[Nonimmunogenic staphylokinase in the treatment of acute ischemic stroke (FRIDA trial results)]. / Neimmunogennaya stafilokinaza ­ novyi tromboliticheskii preparat v lechenii ishemicheskogo insul'ta (rezul'taty issledovaniya FRIDA).

AIM OF THE STUDY: To investigate the efficacy and safety of non-immunogenic staphylokinase (NS) compared with alteplase (A) in patients with acute ischemic stroke (AIS) within 4.5 h after symptom onset. MATERIAL AND METHODS: 336 patients with IS within 4.5 h after symptom onset were included in a randomized, open-label, multicenter, parallel-group, non-inferiority comparative trial of NS vs A (168 patients in each group). NS was administered as an intravenous bolus in a dose of 10 mg, regardless of body weight, over 10 s, A was administered as a bolus infusion in a dose of 0.9 mg/kg, maximum 90 mg over 1 hour. The primary efficacy endpoint was a favorable outcome, defined as a modified Rankin scale (mRS) score of 0-1 on day 90. Safety endpoints included all-cause mortality on day 90, symptomatic intracranial haemorrhage, and other serious adverse events (SAEs). RESULTS: At day 90, 84 (50%) patients reached the primary endpoint (mRS 0-1) in the NS group, 68 (41%) patients - in the A group (p=0.10, OR=1.47, 95% CI=0.93-2.32). The difference between groups NS and A was 9.5% (95% CI= -1.7-20.7) and the lower limit of the 95% CI did not cross the margin of non-inferiority (pnon-inferiority<0.0001). There were no significant differences in the frequency of deaths between the groups: on day 90, 17 (10%) patients in the NS group and 24 (14%) in the A group had died (p=0.32). There was a trend towards significant differences in the frequency of symptomatic intracranial haemorrhage: NS group - 5 (3%) patients, A group - 13 (8%) patients (p=0.087, OR=0.37, 95% CI=0.1-1.13). There were significant differences in the number of patients with SAEs: in the NS group - 22 (13%) patients, in the A group - 37 (22%) patients (p=0.044, OR=0.53, 95% CI=0.28-0.98). CONCLUSION: The presented results of the FRIDA trial are the first in the world to use a drug based on NS in patients with IS. It has been shown that a single bolus (within 10 s) administration of NS at a standard dose of 10 mg, regardless of body weight, allows to conduct fast, effective and safe thrombolytic therapy in patients with IS within 4.5 h after symptom onset. In further clinical tials of NS, it is planned to expand the therapeutic window beyond 4.5 h after symptom onset in patients with IS.

[The in vitro examination of the effectiveness of antiseptic substances for a surface disinfection of teeth inoculated with Escherichia coli]. / Issledovanie in vitro éffektivnosti antisepticheskikh veshchestv dlia poverkhnostnoi dezinfektsii zubov, inokulirovannykh Escherichia coli.

The aim of the study was to assess the possibility of penetration of Escherichia coli bacteria into the dentinal tubules of the samples and determine the antimicrobial efficacy after 5 and 20 min exposition of 3% H2O2 (groups I and II) and 1 and 5 min exposition of 3% NaOCl (groups III and IV) for surface disinfection of bovine teeth. The samples were subjected to inoculation with E. coli suspension. The quality of disinfection was assessed with the three methods. The surface disinfection of samples proved to be effective only in groups II and IV. In the cultures of all dissolutions of dentinal chips suspensions in groups I, III and V there was a growth of E. coli in the form of a continuous pitch. In the group II a growth of Escherichia coli was revealed only in the initial dissolution in the quantity 1,8x101 CFU/ml, whereas in the group IV the growth was nil. Quantitative estimation of bacterial penetration using the method of maximum dissolutions revealed similar quantity of bacteria as in the group II as well as in the calculation of CFU. The application of 3% solution of H2O2 with the exposition of 20 minutes secures the qualitative surface disinfection of teeth without destruction of bacteria inside dental tubules and that allows to discover viable bacteria inside dentinal tubules.

[The specific features of the blood stains depending on their volume]. / Osobennosti sledov kapel' krovi pri ikh razlichnom ob''eme.

The objective of the present study was to determine the minimal and maximum volume of blood droplets freely falling from various droplet-forming surfaces and to characterize the specific morphological features of the resulting stains. The experiments were designed so that the blood droplets were allowed to fall down from the height of 10 cm to 1.5 m. The drop volume varied from 5 mcl to 134 mcl depending on the shape of the objects and the area of the droplet-forming surfaces. The size of the blood stains ranged from 0.4 to 2.4 cm. The stains of a smaller size were regarded as splashes while a stain resulting from the fall of a droplet having a volume greater than 200 mcl was considered to be a result of merging of several droplets and was termed 'blood volume'. The morphological features of the blood stains of different volume are described.

[Thrombolytic therapy of ischemic stroke]. / Tromboliticheskaia terapiia ishemicheskogo insul'ta.

Reperfusion therapy is one of the main treatment strategies of ischemic stroke. The first studies of the efficacy of thrombolytic medications started form the use of streptokinase and fibrinolysin in patients with ischemic stroke in late 50 - early 60 of the XX century in the United States, Soviet Union, and Western Europe. After the development of recombinant tissue plasminogen activator, thrombolysis became one of the main methods of reperfusion in patients with acute ischemic stroke, acute myocardial infarction, or other acute vascular thrombotic events. Later, modified variants of tissue plasminogen activator with prolonged clearance time, high fibrin-selectivity, and bolus delivery were introduced. Another group of thrombolytic agents includes derivatives of flora and fauna - external plasminogen activators, of which streptokinase, staphylokinase, and desmoteplase are most common drugs. These medications are not a structural part of the human organism, and overcoming of immunogenicity while preserving fibrinolytic activity and fibrin specificity is one of the main tasks in applying them in clinical practice.

[Transition of entheropathogenic and saprotrophic bacteria in the eco-niche cycle: animals-excrement-soil-plants-animals].

The possibility of transition of saprotrophic and enteropathohenic bacterial populations following the chain of naturally related habitats--fodder-animal gastrointestinal tract (GIT)-animals excrement-soil-plants and again animals with a cyclic formation--has been investigated quantitatively. All bacteria used in the experiments have been shown to successfully overcome all the mechanical, physical-chemical, and biological barriers in the food chain and to come out into the environment with a quite high number. It has been demonstrated that the same bacterial population can pass the whole cycle without additional introduction of similar populations from the outside.

[The relationship between the conditions of cultivation and sporification of various Bacillus strains and the results of the evaluation of the sporocidal activity of chemical desinfectants].

The researchers compared the main microbiological characteristics of some Bacillus antracoides strains after their cultivation in different nutrient media. The study found that the growth and sporification rate, R-S dissociation ability, and sensitivity to disinfectants are strain properties and significantly depend on the composition of the nutrient medium.

Short-term wavelike dynamics of bacterial populations in response to nutrient input from fresh plant residues.

The objectives of the research were to investigate short-term dynamics of bacterial populations in soil after a disturbance in the form of fresh organic matter incorporation and to investigate how these dynamics are linked to those of some environmental parameters. To reach these objectives, soil bacterial populations, mineral nitrogen, pH, and redox potential (ROP) were monitored daily for 1 month after incorporation of clover-grass (CG) plant material in microcosm experiments. Colony-forming units (CFUs) and direct microscopic counts of FDA-stained and FTTC-stained bacteria increased immediately after incorporation of the plant material, dropped within 2 days, and fluctuated thereafter. Harmonics analysis demonstrated that there were significant wavelike fluctuations with three or four significant peaks within 1 month after incorporation of clover-grass material. Peaks in CFUs were 1-2 days ahead of those in direct counts. Ammonium (NH4) concentrations increased from the start of the experiments until nitrification commenced. Nitrate (NO3) concentrations dropped immediately after plant incorporation, and then rose monotonically until the end of the experiments. There were no wavelike fluctuations in NH4 and NO3 concentrations, so that bacterial fluctuations could not be attributed to alternating mineral N shortages and sufficiencies. pH levels rose and declined with NH4 levels. ROP dropped shortly before NH4 concentrations rose, and increased before NH4 concentrations decreased; there were no regular fluctuations in ROP, so that temporary oxygen shortages may not have been responsible for the observed fluctuations in bacterial populations. Thus, for the first time, regular wavelike dynamics were demonstrated for bacterial populations after perturbation by addition of fresh organic matter to soil, and several potential reasons for the death phase of the fluctuations could be excluded from further consideration.

Wavelike distributions of infections by an introduced and naturally occurring root pathogen along wheat roots.

Previously, we showed that copiotrophic and oligotrophic bacteria fluctuate as moving waves along roots. These waves probably originate as a result of growth and death cycles at any location where a moving nutrient source passed. In this study, we placed sclerotia of Rhizoctonia solani AG8 along growing roots of wheat and showed that the proportions of root sections from which R. solani was isolated fluctuated with distance from the root tip. Similarly, proportions of root sections from which naturally occurring Pythium spp. were isolated fluctuated with distance from the root tip. Fourier analysis showed that these fluctuations constituted significant waves. Cross-correlation analyses demonstrated that there were negative correlations between R. solani infections and colony forming units of copiotrophic bacteria at the time of inoculation at the same locations on the root (lag = 0 cm), indicating that infection by R. solani could have been inhibited by these bacteria. There was a positive correlation between Pythium infections and copiotrophic bacteria at a lag of 6 cm along the roots. It therefore appears that Pythium infection took place shortly after the initial peak in copiotrophic bacteria following the passage of the root tip.

Physiological bases of oligotrophy of microorganisms and the concept of microbial community.

Three groups of physiological processes in microorganisms are considered the physiological basis of oligotrophy: the greater substrate affinity of the oligotrophs' transport systems, efficient or "economical" metabolism, and existence of a "master reaction" or "rate-determining steps" controlling the rate of metabolism. Heterotrophic microorganisms are divided into three unequal groups according to "reaction norma." Two groups representing the extremes are small groups with the "narrow" reaction norma, regarding the concentrations and structure of the assimilated organic compounds and variability limits of the physiological characteristics mentioned above. The third, intermediate group includes the majority of microorganisms with the "wide" reaction norma.

[Possibility of isolating higher-risk factors in the malignant transformation of solitary formations in the thyroid gland]. / O vozmozhnosti vydeleniia faktorov povyshennogo riska malignizatsii solitarnykh obrazovanii shchitovidnoi zhelezy.

Main general clinical symptoms were compared in 450 patients with different solitary formations of the thyroid gland. The authors failed to narrow the group of higher risk of malignization of the solitary formations.

[Adaptation of Candida tropicalis yeasts to increasing hydroquinone concentrations]. / Adaptatsiia drozhzhei Candida tropicalis k vozrastaiushchim kontsentratsiiam gidrokhinona.

The optimal concentration of hydroquinone in the Rieder medium for Candida tropicalis is 0.2 to 0.25%. This yeast is capable of growing in a medium containing up to 0.7-0.9% of hydroquinone. C. tropicalis cultures capable of growing in the Rieder medium containing 2.5% of hydroquinone have been obtained by the method of experimental adaptation. Comparative studies of yeast cultures adapted to 0.5 and 1.5% of hydroquinone have shown that the lag period in the batch culture decreases noticeably as the result of adaptation. The coloured products of hydroquinone transformation are not accumulated any more in the cultural broth and the cells. The generation time of the yeast is the same during cultivation on 0.2 and 0.5% hydroquinone but differs if the content of hydroquinone in the medium is 1%. No increase in the economic coefficient has been found during cultivation of the yeast cultures adapted to 1.5% hydroquinone in media containing 0.2 and 0.5% of hydroquinone, although the activity of phenol monooxygenase increased. The latter peculiarity of the adapted cultures was most pronounced during cultivation in media containing 0.5 to 1% of hydroquinone. No changes have been detected in the regulation mechanisms for biosynthesis of phenol monooxygenase or in the resistance of the enzyme to the substrate and the products of its spontaneous oxidation.

[Effect of zinc ions on Candida utilis]. / Deistvie ionov tsinka na Candida utilis.

The effect of zinc on the growth of Candida utilis was studied as well as on the rates of RNA and protein synthesis, and the uptake of zinc ions by the cells. The kinetics of C. utilis growth inhibition by zinc ions can be described by the equation for noncompetitive inhibition of enzymatic reactions. The uptake of zinc is a two-phase process. Zinc ions are adsorbed by the surface of the cell at the first phase, and are actively transported inside the cell at the second phase. Protein synthesis is suppressed by zinc ions more than RNA synthesis. Apparently protein synthesis is most sensitive to zinc among other metabolic processes and its inhibition caused deceleration of growth and then death of cells.

[Inhibition of the growth of Candida utilis by certain heavy metals]. / Ingibirovanie rosta Candida utilis nekotorymi tiazhelymi metallami.

The effect of Zn2+, Mn2+, Cd2+ and Hg2+ ions on the kinetics of growth was studied with Candida utilis. The inhibition of Candida utilis growth by Zn2+ and Mn2+ ions is described by the equation for noncompetitive inhibition of enzymatic reactions which is not the case with Cd2+ and Hg2+ ions. The inhibition constants (Ki) for these metals have been determined.