[Influence of chronic pain in osteoarthritis on the risk of cardiovascular diseases and modern methods of drug prevention]. / Vliyanie khronicheskoi boli pri osteoartrite na risk razvitiya serdechno-sosudistykh zabolevanii i sovremennye sposoby ikh lekarstvennoi profilaktiki.

The purpose of the review of scientific medical literature was to evaluate the data of the epidemiology of osteoarthritis (OA) and cardiovascular diseases (CVD) with the analysis of risk factors, pathophysiological and pathobiochemical mechanisms of the relationship between OA and the risk of developing CVD in the presence of chronic pain, modern strategies for screening and management of this cohort of patients, the mechanism of action and pharmacological effects of chondroitin sulfate (CS). Conclusions were drawn about the need for additional clinical and observational studies of the efficacy and safety of the parenteral form of CS (Chondroguard) in patients with chronic pain in OA and CVD, improvement of clinical recommendations for the treatment of chronic pain in patients with OA and cardiovascular risk, with special attention to interventions that eliminate mobility restrictions in patients and the inclusion of basic and adjuvant therapy with DMOADs to achieve the goals of multipurpose monotherapy in patients with contraindications to standard therapy drugs.

Production of subtilisin proteases in bacteria and yeast.

In this review, we discuss the progress in the study and modification of subtilisin proteases. Despite longstanding applications of microbial proteases and a large number of research papers, the search for new protease genes, the construction of producer strains, and the development of methods for their practical application are still relevant and important, judging by the number of citations of the research articles on proteases and their microbial producers. This enzyme class represents the largest share of the industrial production of proteins worldwide. This situation can explain the high level of interest in these enzymes and points to the high importance of designing domestic technologies for their manufacture. The review covers subtilisin classification, the history of their discovery, and subsequent research on the optimization of their properties. An overview of the classes of subtilisin proteases and related enzymes is provided too. There is a discussion about the problems with the search for (and selection of) subtilases from natural strains of various microorganisms, approaches to (and specifics of) their modification, as well as the relevant genetic engineering techniques. Details are provided on the methods for expression optimization of industrial subtilases of various strains: the details of the most important parameters of cultivation, i.e., composition of the media, culture duration, and the influence of temperature and pH. Also presented are the results of the latest studies on cultivation techniques: submerged and solid-state fermentation. From the literature data reviewed, we can conclude that native enzymes (i.e., those obtained from natural sources) currently hardly have any practical applications because of the decisive advantages of the enzymes modified by genetic engineering and having better properties: e.g., thermal stability, general resistance to detergents and specific resistance to various oxidants, high activity in various temperature ranges, independence from metal ions, and stability in the absence of calcium. The vast majority of subtilisin proteases are expressed in producer strains belonging to different species of the genus Bacillus. Meanwhile, there is an effort to adapt the expression of these enzymes to other microbes, in particular species of the yeast Pichia pastoris.

Comprehensive geriatric assessment in elderly and senile patients with cardiovascular diseases. Expert opinion of the Russian Association of Gerontologists and Geriatricians.

Senile asthenia syndrome (SAS) is a geriatric syndrome characterized by age-associated decline of the physiological reserve and function in multiple systems, which results in higher vulnerability to effects of endo- and exogenous factors and a high risk of unfavorable outcomes, loss of self-sufficiency, and death. Generally, SAS is observed in elderly patients with comorbidities. In cardiovascular diseases, SAS is associated with a poor prognosis, including a higher incidence of exacerbation and death both during acute events and in chronic disease. However, SAS is often not taken into account in developing diagnostic and therapeutic programs for managing elderly patients with cardiovascular diseases (CVD). This article analyzes available scientific information about SAS, algorithms for SAS diagnosis, and the scales that may be useful in developing individual plans for management of elderly patients with CVD.

Diversity and occurrence of methylotrophic yeasts used in genetic engineering.

Methylotrophic yeasts have been used as the platform for expression of heterologous proteins since the 1980's. They are highly productive and allow producing eukaryotic proteins with an acceptable glycosylation level. The first Pichia pastoris-based system for expression of recombinant protein was developed on the basis of the treeexudate- derived strain obtained in the US southwest. Being distributed free of charge for scientific purposes, this system has become popular around the world. As methylotrophic yeasts were classified in accordance with biomolecular markers, strains used for production of recombinant protein were reclassified as Komagataella phaffii. Although patent legislation suggests free access to these yeasts, they have been distributed on a contract basis. Whereas their status for commercial use is undetermined, the search for alternative stains for expression of recombinant protein continues. Strains of other species of methylotrophic yeasts have been adapted, among which the genus Ogataea representatives prevail. Despite the phylogenetic gap between the genus Ogataea and the genus Komagataella representatives, it turned out possible to use classic vectors and promoters for expression of recombinant protein in all cases. There exist expression systems based on other strains of the genus Komagataella as well as the genus Candida. The potential of these microorganisms for genetic engineering is far from exhausted. Both improvement of existing expression systems and development of new ones on the basis of strains obtained from nature are advantageous. Historically, strains obtained on the southwest of the USA were used as expression systems up to 2009. Currently, expression systems based on strains obtained in Thailand are gaining popularity. Since this group of microorganisms is widely represented around the world both in nature and in urban environments, it may reasonably be expected that new expression systems for recombinant proteins based on strains obtained in other regions of the globe will appear.

An integrated method for taxonomic identification of microorganisms.

For accurate species-level identification of microorganisms, researchers today increasingly use a combination of standard microbiological cultivation and visual observation methods with molecular biological and genetic techniques that help distinguish between species and strains of microorganisms at the level of DNA or RNA molecules. The aim of this work was to identify microorganisms from the ICG SB RAS Collection using an integrated approach that involves a combination of various phenotypic and genotypic characteristics. Key molecular-genetic and phenotypic characteristics were determined for 93 microbial strains from the ICG SB RAS Collection. The strains were characterized by means of morphological, physiological, moleculargenetic, and mass-spectrometric parameters. Specific features of the growth of the strains on different media were determined, and cell morphology was evaluated. The strains were tested for the ability to utilize various substrates. The strains studied were found to significantly differ in their biochemical characteristics. Physiological characteristics of the strains from the collection were identified too, e.g., the relationship with oxygen, type of nutrition, suitable temperature and pH ranges, and NaCl tolerance. In this work, the microorganisms analyzed were combined into separate groups based on the similarities of their phenotypic characteristics. This categorization, after further refinement and expansion of the spectrum of taxa and their metabolic maps, may serve as the basis for the creation of an "artificial" classification that can be used as a key for simplified and quicker identification and recognition of microorganisms within both the ICG SB RAS Collection and other collections.

[The meteopathic reactions as reflected in the indicators of electropuncture diagnostics. A pilot study]. / Otrazhenie meteopaticheskikh reaktsii v pokazateliakh élektropunkturnoi diagnostiki. Pilotnoe issledovanie.

The present article was designed to report the results of the electropuncture diagnostics (EPD) with the use of the 'Prognoz' electropunctural device obtained during the examination of 12 patients who experienced meteopathic reactions (MPR) during magnetic storms. The most frequently detected changes were deviations affecting the acupuncture channels (AC) of the heart, pericardium and triple energizer. The latter underwent the most pronounced deviation from the 'balanced condition'. In 2 cases out of the three (66,6%), its hypofunction was documented The pericardium channel was characterized by extreme asymmetry of its left and right branches. To a lesser extent, a similar asymmetry was apparent in the acupuncture channels of the heart. The present pilot study revealed the noticeable changed in the functional state of two AC (pericardium and triple energizer) in people suffering from meteopathic reactions. It is concluded that the further studies involving a larger population of the weather-dependent subjects is likely to identify other sensitive acupuncture channels; the analysis of their functional condition may be instrumental in determining the typical MPR profiles based on the results of the evaluation of the effectiveness of electropunctural diagnostics. The newly detected patterns may be useful for the development of the personalized approach to the prediction, prevention, and relief of the meteopathic reactions.

Cyanobacteria(?) in iron banded formations of the Kursk magnetic anomaly.

Fossilized cyanobacteria(?) represented by trichomes enclosed in common sheaths were detected in early Proterozoic iron banded formations of the Kursk magnetic anomaly (limonite-martite ores of the Lebedinsky mine and iron banded formations of the Korobkovskoye deposit). These fossils morphologically similar to current representatives of the genus Microcoleus were buried in situ.

UTLS water vapour from SCIAMACHY limb measurementsV3.01 (2002-2012).

The SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY) aboard the Envisat satellite provided measurements from August 2002 until April 2012. SCIAMACHY measured the scattered or direct sunlight using different observation geometries. The limb viewing geometry allows the retrieval of water vapour at about 10-25 km height from the near-infrared spectral range (1353-1410 nm). These data cover the upper troposphere and lower stratosphere (UTLS), a region in the atmosphere which is of special interest for a variety of dynamical and chemical processes as well as for the radiative forcing. Here, the latest data version of water vapour (V3.01) from SCIAMACHY limb measurements is presented and validated by comparisons with data sets from other satellite and in situ measurements. Considering retrieval tests and the results of these comparisons, the V3.01 data are reliable from about 11 to 23 km and the best results are found in the middle of the profiles between about 14 and 20 km. Above 20 km in the extra tropics V3.01 is drier than all other data sets. Additionally, for altitudes above about 19 km, the vertical resolution of the retrieved profile is not sufficient to resolve signals with a short vertical structure like the tape recorder. Below 14 km, SCIAMACHY water vapour V3.01 is wetter than most collocated data sets, but the high variability of water vapour in the troposphere complicates the comparison. For 14-20 km height, the expected errors from the retrieval and simulations and the mean differences to collocated data sets are usually smaller than 10 % when the resolution of the SCIAMACHY data is taken into account. In general, the temporal changes agree well with collocated data sets except for the Northern Hemisphere extratropical stratosphere, where larger differences are observed. This indicates a possible drift in V3.01 most probably caused by the incomplete treatment of volcanic aerosols in the retrieval. In all other regions a good temporal stability is shown. In the tropical stratosphere an increase in water vapour is found between 2002 and 2012, which is in agreement with other satellite data sets for overlapping time periods.

Vertical structure of stratospheric water vapour trends derived from merged satellite data.

Stratospheric water vapour is a powerful greenhouse gas. The longest available record from balloon observations over Boulder, Colorado, USA shows increases in stratospheric water vapour concentrations that cannot be fully explained by observed changes in the main drivers, tropical tropopause temperatures and methane. Satellite observations could help resolve the issue, but constructing a reliable long-term data record from individual short satellite records is challenging. Here we present an approach to merge satellite data sets with the help of a chemistry-climate model nudged to observed meteorology. We use the models' water vapour as a transfer function between data sets that overcomes issues arising from instrument drift and short overlap periods. In the lower stratosphere, our water vapour record extends back to 1988 and water vapour concentrations largely follow tropical tropopause temperatures. Lower and mid-stratospheric long-term trends are negative, and the trends from Boulder are shown not to be globally representative. In the upper stratosphere, our record extends back to 1986 and shows positive long-term trends. The altitudinal differences in the trends are explained by methane oxidation together with a strengthened lower-stratospheric and a weakened upper-stratospheric circulation inferred by this analysis. Our results call into question previous estimates of surface radiative forcing based on presumed global long-term increases in water vapour concentrations in the lower stratosphere.

[Cloning of Escherichia coli K12 xylose isomerase (glucose isomerase) and studying the enzymatic properties of its expression product].

The coding region of Escherichia coli K12 xylose (glucose) isomerase gene was inserted into the pRAC expression vector and cloned in E. coli BL21 (DE3) cells. After induction of expression of the cloned gene, the proportion of recombinant xylose isomerase accounted for 40% of the total protein content. As a result of one-stage purification by affinity chromatography, a protein preparation of 90% purity was obtained. The recombinant enzyme catalyzed the isomerization of glucose to fructose and exhibited maximum activity (0.8 U/mg) at 45 degrees C and pH 6.8. The enzyme required Mg2+ ions as a cofactor. When Mg2+ and Co2+ ions were simultaneously present in the reaction medium, the enzyme activity increased by 15-20%. Complete replacement of Mg2+ with Co2+ decreased the enzyme activity. In the presence of Ca2+ at concentrations comparable to the concentration of Mg2+, the enzyme was not inhibited, although published data reported inhibition of similar enzymes by Ca2+. The recombinant enzyme exhibited a very low thermostability: it underwent a slow inactivation when incubated at 45 degrees C and was completely inactivated after incubation at 65 degrees C for 1 h.

Role of clay content in partitioning, uptake and toxicity of zinc in the earthworm Eisenia fetida.

We studied the effect of clay content on the bioavailability of zinc to pre-clitellate earthworm, Eisenia fetida in the laboratory using OECD artificial soil adjusted to 5%, 20%, and 40% clay. Batches of worms were exposed to a wide range of zinc concentrations. Mortality, growth, maturation (% clitellate), cocoon production, and body zinc concentrations were assessed over and after a period of 4 weeks. Total, DTPA, and CaCl(2) extractable zinc in the substrates were also determined. The results of the biological responses showed that interaction of clay and zinc had a significant influence on mortality but not on the other biological parameters. None of the three extraction methods showed consistent and significant effect of clay content on zinc partitioning. Although total, DTPA, and CaCl(2) extracts of zinc correlated strongly with one another and were in similar relation with the observed biological responses, only the CaCl(2) extract revealed a time dependent availability of this metal. It is concluded that clay content had no significant influence on sub-lethal toxicity of zinc to this earthworm over the range of exposure concentrations.

Retrieval and monitoring of atmospheric trace gas concentrations in nadir and limb geometry using the space-borne SCIAMACHY instrument.

The Scanning Imaging Absorption Spectrometer for Atmospheric Chartography (SCIAMACHY) onboard the European Envisat spacecraft performs continuous spectral observations of reflected, scattered and transmitted sunlight in various observation geometries. A unique feature of SCIAMACHY is the capability of probing the atmosphere in three different observation geometries:The nadir, limb, and occultation measurement modes. In nadir mode, column densities of trace gases are retrieved with a spatial resolution of typically 30 x 60 km using the Differential Optical Absorption Spectroscopy (DOAS) technique (Platt and Perner, 1983). Alternating with the nadir measurement, vertical profiles of absorber concentration in the stratosphere are derived in limb and occultation. In this paper we present an overview over some applications of SCIAMACHY data in space-based monitoring of atmospheric pollution. The DOAS algorithms for the retrieval of total column amounts from nadir spectra are briefly described and case studies of pollution events are presented. We also illustrate the technique used to derive stratospheric concentration profiles from limb observations and show comparisons with other remote sensing systems. Special emphasis will be given to techniques, which take advantage of SCIAMACHY's different viewing geometries. In particular, we will discuss the potential and limits of strategies to infer tropospheric abundances of O3 and NO2.

[Effects of aggressive therapy with simvastatin in patients with acute coronary syndrome and initially normal level of LDLP cholesterol on cardiovascular outcomes (LAOKOON). Pilot randomized trial].

AIM: To examine anti-inflammatory effect of statins on outcomes of acute coronary syndrome (ACS). MATERIAL AND METHODS: The trial included 211 ACS patients without ST elevation at ECG. The patients were followed up for 180 days. The anti-inflammatory action was studied for 30 days. The patients were divided into two groups by the treatment: simvastatin 10 mg + aspirin 325 mg (104 patients, group 1) and simvastatin 40 mg + aspirin 325 mg (107 patients, group 2) for 30 days. RESULTS: Simvastatin in maximal dose lowed LDLP cholesterol from 101 +/- 9.8 to 72 +/- 3.3 mg/dl, in a minimal dose--from 104 +/- 11.3 to 81 +/- 2.1 mg/dl (p < 0.05). Only maximal dose simvastatin produced a significant reduction of C-reactive protein (CRP) to the disease day 14. The integral index including all cases of cardiovascular death +acute myocardial infarction+progressive angina+rehospitalization was 70 scores for group 1 and 137 for group 2 (p = 0.047). CONCLUSION: Use of simvastatin in ACS patients, initially normal level of LDLP cholesterol and elevated level of CRP produced a dose-dependent effect, alleviated inflammation and improved the disease course.

[Activity of cytochrome P-450 aromatase, nitric oxide synthase and level of S-nitrosothiols in rat ovaries and uterus under oxidative stress caused by cobalt chloride]. / Aktivnost' tsitokhorma P-450 aromatazy, sintazy oksida azota i soderzhanie S-nitrozotiolov v iaichnikakh i matke krys pri oksidativnom stresse, vyzvannom khloridom kobal'ta.

Cytochrome P-450 aromatase and nitric oxide syntase activities were established to decrease in the ovaries and uteri of CoCl2 injected Wistar female rats. Respectively the S-nitrosothiols concentration was also decreased. The quantity of malonic dialdehyde was increased in the ovaries and uteri of rats injected by CoCl2. It's assumed that reactive oxygen species formed by CoCl2 inhibit the activities of aromatase and nitric oxide syntase as haem ligands and inhibitors of it's biosynthesis.

[Effect of nonsteroidal estrogen-like substances on aromatase activity]. / Vliianie nesteroidnykh veshchestv s éstrogenopodobnym éffektom na aktivnost' aromatazy.

The effects in vitro of DDT, DDE and genistein on rat uterine purified aromatase activity were studied. It was established that all these compounds were competitive aromatase inhibitor. In the studies in vivo DDT and genistein decrease the rat ovarian and rat uterine aromatase activity. They were identified to decrease the quantity of the aromatase in these organs by inhibiting the expression of corresponding genes.

[Safety and clinical efficiency of long-term complete blockade of renin-angiotensin-aldosterone system in patients with chronic obstructive pulmonary diseases]. / Klinicheskaia éffektivnost' i bezopasnost' dlitel'noi kombinirovannoi blokady deistviia renin-angiotenzin-al'dosteronovoi sistemy u bol'nykh s khronicheskimi obstruktivnymi bolezniami legkikh.

AIM: To study a corrective influence of a complete blockade of renin-angiotensin-aldosterone system (RAAS) on right ventricular failure in patients with chronic obstructive pulmonary diseases (COPD). MATERIAL AND METHODS: 91 COPD patients were randomised into 3 groups who received standard therapy (ST), ST + losartan, ST + losartan + aldactone. The duration of the follow-up was 24 months. RESULTS: A complete RAAS blockade produced a significant decline in the pressure in the pulmonary artery, improved diastolic and systolic right ventricular function. This led to decreased number of hospitalizations because of progressing right ventricular failure. CONCLUSION: Safety of therapy with ACE inhibitor and aldactone was proved by a comparison of the number of side effects in the three groups.

[In vitro study of regulation of rat liver xanthine oxidase activity by antioxidant reducing agents]. / Issledovanie in vitro reguliatsii aktivnosti ksantinoksidazy pecheni krys vosstanoviteliami-antioksidantami.

It was learned the regulation of xanthine oxidase activity from rat liver in the partly purified prepared by ascorbic acid, glutathione-SH, dithiothreitol, cysteine++ and hydrocortisone++. It was shown that ascorbic acid glutathione-SH, dithiothreitol, and cysteine++ can be activators and uncompetitor inhibitors of xanthine oxidase in dependence from concentration. As far as hydrocortisone is concerned, it is a powerful uncompetitor inhibitor of xanthine oxidase, that is bind with it. It was considered the mechanism of activation and inhibition of xanthine oxidase by these reductors-antioxidants.

[Effect of caffeine on xanthine oxidase activity]. / Vliianie kofeina na aktivnost' ksantinoksidazy.

The effect of caffeine on the xanthine oxidase activity in human organism has been studied. It was revealed that caffeine calls the inconsiderable reliable increase of the level of uric acid and the reliable lowering of levels of hypoxanthine and xanthine in urine. The isosteric inhibition of xanthine oxidase activity by caffeine was revealed in the experiments in vitro. It was proved that caffeine cannot be the inhibitor of xantine oxidase in vivo because it demethylases to I-methylxanthine.