Immunohistochemical Analysis of Mitochondrial Dynamics in Different Zones of the Hippocampus during Experimental Modeling of Alzheimer's Disease.

We performed a comparative assessment of the immunohistochemical distribution of markers of mitochondrial fission (Drp-1), mitochondrial fusion (Mfn-2), and mitochondrial biogenesis (PGC-1α) in pyramidal neurons of different zones of the hippocampus in mice with intrahippocampal administration of ß-amyloid peptide 25-35. The most pronounced changes in the dynamics associated with a decrease in the amount of the fission marker and an increase in the amount of the fusion marker were observed in the CA3 field on day 38 after peptide administration. In the CA1 field, a significant decrease in the marker of mitochondrial biogenesis PGC-1α was found on day 38, which can indicate a decrease in the intensity of mitochondrial biogenesis. Early mitochondrial changes can play an important role in the pathogenesis of all types of memory impairment in Alzheimer's disease.

[The role of molecular genetic factors in the development of cholangiocellular carcinoma]. / Rol' molekulyarno-geneticheskikh faktorov v razvitii kholangiotsellyulyarnogo raka.

The article lists the main inducers of cholangiocarcinogenesis. The main inflammatory mediators (IL-6, nitric oxide, COX2) have been considered. Data on the study of gene mutations in cholangiocarcinomas are presented. The spectrum of genetic mutations depends on the biliary cancer origin (FGFR2 with intrahepatic cholangiocarcinoma, PRKACA, PRKACB with extrahepatic cholangiocarcinoma). Mutations in the KRAS, TP53, ARIAD1A genes are common in extrahepatic bile duct cancer. The role of epigenetic changes such as DNA hypermethylation, histone modifications, chromatin remodeling, as well as disturbances in miRNA expression is presented. A number of epigenetic features, such as the presence of a TP53 mutations with hypermethylation of p14ARF, DAPK, and/or ASC, correlate with a more aggressive course of the disease. The role of the SOX17 gene in the development of drug resistance is highlighted. The study of the molecular genetic features of extrahepatic bile duct cancer can help to better understand the pathogenesis of this type of tumor, to establish new prognostic and diagnostic markers of the disease.

[Results of a two-year clinical study of myopia control with bifocal defocus-inducing soft contact lenses]. / Rezul'taty dvukhletnego klinicheskogo issledovaniya kontrolya miopii s pomoshch'yu bifokal'nykh defokusnykh myagkikh kontaktnykh linz.

The development of methods for myopia control remains one of the most topical trends in modern ophthalmology. Optical approaches to myopia control employ the induction of peripheral myopic defocus, which can be done with the use of multifocal soft contact lenses (SCLs). PURPOSE: To review the results of a two-year multicenter clinical study of myopia control with bifocal defocus-inducing SCLs. MATERIAL AND METHODS: The two-year study enrolled 100 patients aged 8 to 16 years who had mild or moderate bilateral myopia with spherical equivalent of (-)0.25 to (-)5.75 D. Based on the degree of myopia and the method of its correction, patients were divided into two main and two control groups. Multifocal SCLs with +4.0 D add power and monofocal SCLs were used for myopia correction. The results were evaluated by the clinical data of refraction, axial length and state of accommodation. The observation times were 3, 6, 12, 18 and 24 months. RESULTS: After 12 months of bifocal SCLs usage, signs of stabilization of myopia progression were identified in 72 and 73.5% of subjects of both main groups, after 24 months - in 54 and 79.5% of subjects, respectively. Statistically significant reduction in axial elongation amounting to 87-88% was also observed in patients using bifocal SCLs. A significant increase in positive relative accommodation (PRA) was observed in all groups. CONCLUSION: The study indicates the effectiveness of bifocal soft contact lenses in slowing the progression of mild and moderate myopia.

[Correcting progressive myopia with bifocal contact lenses with central zone for distant vision: changes in accommodation and axial length (a preliminary report)]. / Korrektsiia progressiruiushchei miopii bifokal'nymi kontaktnymi linzami s tsentral'noi zonoi dlia dali: izmeneniia akkomodatsii i perednezadnei osi (predvaritel'noe soobshchenie).

PURPOSE: To assess the state of accommodation and the dynamics of changes of ocular axial length in patients with progressive myopia who use bifocal soft contact lenses (BFSCLs). MATERIAL AND METHODS: The main and control groups consisted of 50 children (100 eyes) each. Patients of the main group used BFSCLs with distance-oriented central zone and added power of 4 D on the periphery. Patients of the control group were corrected with spherical soft contact lenses (SSCLs). Baseline measurements included amplitude of accommodation (AA), positive relative accommodation (PRA) and the length of anterior-posterior axis of the eye. All patients were examined before wearing SCLs and every 3 months during the entire period of observation lasting 9 to 12 months. RESULTS: Correction of myopia with contact lenses is accompanied by the increase of AA and RPA. The users of BFSCLs with distance-oriented central zone and added power of 4 D on the periphery, which induces myopic peripheral defocus, had their accommodative function normalize much faster than the patients wearing SSCLs. The average increase in the ocular axial length in the BFSCLs group appeared to be significantly smaller than in the SSCLs group (0.11 and 0.58 D, respectively), which can be attributed to the simultaneous formation of the central focus and induced peripheral myopic defocus.

Heat Stress and Agonists of Muscarinic Cholinergic Receptors Modulate Sensitivity of Nicotinic Cholinergic Receptors in Soil Nematode Caenorhabditis elegans.

We studied the effect of moderate heat stress (30oC) and muscarinic cholinergic receptor agonists arecoline and pilocarpine on sensitivity of the behavior of the nematode Caenorhabditis elegans of N2 line to the action of the agonist of nicotinic cholinergic receptor agonist levamisole. Heat stress and muscarinic cholinergic receptor agonists increased the sensitivity of swimming induced by mechanical stimulation to levamisole (32-64 µM), which manifested in dyscoordination of locomotor muscles during swimming and complete loss of ability to swim. Combined exposure to heat stress and muscarinic cholinergic receptor agonists revealed their synergism in the influence on sensitivity of swimming behavior to levamisole: heating to 30oC potentiated the effect of arecoline and arecoline potentiated the effect of heat stress. It is assumed, that the effect of heat stress on the sensitivity of nicotinic receptors is mediated by its effect on muscarinic receptors.

[EFFECT OF LOW-INTENSITY RED LASER ON GROWTH OF STAPHYLOCOCCUS AUREUSAND SENSITIZING EFFECT OF PHOTODITAZIN].

AIM: Study the effect of laser emission in the red spectrum on growth of methicillin- sensitive. and methicillin-resistant strains of Staphylococcus aureus, as well as photodynamic effect of photosensitizer photoditazin. MATERIALS AND METHODS: Effect of light of semiconduc- tor red laser (X 660 nm, 100 mW/cm2) at 30,'60, 90 and 180 J/cm2 on growth of S. aureus colonies was determined. Time of exposure 5; 10, 15 and 30 minutes. In certain series of experiments bacterial cells were sensitized in advance by a Water. solution of photoditazin at a concentration of5xl0-6 M. RESULTS: Red laser emission was established to cause a pronounced suppression of bacterial growth. This effect on standard S. aureus strain only took place dur- ing use of relatively high exposure doses (180 J/cm2). Photosensitivity of methicillin-resistant strain turned out to be significantly higher: bacteriostatic effect of red light was noted already at the dose of 60 J/cm2. Treatment of bacterial cells with photoditazin in advance signifi- cantly enhanced growth-inhibiting effect of laser light.

[MODERN APPROACHES TO THE SURGICAL TREATMENT FOR EARLY-STAGE ENDOMETRIAL CANCER].

The article is devoted to one of the most controversial issues of modern oncogynecology--the volume of surgery for endometrial cancer of early stages. There are discussed the indications for lymphadenectomy and its volume as well as how correlate performing lymphadenectomy and conducting postoperative radiotherapy.

TRAP1 and the proteasome regulatory particle TBP7/Rpt3 interact in the endoplasmic reticulum and control cellular ubiquitination of specific mitochondrial proteins.

Tumor necrosis factor receptor-associated protein-1 (TRAP1) is a mitochondrial (MITO) antiapoptotic heat-shock protein. The information available on the TRAP1 pathway describes just a few well-characterized functions of this protein in mitochondria. However, our group's use of mass-spectrometric analysis identified TBP7, an AAA-ATPase of the 19S proteasomal subunit, as a putative TRAP1-interacting protein. Surprisingly, TRAP1 and TBP7 colocalize in the endoplasmic reticulum (ER), as demonstrated by biochemical and confocal/electron microscopic analyses, and interact directly, as confirmed by fluorescence resonance energy transfer analysis. This is the first demonstration of TRAP1's presence in this cellular compartment. TRAP1 silencing by short-hairpin RNAs, in cells exposed to thapsigargin-induced ER stress, correlates with upregulation of BiP/Grp78, thus suggesting a role of TRAP1 in the refolding of damaged proteins and in ER stress protection. Consistently, TRAP1 and/or TBP7 interference enhanced stress-induced cell death and increased intracellular protein ubiquitination. These experiments led us to hypothesize an involvement of TRAP1 in protein quality control for mistargeted/misfolded mitochondria-destined proteins, through interaction with the regulatory proteasome protein TBP7. Remarkably, expression of specific MITO proteins decreased upon TRAP1 interference as a consequence of increased ubiquitination. The proposed TRAP1 network has an impact in vivo, as it is conserved in human colorectal cancers, is controlled by ER-localized TRAP1 interacting with TBP7 and provides a novel model of the ER-mitochondria crosstalk.

[Stress protection therapy in the prevention of macular morphological lesions in patients with diabetes mellitus at cataract microsurgery].

Patients with a family history of diabetes mellitus should undergo complex antistress protection of the macula for the prevention of its stress-induced lesions during cataract phacoemulsification with intraocular lens implantation. A differential algorithm of stress protection therapy has been developed in relation to the phase of surgical stress, the use of which is to enhance the tolerance of vegetovascular, hemodynamic, and metabolic systems to the aggressive components of surgical stress, thus reducing the incidence of transient subclinical and clinical macular edema.

[Clinical and morphometric macular changes in patients with diabetes mellitus after cataract phacoemulsification].

Optical coherent tomography (OCT) shows that in patients with diabetes mellitus (DM), a macular morphological response to cataract phacoemulsification (CPE) with intaocular lens (IOL) implantation proceeds as 3 types: 1) areactive without macular morphological changes; 2) hyperreactive with the development of reversible subclinical macular edema; and 3) aggressive with the transition of stress-induced retinal morphological lesions to clinically significant diabetic macular edema. Morphological differences in OCT parameters were established to have impact on the effect of visual rehabilitation. Following 3-4 months of CPE with IOL implantation in DM patients with the areactive type of a macular morphological response to surgical stress, the increase in visual acuity exceeded that observed in the hyperactive and aggressive types of a macular response by 12.8 and 57.7%, respectively. The findings suggest that medical preventive measures reducing the negative consequences of surgical stress should be implemented in DM patients at catarrhal surgery.

[Negative selection and computer models of the joint evolution of the patterns of polygenes, transposable elements, and origin identity labels]. / Negativnyi otbor v komp'iuternoi modeli sovmestnoi évoliutsii patternov poligenov, MGE i MIP.

Computer simulation of the population dynamics of the genomic patterns of polygenes, transposable elements (TEs), and origin identity labels (OILs) in the course of negative selection for an additive quantitative trait has been performed. It was demonstrated that active polygene alleles disappear very rapidly, whereas the patterns of TEs and OILs continue their evolution determined by strict selective inbreeding and gene drift. Dendrograms of the patterns of polygenes, TEs, and OILs were constructed for all generations. It was demonstrated that the final consensus pattern of OILs consists of the fragments of the original patterns, which contain neither active polygene alleles nor modifier or marker TEs. Neutral TE copies were present in the final pattern, as should be expected in the case of gene drift. Inbreeding coefficient increased steadily but by generation 100 reached values higher than 0.9. All other parameters and initial conditions being the same, the responses to negative and positive selections were asymmetric.

[Stabilizing selection and computer models of the joint evolution of patterns of polygenes, transposable elements, and origin identity labels]. / Stabiliziruiushchii otbor v komp'iuternoi modeli sovmestnoi évoliutsii patternov poligenov, MGE i MIP.

A computer model of the populations dynamics of the patterns of polygenes, transposable elements (TEs), and origin identity labels (OILs) in the course of stabilizing selection for an additive quantitative trait (with the target value being 0.4 of the maximum) was analyzed. It was demonstrated that the final plateaus of the trait value and the frequencies of the active values of polygenes are reached rapidly, namely, within five to seven generations (the effective selection period). The inbreeding coefficient during this period also grows rapidly and then gradually increases eventually reaching approximately 0.7. The inbreeding coefficient reaches plateau (at approximately 1.0) only in generations 300-350, which suggests the effect of gene drift. Dendrograms of the patterns of polygenes, TEs, and OILs were constructed for all generations. By generation 100 of selection, the final patterns of TEs and OILs were not formed completely. Fixations and losses, especially those of the OIL pattern, were delayed. In general, however, the population heterogeneity with respect to the patterns studied does not stabilize. This heterogeneity decreases the case of stabilizing selection, although more slowly than in the cases of positive and negative selections.

[Computer modeling of joint selection response of MGE patterns and a polygenic system]. / Komp'iuternoe modelirovanie sobmestnogo otklika na otbor patternov MGE i poligennoi sistemy.

Using computer simulation, selection response of three genome patterns--polygenes, mobile genetic elements (MGEs), and labels of identity by origin (LIOs)--were studied. In each generation of selection, variability of each pattern type was described by on UPGMA tree. Stringent positive truncation selection on an additive polygenic trait and recombination between segments of the genetic map were considered. MGEs were classified into three groups: modifiers (enhancers) of the polygenic expression, markers, and independent copies. It was shown that at generations 30 to 40, 95-96% and 70-80% of respectively enforced and non-enforced active polygenic alleles were fixed (2-3% and 16-17% lost). In all generations, Hkn < or = Dkn of the length of the maximal route along the tree. At the same time, modifier MGEs were fixed for 85-88% (lost for 11-12%); marker MGEs, for 60-70 (lost for 21-25%); and independent copies, for 30-40 (lost for 50-60%). The behavior of independent MGE copies was generally consistent with the predictions of the genetic drift theory, modifier MGEs behaved similarly to the modified polygenes, and marker MGEs exhibited intermediate properties. The LIO patterns showed rapid homozygotization: their variability dropped dramatically between generations 10 and 30. In F50, the final consensus pattern of polygenes included 16 out of 18 enforced and 18 out of 21 non-enforced polygenic alleles. The fixation/loss ratios were 16:3 for modifier MGEs, 15:6 for marker MGEs, and 25:28 (with 7 polymorphic) for independent copies. The LIO consensus pattern contained 13 out of 100 original markers, which formed 26 fragments of one to ten map segments in size; 21 fragments contained active polygenic alleles, and 14 of them had also modifier MGEs. Recombinational shuffling of patterns was not completed. In the course of selection, active polygenic alleles take along adjacent segments, including those containing modifier MGEs and markers. These constitute the conservative part of all consensus patterns while the remaining segments are random.

Terbium chelates for fluorescence immunoassays.

The sensitization of terbium(III) ion luminescence in the presence of 1-ethyl-14-dihydro-6,7-methylenedioxy-4-oxoquinoline-3-carboxylic (oxolinic) acid was studied. The terbium label is bound to the antibody with diethylenetriamine-pentaacetic acid anhydride (DTPAA). Optimum luminescence intensity is observed at pH 7.5 and the luminescence significantly increases in the presence of cationic surfactant, cetyltrimethylammonium bromide. The sensitivity of Tb(III) detection is 5 x 10(14) mol l(-1). This luminescence system is proposed for time-resolved fluoroimmunoassay.

Use of sensitized luminescence of lanthanides in analysis of drugs.

The sensitization of the Tb(III) and Eu(III) ions luminescence by drugs, the pyrocatechol, naphthyridine and heterocyclic aromatic acid derivatives, were studied. It was shown that a result of intramolecular energy transfer from the ligand molecule to the lanthanide ion increases the luminescence intensity of the latter by 10(8)-10(10) times. The luminescence properties of the complexes in solutions were investigated. The highly sensitive methods for luminescence determination of dopegyt, levodopum, dophaminum, nevigramon, furosemidum and cinchophenum were developed. The detection limits of the drugs are 0.0005, 0.02, 0.5, 0.01, 0.05 and 0.1, respectively.

[Hygienic expert evaluation in the standardization of the use of polymer and other materials in food industry]. / Opyt gigienicheskoi ékspertizy pri reglamentatsii primeneniia polimernykh i drugikh materialov v pishchevykh otrasliakh promyshlennosti.

Numerous polymers and other materials to be used in food industry should be rapidly assessed from a hygienic view-point. Experience gained in this sphere permits us recommend a method for rapid hygienic expert evaluation of such materials. Approaches to, and potentialities of such expert evaluation are demonstrated.