish the equivalent efficacy and comparable safety profile of biosimilar Acveris and referent eculizumab product Soliris used for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). MATERIALS AND METHODS: Were included in the phase III multicenter 28 PNH patients, open-label clinical trial. Participants were randomized (1:1) into 2 treatment groups: investigational product (Acveris, n=14) and referent product (Soliris, n=14). Patients received eculizumab as the intravenous infusion 600 mg once a week during the first 4 weeks, 900 mg at week 5 and then 900 mg every 14 days (2 days) up to week 27 of the study. The efficacy, pharmacokinetics, pharmacodynamics, safety and immunogenicity of the compared products were analyzed after the end of 27 weeks of the study. The primary efficacy endpoint was the area under the curve LDH concentrationtime (AUCLDH) throughout the study period weeks 527. RESULTS: The difference between the mean AUCLDH values between the Acveris and Soliris groups was 5380.0 [-38 773.87; 49 533.87] U/ldays. The 95% CI limits for the difference in mean AUCLDH values between the groups fit the preset 95% CI [-146 500.9146 500.9] U/ldays and establish the equivalent efficacy of the biosimilar and referent product according to the primary efficacy endpoint. The safety profile of both Acveris and Soliris was expected and comparable according to the proportion of patients with adverse events. The formation of binding antibodies to eculizumab was not detected in both the groups. CONCLUSION: The study established the equivalent efficacy of biosimilar product Acveris and referent eculizumab product with the evidence of effective suppression of intravascular hemolysis in PNH patients along with a comparable favorable safety profile.

Decrease in 130 kDa- amyloid protein precursor protein (APP) and APP protein ratio in schizophrenia platelets.

Cognitive dysfunction is common among people with schizophrenia. The molecular substrates underlying this remain poorly understood. To address this, we analyzed changes in amyloid precursor protein (APP) in platelets of people with acute schizophrenia (n=24) and control subjects (n=20) by ECL-immunoblotting. APP bands corresponding to molecular masses of ∼130, ∼110 and ∼100 kDa, and the APP ratio (APPr: highest APP molecular mass vs lowest APP molecular mass bands) were quantified. The intensity of 130 kDa-APP and the APPr were significantly reduced in schizophrenia patients compared to control subjects. The age-associated decreases in the 130 kDa, ∼110 kDa proteins and APPr were present in patients, but not controls. Our results confirm peripheral APP metabolism is altered in people with schizophrenia. Further work is now warranted on a larger sample of diseased subjects with detailed cognitive assessment to determine the APP role in cognitive processing in schizophrenia, how it is related to severity and disease progression, as well as outcomes.

[Growing of murine tooth in situ by homotopic transplantation of embryonic germ]. / Vyrashchivanie zuba myshi in situ metodom gomotopicheskoi transplantatsii émbrional'nogo zachatka.

Tissue engineering offers to restore the lost tooth using a biological analogue grown from the tooth germ. These technologies provide long-term cultivation of the germ in bioreactor in vitro. The subsequent transfer and growth of the in vitro grown tooth in the jaw is hampered by difficulty of integration of the new tooth with the host tissue. We suggested that growing tooth by homotopic transplantation in situ, that is, immediately in the jaw passing the in vitro stage will help to solve these problems. The aim of the work was to test the hypothesis. The principal possibility of transfer of the tooth germ directly into the jaw and cultivation in situ eliminating the stage in vitro is shown. The results showed a good integration of the grown teeth with the jaw without signs of inflammation and with the appearance of blood vessels in the pulp. At the same time, the results also showed the necessity to improve the preparation of tooth germs for transplantation and surgical procedures.

[The activity of erythrocyte and platelet glutathione reductase and glutathione-S-transferase in paranoid schizophrenia]. / Aktivnost' éritrotsitarnykh i trombotsitarnykh glutationreduktazy i glutation-S-transferazy pri paranoidnoi shizofrenii.

AIM: A comparative evaluation of glutathione reductase (GR) and glutathione-S-transferase (GST) activities in erythrocytes and platelets of patients with schizophrenia. MATERIAL AND METHODS: Fifty patients, 47 men and 3 women, aged 25-56 years (medium 34) with acute paranoid schizophrenia (F20.0 ICD-10) with hallucinatory-paranoid or paranoid syndrome were studied. The control group consisted of 48 healthy people, 45 men and 3 women, aged 21-59 years (medium 38). GR activity was determined by the oxidation of NADP-H in the reduction reaction of oxidized glutathione. GST activity was determined by the rate of chromogenic conjugate formation between glutathione and 1-chloro-2.4-dinitrobenzene. RESULTS: No differences in the erythrocyte GR and GST activities between the control group and patients with schizophrenia were found. The platelet activity of GR and GST was significantly lower in patients compared to the control group (Mann-Whitney U test, p<0.01). Spearman rank correlation analysis showed that the erythrocyte GST activity was significantly correlated with PANSSneg scores when measured at the beginning of the study, GST was higher in those patients who had less PANSSneg scores after treatment (R=-0.41, p<0.05). The activity of platelet GST in patients with schizophrenia was correlated with the severity of positive symptoms (PANSSpos score) at the beginning of the study before taking therapy (R=-0.31, p<0.05), i.e. the more prominent psychotic symptoms were expressed in patients with lower GST activity. Upon completion of therapy, this association disappeared. CONCLUSION: The activity of glutathione-dependent enzymes in the blood cells of schizophrenic patients determined before the beginning of antipsychotic pharmacotherapy may be important for objective assessment of this metabolic system status and the degree of its impairment in patients.

The DNA of Bacteria of the World Ocean and the Earth in Cosmic Dust at the International Space Station.

Cosmic dust samples from the surface of the illuminator of the International Space Station (ISS) were collected by a crew member during his spacewalk. The sampler with tampon in a vacuum container was delivered to the Earth. Washouts from the tampon's material and the tampon itself were analyzed for the presence of bacterial DNA by the method of nested PCR with primers specific to DNA of the genus Mycobacteria, DNA of the strains of capsular bacteria Bacillus, and DNA encoding 16S ribosomal RNA. The results of amplification followed by sequencing and phylogenetic analysis indicated the presence of the bacteria of the genus Mycobacteria and the extreme bacterium of the genus Delftia in the samples of cosmic dust. It was shown that the DNA sequence of one of the bacteria of the genus Mycobacteria was genetically similar to that previously observed in superficial micro layer at the Barents and Kara seas' coastal zones. The presence of the wild land and marine bacteria DNA on the ISS suggests their possible transfer from the stratosphere into the ionosphere with the ascending branch of the global electric circuit. Alternatively, the wild land and marine bacteria as well as the ISS bacteria may all have an ultimate space origin.

[Latent dysphoria: an instrument of screening and diagnosis (preliminary results)]. / Latentnaia disforiia: instrument dlia skriningovoi diagnostiki (predvaritel'nye dannye).

AIM: Latent dysphoria is a kind of emotional disorder. Its key features are floating feeling of dissatisfaction and irritability accompanied with suppression of expression of these emotions. The article is devoted to the development of a screening diagnostic tool (checklist) to screen and evaluate patients with this emotional problem. MATERIAL AND METHODS: Three hundred and ninety-four neurologists (outpatient segment) were surveyed to assess the prevalence of an emotional disorder that met criteria of latent dysphoria suggested by the authors. To develop a diagnostic tool, expert judgement method, with the involvement of 19 experts in different medical fields (psychiatry, psychology, gastroenterology, neurology), was used. RESULTS AND CONCLUSION: The final checklist contained the most typical signs of this disorder according to the opinion of the experts. The procedure of evaluation of these signs was developed. However, the results should be considered as preliminary and clinical psychiatric validation of the tool is needed.

Mechanical Transformation of Compounds Leading to Physical, Chemical, and Biological Changes in Pharmaceutical Substances.

This study demonstrates the link between the modification of the solid-phase pharmaceutical substances mechanical structure and their activity in waters with different molar ratio «deuterium-protium¼. Mechanochemical transformation of the powders of lactose monohydrate and sodium chloride as models of nutrients and components of dosage forms was investigated by the complex of physicochemical and biological methods. The solubility and kinetic activity of substances dispersed in various ways showed a positive correlation with the solvent isotope profile. Substances dissolved in heavy water were more active than solutes in natural water. Differential IR spectroscopy confirmed the modification of substituents in the sample of lactose monohydrate, demonstrating physicochemical changes during mechanical intervention. The biological activity of the compounds was determined by the method of Spirotox. The activation energy was determined by Arrhenius. Compared with the native compound, dispersed lactose monohydrate showed lower activation energy and, therefore, greater efficiency. In conclusion, proposed data confirm the statement that mechanical changes in compounds can lead to physicochemical changes that affect chemical and biological profiles.

[Positive changes in the severity of residual psychotic symptoms in schizophrenic patients switched to treatment with risperidone]. / Polozhitel'naia dinamika rezidual'nykh psikhoticheskikh narushenii u bol'nykh pristupoobraznoi shizofreniei, sviazannaia s zamenoi terapii tipichnymi neiroleptikami na lechenie risperidonom.

AIM: To evaluate the effect of changing therapy from typical antipsychotics to the atypical antipsychotic risperidone in the treatment of difficult-to-treat residual psychotic symptoms. MATERIAL AND METHODS: The study included 15 patients, 8 men and 7 women, mean age 49.1±10.25 years, diagnosed with paranoid schizophrenia, partial remission (ICD-10 F20.04). At the beginning all participants received regular maintenance antipsychotic therapy with typical antipsychotics. The patient assessment with the PANSS, CGI scale and GAF scale was performed at the beginning (before the change of antipsychotics to risperidone) and in the end of the study. The primary efficacy endpoint was a reduction in scores on the PANSS items P1 'delusions' and P3 'hallucinatory behavior' to 1 (no such symptom) or 2 (minimal residual symptom). Secondary criteria were positive changes in the severity of other psychopathological symptoms and an increase in the social functioning level. The average dose of risperidone was 4.62±1.35 mg. The duration of treatment was 2 month. RESULTS: After switching from typical antipsychotics to risperidone and two months monotherapy, there were significant positive changes in the total PANSS score as well as in positive subscale score and CGI-S score. The small, but statistically significant, changes were detected in the overall functioning of the patients (the increase in the GAF score). The dynamics of residual psychotic symptoms was unequal: the severity of hallucinatory symptoms decreased significantly while the delusional symptoms remained unchanged. CONCLUSION: The authors suggest that excessive dopaminergic blockade might play a significant role in the pathogenesis of residual symptoms. This fact may explain the positive effect of treatment in the cases with the less degree of dopaminergic blockade. If it is true, the treatment strategy in the maintenance phase should not be a direct continuation of acute phase therapy and switching to other drugs and changing of the dose are needed.

[Possibilities of using cepeginterferon alpha-2b in double (cepeginterferon alfa-2b and ribavirin) and triple (simeprevir, cepeginterferon alpha-2b, and ribavirin) antiviral therapy regimens for chronic hepatitis C. A review of clinical trials and experience of everyday clinical practice]. / Vozmozhnosti primeneniia tsepeginterferona al'fa-2b v sostave dvukh- (tsepeginterferon al'fa-2b i ribavirin) i trekhkomponentnoi (simeprevir, tsepeginterferon al'fa-2b i ribavirin) skhem protivovirusnoi terapii khronicheskogo gepatita S. Obzor klinicheskikh issledovanii i opyta povsednevnoi klinicheskoi praktiki.

Since the incidence of chronic hepatitis C (CHC) increases steadily, the priority of national health care is to provide antiviral therapy (AVT) for the maximum number of patients infected with hepatitis C virus (HCV). The regimens including pegylated interferons (PEG-IFN) are still in demand in the Russian Federation. A number of clinical trials have been conducted to evaluate the efficacy and safety of cepeginterferon alpha-2b (cePEG-IFN alpha-2b), an original PEG-IFN-α developed in the Russian Federation. Their results have shown that cePEG-IFN alpha-2b in the two-component AVT regimen has at least no less clinical efficacy than PEG-IFN alpha-2b and PEG-INF alpha-2a in HCV monoinfected and HCV/HIV co-infected patients. The pooled analysis of data has indicated that the use of cePEG-IFN alpha-b in combination with ribavirin allows an average of 80% of the patients with HCV genotypes 2 and 3 and 62% of those with HCV genotype 1 to achieve a sustained virological response (SVR). In clinical practice when the two-component AVT regimen (cePEG-IFN alpha-b and ribavirin) was used in patients with early-stage CHC and mild fibrosis, SVR was recorded in 90.7% of the patients with HCV genotype 2/3 and in 75% of those with HCV genotype 1. The experience in using cePEG-IFN alpha-2b as a component of the three-component AVT regimen (simeprevir, cePEG IFN alfa-2b, and ribavirin) has been published. The observational program manly covered young patients with mild or moderate fibrosis. SVR was observed in 94% of the patients. Another paper describes the experience with the triple AVT therapy (simeprevir, cePEG-IFN alfa-2b, and ribavirin) in 22 patients, the majority of whom had advanced fibrosis. SVR was recorded in 71.4% of those who had completed treatment. Thus, an individual approach and assessment of predictive response factors to two- or three-component AVT regimens including cePEG-IFN alpha 2b can achieve successful treatment outcomes in most patients with CHC, which is, in some cases, more economically sound than interferon-free regimens used as first-line therapy.

[Variants of changes in the psychopathological phenomenology of the long-term remission in stable patients with attack-like progressive form of schizophrenia: a longitudinal study].

AIM: An analysis of literature data on schizophrenia shows the change of interest from acute psychosis to phenomenology of remission. The separate objects of research become the impact of symptoms, observed in remission, on everyday life of patients and factors, which influence rapidity and comprehension of reintegration of patients into society. Authors aimed to describe the changes in psychopathological phenomenology and personality functioning during long-term (no less than three years) remission in patients with schizophrenia treated with atypical antipsychotics. MATERIAL AND METHODS: One hundred and thirty stable patients with schizophrenia underwent regular clinical examination during no less than three years. All patients were constantly medicated with atypical antipsychotics. RESULTS: Long-term observation of patients with the similar diagnosis and phase of disease, similar treatment and good treatment response (at least without psychotic exacerbation during the observation period) and tolerability revealed difference in changes of psychopathological phenomenology and personality functioning, which could be grouped into four distinct variants. The description of specificity of each variant is presented. A role of the initial level of personality functioning and its changes during observation period were analyzed. A new concept is introduced in order to name the ability of patients to use rationally recourses, delivered by treatment. The connection of this concept with the level of personality functioning was demonstrated. The hypothesis of mechanisms which underlie the four variants is offered. CONCLUSION: Long-term observation of the changes in the psychopathological phenomenology in the period of disease reveals the variants of the development of remission. The fluctuation of adaptive and regressive phases is registered. More objective factors, which impact on prognosis, are elucidated.

[Description and validation of a new scale for assessment of autonomy in patients with schizophrenia].

OBJECTIVE: During the last years there is a clear shift of interest from acute to non-acute stages of schizophrenia: psychopathology and quality of remission, social functioning, and quality of life of patients. Authors think that in addition to that, a separate object of research should be the ability of patient to independent existence, or phenomenon of autonomy. For systematic research of autonomy in patients with schizophrenia a specialized assessment scale was constructed. MATERIAL AND METHODS: On the basis of preliminary clinical data, we realized that for description of autonomy it is necessary to consider consistency of patients at least in the following areas of life: to possess sufficient level of physical and psychic power; to be able to form specific and realistic goals at least in the nearest future and structure behavior correspondingly to goal achievement; to be able to use support from the social environment in case of deficit of personal resources; to use efficiently and on regular basis contacts with a doctor and other medical resources; to be able to manage everyday needs from hygiene to self-sufficiency, including ability to support compliance. Scale comprises five items. Each of them is assessed on basis of semi-structured interview and other sources of information: medical records, reports from relatives and/or care-givers, medical stuff. In order to study the validity of the scale 40 patients (13 males and 27 females, age 49.8±9, duration of illness 22±8.6), who were diagnosed as schizophrenia according to ICD-10. They were assessed with the help of the scale of autonomy and well-known scales GAF, PSP, PANSS, NSA and CGI-S, cognitive functioning was assessed by BACS. RESULTS: Analysis of internal consistency showed high consistency of items - Cronbach's alfa - 0.83. Analysis of convergent validity demonstrated low or moderate correlations of indices with related scales GAF and PSP. Discriminative validity showed low or moderate correlations only with negative subscale of PANSS, CGI-S score, NSA total score, BACS total score. CONCLUSION: Сompliance of the scale of autonomy to major psychodiagnostic requirements showed that the scale is a new reliable and sensitive psychometric instrument. The study demonstrated that the scale measured specifically ability of patients to be autonomous (self-dependent support of culturally adequate existence in presence of chronic disease) and can't be reduced to existing categories - quality of life, personal or social functioning.

[Plasma levels of antipsychotics and the severity of side-effects in the treatment of schizophrenia exacerbation].

OBJECTIVE: To study a relationship between plasma levels of antipsychotics (AP) and severity of side-effects (SE) during the treatment of inpatients with exacerbation of schizophrenia. MATERIAL AND METHODS: The study included 39 patients treated with risperidone, haloperidol, zuclopenthixol, clozapine, aripiprazole or olanzapine as monotherapy or in combination of two AP. Blood sampling to measure the AP plasma level was performed twice (at 7-10 and 26-30 day from start of treatment), the levels of prolactin and glucose were determined once (at 26-30 day from start of treatment). Patients were assessed by psychometric scales PANSS and NSA and the side-effects scale UKU. RESULTS: The increased concentration of AP was noted in 33% of the patients. The high concentration of AP was significantly associated with akathisia and hyperkinesia (by UKU scale), NSA retardation factor and hyperprolactinemia. Patients with severe hyperprolactinemia were twice as likely to have a clinically significant depression. Increased blood glucose levels were observed in 18% of the patients, there was no significant association with AP plasma levels. Mental SE were most prominent, with a drift towards the neurological SE in the group with higher AP plasma levels. Chlorpromazine equivalent didn't significantly differ in the groups with normal, high and low AP concentrations. CONCLUSION: Elevated AP plasma levels, which were associated with some clinically significant SE and some negative symptoms, were found in most patients. In this regard, therapeutic drug monitoring is a promising method for the individualization of schizophrenia exacerbation treatment in routine clinical practice.

[Theory and practice of pharmacological treatment of acute schizophrenia: a retrospective study].

OBJECTIVE: There is a gap between theory and practice in treatment of acute schizophrenia. It could be visualized in relatively irrational treatment schemes and principles. In order to clarify the situation in Russia, we have analyzed antipsychotic treatment patterns of acute schizophrenia in two Moscow psychiatric hospitals. MATERIALS AND METHODS: Information was collected from the databases of two Moscow city psychiatric hospitals. Inclusion criteria were as follows: admission to hospital due to acute symptoms of schizophrenia in 2000-2010. We studied case histories of 108 patients, aged from 18 to 64 years (mean 36±12 years), 53% of men. Duration of illness was 7±7 years, duration of hospitalization was 77±45 days. RESULTS: Most of the patients (77%) received traditional antipsychotics as a primary drug. Haloperidol was the most common primary antipsychotic drug prescribed (33% of patients). In 71% of cases, a combination of antipsychotics (typical and atypical) was used from the beginning of treatment. High values of average chlorpromazine equivalent were used at the first week of therapy as well as at the discharge from the hospital. Anticholinergic drugs were prescribed to 83.3% of the patients. Therapy had been changed at least 1 time during 2 month in 57.4% of cases. CONCLUSION: There was a significant discrepancy between the domestic routine practice and both treatment guidelines based on scientific data and antipsychotic treatment strategies used in other countries. To overcome these differences, reliable and biologically valid criteria for treatment selection in individual cases are needed. Pharmacokinetic data can serve as one of these criteria.

[The use of acatinol in the treatment of stable patients with schizophrenia with predominance of behaviour disorganization and subcatatonic features].

Our study was based on the hypothesis that a non competitive antagonist of NMDA receptors can improve clinical effects of antipsychotic therapy in a subgroup of patients with schizophrenia with clinical signs of glutamatergic hyperfunction such as catatonic symptoms and disorganization. The study design was open and non-comparative. The duration of the study for each patient was 6 months, the target dosage of acatinol was 20 mg. Forty stable patients with schizophrenia with predominance of signs of disorganization and subcatatonic symptoms were included. The following instruments were used: PANSS, NSA, CGI, BACS, UKU. Adding of acatinol to the antipsychotic treatment improved clinical symptoms, cognitive functioning and social functioning and decreased the number of side effects. The drug was well-tolerated.

[The methods for the protection against counterfeit medications. Part 1. The estimation of the quality of metoprolol succinate substance and tablets from different manufacturers in terms of "identity" and "active ingredient content"].

This paper was designed to report the results of analysis of metoprolol succinate substance and tablets obtained from two manufacturers, Akrikhin (Russia) and AstraZeneca (Sweden). The analysis was performed by spectroscopy in the near IR region and followed by the chemometric treatment of the data obtained. The method was used to confirm the "identity" of metoprolol succinate tablets. The approach to distinguishing the differences between pharmaceutical dosage forms produced by different manufacturers is proposed. Also, the method for the qualitative determination of metoprolol succinate in the pharmaceutical formulations has been developed.