[A Detection of Allelic Variants at Microsatellite Markers by Using Capillary and Traditional Electrophoresis].

Microsatellite alleles are detected by PCR (polymerase chain reaction) that provides a manifold increase in the number of copies (amplification) of a given DNA fragment. The fragment visualization can be reached by two different methods. These are fragment analysis by capillary electrophoresis in denaturing gel and frag- ment separation in non-denaturing gel with subsequent gel staining. The first method is more accurate and automated, but expensive. The second method is much cheaper but less convenient. It requires manual pro- cessing and is presumably less accurate. In this study, we present the results of comparison of the allele typing at nine microsatellite loci using these two methods for one of the species of Pacific salmon, sockeye salmon Oncorhynchus nerka Walbaum. In most cases, both methods give identical fragment sizes or a constant differ- ence if the alleles are relatively small (not larger than 200-220 bp).

[Late pancreatic metastases from renal cell carcinoma: A case report]. / Pozdnie metastazy pochechno-kletochnogo raka v podzheludochnoi zheleze.

Renal cell carcinoma (RCC) is a tumor that is typical of late metastases detected within 3 years after radical nephrectomy in 85% of cases. RCC most commonly metastasizes to the lung, bone, liver, and brain; the pancreas is involved in no more than 0.25-3% of cases. The paper describes a unique clinical case of multiple late pancreatic metastases from clear cell RCC in a 77-year-old woman 27 years after removal of the primary tumor.

DIAGNOSTIC AND TACTICAL IMPORTANCE OF STUDYING SHORT CHAIN FATTY ACIDS IN DIFFERENT BIOLOGICAL SUBSTRATES TOOK PLACE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE, LUNG CANCER AND COMMUNITY-ACQUIRED PNEUMONIA DEVELOPED AFTER ANTICANCER THERAPY.

The main aim of the study is to examine microbiocenosis of lower respiratory tract and intestine in patients with chronic obstructive pulmonary disease (COPD), lung cancer (LC), lung cancer with community-acquired pneumonia (CAP) and to determine their role in the etiological diagnosis of lower respiratory tract infections (LRTi), including those that develop during cancer chemotherapy (CC), to discuss the possibility of optimizing the treatment tactics. MATERIALS AND METHODS: To solve this task were examined 147 patients and 30 healthy individuals were divided into 4 groups, according to nosology. The number of patients in the COPD group was 38 people, m / f-35/3, median age 63 (57; 69) years, in the LC group -60 people, m / f - 56/4, with a median age of 65 (58; 71) year; LC groupwith CAP -21 persons m / f - 17/4, with a median age of 73(69; 75) years, in the LC group with CAP developed in the period up to 30 days after the end of chemotherapy (LC with CAP / CC) -28 persons m / f - 22/6, with a median age of 70 (67; 73) years, the norm group -30 healthy persons m / f- 26/4, median age 48(40,691 years. The spectrum of short-chain fatty acids (SCFA) sputum (in bronchoalveolar lavage standards group) and test groups of feces were studied by gas-liquid chromatographic analysis (GLC analysis). Results of the study. In the norm group: total absolute content of SCFA (X) in sputum was 0.032 mg / g, the relative content of acetic acid (pC2) 0906 u, propionic acid (pC3) 0.085 u, butyric acid (pC4) 0.009 u, anaerobic index (Al) -0.104 units. According to the analysis the total absolute content of SCFA in the sputum may be expressed as follows: ∑ SCPA (C2-C4) norm (0,032) <∑ SCFA (C2-C4) COPD (0,201) <∑ SCFA (C2-C4) RL (0,463) < ∑ SCFA (C2-C4) LC with CAP (0.510) < RCMP ∑ (C2-C4) LC with CAP / CC (0.612) (mg / g), the differences are statistically significant when compared with the norm. The findings of the relative content of C2-C4 show a statistically significant increase of the relative content of propionic and butyric acids: PC3 (0,085) pC4 (0.009) norm pC2 (0.846) COPD> pC2 (0.792) LC> pC2 (0.765) LC with CAP> pC2 (0.719) LC with CAP / CC (u) in patients of all study groups compared to the norm, and between groups. And the more pronounced changes in the content of SCFA in the sputum are ascertained in lung cancer with CAP during chemotherapy. *The values of Al in the studied groups are displaced to more negative values: Al (- 0.104) rate> Al (- 0.190) COPD> Al (- 0.257) RL> Al (- 0.307) LC with CAP> Al (- 0.391) LC with CAP / CC (sing.) compared with the norm and between groups. The findings of SCPA in feces in the group norm: ~1 SCFA 10.51 mg / g, 0.634 units pC2, pC3 0,189 units, 0,176 units pC4, -0.576 Al units. The total absolute content of SCFA in feces can be expressed as follows: ∑ SCFA (C2-C4) LC (4,11) <∑ SCFA (C2-C4) COPD (4,81) <∑ SCFA (C2-C4) norm (10 51) (mg / g), the differences were statistically significant when compared with the norm; depending on the chemotherapy, preceding the development of the CAP: ∑ SCFA (C2-C4) norm (10,51)> ∑ SCFA (C2-C4) LC with CAP / che- motherapy (5,54)> ∑ SCFA (C2-C4) LC CAP (4,96)> ∑ SCFA (C2-C4) LC (4.11) (mg / g). Results of the study of the relative content of C4-C2 also demonstrate a statistically significant increase of the relative content of propionic and butyric acids: pC3 (0.189), pC4 (0.176) norm pC2 (0.590) COPD> pC2 (0,560) LC> pC2 (0.529) LC with CAP> pC2 (0.503) LC with CAP! chemotherapy (u) in patients of all study groups in comparison with the norm. And the more pronounced changes in the content of SCFA in feces are ascertained at LC with CAP during chemotherapy. The values of Al intestinal ecological community of all groups are displaced to more negative values when compared with the norm: Al (- 0.576) norm> Al (- 0.695) COPD> Al (- 0.786) LC> Al ('0.890) LC with CAP> Al (- 0.988) LC with CAP / chemotherapy (u), with the most significant changes were observedin the group of LC with CAP during chemotherapy. Conclusion, Increased absolute SCFA concentration in patients with CQPD, lung cancer, lung cancer with CAP, LC with CAP! CC in comparison with the norm indicates increased number and activity of anaerobic flora, the most significant changes observed in patients with lung cancer with CAP, developed in the period up to 30 days after the end of chemotherapy. The unidirectional changes in SCFA parameters in the sputum and stool demonstrate the dependence of microorganism biocenosis. The resulting information can be used in the etiological diagnosis of LRTI, as well as the development of therapeutic and preventive measures flAw Af infprtiniis rnmnlications and treatment of these patients.

[Repetitive DNA sequences as an indicator of the level of genetic isolation in fish].

Although the functional role is still unknown for most types of nuclear noncoding repetitive sequences, some of them proved to provide adequate phylogenetic and taxonomic markers for studying the genetic relationships of organisms at the species and within-species levels. Several markers were used in this work. First, microsatellite markers were used to examine populations varying in the extent of genetic subdivision in marine and anadromous fish, including the Chilean jack mackerel Trachurus murphyi, anadromous brown trout Salmo trutta, and isolated and anadromous char populations. Locus polymorphism was proportional to the gene flow between populations in all cases. Second, satellite DNA was used to study the phylogenetic relationships within the genera Salmo, Oncorhynchus, Salvelinus, and Coregonus. Genetic distances agreed well with the taxonomic relationships based on morphological traits and various biochemical markers and correlated with the evolutionary ages estimated for the groups by other markers. Third, RAPD PCR with a set of 20-mer primers was performed to study the genus Coregonus and anadromous and isolated populations and species of the genus Salvelinus. The resulting phylogenetic trees may help to resolve some disputable taxonomic issues for the groups. A comparison showed that several RAPD-detected sequences contain conserved fragments of coding sequences and polymorphic repeats (minisatellites) from intergenic regions or introns. The finding point to a nonrandom nature of repetitive DNA divergence and may reflect the evolution of the fish groups examined. Heterochromatic satellite repeats were assumed to contribute to generating a reproductive barrier.

[Microflora metabolites of different habitats in bronchopulmonary diseases].

PURPOSE: To investigate the content and profile of metabolites of bronchopulmonary and intestinal microflora, especially such as short chain fatty acids (SCFA) in various biological substrates in patients with lung malignant tumors on the background of COPD. Estimate their diagnostic and tactical implication. MATERIALS AND METHODS: The study involved 98 patients with diseases of the bronchopulmonary system. According to the basic nosology patients were divided into two main groups: COPD (38 patients), and lung cancer in combination with COPD (hereinafter LC) (60 patients). The diagnosis was verified by modern methods of examination. Group of norm included 30 healthy individuals. Groups matched by gender and age. The microbiological examination of sputum and feces was conducted in the studied groups of patients. SCFA in sputum and feces of patients with COPD and LC were identified by GLC method. In healthy individuals the SCFA investigation was performed in bronchial washings, obtained during bronchoscopy in 20 people, the SCFA investigation in feces was performed in 30 people. RESULTS: Study of the content and profile of short-chain fatty acids (SCFA) in patients with COPD and lung cancer (LC) in various biosubstrates indicate on the obvious changes in microbiocenosis ofbioptate (bronchopulmonary and intes- tinal), characterized by the dominance of residual and facultative anaerobic microorganisms in the spectrum. Except that more pronounced changes are ascertained at LC. Also, changes of the SCFA parameters in the sputum may indicate on the alterations in the metabolism of epithelial cells of the lower respiratory tract (LRT). Unidirectional change the SCFA in sputum and feces can indicate on either translocation of microflora in the LRT out of the intestine, and on the possible systemic changes in themetabolism of epithelial tissue in the oncological process. The identification of SCFA by GLC method in various biological substrates can be used in examination of patients with lung cancer for diagnostic purposes (for objectification of microecological violations), as well as to evaluate the prognosis of the disease and its complications.

[Efficacy and safety of choline alfoscerate in the preventive therapy of dementia in elderly patients with Mild Cognitive Impairment: a three-year prospective comparative study]. / Effektivnost' i bezopasnost' kholina al'fostserata v preventivnoi terapii dementsii u pozhilykh patsientov s sindromom myagkogo kognitivnogo snizheniya: rezul'taty trekhletnego prospektivnogo sravnitel'nogo issledovaniya.

OBJECTIVE: To study the efficacy and safety of the use of annual course therapy of choline alfoscerate (CA) as a drug potentially capable of slowing or preventing the transition of amnesic type mild cognitive impairment (aMCI) into clinically pronounced dementia in a three-year open comparative study, as well as to explore the possibility of predicting the preventive effect of such therapy based on a number of clinical and biological parameters. MATERIAL AND METHODS: The study included 100 patients with aMCI, randomly divided into 2 groups: the therapeutic group consisted of 50 patients who received CA course therapy once a year for 3 years (20 intravenous infusions of 1000 mg (4 ml) in 100 ml of saline solution for 4 weeks) and a comparison group of 50 patients who underwent an annual examination at the center and did not receive therapy. Clinical and psychopathological, psychometric, immunological, follow-up, and statistical methods were used. RESULTS: A comparative three-year prospective study conducted in a group of aMCI patients treated with annual course therapy of CA for 3 years and aMCI patients who did not receive therapy with similar initial demographic, diagnostic, psychometric and immunological characteristics showed a lower progression of cognitive deficits (12.2% and 39.1%, respectively) and a lower conversion rate (8.2% and 26.1%, respectively) to dementia in the therapeutic group compared with the comparison group. The differences between the initial and final (after 1, 2 and 3 years of follow-up) cognitive functioning indicators in the therapeutic group and the comparison group were significant (p<0.05) on all scales and tests in favor of the therapeutic group throughout the entire follow-up period. CONCLUSION: The results allow us to consider CA as a possible model of preventive dementia therapy aimed at preventing the progression of cognitive deficits and the development of dementia in people at high risk of developing AD - patients with aMCI.

[Multi-center open comparative randomized study of efficacy and safety of Akatinol Memantine 20 mg (single-doses) vs Akatinol Memantine 10 mg (double-doses) in patients with vascular dementia]. / Mnogotsentrovoe otkrytoe sravnitel'noe randomizirovannoe issledovanie effektivnosti i bezopasnosti primeneniya preparata Akatinol Memantin, 20 mg (odnokratnyi priem) v sravnenii s preparatom Akatinol Memantin, 10 mg (dvukratnyi priem) u patsientov s sosudistoi dementsiei.

OBJECTIVE: Evaluation of the efficacy and safety of the drug Acatinol Memantine, 20 mg (once daily) in comparison with the drug Acatinol Memantine, 10 mg (twice daily) in patients with moderate to moderate severe vascular dementia. MATERIAL AND METHODS: The study included 130 patients aged 50-85 years of both sexes with instrumentally and clinically confirmed vascular dementia. The patients were randomized into 2 groups. Group I consisted of 65 patients receiving Akatinol Memantine, 20 mg once daily, group II - 65 patients receiving Akatinol Memantine, 10 mg twice daily for 24 weeks. Clinical, parametric and statistical research methods were used. The Alzheimer's disease assessment scale, the cognitive subscale (ADAS-cog), the short mental Status Assessment Scale (MMSE) and the general clinical impression scale for patients condition and illness severity (CGI-C and CGI-S) and the Hamilton Depression Rating scale (HAM-D) were used. Adverse events were collected and analyzed. RESULTS: At week 24, both groups showed statistically significant positive change in ADAS-cog total score: in group I the total score was 27.2±8.76 points (absolute difference from baseline 3.5 points; p<0.01), and in group II - 26.1±7.86 points (absolute difference from baseline 2.5 points; p<0.01) with no statistically significant differences between groups. Evaluation of secondary efficacy criteria (change in ADAS-cog total score at week 12 and MMSE at weeks 4, 12, and 24) also revealed statistically significant benefit in both groups compared to baseline with no significant differences between groups. Statistically significant improvement was noticed on CGI-S and CGI-C scales in both groups. Akatinol Memantine was safe and well tolerated in both groups. CONCLUSION: The study showed no lesser efficacy and safety of Akatinol Memantine, 20 mg (once daily) compared to Akatinol Memantine, 10 mg (twice daily) in patients with moderate and moderately severe vascular dementia.

[Russian experience in using a combination of fixed doses of donepezil and memantine in the treatment of Alzheimer's disease as an observational non-interventional multicenter program]. / Rossiiskii opyt primeneniya kombinatsii fiksirovannykh doz donepezila i memantina v terapii bolezni Al'tsgeimera v ramkakh nablyudatel'noi neinterventsionnoi mnogotsentrovoi programmy.

OBJECTIVE: To evaluate the efficacy, safety, and compliance to therapy with Mioreol, first used as part of routine clinical practice in patients with moderate-to-severe dementia due to AD. MATERIAL AND METHODS: The study was conducted as a non-interventional observational program. The work was performed on a group of 48 patients with moderate-to-severe AD aged from 60 to 90 years (median age 74 [69; 77]). The therapeutic dose of Mioreol was 10 mg donepezil + 20 mg memantine, the drug was taken orally, once a day at the same time, regardless of meals. The duration of the course of therapy was 24 weeks. The effects of the drug were assessed using the MMSE, ADAS-Cog, NPI, and CGI scales before the start of therapy and by the end of 12 and 24 weeks of treatment. RESULTS: The use of Mioreol in six-month therapy of AD patients with moderate-to-severe dementia improved not only cognitive but also a wide range of non-cognitive mental disorders. There was an improvement in the CGI-C scale in more than 50% of included patients, positive dynamics on the ADAS-cog scale (6.5 points reduction in total score) and reduction of non-cognitive mental disorders on the NPI scale (4 points reduction in total score). CONCLUSION: Fixed-dose combination therapy with Mioreol is an effective and well-tolerated treatment option for patients with moderate-to-severe AD. A combination of fixed-dose therapeutic doses of donepezil and memantine is potentially more appropriate than the simultaneous use of two recommended drugs for the treatment of AD, which will improve treatment adherence in patients with moderate to severe AD.

[Contractile properties, transversal stiffness and cytoskeletal protein content in Mongolian gerbils soleus fibers under long-term hindlimb suspension].

Structural and functional changes in Mongolian gerbil soleus fibers were analyzed after a 31-day hindlimb suspension. Contractile properties of muscle fibers were studied by means of tensometry; the transversal stiffness of different parts of the contractile apparatus was measured by atomic force microscopy, resting calcium level was estimated by fluorescence microscopy by using Fluo-4-AM; cytoskeletal protein content was determined by western blotting. It was shown that after gravitational unloading the maximal force of contraction and specific tension of fiber were significantly reduced, as well as calcium sensitivity actually lowered. At the same time, the transversal stiffness of Z-disk in the relaxed and activated state was decreased significantly compared to the control group. Desmin content was at the control level, but alpha-actinin-2, main structural protein of Z-disk, became considerably less after a 31-day hindlimb suspension. Besides, resting calcium level remained at control values during the simulated gravitational unloading. The data suggest that Z-disk destruction, as a result of alpha-actinin-2 content reduction, leads to changes in the lattice spacing and decreases contractile properties.

[Depressions in Alzheimer's disease].

The aim of this work was to study clinical and pathogenetic aspects of depression associated with Alzheimer disease (AD) in 65 patients. Depressive symptoms are shown to frequently occur in all types of the disease and at all stages of its therapy. A variety of syndromic variants of depression are identified in the structure of dementia: anxiety (35.4%), apathetic (29.2%), delusional (16.9%), hypochondriac (10.8%), melancholic (7.7%). Situation-reactive, endoreactive, and endogenous types of depression were distinguished depending on its pathogenetic mechanisms. Great variety of clinical and psychopathological manifestations and mechanisms of depressive pathology in AD suggests its heterogeneous character.

[Prognosis of amnestic mild cognitive impairment: clinical and immunological correlations]. / Prognoz sindroma myagkogo kognitivnogo snizheniya amnesticheskogo tipa: kliniko-immunologicheskie korrelyatsii.

OBJECTIVE: To determine the long-term (three-year) prognosis of the cognitive deficits progression in elderly people with amnestic mild cognitive impairment (aMCI) based on the analysis of the initial clinical and immunological parameters. MATERIAL AND METHODS: This study is based on a clinical and follow-up study of 252 outpatients with aMCI, who were observed in the Federal State Budgetary Scientific Institution «Mental Health Research Center¼ from 2018 to 2020. The psychometric assessment complex included the following scales and tests: MMSE, MoCA, The 10 words test, BNT, David Wechsler's Scale, subtest 6, CDT, Memory test of 5 geometric shapes, BVRT Test, DRS - Mattis Dementia Rating Scale: Verbal fluency, DRS - Mattis Dementia Rating Scale, The Munsterberg Test. As part of the study, the level of cytokines (TNF-a, IL-1, IL-6, IL-8, IL-10) in the blood serum was determined in all patients by enzyme immunoassay (ELISA), using diagnostic kits manufactured by Cytokine LLC. RESULTS: In patients with a progression of aMCI syndrome, an increase in proinflammatory cytokines IL-1, IL-6, IL-8, TNF-α is initially detected, which may reflect the level of systemic inflammation or functional insufficiency of anti-inflammatory mechanisms. In turn, the group with a subsequent improvement in cognitive functioning, on the contrary, is distinguished by an initially increased level of the anti-inflammatory interleukin system (IL-10). CONCLUSION: We provide new data on the presence of systemic inflammation and immune disturbances and their association with clinical course of disease in the majority of elderly patients with aMCI. CONCLUSION: Signs of a chronic low-level systemic inflammatory response in patients with aMCI is the unfavorable prognosis criterion: in such patients, cognitive deficit significantly progresses or dementia due to Alzheimer disease develops within three years.

[Citicoline in the treatment of cognitive impairment in first-degree relatives of AD patients: the influence of the ApoE genotype]. / Tsitikolin v lechenii kognitivnoi nedostatochnosti u rodstvennikov 1-i stepeni rodstva patsientov s bolezn'yu Al'tsgeimera: vliyanie ApoE genotipa.

OBJECTIVE: To study the effects of a three-month course of therapy with citicoline, aimed at preventing the progression of cognitive deficit in 1st-degree relatives of patients with Alzheimer's disease (AD), depending on the carriage of the ApoE4(+) genotype. MATERIAL AND METHODS: Study participants: 82 blood relatives of AD patients, 66 of them with signs of minimal cognitive dysfunction (group 1) objectively confirmed by clinical neuropsychological examination and 16 people with mild cognitive decline syndrome (group 2). Open comparative multidisciplinary study of the dynamics of cognitive status in relatives of AD patients who received a three-month course of citicoline therapy. The baseline indicators of the cognitive functioning of the relatives of the two groups were compared with the indicators at the end of the three-month course of therapy with citicoline in a daily dose of 1000 mg, depending on whether the treated persons had genotypes ApoE4(+) or ApoE4(-). Clinical-psychopathological, neuropsychological, psychometric, molecular-genetic, statistical. RESULTS: An association of the ApoE4(-) genotype with a significantly more pronounced positive effect of the course therapy with citicoline was established according to the general clinical impression (CGI-I scale), indicators of cognitive functioning (MMSE and MoCA scales), as well as according to most psychometric tests (with the exception of the number repetition test in reverse order), as well as for almost all indicators of the neuropsychological «express method¼ (excluding the parameter of the volume of visual memory). CONCLUSION: The results of course therapy with citicoline showed a negative effect of the carriage of the ε4 allele of the ApoE gene on the efficiency of treatment of blood relatives of AD patients who had signs of cognitive decline before the start of therapy, which did not reach the level of dementia. The obtained data can serve as the basis for the development of preventive therapeutic measures aimed at preventing the progression of cognitive deficit and the development of dementia in the group at high risk of developing dementia - in 1st degree relatives of AD patients, especially in carriers of the ApoE4(+) genotype.

[Herpesvirus infections and immunological disturbances in patients with different stages of Alzheimer's disease].

INTRODUCTION: Alzheimer's disease (AD) is a multifactorial disease that leads to a progressive memory loss, visualspatial impairments, emotional and personality changes. As its earliest pre-dementia clinical stage, amnestic mild cognitive impairment syndrome (aMCI) is currently considered. Neuroinflammation plays a role in the development and progression of aMCI and the initial stage of AD, which can be supported by immunological disorders of a systemic character. Study of factors, including infections, influencing immune disorders and systemic inflammatory response in patients with aMCI, is of great importance.The aim of this study was to obtain new data on the possible role of herpesvirus infections in the development and progression of aMCI. MATERIAL AND METHODS: 100 patients with aMCI diagnosis, 45 patients with AD, 40 people from the control group were enrolled into the study. The frequency of DNA detection of herpesviruses (Epstein-Barr virus (EBV), human herpesviruses (HHV) type 6 and 7, cytomegalovirus (CMV)), the levels of viral load and the serological markers of herpesvirus infections (IgG to HHV-1, IgG to CMV) were determined. Immunological studies included an assessment of the level of the main pro-inflammatory and anti-inflammatory cytokines, and indicators of humoral and cellular immunity. RESULTS: The study found an increased detection rate of EBV in saliva and a higher level of EBV DNA in saliva in aMCI and AD than in the control group. A relationship between the presence of active EBV infection and changes in immunological parameters in patients with aMCI were found. It was also discovered that the level of IgG antibodies to CMV is associated with the stage of AD. DISCUSSION: The results indicate a possible role of EBV- and CMV-induced infections in the development of immunological changes which are typical for mild cognitive impairment and in the progression of AD. CONCLUSION: The obtained data can be important for prognostic methods addressing AD development, including its pre-dementia stage, and for new approaches to individualized treatment and prevention.

[Comparative analysis of structural and functional characteristics of soleus muscle in rats and Mongolian gerbils during gravitational unloading of various duration].

A comparative investigation of the dynamics of contractile properties of the whole soleus muscle and its fibers during 3- and 12-day-long hind limb suspension of Wistar rats and Mongolian gerbils (Meriones unguiculatus) has been performed. The data obtained indicate that the structural and functional changes caused by hypogravity in gerbils are slowed down compared with rats. A very intensive drop in water containment in gerbils was found, which can cause shifts in the ionic strength of the intracellular space of the muscle fiber. As a result, the photolytic activity of different enzymes may change, which can induce a less pronounced reduction in Z-disc and M-line stiffness and contractile capabilities in gerbils compared to rats.

[Effectiveness of the DNA double-strand breaks repair system in lymphocytes of patients with cognitive impairments and healthy volunteers]. / Aktivnost' sistemy reparatsii dvunitevykh razryvov DNK v limfotsitakh patsientov s kognitivnym snizheniem v sravnenii so zdorovymi dobrovol'tsami.

The individual differences in the efficiency of DNA DSB repair were estimated by the level of residual γH2AX foci after γ-irradiation at a dose of 2 Gy, in lymphocytes of patients with amnestic mild cognitive impairment (AMCI) and Alzheimer's disease (AD) and of healthy volunteers. Lymphocytes were isolated from the peripheral blood of the examined patients and were frozen in a medium for freezing cells. Before the study, the lymphocytes were thawed, suspended in RPMI 1640 culture medium supplemented with 10% inactivated fetal bovine serum, and half of the cells were γ-irradiated at 4°C from a 60Co source on a GUT-200M facility at a dose of 2 Gy (a dose rate of 0.75 Gy/min). Control and irradiated lymphocytes were cultured for 24 h, collected, fixed, and stored until the study of the number of spontaneous and residual foci of γH2AX using fluorescent microscopy after staining with fluorescent labeled antibodies. In lymphocytes of patients with AMCI and AD a higher number of residual γH2AX foci in lymphocytes and the higher number of lymphocytes with foci were found compared with healthy volunteers. This indicates a decrease in the ability to repair DNA DSB in these patients. Indicators of cellular immunity and the concentration of TNF-α in the blood serum in the group of examined patients were normal. In the group of patients with the cognitive impairments (AMCI+AD), a correlation was found between the number of residual foci of γH2AX and the number of CD3+CD4+ lymphocytes and the concentration of proinflammatory cytokine TNF-α in the blood serum. This suggests the development of stronger neuroinflammation in patients with reduced ability to repair DNA DSB in this pathology.

[Immunological variants of amnestic mild cognitive impairment]. / Immunologicheskie varianty myagkogo kognitivnogo snizheniya amnesticheskogo tipa.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is considered as a possible earliest pre-dementia clinical stage of Alzheimer's disease (AD). Taking into account the prominent role of neuroinflammation in the pathogenesis of AD, it is quite important to study possible immunological markers of the risk of aMCI progression and the changes in immune parameters in patients. OBJECTIVE: To study the immunological variants of aMCI and AD based on the parameters of humoral and cell immunity, levels of key cytokines and presence of systemic inflammation, and to explore the link between changes in the immune parameters and clinical prognosis. MATERIAL AND METHODS: One hundred patients with a diagnosis of aMCI, 45 patients with AD at the stage of mild to moderate dementia and 40 people without cognitive impairment (the control group) were enrolled into the study. Immunological assessment included determination of the concentration of key cytokines, C-reactive protein, circulating immune complexes and immunoglobulins (Ig A, M, G) in blood serum by ELISA, determination of the main subpopulations of lymphocytes by flow cytometry. RESULTS AND CONCLUSION: Four main immunological variants of aMCI syndrome associated with clinical prognosis were identified. The detected changes in immune parameters are important for further studies to assess an effect of viral and bacterial infections, intestinal microflora disorders on a clinical prognosis in patients with different immunological variants of aMCI syndrome.

[Genetic structure of walleye pollock Theragra chalcogramma (Gadidae, Pisces) from Bering Sea and Sea of Okhotsk].

The genetic population structure in 4 spawning aggregations from the Bering Sea of walleye pollock (Theragra chalcogramma, Pallas), that occupies a central place in ecosystems of the North Pacific and is an important object of fisheries, was investigated with the ten microsatellite loci Tch5, Tch10, Tch11, Tch12, Tch14, Tch16, Tch17, Tch19, Tch20 and Tch22. The spatially distanced sample from Sea of Okhotsk was a referent group. The polymorphism of the markers used accounted for 100%, heterozygozity ranged from 41 to 95% in the different populations. It was shown that the aggregations of interest are in goodness-to-fit HWE at whole,but Sea of Okhotsk sample demonstrated the sex bias in the null-allele number in locus Tch16. Loci Tch10, Tch20 and Tch22 were of the most discriminate power. The genetic distances between all pairs of samples were typical for marine fishes. The sample from underwater Shirshov ridge region that is the natural geographic barrier for Olutor-Karagin and Koryak walleye pollock stocks is presumably of mixed genesis. As evident from scatter plots of F(ST) and spatial autocorrelation approach, data obtained (when Shirshov sample is eliminated) are under isolation by distance model on a broad spatial scale. The influence of abiotic factors on the population structure of the Bering Sea walleye pollock is supposed.

[Contractile properties of fibers and cytoskeletal proteins of gerbil's hindlimb muscles after space flight].

The work had the goal to compare the microgravity effects on gerbil's muscles-antagonists, m. soleus and m. tibialis anterior. The animals were exposed in 12-d space microgravity aboard Earth's artificial satellite "Foton-M3". Findings of the analysis of single skinned fibers contractility are 19.7% diminution of the diameter and 21.8% loss of the total contractive force of m. soleus fibers post flight. However, there was no significant difference in calcium sensitivity which agrees with the absence of changes in the relative content of several major cytoskeletal proteins (titin and nebulin ratios to heavy chains of myosin were identical in the flight and control groups) and a slight shifting of the myosin phenotype toward the "fast type" (9%, p < 0.05). These parameters were mostly unaffected by the space flight in m. tibialis anterior. To sum up, the decline of contractility and diminution of gerbil's myofibers after the space flight were less significant as compared with rats and did not impact the sytoskeletal protein ratios.

[Contractile properties of the isolated rat musculus soleus and single skinned soleus fibers at the early stage of gravitational unloading: facts and hypotheses].

The contractile properties of the postural rat soleus muscle at the early stage of the gravitational unloading (3-day rat hindlimb suspension) have been studied using different modes of muscle contraction (twitch and tetanic contraction of the isolated muscle, Ca-induced contraction of isolated skinned fibers). A significant enhancement of the twitch maximal tension of unloaded muscles without changes in time-dependent characteristics was observed, although the half-relaxation time tended to increase. The fiber diameter did not change (42.37 +/- 0.76 vs 43.43 +/- 1.15 microm in controls). The Ca-induced maximal isometric tension in unloaded soleus was significantly decreased (32.1 +/- 1.05 vs 37.6 +/- 1.52 mg in controls, p < 0.05). The maximal specific tension was respectively decreased (23.14 +/- 0.77 vs 27.6 +/- 2.36 kN/m in controls). The pCa50 in unloaded muscle decreased from 6.05 +/- 0.02 in controls to 5.97 +/- 0.02 (p < 0.05), indicating the loss of myofibrillar calcium sensitivity. The analysis with the calcium probe Fluo-4AM demonstrated that the intracellular [Ca2+] was sufficiently increased after hindlimb suspension. At the same time, the relative content of titin and nebulin did not change.

[Clinical efficacy and safety of choline alfoscerate in the treatment of late-onset cognitive impairment]. / Klinicheskaia éffektivnost' i bezopasnost' primeneniia kholina al'fostserata v lechenii dodementnykh kognitivnykh narushenii v pozdnem vozraste.

AIM: To study the efficacy and safety of cereton (choline alfoscerate) in the treatment of elderly patients with amnestic type of mild cognitive impairment (aMCI), which often represents a pre-dementia (symptomatic) stage of Alzheimer's disease (AD). MATERIAL AND METHODS: Fifty patients (40 women and 10 men; mean age 68,8 years) received three-month therapy with cereton in a dose of 1200 mg/day in 3 divided doses. Fifteen patients received the same treatment again within 1 year. Immediate and delayed (7-9 months after treatment) effects of therapy, including those dependent on the ApoE genotype were assessed with a neuropsychological test battery. RESULTS: Psychometric measures showed a significant improvement after treatment with cereton. ApoE4 allele noncarriers performed better on tests of immediate and delayed reproduction of 10 words. Although, most indicators achieved in the end of therapy course decreased 7-9 months after treatment, the level of patients cognitive functioning remained at a higher level than before treatment. A repeated course of cereton treatment prevents cognitive deficit increasing during the follow-up period (10-12 months). CONCLUSION: The drug is well-tolerated and safe and can be recommended for preventive treatment of dementia in patients with high AD risk, in particular in elderly patients with aMCI syndrome.