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Alzheimer's disease (AD), characterized by severe and progressive cognitive decline, stands as one of the most prevalent and devastating forms of dementia. Based on our recent findings showing intermittent hypoxic conditioning improved neuronal function in patients with mild cognitive impairment, the present study aimed at investigating whether the neuroprotective effects of intermittent hypoxia can be replicated in a rat model of AD, which allows us to explore the underlying cellular mechanisms involving neuroinflammation, hypoxia inducible factor 1α (HIF1α), and cytochrome P450 family 2 subfamily E member 1 (CYP2E1). Forty-one adult male Wistar rats were randomly assigned to three groups: 1) Control group: received intracerebroventricular (ICV) injection of saline; 2) STZ group: received ICV injection of streptozotocin (STZ) to induce AD-like pathology; and 3) STZ + IHHT group received ICV injection of STZ as well as 15 daily sessions of intermittent hypoxia-hyperoxia training (IHHT). We observed that ICV injection of STZ inhibited spatial learning and memory in the rats assessed with Morris Water Maze test. The cognitive function declines were accompanied by increased expression of amyloid β peptide (Aβ), HIF1α, CYP2E1, and TNFα in hippocampus. Interestingly, IHHT significantly restored the STZ-induced cognitive dysfunction, while reduced expression of Aβ, CYP2E1, HIF1α and TNFα. We conclude that IHHT with mild hypoxia-hyperoxia can enhance spatial learning and memory and reduce the AD-like pathologic changes in rats. The neuroprotective outcome of IHHT may be related to anti-inflammatory effects in hippocampus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study involved 72 volunteers divided into two groups according to the apnea-hypopnea index (AHI): AHI>15 episodes per hour (ep/h) (main group, n=39, including 28 men, median AHI 44.15, median age 47), 0≤AHI≤15ep/h (control group, n=33, including 12 men, median AHI 2, median age 28). Each participant underwent polysomnography with a recording of 19 EEG channels. Based on wavelet bicoherence (WB), the magnitude of connectivity between all pairs of EEG channels in six bands was estimated: Df1 0.25;1, Df2 1;4, Df3 4;8, Df4 8;12, Df5 12;20, Df6 20;30 Hz. In all six bands considered, we noted a significant decrease in symmetrical interhemispheric connections in OSA patients. Also, in the main group for slow oscillatory activity Df1 and Df2, we observe a decrease in connection values in the EEG channels associated with the central interhemispheric sulcus. In addition, patients with AHI>15 show an increase in intrahemispheric connectivity, in particular, forming a left hemisphere high-degree synchronization node (connections PzT3, PzF3, PzFp1) in the Df2 band. When considering high-frequency EEG oscillations, connectivity in OSA patients again shows a significant increase within the cerebral hemispheres. The revealed differences in functional connectivity in patients with different levels of AHI are quite stable, remaining when averaging the full nocturnal EEG recording, including both the entire sleep duration and night awakenings. The increase in the number of hypoxia episodes correlates with the violation of the symmetry of interhemispheric functional connections. Maximum absolute values of correlation between the apnea-hypopnea index, AHI, and the WB synchronization strength are observed for the Df2 band in symmetrical EEG channels C3C4 (-0.81) and P3P4 (-0.77). The conducted studies demonstrate the possibility of developing diagnostic systems for obstructive sleep apnea syndrome without using signals from the cardiovascular system and respiratory activity.

This paper presents the results of a study of the characteristics of phase synchronization between electrocardiography(ECG) and electroencephalography (EEG) signals during night sleep. Polysomnographic recordings of eight generally healthy subjects and eight patients with obstructive sleep apnea syndrome were selected as experimental data. A feature of this study was the introduction of an instantaneous phase for EEG and ECG signals using a continuous wavelet transform at the heart rate frequency using the concept of time scale synchronization, which eliminated the emergence of asynchronous areas of behavior associated with the "leaving" of the fundamental frequency of the cardiovascular system. Instantaneous phase differences were examined for various pairs of EEG and ECG signals during night sleep, and it was shown that in all cases the phase difference exhibited intermittency. Laminar areas of behavior are intervals of phase synchronization, i.e., phase capture. Turbulent intervals are phase jumps of 2π. Statistical studies of the observed intermittent behavior were carried out, namely, distributions of the duration of laminar sections of behavior were estimated. For all pairs of channels, the duration of laminar phases obeyed an exponential law. Based on the analysis of the movement of the phase trajectory on a rotating plane at the moment of detection of the turbulent phase, it was established that in this case the eyelet intermittency was observed. There was no connection between the statistical characteristics of laminar phase distributions for intermittent behavior and the characteristics of night breathing disorders (apnea syndrome). It was found that changes in statistical characteristics in the phase synchronization of EEG and ECG signals were correlated with blood pressure at the time of signal recording in the subjects, which is an interesting effect that requires further research., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Acute Respiratory Distress Syndrome (ARDS), associated with Covid-19 infections, is characterized by diffuse lung damage, inflammation and alveolar collapse that impairs gas exchange, leading to hypoxemia and patient' mortality rates above 40%. Here, we describe the development and assessment of 100-nm liposomes that are tailored for pulmonary delivery for treating ARDS, as a model for lung diseases. The liposomal lipid composition (primarily DPPC) was optimized to mimic the lung surfactant composition, and the drug loading process of both methylprednisolone (MPS), a steroid, and N-acetyl cysteine (NAC), a mucolytic agent, reached an encapsulation efficiency of 98% and 92%, respectively. In vitro, treating lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages with the liposomes decreased TNFα and nitric oxide (NO) secretion, while NAC increased the penetration of nanoparticles through the mucus. In vivo, we used LPS-induced lung inflammation model to assess the accumulation and therapeutic efficacy of the liposomes in C57BL/6 mice, either by intravenous (IV), endotracheal (ET) or IV plus ET nanoparticles administrations. Using both administration methods, liposomes exhibited an increased accumulation profile in the inflamed lungs over 48 h. Interestingly, while IV-administrated liposomes distributed widely throughout the lung, ET liposomes were present in lungs parenchyma but were not detected at some distal regions of the lungs, possibly due to imperfect airflow regimes. Twenty hours after the different treatments, lungs were assessed for markers of inflammation. We found that the nanoparticle treatment had a superior therapeutic effect compared to free drugs in treating ARDS, reducing inflammation and TNFα, IL-6 and IL-1β cytokine secretion in bronchoalveolar lavage (BAL), and that the combined treatment, delivering nanoparticles IV and ET simultaneously, had the best outcome of all treatments. Interestingly, also the DPPC lipid component alone played a therapeutic role in reducing inflammatory markers in the lungs. Collectively, we show that therapeutic nanoparticles accumulate in inflamed lungs holding potential for treating lung disorders. SIGNIFICANCE: In this study we compare intravenous versus intratracheal delivery of nanoparticles for treating lung disorders, specifically, acute respiratory distress syndrome (ARDS). By co-loading two medications into lipid nanoparticles, we were able to reduce both inflammation and mucus secretion in the inflamed lungs. Both modes of delivery resulted in high nanoparticle accumulation in the lungs, intravenously administered nanoparticles reached lung endothelial while endotracheal delivery reached lung epithelial. Combining both delivery approaches simultaneously provided the best ARDS treatment outcome., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Several studies have assessed the effects of intermittent hypoxia-normoxia training (IHNT), intermittent hypoxia-hyperoxia training (IHHT), and obstructive sleep apnea (OSA) on aging and age-related diseases in humans; however, the results remain contradictory. Therefore, this review aims to systematically summarize the available studies on the effects of IHNT, IHHT, and OSA on aging and age-related diseases. Relevant studies were searched from PubMed, Google Scholar, Cochrane Library databases, and through manual searching from reference lists of eligible studies. A total of 38 eligible studies were included in this systematic review. IHHT and IHNT provide positive effects on several age-related parameters including quality of life, cognitive and physical functions, plasma level of glucose and cholesterol/LDL, systolic blood pressure, red blood cells, and inflammation. Moreover, moderate intermittent hypoxia induces telomerase reverse transcriptase (TERT) activity and telomere stabilization, delays induction of senescence-associated markers expression and senescence-associated β-galactosidase, upregulates pluripotent marker (Oct4), activates a metabolic shift, and raises resistance to pro-apoptotic stimuli. On the contrary, intermittent hypoxia in OSA causes hypertension, metabolic syndrome, vascular function impairment, quality of life and cognitive scores reduction, advanced brain aging, increase in insulin resistance, plasma hydrogen peroxide, GSH, IL-6, hsCRP, leptin, and leukocyte telomere shortening. Thus, it can be speculated that the main factor that determines the direction of the intermittent hypoxia action is the intensity and duration of exposure. There is no direct study to prove that IHNT/IHHT actually increases life expectancy in humans. Therefore, further study is needed to investigate the actual effect of IHNT/IHHT on aging in humans., Systematic Review Registration: www.crd.york.ac.uk/prospero, identifier CRD42022298499., Competing Interests: EE is a co-owner of CellAir Construction GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tessema, Sack, König, Serebrovska and Egorov.)

Intermittent hypoxia-hyperoxia training (IHHT) is a non-pharmacological therapeutic modality for management of some chronic- and age-related pathologies, such as Alzheimer’s disease (AD). Our previous studies demonstrated significant improvement of cognitive function after IHHT in the patients with mild cognitive impairment (MCI). The present study further investigated the effects of IHHT on pro-inflammatory factors in healthy elderly individuals and patients with early signs of AD. Twenty-nine subjects (13 healthy subjects without signs of cognitive impairment syndrome and 16 patients diagnosed with MCI; age 52 to 76 years) were divided into four groups: Healthy+Sham (n = 7), Healthy+IHHT (n = 6), MCI+Sham (n = 6), and MCI+IHHT (n = 10). IHHT was carried out 5 days per week for 3 weeks (total 15 sessions), and each daily session included 4 cycles of 5-min hypoxia (12% FIO2) and 3-min hyperoxia (33% FIO2). Decline in cognitive function indices was observed initially in both MCI+Sham and MCI+IHHT groups. The sham training did not alter any of the parameters, whereas IHHT resulted in improvement in latency of cognitive evoked potentials, along with elevation in APP110, GDF15 expression, and MMP9 activity in both healthy subjects and those with MCI. Increased MMP2 activity, HMGB1, and P-selectin expression and decreased NETs formation and Aβ expression were also observed in the MCI+IHHT group. There was a negative correlation between MoCA score and the plasma GDF15 expression (R = −0.5799, p < 0.05) before the initiation of IHHT. The enhanced expression of GDF15 was also associated with longer latency of the event-related potentials P330 and N200 (R = 0.6263, p < 0.05 and R = 0.5715, p < 0.05, respectively). In conclusion, IHHT upregulated circulating levels of some inflammatory markers, which may represent potential triggers for cellular adaptive reprogramming, leading to therapeutic effects against cognitive dysfunction and neuropathological changes during progression of AD. Further investigation is needed to clarify if there is a causative relationship between the improved cognitive function and the elevated inflammatory markers following IHHT.

The effects of short-term hyperoxia on age-related diseases and aging biomarkers have been reported in animal and human experiments using different protocols; however, the findings of the studies remain conflicting. In this systematic review, we summarized the existing reports in the effects of short-term hyperoxia on age-related diseases, hypoxia-inducible factor 1α (HIF-1α), and other oxygen-sensitive transcription factors relevant to aging, telomere length, cellular senescence, and its side effects. This review was done as described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A systematic search was done in PubMed, Google Scholar, and Cochrane Library and from the references of selected articles to identify relevant studies until May 2021. Of the total 1,699 identified studies, 17 were included in this review. Most of the studies have shown significant effects of short-term hyperoxia on age-related diseases and aging biomarkers. The findings of the studies suggest the potential benefits of short-term hyperoxia in several clinical applications such as for patients undergoing stressful operations, restoration of cognitive function, and the treatment of severe traumatic brain injury. Short-term hyperoxia has significant effects in upregulation or downregulation of transcription factors relevant to aging such as HIF-1α, nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB), and nuclear factor (erythroid-derived 2)-like 2 (NRF2) among others. Short-term hyperoxia also has significant effects to increase antioxidant enzymes, and increase telomere length and clearance of senescent cells. Some of the studies have also reported adverse consequences including mitochondrial DNA damage and nuclear cataract formation depending on the dose and duration of oxygen exposure. In conclusion, short-term hyperoxia could be a feasible treatment option to treat age-related disease and to slow aging because of its ability to increase antioxidant enzymes, significantly increase telomere length and clearance of senescent cells, and improve cognitive function, among others. The reported side effects of hyperoxia vary depending on the dose and duration of exposure. Therefore, it seems that additional studies for better understanding the beneficial effects of short-term hyperoxia and for minimizing side effects are necessary for optimal clinical application., Competing Interests: EE is a co-owner of CellAir Construction GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tessema, Sack, Serebrovska, König and Egorov.)

Advances in medical diagnostic technologies, particularly in ophthalmology, help researchers understand histological characteristics of the human eye and study vision at the cellular level. In addition to its role in the ocular function associated with the control of movements, senses and protective responses, the nervous system plays a key role in regulation of the visual process. Neurodegenerative disorders hold a special place among systemic diseases. Presently, the development of such pathologies are associated with neuroinflammation, which has been proven to also contribute to the glaucomatous process. For this reason, achieving target intraocular pressure does not always guarantee stabilization of the degenerative process. In this context, neuroprotective agents are recommended for glaucoma management to all patients taking into consideration pathogenetic characteristics of the disease. Based on its antioxidative and neuroprotective effects, ethylmethylhydroxypyridine succinate (Mexidol) is commonly used in ophthalmic practice, specifically in the treatment of patients with glaucomatous optic neuropathy and retinal diseases. The results of studies demonstrate that Mexidol is effective in slowing down neurodegeneration and stabilizing visual functions in patients with primary open-angle glaucoma due to its antihypoxic, antioxidant and membrane-stabilizing properties, as well as its positive impact on the neuromediator balance and ocular blood flow.

The article considers the legislative and regulatory acts that specify the tasks in the implementation of breeding processes. The results of the creation, variety testing, patenting and introduction of grape varieties and clones into the State Register of the Russian Federation for 2010-2020 are presented. The article analyzes the relationship between the indicators of industrial development with the production volumes of planting material, the use of domestic varieties that are included in the State Register of the Russian Federation. The characteristic of ampelographic collections - the genetic resources of grapes - is given. A comparative analysis of many years' worth of data on the assessment of the adaptive potential of domestic varieties and introduced varieties is presented. The article describes domestic varieties, from which premium wines are produced, which not only competes with European varieties, but also surpasses the organoleptic properties and biochemical parameters of grape must and wine material. The main problems hindering the wide demand for domestic varieties on the market, including a substantial amount of imported European varietal planting material, are described. The necessity of accelerating breeding processes is actualized, modern methods are identified, including those of generative and genomic selection, transgenic technologies, cellular, mutational, and clone selection, and priority areas in breeding are presented. The numerical and qualitative analyses of the composition of breeding scientists is given, the trends of increasing the number and qualitative composition of breeders, the influx of young people, the growing need for training qualified personnel are noted. The number of bachelor's, master's and post-graduate students specializing in viticulture in general and in selection in particular as well as the number of defended dissertation studies on grape breeding has been found to be insufficient. The main scientific and practical problems in the organization and implementation of breeding processes in ensuring the development of the industry are updated, including a low share of domestic varieties in the produced planting material and planting, the lack of a systemically implemented varietal and technological policy, the imperfection of the legal system for the protection of intellectual property, a low availability of instrumentation and analytical equipment for the implementation of breeding by modern methods., (Copyright © AUTHORS.)

The field of nanotechnology and personalised medicine is undergoing drastic changes in the approach and efficiency of experimentation. The COVID-19 pandemic has spiralled into mass stagnation of major laboratories around the globe and led to increased investment into remote systems for nanoparticle experiments. A significant number of laboratories now operate using automated systems; however, the extension to nanoparticle preparation and artificial intelligence-dependent databases holds great translational promise. The strive to combine automation with artificial intelligence (AI) grants the ability to optimise targeted therapeutic nanoparticles for unique cell types and patients. In this perspective, the current and future trends of automated approaches to nanomedicine synthesis are discussed and compared with traditional methods.

Low frequency hydrophone with a frequency range of 1-300 Hz for marine seismic exploration systems has been developed. The operation principle of the hydrophone bases on the molecular electronic transfer that allows high sensitivity and low level self-noise at low frequencies (<10 Hz) to be achieved. The paper presents a stabilization method of the frequency response within the frequency range at a depth up to 30 m. Laboratory and marine tests confirmed the stated characteristics as well as the possibility of using this sensor in bottom marine seismic systems. An experimental sample of the hydrophone successfully passed a comparative marine test at Gelendzhik Bay (Black Sea) with the technical support of Joint-Stock Company (JSC) "Yuzhmorgeologiya". One of the main results is the possibility of obtaining high-quality information in the field of low frequencies, which was demonstrated in the course of field tests., Competing Interests: The authors declare no conflicts of interest.

Purpose: To evaluate the influence of prolonged neuroprotective therapy on disease progression in patients with primary open-angle glaucoma (POAG) with compensated intraocular pressure (IOP)., Material and Methods: The study included 147 patients with stages I-II POAG (249 eyes) who were randomized into the main (69 patients, 119 eyes) and control groups (78 patients, 130 eyes). Patients of the main group underwent retinalamin treatment course every 6 months. Patients were examined before enrolling and then every 3 months during the 24-months follow-up including optical coherence tomography (OCT; RNFL - retinal nerve fiber layer, NRR - neuroretinal rim, GCL - ganglion cell layer) and static perimetry (MD - mean deviation, PSD - pattern standard deviation)., Results: Visual acuity and refraction did not change in either group ( p >0.05). IOP increased in the control group ( p =0.033). There was no difference between the groups by the 24th month ( p =0.87). No MD changes were noted in the main ( p =0.45) and control groups ( p =0.27). PSD changed in the main (4.84±3.21 and 6.01±2.584 dB in the beginning and the end, respectively, p =0.0004) and the control groups (3.46±2.23 and 5.86±2.26 dB, respectively; p <0.0001). The groups differed in MD and PSD initially ( p =0.15; p =0.02) and became equal by the end ( p =0.59; p =0.53). RNFL did not change significantly in the main group ( p =0.078) and decreased from 83.5±22.47 to 76.7±20.7 µm in the control group ( p =0.001); no differences between the groups were noted in the beginning ( p =0.276) or in the end of the study ( p =0.524). NRR increased in the main group from 222±88.94 to 231±99.3 ( p =0.012), and decreased in the control group from 248±87.09 to 234±96.2 ( p =0.0006); no differences were found between groups in the beginning or in the end of the study ( p =0.109; p =0.909). GCL thickness did not change either in the main, or in the control group ( p =0.211; p =0.16), with no difference between the group noted in the beginning or the end of the study ( p =0.44; p =0.51)., Conclusion: Regular treatment with retinalamin arrests the development of glaucomatous optic neuropathy. Longer-term research is required to study its influence on the visual function and the quality of life.

Background: Intermittent hypoxia/normoxia training (IHT) is considered a possible means to alleviate chronic diseases such as diabetes. In the last decade, another method of intermittent hypoxia/hyperoxia training (IHHT) began to enter the clinical practice, when the periods of breathing with atmospheric air are replaced by breathing a hyperoxic mixture. The present study compared the impact of adaptation to IHHT versus IHT on some metabolic variables in prediabetic patients. Methods: A placebo-controlled trial included 55 patients with prediabetes, sea level residents, ages 51-74 years. Control Group (16 patients) took sham 3-week course, and the IHHT Group (17 patients) and IHT Group (22 patients) received similar actual sessions of IHHT or IHT five times a week for 3 weeks, each session consisting four cycles of 5 minutes of hypoxia (12% O 2 ) followed by 3 minutes of hyperoxia (IHHT, 33% O 2 ) or 5 minutes of normoxia (IHT, breathing room air). Fasting glucose, oral glucose tolerance test (OGTT), blood lipids, and the level of blood oxygen saturation (SpO 2 ) were investigated at baseline, as well as 1 day and 1 month after IHHT/IHT termination. Results: The study showed the same positive effect of two types of training: equal reduction of serum glucose concentrations, both fasting and 2 hours of OGTT; decreased total blood cholesterol and low-density lipoproteins; and an equally smaller drop in SpO 2 during acute hypoxic test (breathing with 12% O 2 for 20 minutes). Improved parameters persisted 1 month after training termination in both groups. Conclusion: One of the advantages of IHHT over IHT observed in this study could be some reduction in the duration of the sessions due to shortening reoxygenation periods. Further studies are required to search for additional beneficial effects of IHHT when using other training modes or other pathologies.

Alzheimer's disease (AD) affects not only the central nervous system, but also peripheral blood cells including neutrophils and platelets, which actively participate in pathogenesis of AD through a vicious cycle between platelets aggregation and production of excessive amyloid beta (Aβ). Platelets adhesion on amyloid plaques also increases the risk of cerebral microcirculation disorders. Moreover, activated platelets release soluble adhesion molecules that cause migration, adhesion/activation of neutrophils and formation of neutrophil extracellular traps (NETs), which may damage blood brain barrier and destroy brain parenchyma. The present study examined the effects of intermittent hypoxic-hyperoxic training (IHHT) on elderly patients with mild cognitive impairment (MCI), a precursor of AD. Twenty-one participants (age 51-74 years) were divided into three groups: Healthy Control ( n = 7), MCI+Sham ( n = 6), and MCI+IHHT ( n = 8). IHHT was carried out five times per week for three weeks (total 15 sessions). Each IHHT session consisted of four cycles of 5-min hypoxia (12% F I O 2 ) and 3-min hyperoxia (33% F I O 2 ). Cognitive parameters, Aβ and amyloid precursor protein (APP) expression, microRNA 29, and long non-coding RNA in isolated platelets as well as NETs in peripheral blood were investigated. We found an initial decline in cognitive function indices in both MCI+Sham and MCI+IHHT groups and significant correlations between cognitive test scores and the levels of circulating biomarkers of AD. Whereas sham training led to no change in these parameters, IHHT resulted in the improvement in cognitive test scores, along with significant increase in APP ratio and decrease in Aβ expression and NETs formation one day after the end of three-week IHHT. Such effects on Aβ expression and NETs formation remained more pronounced one month after IHHT. In conclusion, our results from this pilot study suggested a potential utility of IHHT as a new non-pharmacological therapy to improve cognitive function in pre-AD patients and slow down the development of AD.

Automatic segmentation methods based on deep learning have recently demonstrated state-of-the-art performance, outperforming the ordinary methods. Nevertheless, these methods are inapplicable for small datasets, which are very common in medical problems. To this end, we propose a knowledge transfer method between diseases via the Generative Bayesian Prior network. Our approach is compared to a pre-train approach and random initialization and obtains the best results in terms of Dice Similarity Coefficient metric for the small subsets of the Brain Tumor Segmentation 2018 database (BRATS2018).

Purpose: Intermittent hypoxia training/treatment (IHT) is an emerging therapeutic approach to alleviate chronic diseases, such as diabetes. The present study investigated the effects of IHT on blood leucocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and its relationship with the changes in blood insulin level., Methods: Seven adult healthy volunteers and 11 prediabetic patients participated in this study. A 3-week course of IHT consisted of a 40-min session of 4 cycles of 5-min 12% O 2 and 5-min room air breathing per day, 3 sessions per week for 3 weeks (i.e., total 9 sessions of IHT). Plasma insulin levels and leukocyte PDK-1 mRNA expression were determined at various time points either under fasting condition or following oral glucose tolerance test (OGTT). Correlation between the IHT-induced changes in PDK-1 mRNA and insulin or glucose levels in the same serological samples was analyzed., Results: At pre-IHT baseline, PDK-1 mRNA expression was two times higher in prediabetes than control subjects. IHT resulted in significant augmentation in PDK-1 mRNA expression (> twofold) in prediabetes at the end of 3-week IHT and remained elevated 1 month after IHT, which was correlated with a significantly reduced insulin release and lower blood glucose after glucose loading with OGTT., Conclusion: IHT can trigger beneficial effects in normalizing blood insulin levels in prediabetic patients under oral glucose load, which were closely correlated with an enhanced mRNA expression of PDK-1 in leukocytes. Further clinical trials are warranted to validate the utility of IHT as a non-invasive complementary therapy against diabetes-associated pathologies.

Purpose: To evaluate the efficacy and safety of intramuscular Retinalamin for retinoprotection in patients with open-angle glaucoma and normalized intraocular pressure (IOP)., Material and Methods: The study included 180 patients (355 eyes) randomized into the main (n=90) and control groups (n=90). The patients of the main group received intramuscular Retinalamin injections; the course was repeated 6 months later. Patient examination was performed at 1, 3, 6, 7, 9 and 12 months., Results: Vision acuity did not change in the main group after the treatment courses (p=0.3732, p=0.6862), nor in the control group (p=0.7751). IOP didn't have significant changes during the whole course of the study neither in the main group (p=0.7632), nor in the control group (p=0.3921). MD index in the main group has increased from -5.52±2.76 to -4.82±2.73 dB (measurements from 6 visits: p=0.0391, p=0.0201, p=0.0302, p=0.3708, p=0.0151, p=0.0353). Control group showed negative MD trend (from -3.51±1.84 to -4.60±2.61 dB; p=0.0012). PSD index has changed from 4.63±1.60 to 4.05±1.43 dB (p=0.0081) in the main group, and from 3.73±1.19 to 4.29±1.53 dB (p=0.0027) in the control group. Average thickness of retinal nerve fiber layer (RNFL) and the volume of neuroretinal rim were stable in both the main (p=0.8039, p=0.9005) and the control groups (p=0.7448, p=0.9620). Ganglion cell complex (GCC) thickness remained stable in the main group (p=0.0377), but has decreased in the control group (p=0.0250). P50 amplitude and latency were stable in the main group (6.54±2.61-6.53±2.64 µV, p=0.0479; 48.39±3.69-50.86±4.09 ms, p=0.0271), while in the control group P50 amplitude has decreased (p=0,0031) and the latency has increased (p=0,0194). In the main group, N95 amplitude has stabilized (p=0.0141) with worsened latency (p=0.0492). N95 amplitude in the control group has worsened (p=0.0195), while latency has stabilized (p=0.3401)., Conclusion: Systemic use of Retinalamin has significant retinoprotective effect confirmed by the dynamics of morphological and functional parameters in patients with POAG and IOP compensation.

A high-precision angular accelerometer based on molecular-electronic transfer (MET) technology with a high dynamic range and a low level of self-noise has been developed. Its difference from the analogues is in the use of liquid (electrolyte) as the inertial mass and the use of negative feedback based on the magnetohydrodynamic effect. This article reports on the development of the angular molecular-electronic accelerometer with a magnetohydrodynamic cell for the creation of negative feedback, and the optimization of electronics for the creation of a feedback signal. The main characteristics of the angular accelerometer, such as amplitude-frequency characteristics, self-noise and Allan variance were experimentally measured. The obtained output parameters were compared to its analogues and it showed perspectives for further development in this field., Competing Interests: The authors declare no conflict of interest.

The present study aimed at examining beneficial effects of intermittent hypoxia training (IHT) under prediabetic conditions. We investigate the effects of three-week IHT on blood glucose level, tolerance to acute hypoxia, and leukocyte mRNA expression of hypoxia inducible factor 1α (HIF-1α) and its target genes, i.e. insulin receptor, facilitated glucose transporter-solute carrier family-2, and potassium voltage-gated channel subfamily J. Seven healthy and 11 prediabetic men and women (44-70 years of age) were examined before, next day and one month after three-week IHT (3 sessions per week, each session consisting 4 cycles of 5-min 12% O 2 and 5-min room air breathing). We found that IHT afforded beneficial effects on glucose homeostasis in patients with prediabetes reducing fasting glucose and during standard oral glucose tolerance test. The most pronounced positive effects were observed at one month after IHT termination. IHT also significantly increased the tolerance to acute hypoxia (i.e. SaO 2 level at 20th min of breathing with 12% O 2 ) and improved functional parameters of respiratory and cardiovascular systems. IHT stimulated HIF-1α mRNA expression in blood leukocytes in healthy and prediabetic subjects, but in prediabetes patients the maximum increase was lagged. The greatest changes in mRNA expression of HIF-1α target genes occurred a month after IHT and coincided with the largest decrease in blood glucose levels. The higher expression of HIF-1α was positively associated with higher tolerance to hypoxia and better glucose homeostasis. In conclusion, our results suggest that IHT may be useful for preventing the development of type 2 diabetes. Impact statement The present study investigated the beneficial effects of intermittent hypoxia training (IHT) in humans under prediabetic conditions. We found that three-week moderate IHT induced higher HIF-1α mRNA expressions as well as its target genes, which were positively correlated with higher tolerance to acute hypoxia and better glucose homeostasis in both middle-aged healthy and prediabetic subjects. This small clinical trial has provided new data suggesting a potential utility of IHT for management of prediabetes patients.

Patients undergoing allogeneic hematopoietic stem cell transplantation have a high risk of cytomegalovirus reactivation, which in the absence of T-cell immunity can result in the development of an acute inflammatory reaction and damage of internal organs. Transfusion of the virus-specific donor T-lymphocytes represents an alternative to a highly toxic and often ineffective antiviral therapy. Potentially promising cell therapy approach comprises transfusion of cytotoxic T-lymphocytes, specific to the viral antigens, immediately after their isolation from the donor's blood circulation without any in vitro expansion. Specific T-cells could be separated from potentially alloreactive lymphocytes using recombinant major histocompatibility complex (MHC) multimers, carrying synthetic viral peptides. Rapid transfusion of virus-specific T-cells to patients has several crucial advantages in comparison with methods based on the in vitro expansion of the cells. About 30% of hematopoietic stem cell donors and 46% of transplant recipients at the National Research Center for Hematology were carriers of the HLA-A*02 allele. Moreover, 94% of Russian donors have an immune response against the cytomegalovirus (CMV). Using recombinant HLA-A*02 multimers carrying an immunodominant cytomegalovirus peptide (NLV), we have shown that the majority of healthy donors have pronounced T-cell immunity against this antigen, whereas shortly after the transplantation the patients do not have specific T-lymphocytes. The donor cells have the immune phenotype of memory cells and can be activated and proliferate after stimulation with the specific antigen. Donor lymphocytes can be substantially enriched to significant purity by magnetic separation with recombinant MHC multimers and are not activated upon cocultivation with the antigen-presenting cells from HLA-incompatible donors without addition of the specific antigen. This study demonstrated that strong immune response to CMV of healthy donors and prevalence of HLA-A*02 allele in the Russian population make it possible to isolate a significant number of virus-specific cells using HLA-A*02-NLV multimers. After the transfusion, these cells should protect patients from CMV without development of allogeneic immune response.

The Purpose: The aim of the study was to determine changes in the level of reactive oxygen species (ROS) and high-nitrogen compounds (HNC) of white blood cells of patients with various forms of pulmonary tuberculosis, and attempt to identify the pathogenic importance marked disturbances in protection mechanisms and damaged by the disease., Methods: A prospective study of 92 people, who were divided into 4 groups: I - 25 patients with newly diagnosed infiltrative tuberculosis and localization process within the same lobe of the lung, II - 42 patients with newly diagnosed pulmonary tuberculosis with a limited process (tuberculoma), III - 15 patients with fibrosis - cavernosis pulmonary tuberculosis with disease duration of less than 2 years old and group IV - healthy people - 10., Results: It has been found that chronic TB infection suppresses the phagocytes activity of leukocytes in any form of study of its development. However, in more severe forms of tuberculosis with a predominance of exudative tissue reactions (infiltrative) levels of these metabolites in the white blood cells increases and they become damaging significance. With limited forms of pulmonary tuberculosis - tuberculoma - levels of these metabolites (especially ICA) in white blood cells is reduced, which may have a protective value., Conclusion: The obtained results allow to claim that in the diagnosis and assessment of the nature of the tuberculosis process may be used definition of functional and metabolic characteristics of blood leukocytes and plasma (phagocytosis, peroxide, total lipid, BURST TEST, AFC, ICA and their derivatives), as well as the number of amino acids, taurine and arginine in plasma and leukocytes.

High-throughput sequencing analysis of hypermutating immunoglobulin (IG) repertoires remains a challenging task. Here we present a robust protocol for the full-length profiling of human and mouse IG repertoires. This protocol uses unique molecular identifiers (UMIs) introduced in the course of cDNA synthesis to control bottlenecks and to eliminate PCR and sequencing errors. Using asymmetric 400+100-nt paired-end Illumina sequencing and UMI-based assembly with the new version of the MIGEC software, the protocol allows up to 750-nt lengths to be sequenced in an almost error-free manner. This sequencing approach should also be applicable to various tasks beyond immune repertoire studies. In IG profiling, the achieved length of high-quality sequence covers the variable region of even the longest chains, along with the fragment of a constant region carrying information on the antibody isotype. The whole protocol, including preparation of cells and libraries, sequencing and data analysis, takes 5 to 6 d.

Shatylo, Valerii B., Tetiana V. Serebrovska, Anna V. Gavalko, Egor Egorov, and Oleg V. Korkushko. Acute hypoxic test in patients with prediabetes. High Alt Med Biol. 17:101-107, 2016.-Prediabetes is a state of impaired carbohydrate metabolism when not all of the symptoms required to label a person as diabetic are present, but blood glucose is higher than in healthy subjects. Recent evidence suggests that intermittent hypoxia training (IHT) might provide a cost-effective strategy for improving metabolic functioning. One of the most important aspects of the successful IHT application is individualized approach to hypoxic dose and regimen prescription. To establish the relationships between indices of carbohydrate metabolism and individual resistance to hypoxia, the acute hypoxic test (AHT, breathing gas mixture with 12% O2 during 20 minutes) was performed in 33 healthy volunteers (mean age, 63.0, range, 44-76; fasting plasma glucose (FPG) less than 5.6 mmol/L and 2 hours postoral glucose tolerance test (OGTT) glycemia less than 7.8 mmol/L) and 30 patients with impaired glucose metabolism (mean age, 65.5, range, 44-75; FPG from 5.6 to 6.9 mmol/L and 2 hours post-OGTT glycemia from 7.8 to 11 mmol/L). Negative correlation was found between the SaO2 level at 20th minute AHT and FPG (r = -0.83; p < 0.01) and insulin (r = -0.27; p < 0.05), as well as 2 hours post-OGTT glucose and insulin levels (r = -0.75 and -0.40, respectively). Longer recovery time and less effective functioning of respiratory and cardiovascular systems were also registered in patients with prediabetes showing that their cardiovascular resilience is impaired compared to normoglycemic controls. These patterns of relationship must be considered when assigning the individual modes of IHT.

Introduction: Glaucoma patients frequently exhibit ocular surface side effects during treatment with prostaglandin eye drops. The present work investigated whether glaucoma patients suffering from signs and symptoms of ocular surface disease while using preserved latanoprost eye drops benefited from switching to preservative-free tafluprost eye drops., Patients and Methods: The analysis was based on 339 glaucoma patients enrolled in two Phase IIIb trials. The patients were required to have two symptoms, or one sign and one symptom of ocular surface disease at baseline, and at least 6 months preceding treatment with latanoprost eye drops preserved with benzalkonium chloride. All eligible patients were switched from latanoprost to preservative-free tafluprost for a total of 12 weeks. Ocular symptoms and ocular signs were evaluated at baseline and at 2 weeks, 6 weeks, and 12 weeks after commencing treatment with tafluprost. Intraocular pressure (IOP), drop discomfort, and treatment preference were evaluated to investigate the clinical efficacy and patient-related outcomes., Results: After 12 weeks of treatment with preservative-free tafluprost, the incidences of irritation/burning/stinging, foreign body sensation, tearing, itching, and dry eye sensation had diminished to one-third of those reported for preserved latanoprost at baseline. The incidences of blepharitis and corneal/conjunctival fluorescein staining had in turn decreased to one-half of those reported for preserved latanoprost. Severity of conjunctival hyperemia was halved during treatment with preservative-free tafluprost, and there was significant improvement in tear break-up time and tear production. A further reduction in IOP (~1 mmHg) was seen with preservative-free tafluprost compared with preserved latanoprost. Drop discomfort was alleviated during preservative-free tafluprost treatment, and an outstanding majority of patients (72%) preferred preservative-free tafluprost over preserved latanoprost., Conclusion: This meta-analysis confirmed that IOP remained at the same level after replacing benzalkonium chloride-preserved latanoprost eye drops with preservative-free tafluprost eye drops. Preservative-free tafluprost significantly decreased the symptoms and signs of ocular surface disease and outrated latanoprost in drop comfort and treatment preference.

The introduction of different methods of intermittent hypoxic training (IHT) into fitness, sports, military and medical practice has raised a lot of questions about the most beneficial regimens of such treatment and their optimal instrumental implementation. Low doses of hypoxia might not be sufficient stimuli to mobilize adaptive mechanisms, while severe or prolonged hypoxia may provoke dangerous pathological processes. In this review, we pay attention to narrow practical question of the most effective and convenient technology of IHT implementation, notably the inhalation of hypoxic gas mixtures. Data strongly suggest that in humans the training with 15-13% inhaled oxygen (FiO2) at various time characteristics does not provide marked positive changes. Short-term daily sessions consisting 3-4 bouts of 5-7 min exposures to 12-10% FiO2 alternating with equal durations of normoxia for 2-3 weeks have been shown as a most beneficial without maladaptive consequences for fitness and treatment of some diseases. More severe or longer intermittent hypoxia protocols must be accompanied by strict monitoring of blood oxygen saturation (SpO2), electrocardiogram, breathing pattern and arterial blood pressure in order to avoid unexpected undesirable individual reactions. For sports purposes, the reduction of oxygen content to individually tolerable level for some minutes is justified as far as it maximizes benefits. However, such regimen requires preliminary diagnostics of individual hypoxic tolerance and cardio-respiratory reactivity as well as rigorous monitoring of vital functions during IHT and good feedback device. The use of oxygen concentrations below 12% for treatment of diseases, especially in children and the elderly, are required substantial additional research. Recently, a new mode of adaptive training was explored, which combines periods of hypoxia (12-10% FiO2) and hyperoxia (30-35% FiO2). Limited evidences suggest that such regime can reduce the time of recovery periods, that is shorten the duration of sessions. However, there is still no strong comparative evidence for humans that this method is much more efficient than hypoxic-normoxic mode. We appeal to all scientists working in the field of IHT not to hide their negative results but publish all observations in the open press. It will make a significant contribution in developing of common guidelines for IHT implementation to improve public health of our Planet.

The decision-making is a key event in the clinical practice. The program products with clinical decision support models in electronic data-base as well as with fixed decision moments of the real clinical practice and treatment results are very actual instruments for improving phthisiological practice and may be useful in the severe cases caused by the resistant strains of Mycobacterium tuberculosis. The methodology for gathering and structuring of useful information (critical clinical signals for decisions) is described. Additional coding of clinical diagnosis characteristics was implemented for numeric reflection of the personal situations. The created methodology for systematization and coding Clinical Events allowed to improve the clinical decision models for better clinical results.

Modern molecular electronic transfer (MET) angular motion sensors combine high technical characteristics with low cost. Self-noise is one of the key characteristics which determine applications for MET sensors. However, until the present there has not been a model describing the sensor noise in the complete operating frequency range. The present work reports the results of an experimental study of the self-noise level of such sensors in the frequency range of 0.01-200 Hz. Based on the experimental data, a theoretical model is developed. According to the model, self-noise is conditioned by thermal hydrodynamic fluctuations of the operating fluid flow in the frequency range of 0.01-2 Hz. At the frequency range of 2-100 Hz, the noise power spectral density has a specific inversely proportional dependence of the power spectral density on the frequency that could be attributed to convective processes. In the high frequency range of 100-200 Hz, the noise is conditioned by the voltage noise of the electronics module input stage operational amplifiers and is heavily reliant to the sensor electrical impedance. The presented results allow a deeper understanding of the molecular electronic sensor noise nature to suggest the ways to reduce it.

Allozyme analysis of the parameters of the Nei genetic distances and gene flow between the populations of Scots pine Pinus sylvestris L. along two hypothetical alternative ways of their migrations in the Miocene-Pliocene from Southern Siberia to the Balkans, Central Europe, and Asia Minor was used; a lower probability of their settlement on the southern shores of the East Paratethys than on the northern ones was identified. It is suggested that the Middle Araks Strait of Paratethys in the Miocene and extreme aridity of the climate in the Pliocene headed the migration of the populations on the southern way, while on the northern way there were no essential water and mountain barriers for pine dispersal.

To expand the informational capabilities of molecular genetic research, on the biological microchips, new indotricarbocyanine dyes that fluoresce in the near infrared (IR) spectral region have been synthesized. The developed IR dyes were studied using a biochip-based test system for detection of mutations in the BRCA1/BRCA2 and CHECK2 genes associated with breast cancer. The fluorescent label was introduced to the analyzed DNA during PCR using primers labeled with the synthesized IR dyes. An analyzer that allows recording and processing of images of fluorescent microarrays in the IR spectral region was designed and manufactured. It has been shown that the use of the synthesized dyes enables to conduct analysis in the IR region and improve the reliability of medical diagnostic tests due to low fluorescence intensity of sample components as well as of a biochip substrate and the reagents used for analysis.

The article comprises data on the pathogenesis of primary open-angle glaucoma. Accepted theories and risk factors of glaucoma development are considered from a historical perspective as well as in the light of modern understanding of the essence of glaucomatous optic neuropathy. The impact of different independent factors on particular pathogenetic events and their interrelation is shown. Data on possible mechanisms involved in the neurogenerative process that yet lack substantiation are presented.

Concentration of endogenous dipeptide carnosine in human muscle tissue reaches tens of millimoles. For more than 100 years of research, a lot of data concerning carnosine functions were accumulated, among which anti-aging effects are regarded most important. Heire, effect of carnosine in cell cultures was studied. It has been found that apart from the known action--an increase of the Hayflick limit and morphological rejuvenation--carnosine stimulates cell division in colony-forming assays and in the course of transition of cells to the quiescent state. The analysis of the transcriptome showed that carnosine-induced changes are mainly related to positive regulation of the cell cycle at all levels, from the onset of the DNA synthesis to chromosome condensation. One can suppose that the revealed stimulation of the cell cycle account for the carnosine-induced rejuvenation processes and a high concentration ofcarnosine in muscle tissue is required for the muscle recovery (regeneration) after excess loads.

Phylogenetic diversity (PD) has been successfully used as a complement to classical measures of biological diversity such as species richness or functional diversity. By considering the phylogenetic history of species, PD broadly summarizes the trait space within a community. This covers amongst others complex physiological or biochemical traits that are often not considered in estimates of functional diversity, but may be important for the understanding of community assembly and the relationship between diversity and ecosystem functions. In this study we analyzed the relationship between PD of plant communities and land-use intensification in 150 local grassland plots in three regions in Germany. Specifically we asked whether PD decreases with land-use intensification and if so, whether the relationship is robust across different regions. Overall, we found that species richness decreased along land-use gradients the results however differed for common and rare species assemblages. PD only weakly decreased with increasing land-use intensity. The strength of the relationship thereby varied among regions and PD metrics used. From our results we suggest that there is no general relationship between PD and land-use intensification probably due to lack of phylogenetic conservatism in land-use sensitive traits. Nevertheless, we suggest that depending on specific regional idiosyncrasies the consideration of PD as a complement to other measures of diversity can be useful.

We studied the properties of human skin fibroblast in filamentous polyglycolic microtransplant. Fibroblast adhesion to the microtransplant filaments is followed by the formation of a network cross-linked with fibroblasts. The cells rapidly proliferate during the first few days; after transfer of the microtransplant to the standard culture flask, the cells migrate to the plastic and continue proliferation. The cells are uniform and exhibit high colony-formation capacity. The bundles of microtransplant filaments persist in the culture for several days and through the cells completely leave them, the area around these filaments remains the most populated for 40 days. Mitotic cells are seen in the immediate proximity to the degrading filaments of the transplant. The effect of cell "rejuvenation" in the microtransplant can be explained by selection of cells by their adhesion to relatively thin (about 15 μ) filaments, which excludes large old cells.

Preparation stimulating hair growth (PSHG) was studied on mice of various strains (Balb/c, CBA, C57BI/6, and outbred). It was shown that a long-term (44 months) application of PSHG does not reliably affect the appearance of young healthy mice but does induce increase in the hair follicle size. No adverse consequences of the PSHG application were observed. Naturally occurring propagating regenerative hair waves peculiar to mice were preserved. In older mice (more than 2 years) with signs of alopecia, application of PSHG caused an overgrowing of bald patches within two months. Transcriptome analysis of the PSHG effect performed in fibroblast cell culture showed that PSHG stimulates processes of tissue development and remodeling. These observations together with previous findings showing that PSHG stimulates autophagy and induces death of cells subjected to oxidative stress may suggest that the mechanism of the PSHG effect involves stimulation of regeneration of skin and its derivatives owing to more efficient elimination of senescent and damaged follicle cells.

Purpose was to study efficiency and safety of mexidol in combined therapy in patients with primary open-angle glaucoma (POAG). 94 patients (185 eyes) at the age of 18-75 years old with POAG I-III stages were divided into 3 groups: 50 patients received combined therapy of mexidol 100 mg and picamilon 150 mg, 22 patients received combined therapy of mexidol 300 mg and picamilon 150 mg, 22 patients received only picamilon 150 mg. All medicine was administered qd during 14 or 21 days. Examination included standard ophthalmologic methods, perimetry, electroretinography, retinal and optic nerve heard arterial blood flow. Improvement of visual acuity, perimetric, electrofisiological indicies and increased blood flow velocity of central retinal artery were registrated. Combined mexidol therapy allows improving results in treatment of patients with POAG.

This paper discusses an issue on the development of biophysical methods for biochip analysis. A scheme and construction of a biochip analyzer based on wide-field digital fluorescence microscopy are described. The analyzer is designed to register images of biological microchips labeled with fluorescent dyes. The device developed is useful for high-sensitive throughput recording analyses by biochips after interaction of immobilized probes with fluorescently labeled sample molecules as well as it provides the higher rate of the analysis compared to laser scanning devices. With this analyzer a scope where biological microchips can be applied becomes wider, the development of new protocols of the analyses is possible and standard analyses run faster with the use of biochips, the expenses for the analysis performance can be reduced.

The results of comparative study of efficacy and safety of vision correcting system "Focus" and Picamilon in patients with dry form of age macular degeneration are presented. 60 patients were enrolled into the study, follow-up was 3 months. Routine examination revealed positive impact of "Focus" on dynamics of main visual functions (visual acuity and field). In terms of impact on dynamics of main visual functions "Focus" is comparable with Picamilon, though it is better tolerated. Intake of vision correcting system "Focus" promotes visual functions improvement and prevents progressing of retinal degenerations.

The expression of human telomerase catalytic subunit in HL-60 and HT-1080 malignant transformed cells and telomerized fibroblasts was studied by quantitative PCR. It was found that the number of transcripts of human telomerase catalytic subunit per cell in telomerized fibroblasts could be hundreds of times higher than in HL-60 and HT-1080 cells. Telomerized fibroblast cultures are suggested as experimental systems for selection of basal compounds for creation of anticancer drug prototypes, the molecular target of which is human telomerase catalytic subunit. The effects of human telomerase catalytic subunit expression on the fibroblast proteome are analyzed.

Purpose: This study investigated the efficacy and safety of tafluprost as an adjunctive therapy to timolol in patients with open-angle glaucoma or ocular hypertension, uncontrolled by timolol monotherapy., Methods: This was a randomized, double-masked, parallel-group, multinational and multicenter 12-week phase III study. Tafluprost 0.0015% (once daily: 20:10) or vehicle were administered as adjunctive therapy to timolol 0.5% (twice daily: 08:00 and 20:00) for 6 weeks, after which all patients received tafluprost for 6 weeks. Intraocular pressure (IOP) measurements were conducted at 08:00, 10:00, and 16:00 at baseline, and weeks 2, 4, 6, and 12., Results: A total of 185 patients were randomized to tafluprost (n = 96) or vehicle (n = 89). Reductions in IOP were seen in both groups, which were consistently more pronounced with tafluprost. At week 6, the change from baseline in diurnal IOP ranged from -5.49 to -5.82 mmHg, and the overall treatment difference (tafluprost vehicle) was -1.49 mmHg (upper 95% confidence interval, -0.66; p<0.001, intention-to-treat population, repeated measurements of the analysis of covariance model). At week 12, the change from baseline ranged from -6.22 to -6.79 mmHg in the tafluprost group. Patients switched from vehicle to tafluprost achieved a similar decrease in IOP to those who received tafluprost throughout the study (group difference at 12 weeks, -0.09 mmHg, p=0.812). There were more ocular adverse events with tafluprost compared with vehicle (42% vs. 29%, respectively), but most were mild in severity., Conclusions: As adjunctive therapy to timolol, tafluprost achieved a consistently greater reduction in IOP compared with vehicle, and was well tolerated.

A multiplex analytical system has been developed to carry out microformat latex agglutination tests with video digital registration. The system makes it possible to apply less than 1 microl drops of latex and samples in the matrix format to a carrier and to make the test in 30 points at once, as well as to record and to interpret the results of the test, by keeping analytical information for each sample. Comparison of the results of determination of the serum levels of C-reactive protein, rheumatoid factor, and antistreptolysine in the system developed by the authors with the results obtained in the macroagglutination test by the immunoturbidimetric technique leads to the conclusion that the methods are comparable. The proposed type of a latex agglutination test based on a matrix approach and miniaturization assures efficient production and the quality of laboratory studies.

Clones of telomerized fibroblasts of adult human skin have earlier been obtained. It was shown that despite their fast growth in mass cultures, these cells poorly form colonies. Conditioned medium, antioxidants, and reduced partial oxygen pressure enhanced their colony formation, but not to the level characteristic of the initial cells. The conditioned medium of telomerized cells enhanced colony formation to a much greater extent than that of the initial cells. A study of proteome of the telomerized fibroblasts has revealed changes in the activities of tens of genes. A general trend consists in weakening and increased lability of the cytoskeleton and in activation of the mechanisms controlling protein degradation. However, these changes are not very pronounced. During the formation of immortal telomerized cells, selection takes place, which appears to determine changes in the expression of some genes. It was proposed that a decrease in the capacity of telomerized cells for colony formation is due to increased requirements of these cells to cell-cell contacts. The rate of cell growth reached that characteristic of mass cultures only in the largest colonies. In this respect, the telomerized fibroblasts resembled stem cells: they are capable of self-maintenance, but "escape" to differentiation in the absence of the corresponding microenvironment (niche), which is represented by other fibroblasts. Non-dividing cells in the test of colony formation should be regarded as differentiated cells, since they have no features of degradation, preserve their viability, actively move, grow, phagocytized debris, etc. It was also shown that telomerization did not prevent differentiation of myoblasts and human neural stem cells. Thus, the results obtained suggest the existence of normal mechanisms underlying the regulation of proliferation in the telomerized cells, which opens possibilities of their use in cell therapy, especially in the case of autotransplantation to senior people, when the cell proliferative potential is markedly reduced and accessibility of stem cells is significantly restricted.

The present paper describes the use of the scanner "Expert-Lab Agglutination" system to record the results of latex-agglutination tests in making a reaction on the lids of 96-well immunoassay plates. The described system provides a possibility of having a primary image of all tests carried out on a carrier. Software offers the prospect of contrasting the images of individual and control samples, increasing the size of images, and comparing the latter. The use of special image treating techniques may also yield objective figures characterizing the rate of a reaction. The possibility of archiving primary information and retrospectively appraising the correctness of the result of an analysis at any required moment is of fundamental importance to the latex-agglutination test.

Objective: To determine the usefulness of artificial pneumothorax (AP) in the management of pulmonary tuberculosis (PTB) patients when anti-tuberculosis treatment is ineffective., Design: We evaluated the outcome of therapy in 214 patients with cavitary PTB bacteriologically confirmed by culture treated during 1998-2004, 78.9% of whom had multidrug resistance. AP was applied in 109 patients (56 newly diagnosed TB and 53 retreatment cases). A control group consisted of 105 patients (respectively 55 and 50) treated without AP. The average period of AP application was 4.5 months for newly diagnosed patients and 9 months in retreatment cases. Anti-tuberculosis treatment regimens in both groups were based on drug susceptibility test results., Results: Culture negativity was achieved in patients treated with AP in all new cases and in 81.1% of retreatment cases. Cavity closure occurred in 94.6% and 67.9% respectively. In the control group, culture negativity was achieved in respectively 70.9% and 40.0%, and cavity closure occurred in respectively 56.3% and 24.0%., Conclusion: AP considerably improved the treatment outcome in both newly diagnosed and retreatment patients. This procedure can be considered a useful addition in managing certain patients with cavitary TB, particularly those with drug resistance.

It was shown that the duration of stay of macrophages in the peritoneal cavity of mice and method of their isolation did not affect markedly their capacity for resumption of DNA synthesis in heterokaryons. This means that mouse macrophage undergo such changes during differentiation that reactivation of DNA synthesis in their nuclei is only possible after interaction of telomeres with telomerase, since it was already shown that telomerase was involved in reactivation of DNA synthesis in the macrophage nuclei. The results of experiments did not reveal differences in the length of telomeres in mouse macrophages and other somatic cells. This could depend on the significant length of mouse telomeres and, as a result, their shortening, sufficient for the inhibition of proliferation, is beyond the limits of sensitivity of the current methods. It is also possible that changes in DNA properties in the macrophages occurring during their differentiation depend on changes in the conformation of the telomere complex in these cells. Testing of this suggestion is relevant with respect to recent data that cell hybridization, specifically in the form of heterokaryons, may be essential in realization of the therapeutic effect caused by the introduction of cells during cell therapy.

A hundred and nine patients with complicated destructive pulmonary tuberculosis who had received chemotherapy with reserve drugs, artificial pneumothorax (AP), pneumoperitoneum (PN), physiotherapy, and resection surgery were followed up. The application of video thoracoscopy made it possible to eliminate any types of pleural adhesions. Individualization of therapeutic measures considerably increases the efficiency of treatment. AP is the method of choice in therapy of newly detected patients who have undergone ineffective routine treatment regimens.

In the present work, we review the properties of some stem cell types, namely embryonic, hematopoietic and mesenchymal stem cells, which present the most significant interest for use in medicine. Stem cells are undifferentiated cells capable of both self-maintenance and differentiation into mature specialized cells. According to their origin, stem cells can be classified as embryonic and somatic ones. The first ones can be indefinitely maintained in culture, and possess the ability to differentiate into all cells of the adult organism. The second ones possess the limited capacity to differentiate and, probably, a limited proliferative potential. For therapeutic use, important but hotly debated is the plasticity of somatic stem cells, i.e. context-dependent differentiation into "non-related" cell types. It is assumed that the differentiation of the majority of stem cell types proceeds according to the principle of stepwise hierarchical maturation through the stage of intermediate rapidly proliferating progenitor cells. The use of stem cells in medicine is mostly at the preclinical stage now. Despite the fact that embryonic stem cells are highly promising as therapeutic agents, a number of circumstances substantially limits their therapeutic use in the near future. At the same time, approaches involving autotransplantation of hematopoietic or mesenchymal stem cells are beginning to be applied successfully in the clinical trials for treatment of limb ischaemia and myocardial infarction. It is clear that despite a large number of problems and unsolved questions, the use of stem cells in medicine promises a dramatic progress in the treatment of many severe diseases.

Most human somatic cells have no telomerase activity. This leads to terminal underreplication of chromosomes and, hence, proliferative ageing of cells. We studied the consequences of introduction of the gene of the catalytic component of human telomerase hTERT in the normal fibroblasts of adult human skin. The expression of this gene led to the appearance of telomerase activity in the fibroblasts, elongation of telomeres (to the size characteristic of the embryonic cells), and immortalization. The cells retained their normal karyotype. The activity of ribosomal genes remained unchanged: the degree of their methylation, abundance, and transcriptional activity (two clones were studied). The cells did not undergo significant changes after transition over the Hayflick's limit, retained the constant rate of proliferation (one of the clones was followed to the level of 200 duplications of the population), and resembled, in appearance, young diploid human fibroblasts. The initial cells and cells transfected by an empty vector could pass through no more than 68 duplications, their proliferation slowed down and they acquired the morphology characteristic for the ageing cells. The telomerized cells retained the normal capacity of entering the proliferative rest as a result of serum starvation. Telomerization did not eliminate the contact inhibition of proliferation but led to an increased saturating density of cells, which reached the levels characteristic for the early embryonic cells. The long-term suppression of the telomerase function by azidothymidine led to a shortening of telomeres and significantly slowed down cell proliferation. The cells that did not divided for a long time were enlarged, preserved their viability, and resembled, in appearance, the ageing cells. In the test on heterokaryons (index of telomerase activity on the chromosomes inside the cell), the telomerized cells behaved as other immortal cells. All these data suggest that the telomerized cells preserved the normal mechanisms of regulation of cell proliferation.

The article deals with the use of photodynamic therapy with regard for the modern choice of photosensitizing preparations and with regard for new-generation lasers, which reveal, to a full extent, the possibilities of the above treatment method. Examples of using the photodynamic therapy in the treatment of some oncology pathologies of various localizations, including the ocular pathologies, are depicted in the article. The use of photodynamic therapy at retinal diseases, caused by the onset of new-vascular membranes due to the age-related degeneration of the macular, is under discussion. The application of photodynamic therapy in the treatment of cystic filtration cushions, involving the technique offered by the authors, is described.