[Correction of serum prooncogenic cytokines and metastases by 5-hydroxypyrimidine derivatives and doxorubicin after removal of a primary tumor node in mice with the Lewis lung epidermoid carcinoma]. / Korrektsiia urovnia syvorotochnykh proonkogennykh tsitokinov i metastazirovaniia proizvodnymi 5-oksipirimidina i doksorubitsinom posle udaleniia pervichnogo opukholevogo uzla u myshei s metastaziruiushchim rakom legkogo LLC.

The effect of a single injection of doxorubicin, 8-day administration of two 5-hydroxypyrimidine derivatives, SNK-411 (2-Isobutyl-4,6-dimethyl-5-hydroxypyrimidine) and SNK-578 (hydrochloride of 2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine), on metastases, lifespan and serum cytokines has been investigated in С57ВL/6 mice after removal of a primary tumor node of Lewis lung carcinoma (LLC). LLC cells (1×106) were injected in the footpad of right hind feet of mice in control and experimental groups; after 14 days of tumor development the hind feet with the tumor were amputated at the ankle level. One hour before the amputation mice received a single injection of doxorubicin (4 mg/kg) and 8-day therapy with the 5-hydroxypyrimidine derivatives started. SNK-578 monotherapy was performed at a dose of 10 mg/kg administered intraperitoneally (i.p.). SNK-411 was administered per os at a dose of 25 mg/kg. In the case of combined therapy mice also received a single injection of doxorubicin (4 mg/kg; i.p.). The metastasis inhibition index in mice-treated with SNK-411 and SNK-578 were 53.3% as compared with control mice (with removed tumor). The mice-treated with SNK-411, doxorubicin, and the combination SNK-578 + doxorubicin had lifespan increased by 60.2%, 53.9%, and 42.9%, respectively. A single injection of doxorubicin, the course administration of the 5-hydroxypyrimidine derivative alone and in combination with single injection of doxorubicin completely decreased serum levels of the prooncogenic Th2-cytokines IL-4, and IL-6 and significantly decreased the level of the Th2-cytokine IL-5. Administration of doxorubicin, SNK-411 and SNK-578 did not influence serum concentration of Th1-cytokine interferon gamma (IFN-γ). These data confirm our previous findings that administration of the compounds studied decreased concentrations of prooncogenic IL-4 and IL-6 in tumor-bearing mice with LLC and had no effect on concentrations of the Th1-cytokine IFN-γ.

Unusual congenital polydactyly in mini-pigs from the breeding group of the Institute of Cytology and Genetics (Novosibirsk, Russia).

The article describes a new phenomenon in the breeding group of mini-pigs at the Institute of Cytology and Genetics (ICG, Novosibirsk): polydactyly (extra digits), which is unusual because the additional digits are situated at the lateral surface of legs or at the lateral and medial ones. This anomaly was f irst found here in 2017 in adult animals intended for culling due to incorrect positioning of the legs caused by f lexor tendon laxity and resulting in weight-bearing on the palmar surface of the proximal phalanges ("bear's paw"). Therefore, the polydactyly of mini-pigs has a pronounced negative selection effect. A visual survey of the livestock was conducted, and a description of the detected anomaly was compiled. The polydactyly in mini-pigs is a stand-alone trait and is not part of any syndromes. Individuals with polydactyly may have extra digits either on pectoral or on pectoral and pelvic limbs. On thoracic limbs, there may be either one lateral digit or a lateral digit and a medially located rudimentary hoof let. On pelvic limbs, only lateral extra digits can occur. Anatomical and morphological analyses showed that the lateral extra digit is an anatomically complete ("mature") structure, whereas the medial rudimentary digit consists of only a hoof let without other structures characteristic of normal digits. Cytological examination revealed no specif ic karyotypic features, except for Robertsonian translocation Rb 16;17 previously reported for the mini-pigs of the same livestock. Cytological f indings indicated that the polydactyly and Robertsonian translocation are not linked genetically. Genealogical analysis and results of crosses are consistent with a working hypothesis of recessive inheritance of the trait. Overall, the study shows that this type of polydactyly is anatomically and morphologically unique and not typical of Sus scrofa. In this species, only polydactyly types with medial accessory toes have been described and are usually inherited as a dominant trait with incomplete penetrance. In our case, the results of test crosses indicate recessive inheritance of the trait with varying expression and incomplete penetrance, because of which poorly expressed phenotypes are not visually detectable.

[Effect of 5-hydroxypyrimidine derivatives on tumor growth and cytokine concentration in blood serum of female CBA mice with cervical cancer (RSHM-5)]. / Vliianie proizvodnykh 5-oksipirimidina na rost opukholi i soderzhanie interleikinov v syvorotkakh krovi samok myshei linii SVA s rakom sheiki matki (RShM-5).

The effects of intraperitoneal administration of SNK-411 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine) in a dose of 25 mg/kg (the total dose of 350 mg/kg) and SNK-578 (hydrochloride of 2-isobutyl-4,6-dimethyl-5- hydroxypyrimidine) in a dose of 10 mg/kg (the total dose of 140 mg/kg) on tumor growth and concentration of cytokines in the blood serum were studied in female CBA mice. Substances were administrated from the 2nd to 15th days of tumor development. Tumor growth inhibition (TGI) and serum cytokine level were studied on the 7th day after the end of compounds administration (21st day of tumor growth). In intact control group (n=10) median tumor mass was 1255 mg. TGI in the group of animals treated with SNK-411 was 47%; in the group of mice treated with SNK-578 TGI was 87%, tumor mass demonstrated 7.4-fold reduction. Serum concentrations of cytokines (IL-6, IL-10, IL-17A and IFN-γ) in tumor-bearing group of mice were higher versus the intact control group by 229%, 40%, 60% and 81%, respectively. Highly active SNK-578 decreased concentrations of prooncogenic IL-10, IL-17A and proinflammatory IL-6, by 61%, 70% and 29% as compared to tumor-bearing control group. SNK-411 decreased concentrations of prooncogenic IL-10 and IL-17A by 48% and 60%, respectively, and did not affect concentration of IL-6. Taking into consideration that IL-6 participates in autoimmune reactions, we can assume that the immune control is one of the crucial mechanisms of antitumor effect of SNK-578. All results are statistically significant.

Effects of 5-Hydroxypyrimidine Derivatives on Tumor Growth and Lifespan of C57BL/6 Mice with Epidermoid Lung Carcinoma.

The effects of 5-hydroxypyrimidine derivatives SNK-411 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine) and SNK-578 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine chlorohydrate) on the tumor growth and survival of male C57BL/6 mice with transplanted Lewis lung epidermoid carcinoma (LLC) were studied in animals receiving intraperitoneal treatment on days 2-15 of tumor development. Compound SNK-578 in a dose of 10 mg/kg significantly inhibited tumor growth (by 3.6 times; 72.2%) in 7 days after the treatment was discontinued, while compound SNK-411 in a dose of 25 mg/kg only negligibly reduced tumor volume (by 41.7%). A combination of course of SNK-411 (25 mg/kg) and single intraperitoneal dose of doxorubicin (4 mg/kg) significantly inhibited the tumor growth (by 2.2 times; 55.2%), while the combination of SNK-578 (10 mg/kg) with doxorubicin (4 mg/kg) was in fact ineffective. The median survival of animals with untreated LLC was 28 days. Median survival of mice injected with SNK-578 (10 mg/kg) was 43 days, hence, the lifespan of mice with LLC was by 38.6% longer after the treatment. Two of ten mice in this group developed no tumors.

Effect of 2-Isobutyl-4,6-dimethyl-5-hydroxypyrimidine on the Growth of Lewis Lung Carcinoma and Survival of Mice.

Experiments on male C57Bl/6 mice with transplantable Lewis lung epidermoid carcinoma were performed to evaluate the effect of early or delayed administration of compound SNK-411 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine) on tumor growth and animal survival. Intraperitoneal injection of SNK-411 in doses of 25 and 50 mg/kg on days 2-8 of tumor growth was followed by significant inhibition of tumor growth (by 1.8 and 2.2 times, respectively, in comparison with the untreated control). Administration of this compound on days 8-15 of tumor development had little effect on tumor growth. SNK-411 in doses of 25 and 50 mg/kg (both dosing regimens) significantly increased survival rate and lifespan of animals with tumors. The drugs for verification of this model (Fluorofur, 400 mg/kg; and doxorubicin hydrochloride, 4 mg/kg) were injected intraperitoneally on days 2-4 and 8-10 of tumor development. Administration of Fluorofur and doxorubicin hydrochloride at the late stage was accompanied by significant inhibition of tumor growth (by 1.6 and 1.4 times, respectively). The increase in the survival rate of animals receiving the cytostatic according to standard dosing regimens was less significant than in experiments with SNK-411.

Effects of 5-Pyrimidinol Derivative SNK-41 on Cytokine Profile of Mice with Lewis Lung Carcinoma.

We studied the effects of SNK-411, a new 5-pyrimidinol derivative, on serum cytokine profile of C57Bl/6 mice with Lewis lung carcinoma. The compound was injected intraperitoneally in doses of 25 and 50 mg/kg. A significant (by 3.5 times) increase in serum IL-4 content was detected in mice with tumors on day 9 of tumor development. In mice receiving SNK-411 in doses of 25 and 50 mg/kg, IL-4 content significantly decreased (by 4.0 and 3.6 times) on days 2-8 of carcinoma development; IL-2 content decreased by 1.4 and 1.2 times and IL-6 content decreased by 2.7 and 1.6 times, respectively, in comparison with control mice with tumors. Injections of SNK-411 in the same doses on days 8-15 of carcinoma development led to a significant decrease in IL-4 levels (by 2.2 and 4.5 times, respectively, in comparison with control mice with tumors) and did not affect serum levels of other cytokines.

[Genetic components and the uncertainty of the phenotypic realization of the mass of newborns in domestic pigs Sus scrofa L].

In this article, we discuss the features of the genetic determination of a continuous quantitative trait, the mass of newborn offspring in populations of the domestic pig. We defined several components that determine the phenotypic trait, such as the maternal effect, complete dominance, interaction of the parental alleles in the genotype of the offspring, and the uncertainty of phenotypic realization of genotype. We found that a phenotypic trait of high genetic determinacy can also have a maximum range in phenotypic realization, in which case each genotype encountered in the population can realize within the entire range of possible phenotypes.

[Model of genetic control of the number and location of nipples in domestic pig].

In domestic pig, the number and location of nipples is considered a single quantitative trait, which has a complex spatial structure that includes bilaterality and a linear sequence of repetitive elements. According to this hypothesis, six inadherent biallelic loci are sufficient for a variety of traits observed in domestic pig populations. Verification of representative samplings from five domestic pig populations of different origin (about 20 000 individuals) confirmed the theses of the hypothesis, this fact allows considering it as a model of the studied bilateral trait. Using the model, the intraclass pheno- and genotypic diversity was examined and the relationship of the trait manifestation asymmetry with heterozygosity of loci that control it was shown.

[Ocular and orbital blood flow in apparently healthy adults].

Doppler measurements of ocular and orbital blood flow at rest were studied using duplex ultrasonography in 30 apparently healthy adult volunteers. The following linear and calculated Doppler measurements were estimated at rest: blood flow in ophthalmic artery (OA), central retinal artery (CRA), posterior ciliary arteries, central retinal vein and superior ophthalmic vein (SOV). In 10 patients Doppler measurements of blood flow in OA, CRA SOV were estimated 5 times by 2 observers with different level of skills in ultrasonographic ophthalmologic examination. Statistic analysis showed strong correlation of linear and calculated measurements in OA, CRA and venous blood flow velocity. A number of Doppler measurements with the most significant inter- and intraobserver variation were revealed. Measurements with high reproducibility were determined. Thus, a unique technique should be performed in estimation of Doppler measurements of blood flow in ocular and orbital vessels. The velocities in the main arteries (OA, CRA) and veins (SOV) were showed to have significant strong interobserver correlation. The highest reproducibility and accuracy was revealed for maximal systolic velocity in OA and CRA and maximal velocity for cardiac cycle in SOV.

[Standardized selection and its consequences for genetic population structure (examplified by Sus scrofa L.)].

Type of selection for total fitness, specific for domestic animals and termed by us standardizing selection, is discussed. Consequences of such selection for the population structure genetic are considered taking a population of domestic pigs as an example. Examples of effective and ineffective standardizing selection are presented. Specific features of genetic determination often quantitative traits detected in analysis of standardizing selection are discussed.

[Expression of estrogen and progesterone receptors in the endometrium of fertile and infertile women].

The aim of the research is investigation of the endometrial hormonal status during menstrual cycle infertile and infertile women. 68 endometrial biopsies from 18-45 years old women have been studied. Some changes of ER and PR expression during menstrual cycle both in fertile and infertile women has been founded. However the ER expression in endometrial stroma and PR in the glands in a proliferative stage of cycle of fertile women are higher than in a secretory stage. In infertile women the PR expression in endometrial glands is opposite.

[Dynamics of heterozygosity and its correlation with fitness in a population of domestic pigs].

Variation of heterozygosity at 11 loci for blood group systems (erythrocyte antigens), occurred during 14 years in the domestic pig population of Kemerovskaya breed is described. The two estimates computed for the population examined were represented by expected population heterozygosity, as a measure resistant to stochastic fluctuations, and individual heterozygosity, as a measure with the features of a quantitative trait. Our results showed that relative fitness of genotypic classes, formed by the alleles of erythrocyte antigen loci, was different. It was demonstrated that the population examined carried the alleles responsible for fitness decrease, as well as the alleles with stable and unstable equilibrium points (with increased and decreased relative fitness of heterozygotes). Suggestions based on these results, could be applied not only to the population examined, but also to the domesticated form of Sus scrofa as a whole.

[Frequency of chromosomes carrying endogenous retroviruses in the populations of domestic pig and wild boar].

Statistical analysis of the frequency of chromosomes carrying three types (A, B, and C) of porcine endogenous retroviruses (PERV) was based on molecular-genetic testing of populations of domestic pigs and wild boars. Domestic pigs were shown to have higher frequency of PERV and haplotypes containing two and three types of PERV than wild boars.

[Sex-linked erythrocyte antigens of the domestic pig].

It has been demonstrated that the domestic pig has a blood group systems whose haplotypes (complex alleles) are formed by at least three closely linked loci that are located, like the MIC2 locus of human blood group systems, in the homologous region of sex chromosomes.

[Modeling the structure of supergenes controlling some polyallelic blood group systems in the pig Sus scrofa and horse Equus caballus].

Two polymorphic blood group systems (E and M) of the pig Sus scrofa L. and one blood group system (D) of the horse Equus caballus L. have been studied. On the basis of phenogroup analysis, models describing the formation of the complex allele spectra of these systems and reflecting the contributions of mutations and recombinations have been constructed. The complementary relationships between the antigens determined by the variants of supergenes within the systems, as ell as the probable number and relative positions of the subloci encoding individual groups of antigens in them, have been determined.

[Organization of sanitary and epidemiological measures to protect the Omsk region involved in epizootia of avian flu].

In article organizational aspects of carrying out preventive and antiepidemic actions at a regional level are considered at the bird's flu epizootia. Epizootic researches have shown, that infection of poultry has taken place as a result of contact to a wild bird. Serological inspection 521 persons on presence of antibodies to a influenza A (H5N1) has not revealed seropositive persons. The conclusion, that the forecast of development of a situation for spring of 2006 is made in view of a direction of migration of a wild waterfowl is unfavourable.

[Diversity of wild and domestic pig populations estimated by a set of serum allotypes].

Variation of serum protein allotypes serving as genetic markers of the blood has been analyzed in 29 populations of the domestic pig and subspecies of the wild boar. The population biodiversity and genetic structure have been estimated by two methods: by the frequencies of allotype combinations and with the use of a map constructed in the space of two principal components. The results obtained are the basis for determining the characteristics of the microevolution of wild boars and formation of the breeds of domestic pigs.

[The clinical-morphological estimation of the results of laser osteoperforation in treatment of chronic osteomyelitis]. / Kliniko-morfologicheskaia otsenka rezul'tatov lazernoi osteoperforatsii pri lechenii khronicheskogo osteomielita.

The method of laser osteoperforation was approved in 135 patients with chronic osteomyelitis. The diode laser with wave length 970 mm and peak power up to 30 Wt was used. Energy was delivered by the percutaneous contact method with a quartz light guide of 0.4 mm diameter. All the patients had a distinct positive reaction in the nearest days after operation. The fistulas were closed within 4-10 days. Stable remission was noted during 2-5 years by objective indices (X-ray, fluometry, densitometry, morphological data). Our experiences with clinical use of laser osteoperforation show its high efficiency in treatment of chronic osteomyelitis. The method is minimally invasive and allows to considerably shorten the terms of treatment and rehabilitation.