[Comparative analysis of clinical and functional parameters in patients with stable stage II-III keratoconus after implantation of corneal segments and fitting of scleral rigid contact lenses]. / Sravnitel'nyi analiz kliniko-funktsional'nykh pokazatelei u patsientov so stabil'nym keratokonusom II­III stadii posle implantatsii rogovichnykh segmentov i podbora skleral'nykh zhestkikh kontaktnykh linz.

The modern treatment strategy for keratoconus (KC) involves sequential application of medical technologies aimed at stabilizing pathological changes in the cornea and restoring visual acuity. PURPOSE: This study compares the effect of implantation of intrastromal corneal ring segment (ICRS) and fitting of individual scleral rigid contact lenses (RCLs) on visual functions in patients with stage II-III KC after previously performed corneal collagen cross-linking. MATERIAL AND METHODS: The Helmholtz National Medical Research Center of Eye Diseases examined and treated 34 patients (69 eyes) aged 18 to 33 years with stage II-III KC. The study included patients who had previously undergone standard corneal collagen cross-linking. Depending on the type of optical correction, the patients were divided into two groups: patients in group 1 underwent ICRS implantation using a femtosecond laser; patients in group 2 were fitted with individual scleral RCLs. RESULTS: Improvement in clinical and functional parameters was observed in both groups. A higher clinical and functional result was achieved in group 2. CONCLUSION: For patients with stable stage II-III KC, it is advisable to recommend fitting of individual scleral RCLs for visual rehabilitation.

[Transplantation of the Bowman's layer in combined treatment of recurrent pterygium]. / Transplantatsiya boumenova sloya v kombinirovannom lechenii retsidiviruyushchego pterigiuma.

Pterygium is among the most frequent indications for extraocular ophthalmic surgery. The main method of pterygium treatment - its excision - is often combined with transplantation, non-transplantation, medication and other methods. However, the frequency of pterygium recurrence can exceed 35%, and the cosmetic and refraction outcomes satisfy neither the patient, nor the surgeon. PURPOSE: The study analyses the technical capability and feasibility for transplantation of the Bowman's layer in the treatment of recurrent pterygium. MATERIAL AND METHODS: The transplantation of the Bowmen's layer was performed according to the developed technique on 7 eyes with recurrent pterygium (7 patients aged 34 to 63 years). The combined surgery technique consisted of pterygium resection, laser ablation, autoconjunctival plasty, exposure to a cytostatic drug, non-suture transplantation of the Bowman's layer. Maximum length of the follow-up was 36 months. Analysis involved data from refractometry, visometry (without correction and with spectacle correction), and optical coherence tomography of the retina. RESULTS: There were no complications in any of the studied cases. The cornea and the transplant retained transparency throughout the entire follow-up duration. 36 months after surgery mean spectacle-corrected visual acuity amounted to 0.86±0.2, topographic astigmatism - 1.48±1.4 diopters. Recurrence of pterygium was not observed. All patients were satisfied with the cosmetic outcomes of the treatment. CONCLUSION: Non-suture transplantation of the Bowmen's layer recovers normal anatomy, physiology and transparency of the cornea after repeat surgical intervention for pterygium. No pterygium recurrences were observed throughout the entire follow-up after treatment with the proposed combined technique.

[Experimental study of the effect of corneal hydration and its biomechanical properties on the results of photorefractive keratectomy]. / Vliyanie gidratatsii i biomekhanicheskikh svoistv rogovitsy na rezul'taty fotorefraktsionnoi keratektomii v eksperimente.

Water content in the cornea may affect the outcome of its excimer laser ablation, especially in presbyopic patients with myopic refraction. This hypothesis can be tested by scanning the cornea in the terahertz (THz) range to determine its hydration level. PURPOSE: To study the effect of hydration of the cornea determined by non-contact THz scanning and its biomechanical parameters on the results of photorefractive keratectomy (PRK) in an experiment. MATERIAL AND METHODS: PRK was performed using the Nidek EC-5000 QUEST excimer laser on 8 rabbit eyes. Corneal hydration was evaluated by determining the reflection coefficient (RC) in the THz electromagnetic radiation range before PRK, after 3-5 days, and after 1, 2, 3, and 4 months. Clinical examination included autorefractometry, assessment of corneal thickness and other anatomical and optical parameters of the anterior eye segment (Galilei G6, Ziemer Ophthalmic Systems AG 6.0.2, Switzerland), measurement of corneal hysteresis (CH) and corneal resistance factor (CRF) using the Ocular Response Analyzer (ORA; Reichert, USA), as well as tear production (Schirmer test). RESULTS: The initial water content in the cornea has a significant effect on the thickness of the removed layer, i.e. on the PRK effect, with correlation coefficient of Rs= -0.976 (p<0.01). The correlation between CH and the ablation depth is less pronounced (Rs=0.643), and CRF had no correlation with it (Rs= -0.089). Biomechanical indicators of the cornea depend on its hydration: changes in CH and CRF after excimer laser ablation qualitatively coincide with changes in RC, the correlation coefficient between RC and the initial value of CH is R= -0.619 (moderate negative correlation). CONCLUSION: THz scanning is an effective non-contact technology for monitoring corneal hydration level. The mismatch of the hypoeffect of keratorefractive excimer laser intervention planned for patients with presbyopia with the actual outcome can be caused by individual decrease in the initial water content in the cornea.

[Myocardial infarction in a patient with a single ventricle of the heart].

A clinical case of myocardial infarction in a patient with single ventricle heart defect is described.

Prototype of a DNA Vaccine against Marburg Virus.

The preparation and study of the biological properties of the pVAKS-GPVM DNA immunogen containing a gene encoding Marburgvirus glycoprotein are described. The specificity of blood serum antibodies of guinea pigs immunized with DNA immunogen was analyzed by ELISA. Inactivated viral preparation, recombinant glycoprotein (GP) obtained in the prokaryotic system and virus-like particles based on the recombinant vesicular stomatitis virus exhibiting Marburgvirus GP were used as the antigens. The neutralizing activity of antibodies of immunized animals was tested in vitro using a pseudovirus system. It was demonstrated that the developed immunogen administered to guinea pigs induced the production of specific antibodies that neutralize virus-like particles and Marburgvirus in cultured Vero cells.

[Dynamics of Parameters of Transmitral Blood Flow and Markers of Myocardial Fibrosis in Patients with Myocardial Infarction].

Aim      To study possible correlations between echocardiography (EchoCG) indexes and markers of myocardial fibrosis, procollagen I C-terminal propeptide (PICP) and procollagen III N-terminal propeptide (PIIINP) during one year following ST-segment elevation myocardial infarction (STEMI).Material and methods  120 patients with STEMI were evaluated. EchoCG was used to assess dimensions and volumes of heart chambers, left ventricular (LV) systolic function, mean pulmonary arterial pressure (mPAP), and indexes of LV diastolic function (Em, early diastolic lateral mitral annular velocity; e', peak early diastolic septal mitral annular velocity; E / e', ratio of peak early diastolic transmitral inflow velocity and mitral annular velocity  -, Е / А, ratio of peak early and late transmitral inflow velocities; DT, deceleration time of LV early diastolic filling). EchoCG indexes and serum concentrations of PICP and PIIINP were determined at 1 (point 1) and 12 (point 2) days of disease and one year after STEMI (point 3). The sample was divided into two groups: group 1 (n=86; 71.7 %) included patients with a LV ejection fraction (EF) ≥50 % and group 2 (n=34; 28.3 %) consisted of patients with LV EF ≤49 %.Results At one year, the number of patients with signs of diastolic dysfunction increased by 10% in group 1 whereas myocardial systolic dysfunction worsened in both groups. LV EF decreased in 15 (17.4%) patients of group 1 and in 4 (11.8%) patients of group 2. Concentrations of PIIINP were correlated with Em, E / e', mPAP, PICP, e', and LV EF.Conclusion      Direct correlations between PIIINP concentrations and Em, E / e', and mPAP were found in the group with LV EF ≥50 %. In the group with LV EF <50 %, correlations were observed between PICP concentrations, LV EF, and e'. Also, in this group, the increase in PIIINP was statistically more significant. These results indicate continuing formation of myocardial fibrosis in a year following MI, which may underlie progression of chronic heart failure.

Synthesis and biological evaluation of 6-nitro-1,2,4-triazoloazines containing polyphenol fragments possessing antioxidant and antiviral activity.

Stable σ-adducts of azolo[5,1-c]triazines and azolo[1,5-a]pyrimidines with different polyphenols were synthesized and their antioxidant and antiviral activity were investigated. Their affinity to viral hemagglutinin was assessed using molecular modelling. The phloroglucinol-modified azolo-azines possessed the highest virus-inhibiting activity. According to the results of the study of antioxidant properties of compounds, the most promising ones exhibiting highest antioxidant capacity were adducts containing in their structure pyrogallol and catechol residues and 6-nitro-triazolotriazin-7-ol scaffold. No correlation between antioxidant and virus-inhibiting activity of compounds studied was detected. The most active compounds demonstrated the ability to prevent binding of viral hemagglutinin with cellular receptor as shown in hemagglutination inhibition assay. Our results demonstrate that polyphenol-modified azolo-azines are prospective for further optimization as potential antivirals and that their action is directed against viral hemagglutinin.

An integrated approach to the investigation of antioxidant properties by potentiometry.

An analytical methodology is proposed for a comprehensive study of antioxidant properties of various objects based on the implementation of various mechanisms of antioxidant action. In order to interpret results regarding the action of antioxidants in living organisms it is proposed to adhere to certain requirements for research methods of antioxidant properties, for oxidizing agents of a radical and non-radical nature. The developed integrated approach consists in using the potentiometry method and is based on the antioxidant capacity determination which is founded on the interaction of antioxidants with the К3[Fe(CN)6] by the ET-mechanism and the conjugation mechanism and the antiradical capacity determination based on the interaction of antioxidants with peroxyl radicals by the HAT-mechanism. Individual antioxidants of natural origin, plant materials extracts as well as synthesized 6-nitro-1,2,4-triazoloazin containing polyphenols fragments, which are complex conjugated structures, have been investigated. It has been shown that in the antioxidants study it is advisable to use the integrated approach that will allow to evaluate antioxidant properties from the point of view of various antioxidants action mechanisms.

First Experience of Sutureless Redo on Mitral Valve Using Valve-in-Valve Technique: Two-Stage Implantation on a Large Animal.

Sutureless implantation of the mitral valve bioprosthesis using the valve-in-valve method was performed on a large animal (sheep). According to the results of a two-stage implantation (primary implantation of a xenopericardial 26-mm framed bioprosthesis and reimplantation of the developed 23-mm bioprosthesis), minor changes in quantitative indicators were revealed: an increase in the transprosthetic gradient by 1.3 mm Hg and a decrease in the area of the mitral orifice by 21.6%. Considerable reduction in the intervention time by 18 min was achieved (by 40% in comparison with the primary prosthesis). The absence of adverse events in the animal and complications in the post-operative period, as well as physiological hemodynamic indicators indicate the safety of the developed medical device.

Synthesis and Metabolism of Nitric Oxide (NO) in Chicken Embryos and in the Blood of Adult Chicken.

In chicken embryos, nitric oxide (NO) is accumulated in the pool of NO donors: S-nitrosothiols, nitrosyl-iron complexes, high-molecular-weight nitro-compounds. Oxidation of NO to nitrate occurs with different intensity in the embryos of different chicken breeds. In some embryos, NO donors accumulate almost without oxidation. Stable concentration of NO donors and nitrate in the blood of adult chicken is a result of dynamic equilibrium between NO synthesis and elimination (oxidation, consumption by other tissues, and excretion). As NO oxidation occurs mainly not in the blood, but in other tissues, decomposition of NO donors and NO oxidation are determined the properties of these tissues, in particular, the presence of physiological targets of NO, rather than spontaneous processes. Hence, evaluation of the intensity of NO metabolism is important for prediction of the efficiency of preparations containing NO donors and stimulators of its synthesis.

New antiradical capacity assay with the use potentiometric method.

For the first time, the dependence of a redox potential change during a reaction of peroxyl radical generation and their interaction with antioxidants was studied. A regular change of a potential is due to oxidation of an antioxidant by initiating peroxyl radicals accompanied by an electron transfer. An original direct method for determining induction periods, inhibition coefficients and an antiradical capacity using the potentiometric method is proposed. Using the proposed approach the induction periods and the inhibition coefficients of various OH, NH, SH containing antioxidants were determined. The antiradical capacity of a herbal extract was studied. A high degree of correlation with a DPPH assay was obtained. RSD results obtained using the proposed approach do not exceed 7%.

[Possibilities for the diagnosis of inflammatory reaction in ischemic stroke]. / Vozmozhnost' diagnostiki vospalitel'noi reaktsii pri ishemicheskom insul'te.

AIM: To study diagnostic possibilities for determining the content of nitrite and N-nitroso compounds (NO2-+RNNO) in blood plasma and cerebrospinal fluid (CSF) in patients with acute ischemic stroke (IS). MATERIAL AND METHODS: Twenty-four patients with IS were examined. The content of NO oxidation products was determined in venous blood and CSF by using an enzyme sensor based on the unique property of nitrite (NO2-), N-nitroso compounds (RNNO), S-nitrosothiols and dinitrosyl iron complexes to inhibit the enzyme catalase in the presence of halide ions. The study was conducted on the 1st day of IS. RESULTS AND CONCLUSION: CSF in patients with IS contained nitrite and N-nitroso compounds (NO2-+RNNO) in concentrations ranging from 0.4 to 2.0 µm. The relationship between the size of IS and the concentration of NO2-+RNNO in CSF was shown. It was 1.01±0.13 µm in patients with medium IS and 0.71±0.07 µm in patients with small IS (U-criterion 16.5; p<0.05). There was no correlation between the severity of neurological deficit at the time of hospitalization and discharge from the hospital and the content of NO2-+RNNO in CSF (r=0.134; p>0.5; r=0.155; p>0.5, respectively). Plasma NO2-+RNNO levels were not associated with the presence and size of IS though they were elevated in patients with inflammatory complications. In conclusion, NO2-+RNNO can be considered as a marker of inflammation in patients with IS. Their presence in CSF reflects the extent of brain damage, but not the presence of concomitant inflammatory diseases.

[REVIEW OF EPIDEMIOLOGIC SITUATION ON HEMORRHAGIC FEVER WITH RENAL SYNDROME (HERS) IN RUSSIAN FEDERATION IN 1990 - 2015].

AIM: Analyze HFRS morbidity in Russian Federation during the last 25 years (1990 - 2015). MATERIALS AND METHODS: Official statistics of Federal Service for Surveillance on Consumers' Rights Protection and Human Weillbeing (CPS), including Federal Centre of Hygiene and Epidemiology, were used for the analysis, as well as materials from regional departments of CPS and centers of hygiene and epidemiology. Epidemiologic analysis was the main method. Statistical treatment of the results obtained was carried out using gener- ally accepted methods of variation statistics with elements of system analysis. Results; For the studied period (1990 - 2015) 194 116 cases of HFRS were registered. Morbidity was registered in 8 federal districts of the Russian Federation in 58 subjects. The most intense epidemiologic situation was noted in Privolzhsky Federal District, that accounted for 86.4% of total HFRS morbidity during the -studied period. Analysis of morbidity was carried out in every federal district, most epidemically unfavorable territories are shown. CONCLUSION: The data presented on HFRS morbidity reflect -unfavorable situation for this disease in Russian Federation. Measures to prevent the emergence of diseases to reduce the general level of morbidity in Russian Federation are presented.

The Habituation/Cross-Habituation Test Revisited: Guidance from Sniffing and Video Tracking.

The habituation/cross-habituation test (HaXha) is a spontaneous odor discrimination task that has been used for many decades to evaluate olfactory function in animals. Animals are presented repeatedly with the same odorant after which a new odorant is introduced. The time the animal explores the odor object is measured. An animal is considered to cross-habituate during the novel stimulus trial when the exploration time is higher than the prior trial and indicates the degree of olfactory patency. On the other hand, habituation across the repeated trials involves decreased exploration time and is related to memory patency, especially at long intervals. Classically exploration is timed using a stopwatch when the animal is within 2 cm of the object and aimed toward it. These criteria are intuitive, but it is unclear how they relate to olfactory exploration, that is, sniffing. We used video tracking combined with plethysmography to improve accuracy, avoid observer bias, and propose more robust criteria for exploratory scoring when sniff measures are not available. We also demonstrate that sniff rate combined with proximity is the most direct measure of odorant exploration and provide a robust and sensitive criterion.

[Clinical Case of Severe Heart Failure Treatment, Produced due to the Development of Arrhythmogenic Cardiomyopathy in a Patient With Permanent Junctional Reciprocating Tachycardia (Coumels Tachycardia) With Additional Left Lateral Accessory Pathway].

Thirty two years old man had history of atrioventricular re-entry tachycardia (AVRT) with concealed left-lateral accessory pathway (AP), 3-5episodes per year, 30-40 minutes duration without hemodynamic compromise. Two years ago patient underwent ablation of concealed left lateral AP. After that tachycardia became malignant (high-frequent 150 beats-min, incessant (lasting up to 18 h/day), resistant to AAD, and led to development of tachycardia-induced cardiomyopathy (EF was 16%, and 2 episodes of pulmonary oedema). During redo EPS we verified AVRT with conduction via decremental retrograde left lateral AP which corresponded to the criteria of permanent junctional reciprocating tachycardia (PJRT). Ablation effectively ceased the arrhythmia. After 18 months of follow up there are no symptoms of heart failure and recurrence of arrhythmia. CONCLUSIONS: We present a case of effective treatment of severe heart failure in a patient with arhythtmogenic cardiomyopathy due to malignant course of incessant tachycardia AVRT with retrograde decremental conduction via left lateral AP. Ablation of AP eliminated of arrhythmia. After 18 months of follow up patient had signs of left ventricle reverse remodeling and had not heart failure symptoms.

[Receptor tyrosine kinase KIT may regulate expression of genes involved in spontaneous regression of neuroblastoma].

Hallmark of neuroblastoma is an ability of this malignant tumor to undergo spontaneous regression or differentiation into benign tumor during any stage of the disease, but it is little known about mechanisms of these phenomena. We studied effect of receptor tyrosine kinase receptor KIT on expression of genes, which may be involved in tumor spontaneous regression. Downregulation of KIT expression by RNA interference in SH-SY5Y cells causes suppression of neurotrophin receptor NGFR expression that may promote the loss of sensibility of cells to nerve growth factors, also it causes upregulation of TrkA receptor expression which can stimulate cell differentiation or apoptosis in NGF dependent manner. Furthermore there is an upregulation of genes which stimulate malignant cell detection by immune system, such as genes of major histocompatibility complex HLA class I HLA-B and HLA-C, and interferon-γ receptors IFNGR1 and IFNGR2 genes. Thus KIT can mediate neuroblastoma cell sensibility to neurotrophins and immune system components--two factors directly contributing to spontaneous regression of neuroblastoma.

Effect of Green Light on Nitric Oxide Metabolism in Chick Embryos. A Possible Physiological Role.

The exposure to green light, which serves as a well-known activating factor for myogenesis during incubation of chicken eggs, contributes to intensification of embryonic metabolism of NO. A metabolic product, nitrate, is mainly accumulated in the muscles. These data suggest that light induces a NO-dependent activation of the factor, which intensifies muscle tissue development.

[OPTIMIZATION OF EARLY DIAGNOSIS OF ACUTE KIDNEY INJURY IN NEWBORNS IN CRITICAL CONDITION].

UNLABELLED: Current diagnosis of acute kidney injury (AKI) is one of the most pressing problems in the newborn in critical condition. OBJECTIVE: To determine the diagnostic value of indicators of renal blood flow as a marker of acute kidney injury in critically ill newborns. MATERIALS AND METHODS: The study included 40 infants in critical condition. A clinical assessment of severity of the condition during admission was carried out with Neonatal Multiple Organ Dysfunction Score (NEOMOD) and Neonatal Therapeutic Intervention Scoring System (NTISS). All patients underwent evaluation of clinical and instrumental parameters, including ultrasound of the renal vessels, renal vascular resistance index and speed performance. CONCLUSIONS: 1) biochemical markers used in routine clinical practice were not sufficiently informative for the diagnosis of AKI. 2) For a more accurate assessment of the risk of AKI using serum creatinine, GFR calculation and evaluation on a scale RIFLE it is should be focused on performance standards, appropriate for gestational age and birth weight. 3) Evaluation of blood flow at a particular index in the resistance of the main renal arteries had the greatest predictive value and had a relatively high sensitivity and specificity for the diagnosis of AKI.

Potentiometric study of antioxidant activity: development and prospects.

The increasing interest in the study of the antioxidant activity of different objects is caused by an unbalance between the formation of reactive oxygen species (ROS) and the performance of the antioxidant system in humans under certain conditions, which leads to oxidative stress and pathological states of the organism. This article presents a brief critical review of the methods that are used to measure integrated antioxidant activity (AOA). It is shown that the most promising methods for measuring AOA are electrochemical ones, particularly potentiometry, as it best fits the nature of the processes causing oxidative stress. The article gives the theoretical rational for requirements that an oxidizer of antioxidants (AO) should meet. The work presents the thermodynamic grounds for the use of an earlier proposed mediator system, kinetics of chemical reactions between AO and the mediator system. In order to confirm reliability and accuracy of the results, numerous correlation studies were conducted, aiming to compare the data obtained with the use the proposed method and independent analytical methods. The article presents the results of the potentiometric study of AOA for a variety of objects, including individual antioxidant → nutritional supplements → food → blood and blood fractions.

Cellular oxidative stress response mediates radiosensitivity in Fus1-deficient mice.

Mechanism of radiosensitivity of normal tissues, a key factor in determining the toxic side effects of cancer radiotherapy, is not fully understood. We recently demonstrated that deficiency of mitochondrial tumor suppressor, Fus1, increases radiosensitivity at the organismal, tissue and cellular levels. Since Fus1-deficient mice and cells exhibit high levels of oxidative stress, we hypothesized that dysregulation of cellular antioxidant defenses may contribute to the increased radiosensitivity. To address this potential mechanism, we treated the Fus1 KO mice with an inhibitor of pathogenic oxidative reactions, pyridoxamine (PM). Treatment with PM ameliorated IR-induced damage to GI epithelium of Fus1 KO mice and significantly increased the survival of irradiated mice. In cultured Fus1 KO epithelial cells, IR-induced oxidative stress was enhanced because of inadequate cellular antioxidant defenses, such as low levels and/or activities of cytochrome C, Sod 2 and STAT3. This resulted in dysregulation of IR-induced DNA-damage response and DNA synthesis. Treatment of Fus1 KO cells with PM or Sod 2 mimetic Tempol normalized the oxidative stress response, thus compensating to a significant degree for inadequate antioxidant response. Our findings using Fus1 KO radiosensitive mice suggest that radiosensitivity is mediated via dysregulation of antioxidant response and defective redox homeostasis.