Heterogeneity of the mechanisms of action of antidepressants Kozlovskii, V. L.; Popov, M. Yu; Kosterin, D. N. ...
Obozrenie psihiatrii i medicinskoj psihologii im. V.M. Behtereva/Obozrenie psihiatrii i medicinskoj psihologii imeni V.M. Behtereva,
04/2021, Volume:
55, Issue:
1
Journal Article
Peer reviewed
Open access
The article discusses the heterogeneous mechanisms of the pharmacodynamics of antidepressants that underlie the therapeutic response. Sharing the similar clinical activity, antidepressants determine ...the development of drug-induced homeostasis by means of different molecular mechanisms (selective or nonselective blockade of monoamine reuptake, inhibition of monoamine oxidase, blockade of certain monoamine receptors). However, an increase of serotonin and other monoamines concentrations in the synapses of the central nervous system is only the initiating factor in the development of specific clinical effects. The latter are probably determined by other neurochemical effects, including changes in the density of postsynaptic receptors and an increase in the synthesis of neurotrophic factors. However, the primary mechanisms that increase monoamine concentrations in the synapses might not always “work properly”, leading to the lack of efficacy of the initial antidepressant, while the probability of the therapeutic response to the subsequent antidepressant remains rather high. Thus, the efficacy of an antidepressant may depend on the baseline differences in the neurochemical state contributing to the pathological “depressive” homeostasis. The heterogeneous neurochemical effects of antidepressants can determine the dissociation of existing neuronal interactions, leading to the development of the new — druginduced — homeostasis. At the same time, it is possible that stimulation of general neurotrophic processes by antidepressants may contribute to the progression and chronicity of pathology due to the ambiguous influence on certain stages of the pathological process. This determines the significance of neurophysiological studies of central disturbances in depression and search of fundamentally new neurochemical targets for the treatment of depressive states associated with various mental disorders.
New alien species for the Novosibirsk Region are reported: Corydalis solida, Crataegus chlorosarca, Erigeron strigosus,Hemerocallis lilioasphodelus, Lathyrus oleraceus, Polygonum sabulosum, ...Ranunculus acris (Double Acris Group), Veronica biloba. New localities of rare alien species Astragalus contortuplicatus, Cerinthe minor, Cyclachaena xanthiifolia, Galium aparine, Myosotis stricta, Scleranthus annuus, Symphyotrichum novi-belgii, Symphytum × uplandicum were noted. For each species, its range is given, the distribution in the regions of Siberia is indicated.
The development of psychotic symptoms is traditionally linked to the increase of the functional activity of endogenous dopaminergic system. Antipsychotic effect of existing medications is associated ...with direct blockade of postsynaptic dopamine receptors. However, direct antagonistic activity is «alien» to physiological mechanisms of neurotransmission modulation, and presynaptic autoreceptor blockade mау produce a reverse (agonistic) effect, enhancing neurotransmitter release. On the other hand, anti-dopamine effect can be achieved by indirect antagonistic activity—by presynaptic dopamine depletion, which is consistent with the natural, physiological mechanisms of reducing neurotransmission. It can be assumed that modulation of presynaptic regulation is one of the promising directions for the development of antipsychotic drugs of future generations.
“Adequate dose” in the drug treatment of mental disorders Kozlovskii, V. L.; Kozlovskaya, N. V.; Kosterin, D. N. ...
Obozrenie psihiatrii i medicinskoj psihologii im. V.M. Behtereva/Obozrenie psihiatrii i medicinskoj psihologii imeni V.M. Behtereva,
02/2024
Journal Article
Peer reviewed
Open access
The article discusses the use of different doses of psychotropic drugs in the treatment of mental disorders. It is known that the number of responders is about two thirds of all patients, which ...according to the “three sigma” rule for the normal distribution of cases, fits into the range of one sigma. The hypothetical calculation of the relative proportions of patients responding to treatment in low, mid-range and high doses is given. In accordance with this, the use of a mid-range treatment doses is justified, thereby the number of potential responders increases almost twice as compared with the use of small doses. Within the framework of pharmacodynamics, the probability of the development of dose-dependent effects is assessed, including both desirable and untoward effects of various pharmacological classes of psychotropic drugs in different doses.
The first finding of Centaurium pulchellum in Novosibirsk Province is reported, as well of sucn plant species, rare in Novosibirsk surroundings, as Paeonia anomaia, Campanula tracheiium, Cirsium ...palustre, Inula helenium, Iris pseudacorus, Hemerocallis minor, made in 2019 within the City of Novosibirsk in two bogged areas (the Gladkoe and Kuchino Bogs, and the surroundings of the former), and in the Ob River floodplain. A large population of Cypripedium macranthon was found in unusual conditions of a boggy open stand of pine, larch and birch, with Equisetum fluviatile predominating in the grass layer. Importance of these natural ecosystems inside a city is discussed for nature protection and research purpose.
Hydrazones derived from 5-nitro-2-furfural and 2,3-, 2,4-dihydroxybenzoic acids as well as isoniazid undergo the deprotonation in aqueous and non-aqueous solutions and possesses some antimicrobial ...activity comparable with that of nifuroxazide, a drug of the analogous chemical structure.
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•Four hydrzones of 5-nitrofurfural and 4-nitro-2-formylthiophene are synthesized.•Protonation constants of hydrazones are determined in water and aqueous DMSO.•Anion sensing ability of hydrazones is tested.•Antimicrobial action of hydrazones is tested.
The present paper reports on the synthesis of four hydrazones derived from 5-nitro-2-furfural, 5-nitro-2-thiophenal, isoniazid, 2,4- and 3,4-dihydroxy-N′-methylenebenzohydrazide. The acid-base dissociation constants of these compounds were determined in an aqueous solution. The protolytic equilibria-related ability of hydrazones to “sense” anions in dimethyl sulfoxide-containing water of different concentrations is studied using spectrophotometry, NMR spectroscopy, and quantum chemistry methods. The antimicrobial action of the hydrazones was tested and compared with that of the known drug nifuroxazide.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The article deals with the problem of the expediency of a criminal case’s returning to the prosecutor at the stage of appointment and preparation of a court session in Russian criminal proceedings. ...This problem is relevant to the science of criminal procedure.The purpose of the study is to analyze critically the practice of returning of a criminal case back to the prosecutor in order to correct mistakes made at the pre-trial stages of the proceedings according to the new concept of justice independence and the absence of an accusatory bias in the court functioning.The methodological basis of the study is a set of scientific techniques, focused mostly on the dialectical approach, which made it possible to determine the essential characteristics of the prohibition to turn the criminal proceedings in Russia for the worse. Both general scientific (analysis, synthesis, systematic method) and specific scientific methods (formal-legal, historical-legal, comparative-legal) of knowledge were also used. The analysis helped to formulate the position of understanding the turn for the worse as an independent principle of criminal procedural law, to study the procedural form of the turn for the worse. The synthesis method made it possible to determine the return of the criminal case to the prosecutor at the stage of appointment and preparation of the court session as a holistic institution of the criminal procedure. The systematic approach allowed to determine not only the mixed nature of the mechanism for changing the prosecution to a more serious one, but the investigative organization of pre-trial proceedings and its place in the structure of criminal proceedings, the separation of the investigative and “accusatory powers” of the prosecutors as well as their balance. The historical method let us trace the evolution of the prohibition to turn the Soviet and Russian criminal procedural systems for the worse. The comparative-legal method made it possible to assess the potential of domestic legislators' reception of foreign experience of regulating the prohibition to turn for the worse and formulate proposals to improve the Russian criminal procedural legislation.The main scientific results of this research consist of justification of the conclusion of the conversion expediency of the domestic judicial proceedings to the adversarial model of accusation which is carried out within the trial on the previously filed charge. The presentation of a new charge (criminal action) in court and the procedure of supplementing the charge change it for the worse. This model of re-indictment for the worse for the defendant appears to be fairer and more convenient both for the prosecuting authority and for the legal organization of combating crime. The changeover to the suggested form of implementation of the ban to turn for the worse in the institution of bringing and changing charges in court is possible only in a systematic link with the reform of the preliminary investigation. Conclusion. The institution of the criminal case returning by the court to the prosecutor in order to change the charge to a more serious one when implementing the adversarial model of bringing charges in the criminal procedure system of Russia will fully satisfy the concept of independence of justice administration and the absence of an accusatory bias in the activities of the court, while at the same time with fairly organized the prosecutorial power aimed at countering crime.The section 1 was prepared by N.N. Lysov, section 2 by K.D. Vanyan (together with M.T. Tashilin), section 3 by A.S. Shuisky (together with I.R. Gilmanov), section 4 by V.V. Kosterin.
Aim. To study the diagnostic value of the left atrial stiffness index (LASI) of heart failure with preserved ejection fraction (HFpEF) depending assessed by transthoracic echocardiography (TTE) in ...the diagnosis on diastolic stress test (DST) results. Material and methods. DST was performed in cases of insufficient criteria for increased left ventricular filling pressure assessed by TTE. One hundred patients were examined (52,0% men, 66,1±5,4 years). Patients with a ratio of early transmitral flow velocity to early diastolic mitral annulus velocity (E/e') ratio >15 in DST were included in group I (n=45), patients with E/e' <15 — group II (n=55). The speckle tracking echocardiography was used to assess left atrial reservoir strain (LASr). Results. Significant differences were identified between the groups in sex (40,0% of men in group I and 61,8% in group II, respectively; p=0,044), body mass index (32,9 29,5;36,0 and 29,6 27,3;31,8 kg/m 2 ; p=0,001), hypertension stage (2,9±0,3 and 2,5±0,8, p=0,037), the presence of coronary artery disease (88,9 and 67,3%; p=0,016), NYHA heart failure class (2,0±0,4 and 1,5±0,7; p=0,003). TTE revealed significant differences in the left atrium volume index (31,9 28,5;36,0 and 27,8 24,1;34,6 ml/m 2 ; p=0,039), E/e' ratio (10,9 9,7;12,5 and 9,3 7,4;10,8; p<0,001), LASr (23,5 19,3;28,3 and 28,9 25,6;32,2%, p<0,001) and LASI (0,46 0,38;0,56 and 0,30 0,25;0,39; p<0,001). According to ROC analysis, the largest area under the curve (AUC), optimal sensitivity and specificity in HFpEF diagnosis were observed in LASI (AUC=0,829, p<0,001; 77,8 and 74,5%, respectively). Lower classification quality was shown by the H2FPEF score (AUC=0,701, p=0,001; 66,7 and 69,1%), while the HFA-PEFF score was not significant in the pretest detection of HFpEF (AUC=0,608, p=0,065; 53,3 and 61,8%). Conclusion. LASI with a cut-off point >0,38 has the greatest ability to detect HFpEF among the possible pretest diagnostic methods.
Introduction. Currently the chronic prostatitis (NIH type IV) remains insufciently studied and difcult to treat with antibiotics. When making the diferential diagnosis of chronic prostatitis it is ...generally accepted by the EAU and Russian guidelines that the detected microorganisms in the prostatic fuid and the ejaculate practically do not difer from each other. The tactics of treating patients with asymptomatic prostatitis by means of antibacterial drugs remains disputable. Most reputable authors believe that this category of patients shall receive treatment in case of infertility, pregnancy miscarriage or forthcoming surgery on the prostate gland. Recently, EAU guidelines have expressed doubts regarding the identity of the microbiota found in the prostatic secretions and the ejaculate. The study objective. Comparative analysis of the detectability of microorganisms in prostatic secretions and the ejaculate by means of bacteriological analysis among the men with chronic prostatitis of category IV. Materials and methods . The study involved 117 men who went to the urological clinic to pregravid examination or on the occasion of infertility. All patients were diagnosed with prostatitis of category IV based on a standard examination, and then a bacteriological analysis of prostatic secretions and ejaculate was performed. During the research the prostatic fuid and ejaculate were taken simultaneously and the analysis was carried out in one and the same bacteriological laboratory. In case the titer of the detected microorganisms was signifcant, the patients were ofered to undergo treatment without the use of antibiotics but with combination of bovhyaluronidase azoximer with prostate protectors and/or OM-89; after that a control bacteriological study was performed. Results. In the prostatic secretions and in the semen, the most commonly found gram-positive microorganisms were Staphylococcus spp. and Enterococcus spp.; the representatives of the Enterobacteriaceae were found less frequently. It was statistically proven that the titer of bacteria in the prostatic secretions was considerably higher than that in the ejaculate (p <0.01). Sterile cultures were statistically-proven to be more frequent in ejaculate compared with prostatic secretions (13.7 % vs 3.4 %, p <0.01). When analyzing the coincidences for bacteria, low concordance was obtained for all identifed microorganisms (gram-positive bacteria varied from 48.3 to 79.5 %, gram-negative bacteria varied from 57.1 to 80.0 %). After the combined therapy, the bacterial mass signifcantly decreased in the prostate secretion from 104.3 ± 1.6 CFU/ml to 103.3 ± 2.0 CFU/ml (p = 0.008), while in the semen the bacterial mass decreased from 103.5 ± 1.8 CFU/ml to 102.6 ± 2.1 CFU/ml (p = 0.02). In the prostatic secretions, there was a statistically-proven decrease in the number of gram-negative bacteria (p = 0.05). As soon as the treatment was completed all the patients demonstrated the normalized number of leukocytes according to microscopy of prostate secretions or spermogram. Conclusion. The ejaculate is a more sterile biomaterial compared with the prostatic fuid, which should be taken into account in the diferential diagnostics of the chronic prostatitis of category IV and MAGI. The use of non-antibacterial treatment regimens, such as bovhyaluronidase azoximer, prostate protectors and OM-89, can reduce the titer of bacteria to insignifcant values both in the prostatic secretions and in the semen; and in some cases make the ejaculate sterile.
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