New Data on Distribution of Nereilinum murmanicum (Annelida, Siboglinidae) in the Barents Sea.

The article presents a report on the findings of representatives of frenulate pogonophorans Nereilinum murmanicum in the northern and central parts of the Barents Sea, which significantly expands the range of this species and provides guidance on its distribution in this basin. Here we present the coordinates of new finds with an indication of the depth. Find points were associated with data on known and potential hydrocarbon deposits.

Matrix approach to the simultaneous detection of multiple potato pathogens by real-time PCR.

AIM: Create a method for highly sensitive, selective, rapid and easy-to-use detection and identification of economically significant potato pathogens, including viruses, bacteria and oomycetes, be it single pathogen, or a range of various pathogens occurring simultaneously. METHODS AND RESULTS: Test-systems for real-time PCR, operating in the unified amplification regime, have been developed for Phytophthora infestans, Pectobacterium atrosepticum, Dickeya dianthicola, Dickeya solani, Ralstonia solanacearum, Pectobacterium carotovorum, Clavibacter michiganensis subsp. sepedonicus, potato viruses Y (ordinary and necrotic forms as well as indiscriminative test system, detecting all forms), A, X, S, M, potato leaf roll virus, potato mop top virus and potato spindle tuber viroid. The test-systems (including polymerase and revertase) were immobilized and lyophilized in miniature microreactors (1·2 µl) on silicon DNA/RNA microarrays (micromatrices) to be used with a mobile AriaDNA® amplifier. CONCLUSIONS: Preloaded 30-reaction micromatrices having shelf life of 3 and 6 months (for RNA- and DNA-based pathogens, respectively) at room temperature with no special conditions were successfully tested on both reference and field samples in comparison with traditional ELISA and microbiological methods, showing perfect performance and sensitivity (1 pg). SIGNIFICANCE AND IMPACT OF THE STUDY: The accurate, rapid and user-friendly diagnostic system in a micromatrix format may significantly contribute to pathogen screening and phytopathological studies.

An alternative approach to kinetic analysis of temperature-programmed reaction data.

To date, kinetic computations have been carried out efficiently for a great variety of physico-chemical processes including crystallization, melting and solid-solid transitions. However, appropriate methods for the kinetic analysis of chemical reactions, especially multi-staged reactions, are currently lacking. Here we report on an alternative way of treating temperature-programmed reaction data using the reduction of iron(iii) oxide as an example. The main principle in the suggested approach is to take into account every stage of the studied process, resulting in a system of kinetic differential equations. Kinetic parameters (activation energy and preexponential factors) are optimized for each of the stages, and cubic splines are used to approximate the conversion functions that reflect changes in reaction-specific surface area throughout the process. The applicability of the suggested method has been tested on temperature-programmed reduction (TPR) data for iron(iii) oxide samples produced from the original Fe2O3 powder by annealing it at 600, 700 and 800 °C. Results of kinetic analysis obtained at different temperature regimes demonstrate the good stability and performance of the method. Peculiarities of iron(iii) oxide reduction have been revealed, depending on the stage and heating rate. The influence of material morphology on the reduction kinetics has been assessed by comparing preexponential factors corresponding to the first reduction stage. This approach allows a comparison of the structural characteristics of the materials based on the kinetic analysis of the TPR data. Using optimized conversion functions, the initial particle size distribution has been reproduced. Theoretically found particle size distribution was found to correlate well with the experimental distribution obtained via laser diffraction.

[Prognostic factors in patients with non-ST-segment elevation acute coronary syndrome concurrent with type 2 diabetes mellitus (according to the results of the registry)]. / Faktory prognoza u patsientov s ostrym koronarnym sindromom bez pod''ema segmenta ST v sochetanii s sakharnym diabetom 2-go tipa (po rezul'tatam registra).

AIM: To investigate factors that influence annual prognosis in patients with non-ST-segment elevation acute coronary syndrome ((NSTEACS) concurrent with type 2 diabetes mellitus (DM2). SUBJECTS AND METHODS: The registry of patients with NSTEACS (non-ST-segment elevation myocardial infarction (NSTEMI), unstable angina) included 415 patients, of them 335 had no carbohydrate metabolic disorders, 80 had DM2. The follow-up period, during which the prognosis was evaluated in the patients, was one year after hospital discharge following the index NSTEACS event. Lipidogram readings and the serum levels of endothelin-1 (ET-1), sP-selectin, sE-selectin, and sPECAM were determined on day 10 after admission to hospital. All the patients underwent coronary angiography (CA), Doppler ultrasound of peripheral arteries during their hospital stay. RESULTS: The patients with DM2 versus those without diabetes proved to be significantly older and to have a higher body mass index; among them there were more women, they were noted to have more frequently hypertension and less frequently smoked. The presence of DM2 was associated with significantly increased intima-media thickness and higher GRACE scores (p=0.013) as compared to those in the patients with normal carbohydrate metabolism. There were significant differences in high-density lipoprotein levels that were lower, as well as in triglyceride levels and atherogenic index, which were higher in patients with DM2 than in those without this condition. In addition, there were significant differences in ET-1, sP-selectin, sE-selectin, and sPECAM levels that were significantly higher in the DM2 group. Moreover, the levels of ET-1 and sPECAM were above normal in both the DM and non-DM2 groups. Assessment of poor outcomes at one year of the observation established that cardiovascular mortality rates were significantly higher and coronary angiography was performed much less frequently in the DM2 group. The most significant prognostic factors associated with a poor prognosis were as follows: multifocal atherosclerosis, reduced left ventricular ejection fraction (LVEF) less than 51%, and increased ET-1 levels more than 0.87 fmol/ml. CONCLUSION: The register-based study has shown that the presence of DM2 statistically significantly increases cardiovascular mortality rates during a year after the index ACS event; the patients of this category are less commonly referred for CA for the estimation of the degree of coronary bed lesion. The most important factors of recurrent cardiovascular events in patients with DM2 within a year after prior ACS are multifocal atherosclerosis, reduced myocardial contractility (LVEF less than 51%), and increased vasospastic endothelial function (an increase in ET-1 levels more than 0.87 fmol/ml).

[PECULIARITIES OF DIAGNOSTICS AND TREATMENT OF PATIENTS WITH RECURRENT MYOCARDIAL INFARCTION].

The aim of the study was to evaluate the efficiency of invasive strategies for the treatment of 306 patients with recurrent myocardial infarction (IM) admitted to our clinic in 2003-2007. We compared the results of three approaches: various forms of transdermal coronary interventions (TDI) including delayed (24-72 hr) ones (n = 30), surgical myocardial revascularization within 8-12 weeks after the onset of recurrent myocardial infarction (n = 25), and conservative therapy (n = 251). Overall cardiovascular lethality was estimated during 5 years in 101 patients. It was shown that recurrent myocardial infarction is a predictor of high risk of death associated, in the absence of reperfusion therapy, with high intra-hospital and long-term lethality. TD1 soon after recurrent IM does not exclude possibility of its application in a later period. Various interventions including delayed ones markedly decrease the frequency of complications and lethal outcome that remains high in their absence. At the same time, severe lesions of the coronary bed in many patients with recurrent MI limit the possibility of using TDI and should be regarded as indications for planned surgical myocardial revascularization. Coronary bypass surgery after myocardial scarring prevents progress of left ventricle dysfunction, improves its contractility and increases life expectancy. Enhanced availability of reperfusion strategies in the form of TDI and/or delayed surgical myocardial revascularization opens up new possibilities for effective treatment of recurrent Ml.

[DELAYED CORONARY SURGERY FOR THE TREATMENT OF ACUTE MYOCARDIAL INFARCTION WITH ELEVATED ST SEGMENT].

AIM: To develop algorithms of reperfusion therapy (RT) based on the assessment of the initial risk of death determining the priority use of delayed transdermal coronary surgery (TCS) unavailable in the early period. We compared effectiveness of different strategies for the treatment of 1245 patients with acute myocardial infarction (MI) and elevated ST segment in 2003-2007 including various TCS modalities at recommended time (n = 88), delayed TCS within 24-72 hr after the onset of MI (n = 194), thrombolytic therapy without subsequent TCS (n = 275), and conservative therapy (N = 688). The general and cardiovascular lethality was evaluated among 474 patients 5 years after discharge. The results suggest that unavailability of TCS in recommended time in case of enhanced risk of death does not exclude the possibility of its delayed application. TCS 24-72 hr after the onset of MI prevents complications and the fatal outcome the frequency of which remains high remains high not only in the early but also in the late post-infarction period. Delayed TCS can be effectively used to treat patients in case of their late admission or referral from other hospitals where X-ray endovascular methods for the treatment of acute MI are not used.

[Rare case giant cancerous tumor forgotten after kidney heterotopic transplantation].

The annual number of cases of kidney transplantation in the Russian Federation varies from 900 to 1000. The generally accepted method of operation is the heterotopic allotransplantation into one of the iliac region. Proper kidney recipient are psychologically "forgotten", often completely lost sight of postoperative monitoring, especially in the long term, but may remind of itself in extraordinary cases like ours.

Furthering benefit/risk ratio and cost effectiveness of anticancer drugs.

BACKGROUND: In Russia, the incidence of melanoma is increasing steadily. The approved standard of specialized medical care for melanoma of the skin defined the range of drugs, recommended for the provision of quality health care. However, it appears that the most effective innovative and safe medicines are at the same time the most expensive drugs. The most important is the assessment of drug use, taking into account their relative efficacy, safety (risk/benefit) and cost (economic efficiency), which may help to create the conditions for controlling their use. Based on this analysis, it is necessary to introduce drugs on the lists of drugs within the framework of the provision of state guarantees of free medical care to citizens (patients). OBJECTIVE: To analyze the drug use according to the standard of specialized medical care for melanoma of the skin, to perform information retrieval in specialized libraries and databases Cochrane, Pubmed, Medline, as well as in the database of the state register of medicines (GRLS) of Russian Ministry of Health. METHODS: The nomenclature of drugs was determined according to the standards of specialized medical care for 2006 and 2012, to the data of GRLS; information searches were performed in specialized libraries and databases Cochrane, Pubmed, Medline. RESULTS: Analysis of anticancer drugs for melanoma of the skin consisted of determining of nomenclature of drugs, included in the standard of specialized medicine care. The standard of specialized medicine care for patients with malignant melanoma of the skin (with specialized assistance) (Order dated December 6, 2006 № 828) includes the following anticancer drugs: dacarbazine (alkylating agents), vinblastine (antineoplastic agent - an alkaloid), cisplatin (platinum), lomustine (nitrosoureas), bleomycin (antitumor agent, an antibiotic) [1]. The standard of specialized medical care in melanoma skin generalization or recurrent disease (chemotherapy) (Order of November 7, 2012 № 604n) includes the following anticancer drugs: lomustine and fotemustine (nitrosoureas), dacarbazine and temozolomide (alkylating agents), cisplatin (platinum) [2]. So, the standard of specialized medical care for for melanoma of the skin by 2012 compared with the standard of care by 2006 includes temozolomide and fotomustin and excludes vinblastine and bleomycin. Based on the database GRLS of Russian Ministry of Health Care [3], as well as information retrieval in databases of Cochrane, Pubmed, Medline the efficacy and safety of melanoma of the skin have proven innovative products, in particular, such as vemurafenib (Zelboraf) dobrafenib (Tafinlar) and trametinib (Mekinist) that are already registered in Russia. At the stage of the clinical study are targeted drugs, such as GSK1120212, AMG 678, pembrolizumab, ipilimumab, tremilimumab, nivolumab and etc. The inclusion or exclusion of data from the restrictive drug lists, such as lists of "Vital and essential medicines", "Drugs for certain categories of citizens", the "Minimum range", according to the Russian Government Decree №871 of 28.08.2014 [4] is carried out after the risk/benefit ratio and cost effectiveness assessment to increase their availability. The availability of high-quality, effective and safe drugs for medical use within the reduced budget, taking into account the formation of a rational and balanced system of health care is the main task of the strategy of the drug provision of the population of Russia for the period till 2025 [5]. CONCLUSIONS: The most rational use of limited resources and cost containment within the framework of state regulation refers to modern trends in the health care of the Russian Federation. There is a need to develop targets aimed at all subjects of the pharmaceutical market, to increase the availability of innovative drugs for melanoma of the skin treatment. This strategy should be based on evidence and assessments of the efficacy, safety and economic viability of anticancer drugs.

[CONTENT OF OXIDATIVE STRESS MARKERS IN BLOOD PLASMA UNDER THE ACTION OF EXTRACTS OF GRATIOLA OFFICINALIS L., HELICHRYSUM ARENARIUM (L.) MOENCH, AND ANTHOCYANIN FORMS OF ZEA MAYS L].

The effect of aqueous solutions of dry ethanol extracts of Gratiola officinalis L., Helichrysum arenarium (L.) Moench, and anthocyanin forms of Zea mays L. on the dioxidin-induced lipid peroxidation in blood has been studied on rats. It is established that all these extracts are capable of reducing the amount of avera- ge-mass (AM) molecules and malonic dialdehyde (MDA) in rat blood plasma. The extract of Gratiola officinalis L. reduces the concentration of AM and MDA moleules by 43%. The extract of Helichrysum arenarium (L.) Moench reduces the concentration of AM molecules on the average by 18.66% (within 9.22 -34.81%) and MDA by 49.36% (within 34.12-79.75%). The Extract of anthocyanin forms of Zea mays L. does not reduce the concentration of AM mo- lecules, but reduces the amount of MDA in the blood of rats on average by 27.88% (within 21.58-37.82%) (p < 0.01).

[Efficacy of reperfusion therapy in syndrome of predominant right ventricular dysfunction associated with inferior myocardial infarction].

Aim of the study was choice of optimal tactics of treatment of patients with syndrome of predominant right ventricular (RV) dysfunction, associated with inferior myocardial infarction. We compared immediate and remote results of 3 strategies of treatment of 100 patients admitted to N.V. Sklifosovsky Research Institute for Critical Care in 2003-2007: various methods of percutaneous coronary intervention (PCI), including delayed PCI in the acute period (n=48), thrombolytic therapy without subsequent PCI (n=20), conservative therapy without reperfusion therapy (n=32). Indications to delayed interventions were based on high risk of death due to RV infarction. It follows from the data obtained that optimal tactics of treatment of RV infarction is provision of availability of reperfusion therapy in the form of various types of PCI. Preferable are primary PCIs in the absence of which delayed PCIs acquire practical value. Thrombolytic therapy can be used as a component of combined reperfusion. Absence of signs of its efficacy on electrocardiogram during first 90 minutes serves as absolute indication for rescue PCI. Inaccessibility of the latter is a reason for provision of delayed interventions. Electrocardiographic signs of achieved pharmacological reperfusion do not exclude high probability of early recurrences of ischemia, expediency of application of PCI during the time preceding these recurrences. In the absence of PCI hospital and remote mortality have been very high. Optimization of accessibility of mechanical reperfusion including delayed allows to achieve efficacy of treatment of RV infarction, prevent development of complications and lethal outcomes.

Separation and study of the range of plasminogen isoforms in patients with prostate cancer.

Using affinity chromatography, two-dimensional electrophoresis, and MALDI-TOF mass spectrometry, plasminogen isoforms were separated and identified in blood plasma. Healthy donors and patients with prostate cancer in various stages of development were included in the studied sample. With the development of prostate cancer, four additional specific plasminogen isoforms are registered in blood plasma; they are characterized by lower molecular weights and higher pI values compared to isoforms found in the control group.

[Efficacy of early invasive strategy of diagnostics and treatment of unstable angina at the background of preexisting ischemic heart disease].

Study aim was assessment of efficacy of early invasive tactics of treatment of patients with various forms of unstable angina at the background of preexisting ischemic heart disease. We compared noninvasive and invasive estimation of risk in 354 patients admitted to the N.V.Sklifosofsky Institute of Urgent Aid in 2002 to 2008. Percutaneous coronary interventions on infarct related artery (IRA) during 1 procedure were carried out in 144 patients (41%), indications to coronary artery (CA) bypass surgery were found in 167 patients (47%), 43 patients (12%) were treated conservatively. Coronary angiography performed in the first 48 hours gives an opportunity to determine indications to myocardial revascularization, to avoid discrepancy between choice of treatment tactics and noninvasive assessment of risk. The latter can be used with the aim of optimization of timing of early invasive strategy. In high risk it is expedient to employ it immediately, in medium - without delay allowed in recommended time intervals. Rentgenoendovascular restoration of IRA conducted during one procedure is an optimal type of myocardial revascularization in many patients including those with multiple CA involvement. Method of choice in patients with stenoses of left CA trunk or its equivalents is surgical revascularization of the myocardium. Detection of indications for myocardial revascularization in patients with unstable angina including those at medium and low risk confirms necessity of application of early invasive strategy as conventional strategy ensuring timeliness of pathogenetic treatment. Absence of indications to myocardial revascularization in a limited group of patients gives an opportunity to clarify diagnosis, prescribe drug therapy and prevent unjustified hospitalizations.

[The oxidation stress, lipid metabolism and their relationship in patients with severe course of hypertension disease in aggregate with carotid stenosis].

The experimental samplings consisted of 25 patients with severe course of hypertension disease in aggregate with atherogenic carotid stenosis before and after carotid endarterectomy and 21 donors. The study was organized to analyze in lipid profile blood serum the content of malonic dialdehyde, ceruloplasmin, alpha-tocopherol, nitric oxide and angiotensin converting enzyme. The study established that in patients took place a reliably increased level of malonic dialdehyde, ceruloplasmin, alpha-tocopherol, nitric oxide and angiotensin converting enzyme. The patients with this pathology have a reliable positive correlation between the concentration of malonic dialdehydeand lipoproteids of very low density (r = 0.51), malonic dialdehyde and triglycerides (r = 0.36), malonic dialdehyde and cholesterol (r = 0.3). This data confirms the important role of peroxidation of lipids in the development of atherosclerosis. Therefore, the enhancement of oxidation stress and expressed dislipoproteidemia are established in patients with hypertension disease with carotids atherosclerosis as a background. This result testifies the pathogenic significance of these phenomena in the mechanisms of homeostasis disorders.

[Early and postponed percutaneous coronary interventions in acute period of myocardial infarction].

Aim of the study was elaboration of indications to the application of postponed percutaneous coronary interventions (PCI) in acute period of myocardial Infarction (Ml) in patients without prior thrombolytic therapy. We fulfilled comparative assessment of efficacy of 3 strategies of treatment of 810 patients admitted to the N.V. Sklifosovsky Institute of Urgent Aid from 2003 to 2007: primary PCI carried out within first 12 hours (n=32), postponed PCI in acute period because of initially elevated risk (n=90), conservative treatment without reperfusion therapy (n=688). Elevated risk of death according to TIMI score was used as the basis for establishment of indications for postponed interventions. Right ventricular involvement and repeat MI were considered as additional predictors. The data obtained indicate that elevated risk of death allows to detect patients with high rate of persisting occlusions and subtotal stenoses in infarct related artery. Reperfusion therapy appears to be the main component of treatment of such patients. Necessity to perform primary PCI within first 12 hours does not exclude possibility of its later use in acute period of MI. Both strategies allow to substantially lower rates of complications and lethal outcomes. Shortening of terms of application of reperfusion therapy gives an opportunity to prevent most of unfavorable outcomes. Success of postponed interventions in acute period of MI opens opportunities of their active use in patients from other hospitals.

[Effectiveness of early invasive strategy of treatment of angina of new onset].

Aim of the study was to assess effectiveness of early invasive strategy of treatment of angina of new onset (ANO). We conducted comparative assessment on invasive and noninvasive risk estimation in 106 patients admitted to N.V.Sklifosofsky Institute of Urgent Aid in 2003-2007. Percutaneous coronary interventions (PCI) on symptom related artery (SRA) within single procedure were carried out in 74 cases (70%), indications to coronary artery bypass surgery were detected in 16 cases (15%), in 16 more cases conservative treatment was used. The data obtained showed that it is rational to consider ANO as unstable angina in all cases including those without progression. Visualization of coronary arteries gives possibility to define significance of SRA and zone at risk of injury, determine indications to myocardial revascularization, and avoid inadequacy of noninvasive assessment of risk and choice of treatment tactics. The method of choice in the treatment of patients with ANO is PCI performed during single procedure. Detection of indications to coronary artery bypass surgery in low risk patients and in absence of progression confirm necessity of routine use of invasive strategy which provides timely pathogenetic treatment. Absence of indications to myocardial revascularization detected in sporadic cases provides possibility to avoid groundless hospitalizations.

[Percutaneous coronary interventions in patients with acute myocardial infarction after unsuccessful thrombolysis].

In 176 patients with acute myocardial infarction admitted to N.V. Sklifosofsky institute of urgent aid in 2003-20007 we compared efficacy of 3 strategies of treatment after unsuccessful thrombolytic therapy (TLT): percutaneous coronary intervention (PCI) during first 24 hours (n = 30), PCI on days 2 or 3 (n = 38); conservative treatment (n = 108). The data obtained show that it is expedient to consider absence of 50% reduction of STAsegment elevations in 90 min after start of TLT as indication to urgent late PCI when possibilities for immediate intervention after unsuccessful thrombolysis are lacking. Alternative reperfusion is the only type of effective treatment of patients with failed pharmacological reperfusion. Necessity to perform PCI during first 12 hours after unsuccessful TLT does not exclude possibility of its later fulfillment in acute period of myocardial infarction. Efficacy of the latter is comparable with success rate of rescue PCI. The use of both invasive strategies has allowed to lessen rate of complications and prevent lethal outcomes. Success of late urgent interventions in acute period of infarction after failed thrombolysis opens possibilities for their active use in patients transferred from other hospitals.

[Percutaneous coronary interventions in patients with acute myocardial infarction after successful thrombolysis].

In 259 patients with acute myocardial infarction admitted to N.V. Sklifosofsky Institute of Urgent Aid in 2003-20007 we compared efficacy of 3 strategies of treatment after successful thrombolytic therapy (TLT): percutaneous coronary intervention (PCI) because of recurrent ischemia within 5 days after thrombolytic therapy (n = 66), PCI in patients with elevated risk of death according to TIMI during 12-24 hours after TLT (n = 26); conservative treatment after TLT (n = 167). Differences at comparison of two invasive strategies were related to the state of infarct-related artery and clinical effect. The use of PCI in patients with elevated risk of death in 12-24 hours after TLT was in all cases associated with timely provision of completed reperfusion, improvement of contractility, prevention of development of left ventricular aneurism. The use of both invasive strategies allowed to lessen rate of complications, and achieve several fold lowering of mortality. The data obtained show that for more objective and timely selection of patients for PCI after effective TLT it is expedient to use quantitative estimation of risk according to TIMI. Such approach allows without waiting for ischemia recurrence to detect patients with elevated risk and critical stenoses being in acute need of combined reperfusion.

[Atrial fibrillation after coronary artery bypass grafting].

The review is focused on atrial fibrillation soon after coronary artery bypass grafting. The most popular algorithms for the prevention and management of this condition are discussed including the protocol accepted in the Cardiosurgical Centre of P. V. Martynov 2nd Central Military Hospital. Modern concepts of pharmacotherapy of atrial fibrillation, restoration, and maintenance of sinus rhythm are considered.