AN INVESTIGATION OF PSYCHOLOGICAL AND PHYSIOLOGICAL FACTORS AFFECTING PERFORMANCE IN ADOLESCENT JUDOKAS.

The purpose of this study was to investigate the psychological and physiological factors affecting performance levels in adolescent judokas. The research was performed in the "Sport EMI" scientific-research center of Armenian State Institute of Physical Culture and Sport. Participants' performance levels were assessed based on their kyu rankings, a hierarchical ranking system in judo. The psychological assessment involved the completion of the Well-being, Activity, and Mood (WAM) test. The physiological assessment focused on heart rate variability (HRV) measurements, which were obtained using the Varikard 2.51 complex equipment. A total of 23 male teenage judokas, aged between 10 and 16 years, were randomly selected from a judo club to participate in this study. Participants demonstrated high levels of well-being, activity, and positive mood, indicating positive psychosocial outcomes associated with judo practice. Analysis of heart rate variability (HRV) revealed deviations in certain variables, suggesting potential irregularities in autonomic nervous system regulation. Specifically, the Index of Activity of Regulatory Systems (IRSA), low-frequency power (LF), and total power (TP) exceeded normal ranges, indicating increased tension and overall activity in the regulatory systems. In addition, one-way analysis showed significant main effects of age, training duration, and high-frequency power (HF) on the participants' performance level (Kyu). The findings suggest that psychological and physiological factors play significant roles in the performance levels of adolescent judokas. Coaches and practitioners should consider both aspects in optimizing training strategies for young athletes.

[The criterion mode of evaluating functioning of stomatologic polyclinic].

To improve quality and efficiency of primary health care and to strengthen its preventive directivity is possible through health care modernization including implementation of management technologies, development of database for evaluation and control. The purpose of the study is to develop method of evaluating activity of stomatologic clinic. The methodology was based on concepts of "functional systems" and "decision making". The listing of informative criteria was based on data analysis of functioning of stomatologic service of the Chechen Republic in 2002-2016 and results of sociological survey of stomatologists (n=181), health care administrators in stomatology (n=45), paramedics (n=220) and patients (n=359). The experts (n=13) developed required number of criteria and their gradation. The algorithm of evaluating activity of stomatologic clinic was developed using systematic approach. The listing of 52 criteria and their 10 blocks were established. The experts established coefficients of significance of criteria (0.0084-0.0781; ≥0.0224 - more significant, <0.0224 - less significant). Three levels were determined for each criterion (according principle of minimization) that became a basis for calculation of integrated indicator of efficiency of functioning of stomatologic polyclinic. The expanded methodological approaches ensure comparartivity of estimates of stomatologic polyclinic in various time periods. The health care authorities have opportunity to objectify analysis of functioning of a number of polyclinics in different periods.

Experimental models of ecological niches for African swine fever virus.

In this study, we investigated the possible biological factors affecting the survival of the African swine fever virus (ASFV) in the environment and their potential to influence the ecology of the ASFV. Specifically, we tested the survival and replication of ASFV in four phylogenetically distinct organisms: Paramecium caudatum, Dendrobaena alpine, Aedes aegypti andXeropicta derbentina using qReal-Time PCR and hemadsorbtion analysis. Levels of ASFV in earthworms (Dendrobaena alpina) and soil declined at similar rates, suggesting that earthworms likely have no influence on the ecology of the ASFV. Ciliates (Paramecium caudatum) significantly increase the rate of ASFV disappearance from the aquatic environment, probably using the virus as a food source. Mosquitoes (Aedes aegypti) do not provide significant support for the persistence of ASF virus in the environment, with no evidence for transmission to their offspring or pigs that ingested mosquitoes. ASFV persisted for much longer in air-breathing land snails (Xeropicta derbentina) than in the soil. Moreover, transcription of viral genes was maintained within the snail, although the question of full-fledged viral replication is still open. In addition, the active movements of snails suggests that they could play a role in the spread of the virus. The virus is likely to be localized in the intestines of snails as it is regularly excreted from their feces. These results highlight the importance of investigating invertebrates for understanding ASFV surviving, spreading and transmission in natural populations with zoonotic transmission potential.

Measurement of the Charge-Averaged Elastic Lepton-Proton Scattering Cross Section by the OLYMPUS Experiment.

We report the first measurement of the average of the electron-proton and positron-proton elastic scattering cross sections. This lepton charge-averaged cross section is insensitive to the leading effects of hard two-photon exchange, giving more robust access to the proton's electromagnetic form factors. The cross section was extracted from data taken by the OLYMPUS experiment at DESY, in which alternating stored electron and positron beams were scattered from a windowless gaseous hydrogen target. Elastic scattering events were identified from the coincident detection of the scattered lepton and recoil proton in a large-acceptance toroidal spectrometer. The luminosity was determined from the rates of Møller, Bhabha, and elastic scattering in forward electromagnetic calorimeters. The data provide some selectivity between existing form factor global fits and will provide valuable constraints to future fits.

[Morphological characteristics of pulmonary tuberculosis concurrent with lung cancer]. / Morfologicheskie osobennosti sochetaniya tuberkuleza i raka legkikh.

The pathogenetic relationship between pulmonary tuberculosis and lung cancer in their concurrence is now still the subject of discussion. OBJECTIVE: To study the pathogenetic relationship between pulmonary tuberculosis and lung cancer. MATERIAL AND METHODS: The investigators examined surgical material from 51 patients (41 men) aged 41-73 years (mean age, 63.7 years) with pulmonary tuberculosis concurrent with lung cancer. They also studied tumors, tuberculous caverns, infiltrates, and foci with surrounding macroscopically intact lung tissue, as well as fibrotic changes by histological, histochemical and immunohistochemical examinations. RESULTS: Previous tuberculosis can be considered as a risk factor for lung cancer. Central cancer was more common in patients with inactive, chronic tuberculosis with a predominance of fibrotic processes in the root of the lung and in its hilar zones. Fibrous-cavernous tuberculosis and cavernous tuberculosis were more frequently concurrent with central cancer; peripheral tumors mainly occurred in infiltrative tuberculosis and tuberculomas. CONCLUSION: The findings suggest that in a number of cases, cancer and tuberculosis may be anatomically close, developing in the same anatomical unit - the lung. However, this does not indicate an unambiguous etiopathogenetic relationship between pulmonary tuberculosis and lung cancer. The relationships between pulmonary tuberculosis and lung cancer are much more complex and do not fit into the simple scheme of cause-and-effect relations.

[Medical-organizational and sociological characteristics of the staff of the dental service in a subsidiary subject of the Russian Federation]. / Mediko-organizatsionnaya i sotsiologicheskaya kharakteristika kadrovogo sostava stomatologicheskoi sluzhby dotatsionnogo sub"ekta Rossiiskoi Federatsii.

OBJECTIVE: To assess the working conditions of dentists in the Chechen Republic based on the results of a voluntary anonymous survey, to identify the shortcomings and problems in the functioning of the dental service that need to be corrected. MATERIAL AND METHODS: With the help of specially developed questionnaires, a voluntary anonymous survey of dentists providing primary medical and sanitary dental care in the Chechen Republic was conducted. The questionnaires included several blocks of questions, each of which pursued specific goals: first, to compose a social and professional «portrait¼ of a dentist; the second is to identify the opinions of respondents about the prevalence of dental pathology among the population, their attitude to the work of the dental service; the third is to identify certain shortcomings and problems that need to be corrected. RESULTS: The analysis of the respondents' answers received during the survey contributed to the compilation of an objective social and professional «portrait¼ of a dentist performing professional activities in the Chechen Republic, to study working conditions and satisfaction with them, legal regulation of activities, material support, the degree of professional training, to establish peculiarities of relationships with patients. Also indicated are the actual (according to dentists) problems of providing patients with medical dental care, shortcomings in the organization of the functioning of the dental service in the region. The issues of organizing preventive work, including the commitment of the population to maintaining their dental health and a number of other positions were studied. CONCLUSION: The method of voluntary anonymous questioning of dentists has shown its effectiveness, simplicity, convenience in assessing the state of dental care for the population, designating the range of characteristic specific problems that occur in a particular region (according to dentists), make it possible to establish what exactly is necessary to improve the quality provided medical care, and, therefore, allows you to outline ways to optimize activities.

[The influence of the degree of sanogenetic education of the population in a subsidized subject of the Russian Federation on dental health]. / Vliyanie stepeni sanogeneticheskoi podgotovki naseleniya v dotatsionnom sub"ekte Rossiiskoi Federatsii na sostoyanie stomatologicheskogo zdorov'ya.

OBJECTIVE: To determine the effect of healthy lifestyle (HLS) on dental health (prevalence and intensity of dental diseases). MATERIAL AND METHODS: The study was conducted in the standard age group 35-44 years. According to the results of a sociological survey, two groups were formed: leading HLS (1st group, 30 respondents) and those not leading HLS (2nd group, 34 respondents). The presence and prevalence of caries, its intensity (DMFT index), the hygienic state of the oral cavity (Green-Vermillion index (GRVI) and the effectiveness of oral hygiene (PHP), the state of periodontal tissues (CPITN)) were assessed. RESULTS: The prevalence of caries in group №1 was 77%, in 2nd group - 100%, the average value of the DMFT in group №1 was 8.9±0.2, in 2nd group - 17.1±0.3; the values of the GRVI index differed 5 times (1.1 and 5.2), the PHP index - 9 times (0.2 and 1.8, correspondently). In 2nd group, the high prevalence of dentition defects was revealed (40%), only 6% of patients had a normal periodontal condition, pathological periodontal pockets with a depth of 6 and more mm in patients were 3 times higher (9%) comparing to 1st group (3%). Periodontal care was required 94% of patients in the 2nd group (in 1st group - 72%). Patients in the 1st group took much better care of their teeth: the level of hygiene index was within 1.1 (in 2nd group - 5.2 - poor) Adequate oral hygiene regimen was found in 93% of patients in 1st group and only in 38% in 2nd group. CONCLUSIONS: The data obtained indicate not only poor dental health of the population, but also about significant shortcomings in the medical care and the low efficiency of preventive work on the part of the dental service.

Presence and survival of African swine fever virus in leeches.

This research is focused on the study of African swine fever virus (ASFV) survival in the leech Hirudo medicinalis. To detect the infection route of the virus in leeches, two introduction methods were used: blood-feeding from infected swine hosts and exposure to ASFV-contaminated water (leeches cultivated with ASFV). This study found that the survival of ASFV in leeches was much longer than that in leech-free medium. The persistent presence of the virus in leeches and leech excretion was detected in both groups. The virus excreted from both groups of leeches in the terminal stages of the experiment was able to induce productive infection in porcine alveolar macrophages. In an attempt to understand ASFV, transmission to pigs was conducted through the ingestion of leech-cultivated water and leeches that had fed on ASFV-infected animals or that were cultivated environmentally with the virus. The ingestion of some samples at 60-80 days after cultivation demonstrated successful ASFV transmission via per os infection. In conclusion, leeches can serve as a possible reservoirs for ASFV in the absence of its main hosts - pigs and some ticks of the genus Ornithodoros.

Disruption of Functional Activity of Mitochondria during MTT Assay of Viability of Cultured Neurons.

The MTT assay based on the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium in the cell cytoplasm to a strongly light absorbing formazan is among the most commonly used methods for determination of cell viability and activity of NAD-dependent oxidoreductases. In the present study, the effects of MTT (0.1 mg/ml) on mitochondrial potential (ΔΨm), intracellular NADH, and respiration of cultured rat cerebellum neurons and isolated rat liver mitochondria were investigated. MTT caused rapid quenching of NADH autofluorescence, fluorescence of MitoTracker Green (MTG) and ΔΨm-sensitive probes Rh123 (rhodamine 123) and TMRM (tetramethylrhodamine methyl ester). The Rh123 signal, unlike that of NADH, MTG, and TMRM, increased in the nucleoplasm after 5-10 min, and this was accompanied by the formation of opaque aggregates of formazan in the cytoplasm and neurites. Increase in the Rh123 signal indicated diffusion of the probe from mitochondria to cytosol and nucleus due to ΔΨm decrease. Inhibition of complex I of the respiratory chain decreased the rate of formazan formation, while inhibition of complex IV increased it. Inhibition of complex III and ATP-synthase affected only insignificantly the rate of formazan formation. Inhibition of glycolysis by 2-deoxy-D-glucose blocked the MTT reduction, whereas pyruvate increased the rate of formazan formation in a concentration-dependent manner. MTT reduced the rate of oxygen consumption by cultured neurons to the value observed when respiratory chain complexes I and III were simultaneously blocked, and it suppressed respiration of isolated mitochondria if substrates oxidized by NAD-dependent dehydrogenases were used. These results demonstrate that formazan formation in cultured rat cerebellum neurons occurs primarily in mitochondria. The initial rate of formazan formation may serve as an indicator of complex I activity and pyruvate transport rate.

Hard Two-Photon Contribution to Elastic Lepton-Proton Scattering Determined by the OLYMPUS Experiment.

The OLYMPUS Collaboration reports on a precision measurement of the positron-proton to electron-proton elastic cross section ratio, R_{2γ}, a direct measure of the contribution of hard two-photon exchange to the elastic cross section. In the OLYMPUS measurement, 2.01 GeV electron and positron beams were directed through a hydrogen gas target internal to the DORIS storage ring at DESY. A toroidal magnetic spectrometer instrumented with drift chambers and time-of-flight scintillators detected elastically scattered leptons in coincidence with recoiling protons over a scattering angle range of ≈20° to 80°. The relative luminosity between the two beam species was monitored using tracking telescopes of interleaved gas electron multiplier and multiwire proportional chamber detectors at 12°, as well as symmetric Møller or Bhabha calorimeters at 1.29°. A total integrated luminosity of 4.5 fb^{-1} was collected. In the extraction of R_{2γ}, radiative effects were taken into account using a Monte Carlo generator to simulate the convolutions of internal bremsstrahlung with experiment-specific conditions such as detector acceptance and reconstruction efficiency. The resulting values of R_{2γ}, presented here for a wide range of virtual photon polarization 0.456<ε<0.978, are smaller than some hadronic two-photon exchange calculations predict, but are in reasonable agreement with a subtracted dispersion model and a phenomenological fit to the form factor data.

Characterization of the atypical lymphocytes in African swine fever.

AIM: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV) infection, bone marrow, peripheral blood, and in vitro model were investigated. MATERIALS AND METHODS: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. RESULTS: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. CONCLUSIONS: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection.

Mitochondrial Dysfunction in Neocortex and Hippocampus of Olfactory Bulbectomized Mice, a Model of Alzheimer's Disease.

Structural and functional impairments of mitochondria in brain tissues in the pathogenesis of Alzheimer's disease (AD) cause energy deficiency, increased generation of reactive oxygen species (ROS), and premature neuronal death. However, the causal relations between accumulation of beta-amyloid (Aß) peptide in mitochondria and mitochondrial dysfunction, as well as molecular mechanisms underlying deleterious effects of both these factors in sporadic AD, the most common form in humans, remain unknown. Here we used olfactory bulbectomized (OBX) mice of NMRI strain as a model for sporadic AD. Five weeks after surgery, the OBX mice developed major behavioral and biochemical features of AD neurodegeneration, including spatial memory loss, increased brain levels of Aß, and energy deficiency. Mitochondria isolated from the neocortex and hippocampus of OBX mice displayed severe functional impairments, such as low NADH oxidation rate, reduced transmembrane potential, and decreased cytochrome c oxidase (complex IV) activity that correlated with high levels of soluble Aß1-40. Mitochondria from OBX mice showed increased contents of lipid peroxidation products, indicative of the development of oxidative stress. We found that neurodegeneration caused by olfactory bulbectomy is accompanied by energy metabolism disturbances and oxidative stress in brain mitochondria similar to those occurring in transgenic animals - familial AD models and patients with sporadic AD. Therefore, OBX mice can serve as a valid AD model for investigating the mechanisms of AD neurodegeneration, drug testing, and development of therapeutic strategies for AD treatment.

3D printed microfluidic circuitry via multijet-based additive manufacturing.

The miniaturization of integrated fluidic processors affords extensive benefits for chemical and biological fields, yet traditional, monolithic methods of microfabrication present numerous obstacles for the scaling of fluidic operators. Recently, researchers have investigated the use of additive manufacturing or "three-dimensional (3D) printing" technologies - predominantly stereolithography - as a promising alternative for the construction of submillimeter-scale fluidic components. One challenge, however, is that current stereolithography methods lack the ability to simultaneously print sacrificial support materials, which limits the geometric versatility of such approaches. In this work, we investigate the use of multijet modelling (alternatively, polyjet printing) - a layer-by-layer, multi-material inkjetting process - for 3D printing geometrically complex, yet functionally advantageous fluidic components comprised of both static and dynamic physical elements. We examine a fundamental class of 3D printed microfluidic operators, including fluidic capacitors, fluidic diodes, and fluidic transistors. In addition, we evaluate the potential to advance on-chip automation of integrated fluidic systems via geometric modification of component parameters. Theoretical and experimental results for 3D fluidic capacitors demonstrated that transitioning from planar to non-planar diaphragm architectures improved component performance. Flow rectification experiments for 3D printed fluidic diodes revealed a diodicity of 80.6 ± 1.8. Geometry-based gain enhancement for 3D printed fluidic transistors yielded pressure gain of 3.01 ± 0.78. Consistent with additional additive manufacturing methodologies, the use of digitally-transferrable 3D models of fluidic components combined with commercially-available 3D printers could extend the fluidic routing capabilities presented here to researchers in fields beyond the core engineering community.

Photo-production of (99)Mo/(99m)Tc with electron linear accelerator beam.

We report on the development of a relatively new method for the production of (99)Mo/(99m)Tc. The method involves the irradiation of natural molybdenum using high-intensity bremsstrahlung photons from the electron beam of the LUE50 linear electron accelerator located at the Yerevan Physics Institute (YerPhi). The production method has been developed and shown to be successful. The linear electron accelerator at YerPhi was upgraded to allow for significant increases of the beam intensity and spatial density. The LUE50 was also instrumented by a remote control system for ease of operation. We have developed and tested the (99m)Tc extraction from the irradiation of natural MoO3. This paper reports on the optimal conditions of our method of (99)Mo production. We show the success of this method with the production and separation of the first usable amounts of (99m)Tc.

D- shallow donor near a semiconductor-metal and a semiconductor-dielectric interface.

The ground state energy and the extent of the wavefunction of a negatively charged donor (D(-)) located near a semiconductor-metal or a semiconductor-dielectric interface are obtained. We apply the effective mass approximation and use a variational two-electron wavefunction that takes into account the influence of all image charges that arise due to the presence of the interface, as well as the correlation between the two electrons bound to the donor. For a semiconductor-metal interface, the D(-) binding energy is enhanced for donor positions d > 1.5a(B) (a(B) is the effective Bohr radius) due to the additional attraction of the electrons with their images. When the donor approaches the interface (i.e. d < 1.5a(B)) the D(-) binding energy drops and eventually it becomes unbound. For a semiconductor-dielectric (or a semiconductor-vacuum) interface the D(-) binding energy is reduced for any donor position as compared to the bulk case and the system becomes rapidly unbound when the donor approaches the interface.

The stability of DNA-porphyrin complexes in the presence of Mn(II) ions.

The complex formation of porphyrins with DNA leads to changes of stability of DNA. In the present study we investigated binding properties and the thermodynamic parameters of a water-soluble, cationic planar Cu(II)-containing meso-tetrakis(4-N-butyl-pyridiniumyl)porphyrin [CuTButPyP4] and nonplanar Co(II)-containing meso-tetrakis(4-N-butyl-pyridiniumyl)porphyrin [CoButPyP4] with calf thymus DNA in the presence of divalent manganese ions. For displaying the changes of thermodynamic parameters (T(m) and ΔT) the melting curves of DNA-porphyrin complexes in the presence of Mn(2+) ions have been obtained. The enthalpy (ΔH) of helix-coil transition has been also evaluated. It was shown that the binding of ions to DNA proceeds in two stages depending on the manganese/DNA phosphates molar ratio [Mn]/[P]. At the first stage (0.001<[Mn]/[P]<1), the interaction of manganese ions with DNA phosphates occurs, causing an additional screening of their negative charge and the stabilization of the double helix. As a result, the best conditions for intercalation of CuTButPyP4 or of peripheral rings of CoButPyP4 occur. The significant increase of T(m), but less changes of ΔT were observed. At the second stage (1<[Mn]/[P]<4), the ions interact with both the phosphates and the nitrogen bases of DNA. At this stage, it is possible for the manganese ion to coordinate simultaneously to the oxygen atom of the phosphate and the neighboring base of DNA. At a higher [Mn]/[P] ratio, the destabilization of the double helix begins, and partial breakage of the hydrogen bonds between the nitrogen bases occurs. Respectively the destabilization of DNA in the presence of both porphyrins takes place.

Phenotypic and cytologic studies of lymphoid cells and monocytes in primary culture of porcine bone marrow during infection of African swine fever virus.

We have modeled in vitro infection of African swine fever virus (ASFV) in primary unstimulated cells of the porcine bone marrow and have studied the phenotypical changes in the population of porcine lymphoid cells by cytophotometry. Monocytes and large-sized lymphocytes completely vanished in 72 h of infection which is result of high sensitivity of those cells to ASFV. We describe DNA synthesis in monocytes at 24 h post infection. Cytophotometry of the uninfected cells revealed the few number of atypical lymphocytes and lymphoblasts after 72 h of cultivation; whereas in viral infected cultures, atypical cells appeared in large quantity (about 14%) with 24 h. Most of atypical lymphocytes and lymphoblasts had altered nucleus, and only a small number of atypical cells had additional nucleus. The cytophotometry of main and additional nuclei showed that DNA content didn't exceed diploid standard which indicates that the additional nuclei were consequence of fragmentation of nuclei in lymphocytes.

Mitochondria as source of reactive oxygen species under oxidative stress. Study with novel mitochondria-targeted antioxidants--the "Skulachev-ion" derivatives.

Production of reactive oxygen species (ROS) in mitochondria was studied using the novel mitochondria-targeted antioxidants (SkQ) in cultures of human cells. It was shown that SkQ rapidly (1-2 h) and selectively accumulated in mitochondria and prevented oxidation of mitochondrial components under oxidative stress induced by hydrogen peroxide. At nanomolar concentrations, SkQ inhibited oxidation of glutathione, fragmentation of mitochondria, and translocation of Bax from cytosol into mitochondria. The last effect could be related to prevention of conformational change in the adenine nucleotide transporter, which depends on oxidation of critical thiols. Mitochondria-targeted antioxidants at nanomolar concentrations prevented accumulation of ROS and cell death under oxidative stress. These effects required 24 h or more (depending on the cell type) preincubation, and this was not related to slow induction of endogenous antioxidant systems. It is suggested that SkQ slowly accumulates in a small subpopulation of mitochondria that have decreased membrane potential and produce the major part of ROS under oxidative stress. This population was visualized in the cells using potential-sensitive dye. The possible role of the small fraction of "bad" mitochondria in cell physiology is discussed.

Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies.

Synthesis of cationic plastoquinone derivatives (SkQs) containing positively charged phosphonium or rhodamine moieties connected to plastoquinone by decane or pentane linkers is described. It is shown that SkQs (i) easily penetrate through planar, mitochondrial, and outer cell membranes, (ii) at low (nanomolar) concentrations, posses strong antioxidant activity in aqueous solution, BLM, lipid micelles, liposomes, isolated mitochondria, and cells, (iii) at higher (micromolar) concentrations, show pronounced prooxidant activity, the "window" between anti- and prooxidant concentrations being very much larger than for MitoQ, a cationic ubiquinone derivative showing very much lower antioxidant activity and higher prooxidant activity, (iv) are reduced by the respiratory chain to SkQH2, the rate of oxidation of SkQH2 being lower than the rate of SkQ reduction, and (v) prevent oxidation of mitochondrial cardiolipin by OH*. In HeLa cells and human fibroblasts, SkQs operate as powerful inhibitors of the ROS-induced apoptosis and necrosis. For the two most active SkQs, namely SkQ1 and SkQR1, C(1/2) values for inhibition of the H2O2-induced apoptosis in fibroblasts appear to be as low as 1x10(-11) and 8x10(-13) M, respectively. SkQR1, a fluorescent representative of the SkQ family, specifically stains a single type of organelles in the living cell, i.e. energized mitochondria. Such specificity is explained by the fact that it is the mitochondrial matrix that is the only negatively-charged compartment inside the cell. Assuming that the Deltapsi values on the outer cell and inner mitochondrial membranes are about 60 and 180 mV, respectively, and taking into account distribution coefficient of SkQ1 between lipid and water (about 13,000 : 1), the SkQ1 concentration in the inner leaflet of the inner mitochondrial membrane should be 1.3x10(8) times higher than in the extracellular space. This explains the very high efficiency of such compounds in experiments on cell cultures. It is concluded that SkQs are rechargeable, mitochondria-targeted antioxidants of very high efficiency and specificity. Therefore, they might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo.

Bioenergetics and death.

Specific inhibitors of mitochondrial functions were used in studies on the relation between bioenergetics and programmed cell death. The data of the authors are discussed in the review.