[Dynamics of cognitive functions using the rehabilitation program of cognitive training]. / Dinamika kognitivnykh funktsii pri ispol'zovanii reabilitatsionnoi programmy kognitivnogo treninga.

OBJECTIVE: To study the efficiency of the neuropsychological rehabilitation of patients with mild cognitive impairments. MATERIAL AND METHODS: The study included 103 elderly people, aged 59 to 88 years, including 90 women and 13 men with subjective complaints of memory loss (ICD-10: F06.70; F06.71; F06.78; F06.79). Participants were divided into experimental group (n=43) and comparison group (n=42). The estimated impact was the rehabilitation program «The psychosocial therapy and neurocognitive rehabilitation of elderly patients with cognitive impairments¼, within which the principle of complex stimulation of various parameters of the cognitive sphere was used in rehabilitation work with patients in the experimental group in accordance with the «Memory Clinic¼ program. The study was conducted using randomized, equalized comparison groups, and the principle of «triple-blind¼ research. Non-parametric statistics (SPSS) methods were used to assess differences. RESULTS: A significant difference between the comparison and experimental groups has been identified, primarily in relation to high-level mental processes associated with the function of the third structural-functional block according to A.R. Luria. After the training, the number of correct answers significantly increased (t(42)=-2.67, p<0.001) in the experimental group, while in the comparison group the indicator did not change (t(41)=0.50, p=0.617). The number of false alarms in the experimental group decreased significantly (t(42)=2.13, p=0.039). CONCLUSION: The results confirm the leading role of these processes in the hierarchy of mental functions, which suggests that they should primarily be targets of rehabilitation interventions.

The Effect of Therapy Regimen on Antitumor Efficacy of the Nanosomal Doxorubicin against Rat Glioblastoma 101.8.

One of the key problems of glioblastoma treatment is the low effectiveness of chemotherapeutic drugs. Incorporation of doxorubicin into PLGA nanoparticles allows increasing the antitumor effect of the cytostatics against experimental rat glioblastoma 101.8. Animal survival, tumor volume, and oncogene expression in tumor cells were compared after early (days 2, 5, and 8 after tumor implantation) and late (days 8, 11, and 14) start of the therapy. At late start, a significant increase in the expression of oncogenes Gdnf, Pdgfra, and Melk and genes determining the development of multidrug resistance Abcb1b and Mgmt was revealed. At early start of therapy, only the expression of oncogenes Gdnf, Pdgfra, and Melk was enhanced. Early start of treatment prolonged the survival time and increased tumor growth inhibition by 141.4 and 95.7%, respectively, in comparison with the untreated group; these differences were not observed in the group with late start of therapy. The results indicate that the time of initiation of therapy is a critical parameter affecting the antitumor efficacy of DOX-PLGA.

Melatonin and its bioisosteres as potential therapeutic agents for the treatment of retinopathy of prematurity.

We conducted a study on the impact of intraperitoneal injections of melatonin and its three bioisosteres (compounds 1-3) on the development of oxygen-induced retinopathy in newborn rats during a 21-day experiment. It was demonstrated that melatonin and its analogues 1-3 effectively reduce the total protein concentration in the vitreous body of rat pups, decrease concentration of VEGF-A, and lower the level of oxidative stress (as indicated by normalization of antioxidant activity in the vitreous body). Melatonin and its analogues 1-3 equally normalize the level of VEGF-A. Analogues 1 and 2 even exceed melatonin in their ability to reduce protein influx into the vitreous body. However, analogue 2 had no effect on antioxidant activity, while analogues 1 and 3 caused a significant increase in this parameter, with analogue 3 even slightly exceeding melatonin. Thus, it can be concluded that analogues 1-3 are comparable to melatonin and can be utilized as potential therapeutic agents for the treatment of retinopathy of prematurity.

[Structure and dynamics of depressive disorders in patients with a new coronavirus infection]. / Struktura i dinamika depressivnykh rasstroistv u patsientok, perenesshikh novuyu koronavirusnuyu infektsiyu (COVID-19).

OBJECTIVE: To analyze the dynamics of depressive disorders in patients who underwent COVID-19. MATERIAL AND METHODS: The study included female patients (n=30) with mean age 35.4±3.0 years, who received inpatient treatment of depressive spectrum symptoms in accordance with ICD-10 rubrics F31-F34 and who have undergone COVID-19 (U04.9, U07.1, U07.2). Clinical-psychopathological and statistical methods were used. RESULTS: Among all patients, who underwent inpatient treatment for affective disorders, the most common symptoms were: low mood (96.7%), anxiety (83.3%), decreased interest in daily activities (40%), loss of appetite (36.7%). In patients who have had depressive symptoms before COVID-19, an increase in the number of affective spectrum symptoms (suicidal thoughts - 83.3%), as well as in asthenic manifestations in the form of increased fatigue (60%), sleep disorders (73.3%), feelings of fatigue, weakness (60%), emotional lability (40%). CONCLUSION: In patients with depressive disorders who underwent COVID-19, hypothymia is most often accompanied by anxiety, suicidal thoughts, as well as asthenic manifestations in the form of fatigue, sleep disturbances, and emotional lability. An increase in the number of asthenic spectrum symptoms in patients with depressive disorders may indicate a possible link between COVID-19 and affective pathology. The impact of coronavirus infection on the structure and dynamics of depressive disorders requires further study, taking into account the severity of affective symptoms, the impact of psychopharmacotherapy, and the severity of the infectious disease.

Enalaprilat as a new means of preventing the development of retinopathy of prematurity.

In a rat model of experimental retinopathy of prematurity (ROP), the safety of enalaprilat and its effect on the level of angiotensin-converting enzyme (ACE) and angiotensin-II (AT-II) in the vitreous body and retina were investigated. The study was performed on 136 newborn Wistar rat pups divided into 2 groups: group A - experimental (animals with ROP, n=64) and group B - control (n=72). Each group was further divided into 2 subgroups: A0 and B0 (n=32 and n=36, respectively) - animals that did not receive injections of enalaprilat, and A1 and B1 (n=32 and n=36, respectively) - animals treated with daily intraperitoneal (i.p.) injections of enalaprilat (0.6 mg/kg of body weight). This treatment started on day 2 and lasted either to day 7 or to day 14 in accordance with the therapeutic scheme. Animals were taken out of the experiment on day 7 and day 14. In samples of the vitreous body and retina, the content of ACE and AT-II was determined by enzyme immunoassay. On day 7 in subgroups A1 and B1 the levels of ACE and AT-II in the vitreous did not differ, while on day 14 were lower than in subgroups A0 and B0, respectively. Changes in the parameters studied in the retina were somewhat different from those found in the vitreous body. On the seventh day, the level of ACE in the retina of animals of subgroup B1 did not differ significantly from subgroup B0, and in subgroup A1 it was increased compared to subgroup A0. On day 14, its significant decrease was noted in subgroups A1 and B1 as compared with subgroups A0 and B0. At the same time, the level of AT-II in the retina of rat pups of subgroup B1 was lower than in subgroup B0, both on day 7 and day 14. On day 7, the concentration of AT-II, as well as the concentration of ACE, increased in subgroup A1 as compared to subgroup A0. On day 14, this parameter in subgroup A1 was significantly lower as compared to subgroup A0, but significantly higher than in subgroup B1. It should be noted that i.p. injections of enalaprilat, increased a death rate of animals of both groups. The use of enalaprilat, starting from the preclinical period of the ROP development, led to a decrease in the activity of the renin-angiotensin system (RAS) in ROP animals at the onset of retinopathy in the experimental model used. This opens up prospects for considering enalaprilat as a means of preventing the development of this pathology; however, the recognized high toxicity of the drug requires further studies and correction of the timing of its administration and dosage in order to achieve a balance of efficacy and safety of use in order to prevent the development of ROP in children.

Changes in Oncogene Expression in Experimental Glioblastoma 101.8 Rats during Therapy with PLGA Nanoparticles Loaded with Doxorubicin.

We compared the expression of the main glioblastoma oncogenes during therapy with doxorubicin (Dox) and Dox in nanoparticles based on a copolymer of lactic and glycolic acids (Dox-PLGA) at a delayed start of treatment. Late initiation of Dox-PLGA therapy of glioblastoma showed an increase in the expression of multiple drug resistance genes, such as Abcb1b and Mgmt, and a decrease in Sox2 expression. Increased expression of other oncogenes (Melk, Wnt3, Gdnf, and Pdgfra) were observed during both Dox and Dox-PLGA therapy. These changes indicate increased tumor aggressiveness and its resistance to cytostatics at the late start of therapy.

Poplar tree (Populus balsamifera L.) as indicator of mercury emission from a point source.

The article provides original data on the ecological and geochemical characteristics of the distribution of Hg in the leaves and annual rings of balsam poplar (P. balsamifera L.) in the zone of influence of lithium production (Novosibirsk). In 2017 high Hg concentration (1300 ng/g) in the poplar leaves was recorded in the northeastern part of the city near the industrial facility of the lithium plant. The investigation showed a clear trend of increased Hg accumulation in the poplar leaves during the growing season. The maximum average Hg content was detected in the leaf litter in 2006 (1153-2425 ng/g). However, the average Hg content in the soil is 294 ng/g, which is significantly lower than the threshold limit value (2100 ng/g). Studies of changes in the content of Hg with the height of the crown of the tree revealed an increase in the upwind side of the emission source, the concentration of Hg in the leaves is on average 1.5 times higher than on the side of the "wind shadow". Hg in poplar leaves, leaf litter, and soils is mainly found in free and physically bonded forms - the most mobile, prone to increased migration, transformation and methylation under environmental conditions. According to the Hg content in the poplar cores, an increase in the Hg input near the source was established with the beginning of Li production - in the period 1967-1985 years (441 ng/g) with a subsequent decrease to 6 ng/g in 2000-2017.

Prognostic Value Estimation of Monoamines Systemic Level in Retinopathy of Prematurity in Experiment.

The aim of the investigation was to study a systemic level of L-DOPA, dopamine, and norepinephrine, and assess their prognostic value in retinopathy of prematurity (ROP) development on an experimental disease model. MATERIALS AND METHODS: The investigation was carried out on infant Wistar rats (n=36) divided into a study group (rat infants with experimental ROP, n=17) and a control group (n=19). The animals of both groups were sacrificed on days 14, 21-23, and on days 28-30. The choice of the indicated periods corresponded to the key stages of ROP development in an experiment and was based on the findings of our previous histological studies. Dopamine, L-DOPA, and norepinephrine levels in infant rat blood plasma samples were determined. RESULTS: On day 14 of the experiment (the period corresponds to the pathological neovascularization induction in the applied model and preclinical ROP in children), mean L-DOPA level in infant rats with ROP (0.31 ng/ml) was significantly decreased compared to that in the controls (0.42 ng/ml) (p≤0.01). On days 21-23 of the experiment (the period corresponds to the growth of pathological extraretinal neovascularization in the applied model and ROP stage 3 in children) the systemic level of L-DOPA was still statistically reduced in the study group (0.87 ng/ml) compared to the control group (1.53 ng/ml) (p≤0.01). On days 28-30 of the experiment (the period corresponds to the regress of neovasculature in the applied model and a spontaneous ROP regress stage in children) the L-DOPA level in blood plasma in the study group (0.33 ng/ml) showed an insignificant upward tendency in reference to the controls (0.21 ng/ml). Mean dopamine and norepinephrine levels had no difference in the groups under study of infant rats within all follow-up periods. CONCLUSION: Low systemic level of L-DOPA at the preclinical stage of experimental ROP should be considered as a laboratory prognostic criterion of a developing pathological process; it will enable to use the criterion when working out the measures to optimize the existing screening system for the disease in children.

[Pathogenetically oriented approach to prevention of retinopathy of prematurity (experimental study)]. / Patogeneticheski orientirovannaya profilaktika retinopatii nedonoshennykh (eksperimental'noe issledovanie).

Intraperitoneal injections of exogenous melatonin during the development of the retinal vascular system in experimental rats has been shown in a number of experimental studies on the model of EROP to prevent the appearance of histological signs of the development of experimental retinopathy of prematurity (EROP), stabilize the blood-retinal barrier and have a pronounced antioxidant effect, but pathogenetic basis for these phenomena hasn't been studied. PURPOSE: To study the influence mechanism of melatonin and its analogues on the development of EROP at the preclinical stage of the pathological process to substantiate new approaches to prevention of ROP. MATERIAL AND METHODS: The study included 42 Wistar rat pups (84 eyes) divided into 6 groups: control group, experimental group (rat pups with EROP), experimental groups who underwent injections of melatonin and its analogues K-148, AL-3, K-096. The pups were euthanized on day 7 (4-5 pups from each group at each study period), binocular enucleation was performed, and the content of hypoxia-induced factor1α (HIF-1α) and VEGF-A was determined in retinal samples. RESULTS: The intraperitoneal injections of melatonin and its analogs led to a significant decrease in the level of HIF-1α and VEGF-A in the retina of the rat pups of the experimental group until the beginning of pathological vasoproliferation. CONCLUSION: Melatonin and its analogues are able to prevent the development of EROP by reducing the level of angiogenic factors in the retina of rat pups at the stage of existing avascular zones, which allows for them to be considered as a new promising approach to preventing the development of ROP.

[Predictors of suicidal behaviour in adolescents with depressive disorders]. / Prediktory suitsidal'nogo povedeniia u podrostkov s depressivnymi rasstroistvami.

A review of recent publications is devoted to risk factors for suicidal behavior in adolescents with depressive disorders. The authors summarized Russian and international studies on the clinical course of affective disorders, in particular bipolar disorders, their clinical heterogeneity and incompleteness in adolescence. Particular attention is given to the complexity of early identification of predictors of suicidal behavior in depressive disorders due to comprehensiveness of exogenous and endogenous effects characteristic of adolescence. The role of genetic loading for affective disorders, problems of children having parents with affective disorders, social and psychological factors (violence in families, school bullying etc.) and risks of suicidal behavior are described. It is of great significance to investigate premorbid adjustment, subaffective manifestations of disorders in adolescence to predict the trajectory of the disease, its complications in the form of suicidal behavior and opportunities for early intervention.

The Role of Catecholamines in the Development of Pathological Retina Neovascularization in an Experimental Model of Retinopathy of Prematurity in Rats.

This work is dedicated to proving our hypothesis that catecholamines and their metabolites play a crucial role in the development of retinopathy of prematurity, which leads to progressive uncontrollable vascularization in the retina, leading to blindness. The study was performed in an animal model of retinopathy of prematurity, which was achieved by hyperoxygenation in rats on postnatal days 7, 14, 21, and 30. The content of catecholamines and their metabolites in the retina of rats was determined by high performance liquid chromatography with electrochemical detection. It was shown that, in the rats with retinopathy, the content of L-DOPA on days 21 and 30 was decreased as compared to the control, whereas the content of noradrenaline on day 14 life increased compared to the control. However, we did not observe changes in the content of dopamine in the experimental animals relative to the control in any period studied. Given the published data on the involvement of catecholamines in the regulation of vasculogenesis in the retina in normal state, our data on the changes in the catecholamine metabolism in the retina in the model of retinopathy of prematurity can be regarded as evidence of the important role of catecholamines in the pathogenesis of this severe disease.

Simultaneous determination of rifabutin and human serum albumin in pharmaceutical formulations by capillary electrophoresis.

Capillary zone electrophoresis (CZE) was used for determination of rifabutin (RFB), an anti-tuberculosis antibiotic drug, in various pharmaceutical formulations. Apart from that, simultaneous determination of RFB and human serum albumin (HSA) was performed. Electrophoretic behaviour of RFB was examined at various pH levels. CE conditions: a quartz capillary tube (internal diameter 75mm, effective length 50cm, total length 60cm), the capillary temperature was 25°Ð¡, the voltage applied to the capillary tube was +20kV, the UV detection wavelength was 214nm, hydrodynamic injection of the sample was performed at 30mbar for 5s, tetraborate buffer solution (0.01М, рН9.2). The obtained results are characterized by high efficiency (number of theoretical plates up to 260,000) and sufficient sensitivity (LOQ starting from 0.02µg/ml for RFB). The obtained data are in good accord with both HPLC results (for RFB) and spectrophotometry (for HSA).

[Melatonin as a new promising agent for the treatment and prevention of retinopathy of prematurity]. / Eksperimental'noe issledovanie vozmozhnosti primeneniya melatonina v lechenii i profilaktike retinopatii nedonoshennykh.

AIM: To evaluate the effect of exogenous melatonin on the blood-retinal barrier and oxidative status of the vitreous in rats with oxygen-induced retinopathy (OIR) and analyze its prospects in the treatment and prevention of retinopathy of prematurity (ROP). MATERIAL AND METHODS: The study was performed on 48 Wistar rat pups (96 eyes) divided into 4 groups 12 animals each: OIR group, melatonin group and two control groups. In order to induce retinopathy, rat pups and does were placed in an incubator for 14 days after birth. Oxygen concentration in the incubator changed from 60 to 15% every 12 hours. The controls for this experiment were rats that grew under normoxic conditions (21%). The two other groups of rats were injected with 30 ml intraperitoneal melatonin (Sigma-Aldrich) in sterile 0.05 M phosphate buffer (pH 7.4) at a dose of 10 mg/kg for 14 days starting on day 1. The pups were killed on days 7 (n=16), 14 (n=16), and 18 (n=16). Binocular enucleation was performed in all cases. The total protein level and antioxidative activity (AOA) were then measured in vitreous samples. RESULTS: Oxygen-induced retinopathy had two phases and was accompanied by a sharp increase in the vitreal AOA and total protein. After intraperitoneal melatonin injections made during the period of early OIR-associated vascular changes, the said parameters were decreased down to near-control values at any times during the follow-up period. CONCLUSION: Exogenous melatonin, due to its strong antiangiogenic and antioxidant activity, helps stabilize the blood-retinal barrier in OIR.

[Toxicological Evaluation of Intravenous Formulation of Rifapentine.]

Rifapentine belongs to the most potent antituberculosis drugs. Nevertheless, there are some limitations for its clinical use because of the low aqueous solubility and side effects. A technological approach to development of rifapentine intravenous formulation based on human serum albumin was described earlier and its efficacy against experimental tuberculosis was estimated. Toxicological evaluation of that water-compatible form of rifapentine revealed its low acute toxicity (LD50 340 mg/kg). Chronic toxicity tests of both the oral substance and the injectable formulation of rifapentine demonstrated similar adverse effects. However, in contrast to the conventional oral formulations, the intravenous formulation of rifapentine had no gastrointestinal toxic effects or cardiotoxicity, thus suggesting its usefulness for clinical application.

[STAGES OF OPIOID THERAPY OF CHRONIC PAIN IN RUSSIA: ANCIENT AND COMING].

There is history of the introduction and development of systemic and invasive opioid treatment of chronic cancer pain in Russia presented by the authors--experts with experience in thisfield over 30 years. The earliest researchers are no more among us, but their memory is still alive in the publications of the early 1980's. Along with the analysis of accumulated by Russian specialists positive clinical experience of opioids using, authors discuss main problems of organization and availability of adequate opioid therapy of chronic pain in Russia. Ways of further development ofpalliative care and pain management in oncology is discussed as well as.

[Trends in world science and practice of pain treatment].

In recent days there are two main conceptions of the treatment of strong pain. The first conception is a system multimodal analgesia and the second is a multidisciplinary therapy including invasive techniques (local nervous blockades, neuroaxial blockades, neurostimulating or drug therapy with implanted systems etc.), physical, manual, and psychological effecting on peripheral and central nervous system. A physician (anaesthesiologist, oncologist, neurologist etc.) treats the pain according to interests of a patient. Multidisciplinary pain treatment, which is recommended by the American Pain Association, requires the use of special equipment for effecting on nervous system of the patient and contains conflict of interests of managers, medical workers, equipment providing companies and other parts of the multidisciplinary process. Therefore there is a risk that commercial benefit can get a main role in the process of pain treatment, but not interests of the patient. The "industrial" approach in the pain treatment is connected with many negative outcomes such as a minimizing of the role of pain science, increasing of complications risks due to invasive techniques of the pain relief etc. Therefore an objective analysis of pain treatment outcomes is needed Helsinki Declaration of a patient safety in surgery approved by European Society of Anaesthesiology in June, 2010 requires an accounting system of critical incidents, complications and assessment of outcomes in perioperative anaesthesiological practice. The same study is very actual for Russia especially to compare a safety of the system multimodal anaesthesia/analgesia and epidural blockades in major surgery.

[Allogeneic hematopoietic stem cell transplantation for acute myeloblastic leukemia in first remission].

AIM: To evaluate the efficiency of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloblastic leukemia in first remission depending on the regimens of conditioning, the source of a graft, and the characteristics of a donor and a recipient. SUBJECTS AND METHODS: In 66 treated patients, including from partially HLA-mismatched relatives (n=4), the efficiency of allo-HSCT from related donors (n=26) and unrelated donors (n=40), were compared. According to cytogenetic findings, 7 (11%), 31 (47%), and 10 (15%) patients belonged to low-, intermediate-, and high-risk groups, respectively. RESULTS: Five-year overall survival (OS) and mortality associated with transplantation were 56 and 22% for allo-HSCT from related donors, 68 and 23% for that from HLA-matched donors, and 71 and 25% for that from partially HLA-mismatched donors, respectively (p=0.8 and p=0.7). The relapse risk after allo-HSCT from unrelated donors was significantly lower than after that from related donors (13 and 35%, respectively; p=0.8). Univariate analysis showed that the OS rates depended on the cytogenetic risk group (OS was 24 and 64% in the high- and intermediate-risk groups, respectively (p=0.027). The relapse risk in chronic graft-versus-host reaction (GVHR) and in grade 3 acute GVHR (p=0.01) was shown to be less than that in grades 1-2 acute GVHR (p=0.06). CONCLUSION: OS rates after allo-HSCT from related and unrelated donors were comparable and unrelated to the source of a graft, the regimen of conditioning, and other characteristics of a donor and a recipient.

[The algorith of preoperative cardiovascular therapy in high risk elderly oncology patients].

The study was based on 478 oncology patients (72.1 +/- 3.6 years old) with cardiovascular comorbidities operated from 1991 to 2008 in regards of abdominal and pelvic mainly 3rd stage tumors with multimodal general anesthesia (4.2 +/- 1.6 hours). In prospective group (n = 302) all patients received cardiovascular treatment, while in retrospective group (n = 176) only 48.9% received it. The evaluation of the cardiovascular therapy effect was based on the peri-operative and postoperative HR and BP dynamics. The occurrance of noticeable bradycardia and drop of BP lower than 90/60 mm Hg was considered as a deviation. It is revealed that the cardiovascular therapy with beta adrenoblockers and calcium antagonists leads to an intraoperative bradycardia in 59.8% and 73.7% of cases, while in patients without the aforementioned therapy in 26.6% and 46.4% of cases respectively (p < 0.05). Antiarrhythmics don't have a noticeable impact on the development of bradycardia (p = 0.204). Intraoperative hypotension on the basis of ATP inhibitor treatment developed in 92.2% of patients statistically significant (p < 0.01). Monotherapy with calcium antagonists or nitrates leads to the development of hypotension in 55.2% and 41.4% of cases respectively, though in patients without the given therapy a lot more often (p < 0.05). In the case of combined calcium antagonist/nitrate therapy hypotension develops in 55.5% of cases, and in 72.3% without the therapy (p < 0.05). For the means of prevention of cardiovascular complications during the surgical treatment it is appropriate to keep the therapy with nitrates, though vasodilatives should be canceled 12 hours before the surgery.

[Prevention and treatment of postoperative pain syndrome in extensive thoracoabdominal oncological surgery].

A procedure has been developed and tested to prevent and treat postoperative pain syndrome during extensive thoracoabdominal surgery for esophageal cancer. The procedure is based on the preventive (12 hours before anesthesia and surgery) application of Durogesic (fentanyl transdermal therapeutic system (TTS)) at an opioid release rate of 50 microg/h for 72 hours. By the end of surgery and anesthesia when intravenous injection of fentanyl is stopped, analgesia continues to be maintdined due to its therapeutic dose coming from TTS. This prevents the development of acute opioid tolerance, hyperalgesia, and destabilization state in the early postanesthetic period and creates the basis for continuous multimodal postoperative analgesia in combination with nonopioid components (lornoxicam, perfalgan) and with none or minimal need for the injectable opioid. This allows an operated patient to have a comfort and stable state. A further investigation on the comparative assessment of the developed procedure with other variants of perioperative systemic and combined anesthesia-analgesia is to be conducted.