Cowpox in a human, Russia, 2015.

We investigated the first laboratory-confirmed human case of cowpox virus infection in Russia since 1991. Phylogenetic studies of haemagglutinin, TNF-α receptor-like protein and thymidine kinase regions showed significant differences with known orthopoxviruses, including unique amino-acid substitutions and deletions. The described cowpox virus strain, taking into account differences, is genetically closely related to strains isolated years ago in the same geographical region (European part of Russia and Finland), which suggests circulation of viral strains with common origin in wild rodents without spread over long distances and appearance in other parts of the world.

[The influence of STAT4 rs7574865 (G/T) polymorphism on the risk of clinical and immunological phenotypes of systemic sclerosis in a Russian patient population: Results of a pilot study]. / Vliianie polimorfizma rs7574865 (G/T) gena STAT4 na risk razvitiia klinicheskikh i immunologicheskikh fenotipov sistemnoi sklerodermii v russkoi populiatsii bol'nykh: rezul'taty pilotnogo issledovaniia.

AIM: To examine the association of signal transducer and activator transcription 4 (STAT4) rs7574865 G/T polymorphism with a predisposition to systemic sclerosis (SSC) and associated clinical and autoimmune phenotypes in a Russian population. SUBJECTS AND METHODS: A total of 102 patients with SSC and 103 healthy individuals as controls were examined. STAT4 rs7574865 polymorphism was investigated by real-time polymerase chain reaction. RESULTS: The carriers of the T allele showed a statistically significant association with SSC, a diffuse form (DF), the presence of interstitial lung disease (ILD), cardiac injury (CI), and seropositivity for anti-topoisomerase I antibodies (ATA). CONCLUSION: The findings results confirm the important role of STAT4 gene in the predisposition to SSC and its phenotypes, such as DF, ILD, CI, and ATA in the Russian population.

[The identification of the AB0 blood type system by means of the single nucleotide polymorphisms analysis]. / Opredelenie gruppovoi prinadlezhnosti po sisteme AV0 metodom SNP-analiza.

The authors describe a domestically produced test-system for the determination of the AB0 blood type by means of the single nucleotide polymorphisms (SNP) analysis. The results of the trials indicate that the proposed test-system can be employed for the investigation of DNA specimens of individual origin obtained from any objects of expertise including micro-objects containing human nuclear DNA.

[Direct human DNA damage by unfavorable environmental and climatic factors].

AIM: To study the impact of simulated climatic conditions of the 2010 summer in Moscow on the telomere repeats of chromosomes in human blood cells. MATERIALS AND METHODS: The climatic conditions of July-August 2010 in Moscow were simulated at the Medical Technical Complex, Institute of Biomedical Problems, Russian Academy of Sciences. The relative length of the telomeric repeats of blood cell chromosomes from 6 apparently healthy volunteers was measured by quantitative real-time polymerase chain reaction. RESULTS: These conditions were ascertained to lead to a statistically significant decline in the length of telomere repeats in the terminal portions of chromosomes by 15%. CONCLUSION: Environmental changes and abnormal temperature rises may result in oxidative stress accompanied by telomere shortening, which can be, in turn, a factor of premature aging.

[Polymorphisms of genes CYP2C9 and VKORC1 in patients with venous thromboembolic complications in Moscow population: effects on stability of anticoagulant therapy and frequency of hemorrhage].

AIM: To investigate frequency of carriage of genetic polymorphisms CYP2C9 and VKORC1 in patients with venous thromboembolic complications (VTEC) in Moscow population given warfarin treatment and effects of this carriage on stability of anticoagulation and frequency of hemorrhagic complications (HC) in warfarin treatment. MATERIAL AND METHODS: The study included 111 patients with the history of deep vein thrombosis and/ or pulmonary artery thromboembolism. All the patients received non-fractionated or low-molecular heparin for at least 5 days, then warfarin (target INR 2.0-3.0). Warfarin dose was selected empirically. Gene CYP2C9 and VKORC1 polymorphisms were studied. HC were endpoints. RESULTS: Genotype CYP2C9*1/*1 (a "wild" type) was detected in 94 (84.7%) patients. Of other genotypes - heterozygotes CYP2C9*1/*2 (4.5%) and CYP2C9*1/*3 (10.8%). Genotyping by VKORC1 detected genotype GG (a wild type) in 42.3%, genotype GA--in 48.6%, genotype AA--in 9.1% patients. A mean warfarin dose, supporting an adequaite INR, was asspciated with both genotype CYP2C9 and VKORC1. Warfarin doses were highest in carriers of wile genotypes CYP2C9 and VKORC1 (6,9 and 8,8 mg/day), the lowest--in patients with genotypes CYP2C9*1/*3 and VKORC1 (4,5 and 4,0 mg/day). The carriers of polymorphisms CYP2C9*1/*3 and VKORC1 showed less stable anticoagulation vs carriers of allele variants CYP2C9*1/*1, CYP2C9*1/*2 and genotypes GG, GA VKORC1. An HC rate depended, as a rule, on carriage of genotypes CYP2C9*1/*3 and AA VKORC1. The highest risk of HC was associated with genotype CYP2C9*1/*3. The results of multifactorial regression analysis also indicated that carriage of genotype CYP2C9*1/*3, a female gender and the range of INR in warfarin treatment > or = 2,66 are independent predictors of HC in VTEC patients on warfarin treatment. CONCLUSION: Carriage of gene CYP2C9 and VKORC1 polymorphisms affects suppoting dose of warfarin and rate of hemorrhage in patients with VTEC in Moscow population. Frequency of HC is the highest in carriers of genotypes CYP2C9*1/*3 and AA VKORC1, they need minimal supporting dose of warfarin. Carriage of genotype CYP2C9*1/*3 in line with a female gender and instability of INR is an independent predictor of HC in VTEC patients in Moscow population on warfarin treatment.

[Independent predictors of deep vein thrombosis (results of prospective 18 months study)].

We followed for 18 months 90 patients who had had deep vein thrombosis (DVE) and/or pulmonary embolism (PE) and received therapy with anticoagulants either for 3-12 months or for indefinitely long time. During follow-up rate of recurrent DVE was 16.7%, no recurrences of PE were registered. Predictors of recurrent PE were selected among 165 demographic, anthropometric, anamnestic, clinical, genetic, instrumental, and laboratory parameters, as well as risk factors of development of thromboembolic complications. According to results of multifactorial regression analysis we established the following independent predictors recurrent DVE during 18 months of follow-up: elevated level of DAdimer after 1 month of anticoagulant therapy (p=0.005; relative risk--relative risk [RR] 8.1, 95% confidence interval [CI] 1.9 to 34.8), homozygosity for C249T polymorphism in beta-fibrinogen gene (p=0.044; RR 8.4 95% CI 1.1 to 65.7), and percentage of all values of international normalized ratio within therapeutic interval 2.0-3.0 (p=0.009; RR 0.94, 95 CI 0.89 to 0.98).

Chickens productivity selection affects immune system genes.

The quantitative trait loci associated with the immune properties of chickens are of interest from the point of view of obtaining animals resistant to infectious agents using marker-assisted selection. In the process of selecting markers for genomic selection in broiler-type chickens, a non-standard genotype frequency of the RACK1 gene allele (SNP Gga_rs15788101) in the B5 line of broiler-type chicken cross Smena 8 was identified and it was suggested that this gene was involved in selection. Therefore, it was decided to investigate the available polymorphisms in the three genes responsible for the IgY titer (DMA, RACK1 and CD1B). Molecular typing of single nucleotide polymorphisms of three loci revealed an approach to fixation of the unfavorable allele of the DMA gene (SNP Gga_rs15788237), an approach to fixation of the unfavorable allele of the RACK1 gene and the prevalence of the favorable CD1B gene allele (SNP Gga_rs16057130). Analysis of the haplotypes revealed a strong linkage disequilibrium of these genes. This suggests that these genes experience selection pressure. Analysis of the protein-coding sequences of the CD1B and DMA genes of various breeds of chickens revealed a negative selection of these genes. In order to understand whether the fixation of the studied alleles is the result of artificial selection of the B5 line of the cross Smena 8, an analysis of similar loci in layer chickens Hisex White was carried out. The frequencies of the alleles at the loci of the CD1B gene (Gga_rs16057130) and the RACK1 gene (Gga_rs15788101) in the Hisex White chicken genome differ from the frequencies of the alleles obtained for chickens of the B5 line of the cross Smena 8. It can be assumed that the fixation of the allele in the DMA gene (SNP Gga_rs15723) is associated with artificial or natural selection, consistent in broilers and layers. Changes in the loci Gga_rs16057130 and Gga_rs15788101 in the B5 line of the Smena 8 chickens are most likely associated with artificial selection of broiler productivity traits, which can subsequently lead to fixation of alleles at these loci. Artificial breeding of chickens leads to degradation of the variability of genes encoding elements of the immune system, which can cause a decrease in resistance to various diseases. The study of the negative impact of selection of economic traits on immunity should provide means to mitigate negative consequences and help find ways to obtain disease-resistant animals.

[Study of the genetic markers of thrombosis in hypertensive patients of the native population in the Republic of Mordovia].

The genetic markers (encoding factor of blood coagulation, the PAI-1 gene, the prothrombin gene, the GP IIb/IIIa gene, and the MTHFR gene) of thrombosis were studied in the Mordovians and Russians with essential hypertension (EH), who were residents of the Republic of Mordovia. One hundred and forty patients with TH and 90 healthy individuals of three nationalities, such as Russian, Moksha-Mordovian, and Erzya-Mordovian, were examined. Along with the routine clinical and instrumental studies, alleles of polymorphic markers were identified by the polymerase chain reaction (PCR). The polymorphic markers of the Arg 506 Gln gene, encoding factor V of blood coagulation, 4G5G of the PAI-1 gene, the G 20210 A prothrombin gene, the GP IIb/IIIa gene, and the A 1298 C MTHFR gene were also studied. The data were statistically analyzed using a package of the programs: Statistica for Windows 6.0 (Stat Soft), SPSS (version 14.0), and MS Excel XP (Microsoft). The authors used a chi-2 (chi-square) test was used to compare the incidence of genotypes and alleles in the patient groups. Hypertensive and normotensive persons were found to have no significant differences in the distribution of genotypes (encoding factor of blood coagulation, the PAI-1 gene, the prothrombin gene, and the GP IIb/IIIa gene) with regard to ethnicity in the Russian, and Moksha-Mordovian, and Erzya-Mordovian groups). Meanwhile, there was a significant preponderance of MTHFR gene mutation with the unfavorable genotype for Moksha-Mordovian patients with EH. The findings suggest that drug therapy for preventing venous thrombosis in patients with EH should be adjusted in relation to ethnicity.

[Determinants of morbidity in the areas situated along the Techa and Iset Rivers].

Due to the massive pollution of the Techa-Iset river system with the radioactive sewage of the Mayak industrial association in the 1950s, the factors responsible for the incidence of diseases were studied in 5 districts of the Kurgan Region along the territory of which rivers flow. There is a direct relationship of children's morbidity to ambient air pollution. The determinants of adult morbidity are air pollution and water quality. There is an inverse correlation of morbidity with the provision with therapists and with the economic indices of districts. The prevalence of some types of diseases, such as those of the endocrine and respiratory systems, ulcer disease correlates with the ranking position of a district in the level of pollution in the Techa and Iset Rivers.

[Nonenzymatic covalent modification of human hemoglobin by pyridoxal-5-phosphate under the effect of visible light]. / Neénzimaticheskaia kovalentnaia modifikatsiia gemoblobina cheloveka piridoksal'-5-fosfatom pod deistviem vidimogo sveta.

Under the action of visible light, PLP with apo-, oxy- and deoxy-Hb at 4-20 degrees C and neutral pH produced adducts stable to dialysis and Sephadex gel filtration. The stable adduct formation enhanced with an increase in radiation intensity and/or irradiation time. Under light, production of stable adducts occurred most effectively for apo-Hb and was significantly slowed down in the case of met-Hb as well as in the presence of an electron acceptor, methylene blue. PLP-Hb adducts possessed intense fluorescence coinciding in properties with the fluorescence of stable PLP adducts obtained after Schiff base reduction by NaBH4. Stable adduct formation is assumed to proceed owing to Schiff base aldimin link reduction by photoejected electrons. During isoelectrofocusing of hemoglobins which had formed stable adducts with PLP under light or after NaBH4 treatment of solutions, essentially the same pictures were observed as to the number of new bands and their position in the isoelectroforegram, with the band intensity being different. This is related to the distinctions in the electron seeking properties of the Schiff bases produced by PLP with alpha-NH2 groups of Val-1 and epsilon-NH2 groups of lysine residues of the protein alpha- and beta-chains.

[the synthesis of diporphyrin systems on the basis of tetraphenylporphyrin derivatives bridged with peptide spacers]. / Sintez diporfirinovykh sistem na osnove proizvodnykh tetrafenilporfinina, soedinennykh peptidnymi speiserami.

Diporphyrin systems based on tetraphenylporphyrin derivatives bridged with dipeptide or tripeptide spacers containing Gly and Phe residues were synthesized, and their physicochemical properties were studied.

[Nonenzymatic reduction of Met-Hb under the action of NAD radicals generated in the presence of HAD.H and Fe(II) salts. Antioxidant properties of Met-Hb]. / Neénzimaticheskoe vosstanovlenie Met-Hb pod deistviem radikalov NAD, generiruemykh v prisutstvii NAD.H i solei Fe(II). Antioksidantnye svoistva Met-Hb.

It has been found that superoxide radicals formed at autooxidation of Fe(II) ions or of their complexes with EDTA in the presence of NAD.H cause reduction of met-Hb into deoxy or oxy-form. Under the effect of hydroxyl radicals generated in the ultrasonic field in the presence of NADH reduction of met-Hb into the ferro-form (carboxy-Hb) was observed in Co atmosphere and not in O2 atmosphere. It was induced by a high oxidation rate of oxy-Hb by hydroxyl radicals into met-Hb as compared to carboxy-Hb. Reduction of met-Hb was shown to be accompanied with the formation of NAD+. The role of NAD. radicals in the reduction of met-Hb which acts as an antioxidant in respect to organic free radicals was discussed.

[Localization of pyridoxal-5-phosphate, covalently bound with human hemoglobin. Spectrofluorimetric studies]. / Lokalizatsiia piridoksal'-5-fosfata, kovalentno sviazannogo s gemoglobinom cheloveka. Spektrofluorimetricheskie issledovaniia.

Human apohemoglobin tryptophan residues were localized in the regions of the protein globule with restricted mobility. By the method of dynamic quenching of phosphopyridoxyl chromophore fluorescence, the heterogeneity of pyridoxal-5-phosphate molecules covalently bound to the human hemoglobin molecules was determined from the accessibility to solvent. The first four pyridoxal-5-phosphate molecules are localized in the hydrophobic regions of the hemoglobin molecule; at the same time, they have a high mobility. One of these molecules is situated at the site inaccessible to the solvent, which coincides with the anion-binding center of the oxyhemoglobin molecule. The next pyridoxal-5-phosphate molecules modify the surface amino groups of the protein. In the apohemoglobin molecule, the pyridoxal-5-phosphate binding sites are more exposed to the solvent, as compared to hemoglobin. In the hemoglobin molecule modified by pyridoxal-5-phosphate, an effective electron excitation energy transfer from tryptophan residues to phosphopyridoxyl chromophores occurs. The effective distances between tryptophanyls of single subunits of hemoglobin and the covalently bound pyridoxal-5-phosphate molecule were estimated to be 19 A for the alpha-subunit and 17 A for the beta-subunit.

[Taufon and emoksipin in the combined treatment of sclerotic macular dystrophies]. / Taufon i émoksipin v kompleksnom lechenii skleroticheskikh makulodistrofii.

The paper analyses results after complex treatment of 105 patients with sclerotic macular dystrophies. Taufon was added for treatment of early sclerotic macular dystrophies in 37 patients, emoxipine--of exudative sclerotic macular dystrophies in 23 patients. The treatment resulted in a more pronounced rise of visual functions, and stabilization of the dystrophic process in the retina ensued in earlier terms as compared with results achieved in 45 patients treated by traditional methods. Remote results of the treatment, followed up for two years in 70 patients, have shown that the usage of taufon and emoxipine allowed to achieve stabilization of visual functions in 76% of patients, while traditional methods of treatment stabilized visual functions in 61.6%. Differential prescription of the above preparations allowed to achieve the rise of visual functions and a more complete stabilization of the dystrophic process.

Laser kinetic spectroscopy studies of the bimolecular oxygenation of alpha- and beta-subunits within the R-state of human hemoglobin.

Bimolecular oxygenation of tri-liganded R-state human hemoglobin (HbA) is described by bi-exponential kinetics with association rate constants k(alpha) = 27.2 +/- 1.3 (micro M*sec)(-1) and k(beta) = 62.9 +/- 1.6 (micro M*sec)(-1). Both the observed processes have been assigned to the bimolecular oxygenation of alpha- and beta-subunits of the native tetrameric protein by molecular oxygen. The quantum yields of photodissociation within the completely oxygenated R-state HbA are gamma(alpha) = 0.0120 +/- 0.0017 and gamma(beta) = 0.044 +/- 0.005 for alpha- and beta-subunits, respectively. The oxygenation reactions of isolated alpha(PCMB)- and beta(PCMB)-hemoglobin chains are described by mono-exponential kinetics with the association rate constants k(alpha) = 44 +/- 2 (micro M*sec)(-1) and k(beta) = 51 +/- 1 (micro M*sec)(-1), respectively. The quantum yields of photodissociation of isolated alpha(PCMB)- and beta(PCMB)-chains (0.056 +/- 0.006 and 0.065 +/- 0.006, respectively) are greater than that observed for appropriate subunits within the R-state of oxygenated HbA.

[Immunopharmacological activity of perfluorotributylamine]. / Issledovanie immuno-farmakologicheskoi aktivnosti perftortributilamina.

It was shown in experiments on mice that the chemically inert compound perfluortributylamine has sufficiently expressed immunopharmacological activity. Its intraperitoneal administration causes a drop in the immune response of mice, immunized with sheep erythrocytes. These animals had a marked durable resistance to the soporific action of hexenal.

Interaction of ethanol with blood proteins.

At concentrations arising in alcohol intoxication ethanol was reversibly bound to human serum albumin and hemoglobin. Alcohol altered the conformation and stability of the proteins, reduced the domain-domain interactions in the molecule of albumin and changed the binding of such hydrophobic ligands as ANS and bilirubin.

[Hematopoietic study of rats in experiments with exchange blood replacement by an emulsion of perfluorotributylamine]. / Izuchenie krovetvoreniia u krys v opytakh s obmennym zameshcheniem krovi émul'siei perftortributilamina.

In experiments on nonanesthetized rats blood was substituted with perfluorotributyl emulsion (PFTBA). The mean volume of transfused PFTBA was 10 ml/100 g of body weight. During the period of blood replacement and the following 5 days the rats were kept in an atmosphere with increased oxygen content, and then they were placed under normal atmospheric conditions. The influence of PFTBA solution on hemopoiesis was studied in these experiments. A marked erythropoiesis activation in the bone marrow combined with expressed peripheral blood reticulocytosis was observed 6 days after the exchange blood substitution. Hemoglobin content decreased to 8.2 g% mature and immature white cell count rose; immature erythropoiesis cells were found: polychromatophilic erythro- and normoblasts (4.2% on the average). By the 13th day there was complete normalization of hemopoiesis which lasted 12 months without any significant deviations. Basing upon the results obtained it may be concluded that the PFTBA emulsion under study produces no negative effect on the animal hemopoiesis, and does not disturb the normal regulation process under conditions of the experiment conducted.

[The therapeutic efficacy of phonophoresis of ribonucleic acid hydrolysate in toxic retinal lesions]. / Izuchenie terapevticheskoi éffektivnosti fonoforeza gidrolizata ribonukleinovoi kisloty pri toksicheskikh porazhennykh setchatki.

Experiments on 82 rabbits (162 eyes) have shown that RNA hydrolysate phonophoresis possesses a pronounced protective action by stimulating a rapid cupping of metabolic disturbances and a restoration of the chemical state of cellular elements of the retina in a relatively remote terms after the introducing of a monobromoacetate inhibitor (within first 3 days). Experimental therapy beginning 10 days after the introducing of monobromoacetate, i. e. in the period when, besides metabolic disturbances histomorphologic changes were also seen, considerably stimulated activation of compensatory-inflammatory processes. The investigations carried out allow to recommend RNA hydrolysate phonophoresis for clinical examination in dystrophic diseases of the retina.