Impaired post-irradiation survival of cyclooxygenase-2-deficient mice.

We investigated and evaluated post-irradiation survival in cyclooxygenase-2-deficient (COX-2 KO) mice. Thirty-day survival following exposure of COX-2 KO mice to a lethal dose of 8.5 Gy of gamma-rays was observed to be statistically significantly lower in both males and females, as well as when the sexes were merged, in comparisons with their wild-type counterparts. These findings were related to the previous observations concerning the detrimental influence of the COX-2 genetic disruption on hematopoiesis in sublethally irradiated mice. Deteriorated post-irradiation survival of COX-2 KO mice confirmed the previously anticipated conclusion regarding negative influence of the antiinflammatory action of COX-2 deficiency under the conditions of exposure of the animals to ionizing radiation.

Climate Degradation and Extreme Icing Events Constrain Life in Cold-Adapted Mammals.

Despite the growth in knowledge about the effects of a warming Arctic on its cold-adapted species, the mechanisms by which these changes affect animal populations remain poorly understood. Increasing temperatures, declining sea ice and altered wind and precipitation patterns all may affect the fitness and abundance of species through multiple direct and indirect pathways. Here we demonstrate previously unknown effects of rain-on-snow (ROS) events, winter precipitation, and ice tidal surges on the Arctic's largest land mammal. Using novel field data across seven years and three Alaskan and Russian sites, we show arrested skeletal growth in juvenile muskoxen resulting from unusually dry winter conditions and gestational ROS events, with the inhibitory effects on growth from ROS events lasting up to three years post-partum. Further, we describe the simultaneous entombment of 52 muskoxen in ice during a Chukchi Sea winter tsunami (ivuniq in Iñupiat), and link rapid freezing to entrapment of Arctic whales and otters. Our results illustrate how once unusual, but increasingly frequent Arctic weather events affect some cold-adapted mammals, and suggest that an understanding of species responses to a changing Arctic can be enhanced by coalescing groundwork, rare events, and insights from local people.

Hematological profile of untreated or ionizing radiation-exposed cyclooxygenase-2-deficient mice.

We investigated hematopoiesis in untreated and ionizing radiation-exposed cyclooxygenase-2-deficient (COX-2 KO) mice. We performed a complex hematological analysis of 16 parameters in untreated COX-2 KO male mice or COX-2 KO male mice irradiated with the dose of 4 Gy of gamma-rays and their wildtype littermates. At baseline, hematopoiesis was increased in COX-2-deficient mice, but attenuated by irradation in COX-2-deficient mice compared to wildtype. To conclude, the anti-inflammatory action of the COX-2 genetic disruption plays a positive role in hematopoiesis under basal conditions but is detrimental following radiation exposure.

[Extinction of large herbivore mammals: niche characteristics of musk ox Ovibos moschatus and reindeer Rangifer tarandus coexisting in isolation].

The extinction of large northern herbivores is a puzzle for many biologists. It is long debated whether climate change or human activity was the main factor of the extinction. The survival of the weak trophic competitors should reject the climatic hypothesis. Extant species of Pleistocene communities allow testing this explicitly. Up to date, reindeer and musk ox coexist in the Arctic territory. Their island populations provide a unique natural experiment to assess the role of competition. On Wrangel Island, their population sizes show the opposite trends and the same situation recurs on other Arctic islands--the reindeer population size decreases with the muskoxen population increasing. We have shown that the trends are defined by food-web structure. Niche overlap between species is found to .be considerable and cannot be facilitated by habitat partitioning. The number of plant species in the muskoxen diet was higher than in the reindeer. The exclusive part of the muskoxen diet was higher as well. Food webs in all of the habitat types showed the same relation. However, the changes in herbivores distribution during the Pleistocene demonstrate the opposite pattern. Therefore, the competitive advantage could not save the Palaearctic musk ox, and the extinction seems to be a result of selective overkill. Conclusively, the human activity may be considered as the main factor of the Late Pleistocene herbivore extinctions, and the musk ox reintroducing should be coupled with extensive conservational measures.

[The prevalence of different Streptococcus pneumoniaе serotypes in the children presenting with ENT infections or carrying nasopharyngeal pathogens].

The objective of the present study was to elucidate the etiopathological significance of various Streptococcus pneumoniae serotypes in the children presenting with ENT infections and carrying nasopharyngeal pathogens. The incidence of the latter condition was 19.5% in the children free from S. pneumoniae infection in comparison with 20.9% and 30.7% in those having diagnosis of otitis media and rhinosinusitis respectively. Fifty five (88.8%) of the 62 isolated streptococcal strains were grouped into types with the use of multiplex PCR. Twelve serotypes were identified in the patients presenting with rhinosinusitis with the predominance of 6A/6B and 3 (40.5%) compared with seven isolated from the carriers of nasopharyngeal pathogens. In this group, type 3 also prevailed (26.5%) whereas other serotypes occurred less frequently: 23F (13,4%), indivisible totality of 8, 9V, 9A, 1F, 11A, 211B, 11C, 11D, 12F, 15A, and 33F (13.4%), 20 (6.7%), 19A (6.7%), 14 (6.7%), 6A,6B (6.7%). The serotypes of S. pneumoniae isolated from the patients with rhinosinusitis were found to show 55.3% identity with those present in the composition of the conjugated 7-valent pneumococcal vaccines, 63.2% identity with the 10-valent vaccine, 81.6% identity with the 11p-valnet vaccine, and 84.2% identity with the 13-valent vaccine.

[Cyclooxygenase inhibitors and antiplatelet effect of acetylsalicylic acid. selective approach to nonsteroidal anti-inflammatory drugs in cardiological practice].

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent class of medicines which is wide concerning chemical structure and mechanism of action. In the light of contradictory data on efficacy and safety of NSAID in cardiovascular patients selection of most appropriate NSAID (basing on profile of efficacy and safety) in patients receiving continuous therapy with low dose aspirin appears to be a problem. In this paper we discuss peculiarities of drug interaction between cyclooxygenase inhibitors and acetylsalicylic acid, and principles of selection of adequate NSAI.

[Effect of lornoxicam on inflammatory markers in patients with non-ST-segment elevation acute coronary syndrome].

AIM: To evaluate the clinical efficacy, safety, and effects of the nonsteroidal anti-inflammatory drug lornoxicam on inflammatory markers in non-ST-segment elevation acute coronary syndrome (NSTEACS). SUBJECTS AND METHODS: Eighty-five patients with NSTESCS were enrolled in a prospective randomized study. They were divided into 2 groups: 1) patients received lornoxicam (8 or 12 mg/daily) for 15 days in addition to standard treatment and 2) controls. Cardiovascular outcomes and the levels of C-reactive protein (CRP), IL-6, and IL-10 were determined. RESULTS: The lornoxicam group exhibited a significant reduction in CRP and a decrease in IL-6. There was also a significant increase in IL-10 levels in this group. A 6-month follow-up indicated a significant reduction in the number of cardiovascular events (nonfatal myocardial infarction, unstable angina, coronary death). CONCLUSION: Lornoxicam reduces the risk of poor cardiovascular outcomes in patients with NSTEACS and the levels of inflammatory markers.

[Microsatellite DNA variability in the populations of muskoxen Ovibos moschatus acclimated to the Russian North].

The muskoxen populations introduced to the Taimyr Peninsula and Wrangel Island in 1974 to 1975 were examined for sequence variation at seven microsatellite loci. Donor material originated from the populations of Banks Island (Canada) and Eastern Greenland. Relative to the allele frequencies, both introduced populations demonstrated rather strong deviation from the populations of the native range. At the same time, population allelic structures evidenced that they were closer to the Greenland populations. Estimates of genetic diversity at microsatellite loci (expected heterozygosity and the allele number) in the introduced muskoxen were found to be high for populations originating from a small number of founder individuals. In the immigrants, linkage disequilibrium and deviation of the genotype frequencies from the Hardy-Weinberg proportions were observed, which was mainly caused by the deficit of heterozygotes. The same pattern was also typical of native populations and was explained in terms of specific population structure and demographic processes. The latter were manifested as a periodic decline of the effective population size, resulting in the prevailing influence of genetic drift and inbreeding. The consequences of genetic drift were not as dramatic, as could be expected, which may be explained by a high mutation rate of neutral microsatellite loci and fast growth of the new populations.

[The efficacy of alteplase in pulmonary embolism treatment].

The results of pulmonary embolism treatment with streptase in 76 patients are discussed. All patients had submassive or massive pulmonary embolism. 66 (86%) of patients recovered. Thrombolysis with the use of heparin was performed in 9 patients, death occurred in 5 of them. Of 20 patients treated with "Actilize", death was reported in three cases. Authors consider alteplase to be highly effective in the treatment of massive pulmonary embolism. In case of late diagnostics of pulmonary embolism, especially recurrent, thrombolytic therapy remains to be effective up to 2 weeks after primary embolization.

[The use of intraaortic balloon counterpulsation in patients with acute myocardial infarction]. / Primenenie vnutriaortal'noi ballonnoi kontrpul'satsii u bol'nykh ostrym infarktom miokarda.

Intraaortic balloon counterpulsation was implemented in 11 patients with acute myocardial infarction and 1 patient with unstable angina. All patients had severe multivessel coronary artery disease. In 9 patients counterpulsation was used in conjunction with percutaneous transluminal coronary angioplasty, in 3 - with thrombolytic therapy. During hospitalization 2 patients died of progressing heart failure, while significant improvement of hemodynamic parameters occurred in other patients. Thus intraaortic balloon counterpulsation used in combination with angioplasty and thrombolytic therapy is an easily accessible highly effective method of treatment of cardiogenic shock in patients with acute myocardial infarction

[Comparative evaluation of carbohydrate metabolism in perch (Perca fluviatilis L.) from water bodies with different contents of humic acids]. / Sravnitel'naia otsenka uglevodnogo obmena okunei (Perca fluviatilis L.) iz vodoemov s razlichnym urovnem soderzhaniia guminovykh kislot.

Characteristic features of energy metabolism, related to the adaptation of fish to adverse environmental conditions, were detected in perch (Perca fluviatilis L.) inhabiting the lake with a high humus content, compared to perch from the control lake. We studied a complex of enzymes involved in carbohydrate metabolism and assessed the relationship between metabolic pathways using correlation analysis. The intensity of oxidative metabolism was greater in the gulls. The activation of energy metabolism in the liver was characterized by an increased consumption of carbohydrates. In addition, the role of the liver-specific lactate dehydrogenase (LDH) isoform D4 also increased. The activity of enzymes involved in carbohydrate metabolism decreased most strongly in white skeletal muscles, whereas the role of the pentose-phosphate pathway (along with glycolysis) in the production of muscle lactate increased. The adaptation of fish to a high-humus aquatic environment was accompanied by a slight decrease in their fatness.

[Long term use of a non-selective beta-blocker with vasodilating properties carvedilol in patients with severe heart failure]. / Dlitel'noe primenenie neselektivnogo beta-adrenoblokatora s vazodilatiruiushchimi svoistvami karvedilola u bol'nykh s tiazheloi khronicheskoi serdechnoi nedostatochnost'iu.

Results of drug treatment of 51 patients (41 men, 10 women) aged 35-86 years (mean age 62 years) included into COPERNICUS trial are presented. All patients had compensated NYHA class IV chronic heart failure and left ventricular ejection fraction less than 25%. For at least 2 months the patients received therapy with diuretics and angiotensin converting enzyme inhibitors (84%) or angiotensin receptor blockers (16%) and then were randomized to either carvedilol or placebo. Average duration of follow-up was 17 months. Carvedilol was well tolerated both during dose titration and during maintenance therapy. Addition of carvedilol to standard therapy of patients with severe heart failure was associated with increase of average ejection fraction from 21.7 to 30.3%. Rates of cardiovascular and sudden deaths, risk of hospitalization among carvedilol treated patients were 25, 33 and 57% less than among patients subjected only to standard therapy.

DNA topology in heterochromatin (a hypothesis).

A hypothesis explaining the known heterochromatin features--a compact DNA packaging, transcriptional inactivity, propensity to aggregate (stickiness) and position effect variegation-is described. The hypothesis is based on the assumption that DNA molecules in heterochromatin are topologically open and contain single-strand breaks in the regions with identical or similar primary sequences.

[Maintenance of torsional tension in DNA of transactivated genes during the cell cycle]. / Sokhranenie v kletochnom tsikle torsionnogo napriazheniia v DNK transkriptsionno-aktivnykh genov.

Changes in DNA topology during the cell cycle of murine fibroblasts in vitro were studied by microfluorometric method. At interphase stage, 21% of DNA were found to be torsionally stressed and hypersensitive to the relaxing activity of DNAase I. This DNA is presumably transcriptionally active. At metaphase stage, about 75% of DNA are under torsional stress with low sensitivity to DNAase I. After cytokinesis, one half of the stressed DNA relaxes, the other half of DNA remains under the stress. Later, one hour after cytokinesis, the stressed DNA attains hypersensitivity to DNAase I and remains hypersensitive during interphase. Taking into account that the cells in vitro steady maintain some domains of torsionally stressed DNA during the whole cell cycle, we suppose that these DNA domains contain genes, activated to transcription after mitosis. This may mean that the torsional stress preserved after mitosis is necessary for activation of the genes, which were active at the previous interphase stage.

[Torsional tension in metaphase chromosome DNA]. / Torsionnoe napriazhenie v DNK metafaznykh khromosom.

The torsional tension in DNA of isolated metaphase chromosomes from murine fibroblasts was measured by the microfluorescent method. The method is based on the ability of a fluorescent dye ethidium bromide to compensate for the negative torsional tension in topologically closed DNA by intercalation between DNA base pairs. The value of the relative twist difference delta Tw/Tw = -0.1 was found in a bulk (about 3/4) of unconstrained chromosomal DNA. In interphase nuclei, the torsionally stressed DNA comprises about 15%, with value of delta Tw/Tw = -0.075. We suppose that the tension in chromosomal DNA was created in the prophase stage of mitosis by condensines, the drivers of chromosomal condensation.

[Heterochromatin and single-strand DNA breaks (a hypothesis)]. / Geterokhromatin i odnonitevye razryvy DNK (gipoteza).

A hypothesis is put forward which explains the known heterochromatin properties: dense DNA packing, transcriptional inactivity, a tendency for aggregation (adhesiveness) and ectopic contacts. The basic assumption of the hypothesis is that the DNA molecules in heterochromatin are topologically open and contain single-strand breaks in the regions with the same or similar base sequence.

[Preparation of Drosophila mitotic chromosomes for electron-microscopic studies]. / Prigotovlenie preparatov mitoticheskikh khromosom drozofily dlia élektronno-mikroskopicheskogo issledovaniia.

A method of chromosome spreading on microscopic slides was modified for electron microscopy of metaphase chromosomes in Drosophila tissues. The slides covered with an electron transparent film were plasmochemically modified to make them hydrophilic. A piece of fixed tissue was macerated in 60% propionic acid before spreading chromosomes over the slide. The parts of preparation selected under light microscope for electron microscopic examination were cut and peeled of the slide to the top of a water drop. It was shown that the resolution of chromosomal structures was significantly higher than seen under optical microscope, but lower than in serial sections.

Torsional state of DNA in a transcriptionally hyperactive Balbiani ring of polytene chromosomes.

The torsional tension of unconstrained double-helical DNA was determined in transcriptionally hyperactive Balbiani ring 2 (BR2) and in inactive polytene chromosome bands of Chironomus tentans. The method used is based on the dual ability of small intercalating ligands to (a) sense, by differential binding, twists that deviate from that of regular B-form DNA and (b) create positive torsional tension in closed double-stranded DNA, thereby compensating for any negative torsional tension that existed before intercalation. Isolated nuclei of salivary glands were stained with the intercalating fluorescent dye ethidium bromide (EtBr) at various concentrations, and the temporal fluorescence intensity changes (deltaI/I per min) occurring in BR2 and in inactive bands were monitored under a confocal laser scanning microscope during the process of DNA nicking by laser irradiation or DNAase I. From the EtBr concentration at which deltaI/I per min was neither positive nor negative after nicking (i.e. at the equivalence point), the relative twist difference (RTD) was calculated. In bands, it was found to be very small, suggesting that their unconstrained DNA is under low torsional stress. In contrast, the RTD of DNA in highly expanded areas of BR2 was estimated to be negative and of a significant magnitude in absolute terms. This indicates that transcriptionally hyperactive DNA is under considerable negative torsional tension.