[The comparative evaluation of accessibility of stomatological care for municipal and rural population of the Belgorod Oblast].

At the actual stage of becoming of Russian stomatology, the problem of sustainable development of rural stomatological care, as system of local formations of complex medical social nature belongs to national priorities and is considered as one of most important directions of public social policy. The stomatological health of rural population is to be considered as indicator of national stomatological health. This is confirmed by spatial structure: rural territories (inhabited territories outside cities) cover 2/3 of territory of the Russian Federation with population of 37.3 million or 1/4 of total population. The spatial structure of the Belgorod Oblast is reliably similar to the all-Russian one. The number of national and foreign studies proved that accessibility, quality and timeliness of insurance (state) stomatology is lower for rural residents that can be considered as one of signs of social inequality. Depending on the social economic status of region, signs of social inequality in the stomatology field are conditioned by broad spectrum of factors. Some of them are discussed in the article.

[The accessibility of stomatological care for patients with limited capacities in conditions of COVID-19 pandemic].

The article considers the problem of access to stomatological care, in particular to prosthetic dentistry, for people with limited health capacities in conditions of the COVID-19 pandemic. The range of factors impeding to get quality dental services in state stomatological polyclinics and at home was established by empirical study organized in two Subjects of the Russian Federation located in the Central Federal Okrug.

Effect of the chemical structure of an equatorial ligand on the spin crossover properties of the Fe(III) complex with 4-styrylpyridine axial ligands.

In order to study the effect of the chemical structure of the equatorial ligand on the spin state of the Fe(iii) ion in complexes with invariable photoisomerizable 4-styrylpyridine axial ligands and different tetradentate Schiff bases, several new Fe(iii) complexes have been first synthesized, characterized, and studied by UV-vis, NMR, and EPR spectroscopies. The general chemical formula of the complexes is [Fe(SB)Sp2]BPh4·MeOH, where Sp is trans-4-styrylpyridine and SB are dianions of Schiff bases: salen, bzacen, and acen [salen = N,N'-ethylenebis(salicylaldimine) 1, acen = N,N'-ethylenebis(acetylacetonylideneimine) 2, and H2bzacen = N,N'-ethylenebis(benzoylacetonylideneimine) 3]. The results of the EPR and NMR measurements of the complexes both in the solid state and in solutions showed that the more methyl groups and less aromatic rings in the equatorial ligand, the more abrupt spin-crossover was observed in the complex. The dependence of the magnetic properties of the complexes on the state of matter and the presence of a solvent (powder, liquid solutions, and vitrified solutions) are noted.

[Use of stents with bioactive coating in treatment of patients with lesions of the superficial femoral artery]. / Primenenie stentov s bioaktivnym pokrytiem v lechenii bol'nykh s porazheniem poverkhnostnoi bedrennoi arterii.

The authors analysed the immediate outcomes of implanting stents with bioactive coating in treatment of patients presenting with atherosclerotic lesions of the superficial femoral artery. Over the period from January 2014 to December 2015, endovascular interventions on the superficial femoral artery were carried out in a total of 18 patients (mean age 61.3±9.2 years). The implants inserted were stents with bioactive coating based on titanium oxinitride, measuring 6 to 8 mm in diameter and being from 50 to 200 mm long. Prior to operation and 7 days after implantation of the stent, the immunoenzymatic assay was used to determine the level of nitrogen nitric oxide (NO) in blood. The stents' patency was assessed by the findings of ultrasound duplex scanning performed at 30 days, and then 6 and 12 months after the intervention. There were no complications either during the operation or in the early postoperative period. An increase in the ankle-brachial index was observed in all patients: with the average value prior to treatment amounting to 0.4±0.3 and equalling 1.1±0.2 after stenting (p<0.0001). Normalization of the blood NO level was revealed (was noted to normalize): the mean value prior to operation amounted to 18.9±2.3 µmol/L and after operation to 28.9±4.1 µmol/L (p<0.05). Primary patency rate of the stents was 100% at 30 days, 94.5% (1 occlusion) at 6 months and 88.8% (1 restenosis and 1 occlusion) at 12 months. The patients with occlusion or restenosis were subjected to repeat endovascular interventions, with restoration of patency of the construction (with the construction's patency restored). By now all the 18 patients show preserved patency (currently patency was preserved) of lower-limb arteries, with no evidence of restenosis in the zones of operations. It was concluded that using stents with bioactive coating based on titanium oxinitride results in normalization of the level of NO in blood, which may contribute favourably to prolongation of the period of functioning of endovascular constructions. The first data concerning primary patency of stents of this type make it possible to count on betterment of the remote results of treatment of patients presenting with atherosclerotic lesions of the superficial femoral artery.

[An investigation of extracellular HER-2/NEU domain level in blood serum from breast cancer patients].

A series of 159 tests on HER2 ECD in blood serum from breast cancer patients established the following correlations: enhanced levels of the marker occurred more often in patients with multiple metastases to different organs alongside those with bone metastases; patients in loco-regional relapse tended to show elevated levels too. It is suggested that the method be used for prognosis and monitoring.

[Predictive value of serum PSA in detection of prostate cancer by fine needle biopsy].

Parallel study of PSA and needle biopsy were performed in 356 men, aged 42-92 years; prostate cancer was detected in 182 cases while no cancer--in 174. When PSA level ranged 4-20 ng/ml, at density of 0.1-0.3, its specificity was low and cancer detection was under 50%. There was a direct correlation between the PSA indices and cancer detection rate, and nearly 100% of tumors were detected at the values of 25-30 ng/ml and 0.5-0.9 respectively. PSA level and especially results of morphological examination by means of prostate needle biopsy (Gleason) offer possibility to visualize tumor size and its malignant potential.

Vasorelaxant and antiplatelet activity of 4,7-dimethyl-1,2, 5-oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide: role of soluble guanylate cyclase, nitric oxide and thiols.

1. Certain heterocyclic N-oxides are vasodilators and inhibitors of platelet aggregation. The pharmacological activity of the furoxan derivative condensed with pyridazine di-N-oxide 4,7-dimethyl-1,2, 5-oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide (FPTO) and the corresponding furazan (FPDO) was studied. 2. FPTO reacted with thiols generating nitrite (NO), S-nitrosoglutathione and hydroxylamine (nitroxyl) and converted oxyHb to metHb. FPDO did not generate detectable amounts of NO-like species but reacted with thiols and oxyHb. 3. FPTO and FPDO haem-dependently stimulated the activity of soluble guanylate cyclase (sGC) and this stimulation was inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and by 0.1 mM dithiothreitol. 4. FPTO relaxed noradrenaline-precontracted aortic rings and its concentration-response curve was biphasic (pIC(50)=9. 03+/-0.13 and 5.85+/-0.06). FPDO was significantly less potent vasodilator (pIC(50)=5.19+/-0.14). The vasorelaxant activity of FPTO and FPDO was inhibited by ODQ. oxyHb significantly inhibited only FPTO-dependent relaxation. 5. FPTO and FPDO were equipotent inhibitors of ADP-induced platelet aggregation (IC(50)=0.63+/-0.15 and 0.49+/-0. 05 microM, respectively). The antiplatelet activity of FPTO (but not FPDO) was partially suppressed by oxyHb. The antiaggregatory effects of FPTO and FPDO were only partially blocked by sGC inhibitors. 6. FPTO and FPDO (10 - 20 microM) significantly increased cyclic GMP levels in aortic rings and platelets and this increase was blocked by ODQ. 7. Thus, FPTO can generate NO and, like FPDO, reacts with thiols and haem. The vasorelaxant activity of FPTO and FPDO is sGC-dependent and a predominant role is played by NO at FPTO concentrations below 1 microM. On the contrary, inhibition of platelet aggregation is only partially related to sGC activation.

Spinocerebellar ataxia type 1 in Russia.

Spinocerebellar ataxia type 1 (SCA1) is one form of autosomal dominant cerebellar ataxia (ADCA) caused by trinucleotide (CAG) repeat expansion within a mutant gene. We investigated 25 patients from 15 Russian ADCA families for SCA1 mutation and found an expanded CAG repeat in 5 families. Mutant chromosomes contained 41-51 CAG repeats (mean 46.1, SD 3.1), and normal chromosomes displayed 21-27 repeat units (mean 24.7, SD 1.3). Progressive cerebellar ataxia in our series of SCA1 patients was very commonly associated with dysarthria (in all cases) and pyramidal signs (in 10 of 11 cases). In three patients from one family we found optic atrophy, which has never been described before in genetically proven cases of SCA1. We observed no specific clinical features distinguishing SCA1 from non-SCA1 patients. In contrast to the high frequency of SCA1 in our series, we found no patients with Machado-Joseph disease, another form of ADCA caused by expanded CAG repeat.

Synthesis and vasodilating properties of N-alkylamide derivatives of 4-amino-3-furoxancarboxylic acid and related azo derivatives.

A series of N-alkylamide derivatives of 4-amino-3-furoxancarboxylic acids 5a-11a and their oxidation products, the azo derivatives 5b-11b, were synthesised and studied for their vasodilating properties. All the products were able to release rat aorta strips precontracted with (-)noradrenaline. Azo derivatives proved to be 20-200 times more potent than the parent amines. The large variation of lipophilicity within the two series does not seem to influence significantly the activity. Experiments carried out in the presence of oxyhaemoglobin (HbO(2)) suggest the involvement of nitric oxide (NO*) in the vasodilation.

[Use of the polymerase chain reaction for typing allelic variants of the human HLA-DQA1 by hybridization with oligonucleotide probes, specific for specific alleles]. / Ispol'zovanie polimeraznoi tsepnoi reaktsii dlia tipirovaniia allel'nykh variantov gena HLA-DQA1 cheloveka po gibridizatsii s oligonukleotidnymi zondami spetsifichenymi k opredelennym alleliam.

Class II HLA molecules are the most useful markers for susceptibility to different autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM) and rheumatoid arthritis (RA). Polymerase chain reaction and hybridization with a set of allele-specific oligonucleotide have been used for analysis of allelic sequence variation. The analysis of frequencies of HLA-DQA1 alleles among 10 patients of the russian population revealed a uneven distribution. We have developed a method for preparing non-radioactive oligonucleotide probes with terminal deoxynucleotidyl transferase and Bio-11-dUTP. Comparison of biotinylated and 32P-labeled hybridization probes gave the same sensitivity for HLA-DQA1 typing of amplified DNA. Amplification of the HLA-DQA1 gene has been successful on 10 pg of total DNA. This amount of DNA is close to the amount of DNA in a single cell. Alternatively, HLA-DQA1 typing could be based on the analysis of buccal cells of saliva that would avoid the problem of individuals who object to giving blood samples.

[Analysis of the distribution of alleles of four hypervariable tandem repeats among unrelated Russian individuals living in Moscow, using the polymerase chain reaction]. / Analiz racpredeleniia allelei chetyrekh gipervariabel'nykh tandemnykh povtorov sredi nerodstvennykh predstavitelei russkoi natsii, prozhivaiushchikh v Moskve, s pomoshch'iu polimeraznoi tsepnoi reaktsii.

Allele frequencies of four VNTR regions (loci D1S80, D17S30, APOB and IGHJ) were determined in 120 unrelated Russian individuals living in Moscow. The high level of length polymorphism was discovered among alleles of these VNTRs. The genotype distribution of these hypervariable regions was established on the basis of experimental data. The comparative analysis showed the likeness between the allele distributions of these VNTRs among Russians and other groups of Caucasians living in Europe and North America.

[DNA genotyposcoy in determining paternity: use of hybridized probes]. / Genotiposkopiia DNK v opredelenii spornogo ottsovstva: ispol'zovanie gibridizatsionnykh zondov.

Analysis of hybridization probes for DNA genotypescopy (DNA genotyping and genome fingerprinting) was performed to detect 21 cases of paternity testing. A system with the highly informative multilocus DNA probe Red4, isolated by us earlier, and two single-locus probes (YNH24 and CMM101) detecting highly polymorphic (H > 96%) loci D2S44 and D14S13 was tested. In the cases analyzed, the Red probe was shown to detect, on average, 19.28 +/- 3.6 polymorphic BsuRI fragments in the DNA profile of presumable fathers and 19.67 +/- 5.84 BsuRI fragments in the DNA profile of mothers. The average number of DNA fragments inherited by a child from either parent was approximately equal (8.72 +/- 3.77 and 7.11 +/- 2.66, respectively). The low population frequency of DNA fragments detected by the Red4 probe allowed highly effective positive paternity identification to be performed. Paternity was established in 86% (with probability > 99.75 or > 99.99%) and excluded in 14% of expertises. Single-locus probes YNH24 and CMM101 were used as an additional criterion in cases when, in the DNA profile of a child, a single band (probable de novo mutation) or several bands (probable false paternity or maternity) were revealed but absent in both presumable parents. In once case, a de novo mutation for the YNH24 probe, not described earlier, was revealed. Therefore, a combination of multilocus and single-locus hybridization probes appeared to be the most promising method for significant paternity testing in forensic and medical genetic practice.

[Comparison of mitochondrial DNA sequences of T.N. Kulikovskii-Romanov, the nephew of Tsar Nikolai II Romanov, with DNA from the putative remains of the Tsar]. / Sravnenie posledovatel'nostei mitokhondrial'noi DNK T.N. Kulikovskogo-Romanova, plemiannika tsaria Nikolaia II Romanova, plemiannika tsaria Nikolaia II Romanova, i DNK predpolagaemykh ostankov tsaria.

Analysis of two polymorphic regions of mitochondrial DNA obtained from T. N. Kulikovskii-Romanov, the nephew of the last Tsar of the Russian Empire Nikolai II Romanov, was performed. The mitochondrial DNA sequences of T. N. Kulikovskii-Romanov and earlier reported DNA sequences obtained from the putative remains of Nikolai II showed almost complete coincidence except for a single nucleotide at the position 16169. At this position, C was found in mitochondrial DNA of T. N. Kulikovskii-Romanov, C/T in that from the putative remains of Nikolai II Romanov, and T in mitochondrial DNA from great great grandson and great great grand-daughter of Louise Hesse-Cassel. These data suggest independent mutations in the maternal lineage of Louise Hesse-Cassel's descendants and/or a mutation leading to a heteroplasmia in the lineage of Louise Hesse-Cassel.

[Presymptomatic DNA diagnosis of spinocerebellar ataxia type 1]. / Presimptomnaia DNK-diagnostika spinotserebelliarnoi ataksii 1-go tipa.

Hereditary autosomal dominant ataxias is a clinically and genetically heterogeneous group of diseases characterized by a progressive ataxia combined with the signs of multisystem involvement of the brain and spinal cord. The modern classification of these disorders of the central nervous system is based on recent advances in molecular genetics. In a form of dominant ataxia, spinocerebellar ataxia type 1 (SCA1), the mutation consists of an increased number of copies (expansion) of trinucleotide repeats within the causative gene. This mutational mechanism is characteristic of a group of hereditary neurodegenerative diseases. Revealing this phenomenon provided a tool for direct DNA diagnosis of SCA1 at any stage of the disease, including the preclinical one. This is the first reported case of a direct DNA diagnosis of SCA1 in Russia. The diagnosis was performed in five healthy persons from the risk group, i.e., relatives of patients with a molecularly proven SCA1. Three persons were diagnosed to be presymptomatic carriers of the mutant SCA1 gene; in two persons, the mutation was not found. A complex of moral, ethical, medical, and social problems connected with the application of direct DNA testing of SCA1 in genetic counselling is discussed.

[Molecular genetic analysis--a new stage in the study of hereditary diseases of the central nervous system]. / Molekuliarno-geneticheskii analiz--novyi étap v izuchenii nasledstvennykh zabolevanii tsentral'noi nervnoi sistemy.

Molecular genetics is currently the most powerful tool for studying hereditary diseases of the central nervous system: Huntington's disease, dopa-nonresponsive dystonia, Friedreich's disease, etc. The review presents the most important results obtained in this field by the Department of Neurogenetics, Institute of Neurology, in collaboration with several Russian and foreign research institutes. The authors were the first to perform a molecular analysis of mutations and haplotypes in Huntington's disease, dopa-nonresponsive dystonia, Wilson's disease and studied the frequencies of various mutations and main genotype-phenotype correlations in the Russian population. The first direct diagnosis of Huntington's disease in Russia, as well as indirect diagnosis of Friedreich's disease, dopa-nonresponsive dystonia and Wilson's disease have been made. The authors began to investigate trinucleotide repeat expansion in dominant spinocerebellar ataxias and related disorders. The Department of Neurogenetics collected a valuable bank of DNA samples, which is sufficient to perform linkage analysis in essential tremor, novel forms of congenital cerebellar atrophy and progressive muscular atrophy.

[Effect of anaprilin on the clinical course of stenocardia and the carbohydrate metabolic indices of ischemic heart disease patients in relation to the nature of their glucose tolerance]. / Vliianie anaprilina na klinicheskoe techenie stenokardii i nekotorye pokazateli uglevodnogo obmena u bol'nykh ishemicheskoi bolezn'iu serdtsa v zavisimosti ot kharaktera tolerantnosti k gliukoze.

Fourteen-day anaprilin treatment of coronary patients with varying glucose tolerance has demonstrated that the drug's therapeutic efficiency was greater in patients with normal glucose tolerance. Anaprilin caused a moderate drop in baseline glucose level and considerably limited the degree of hyperglycemia in response to the glucose tolerance test in coronary patients with abnormally low glucose tolerance. Insulin content was virtually unaffected by the drug, irrespective of the type of glucose tolerance.

[The effect of succinate combined with cytochrome C on postischemic disorders in the skeletal muscle of the extremities]. / Vliianie suktsinata v sochetanii s tsitokhromom C na postishemicheskie rasstroistva v skeletnoi myshtse konechnosti.

A combination of succinic acid and cytochrome c was studied for effects on skeletal muscle carbohydrate metabolism in the extremities of rats with experimental arterial occlusion. The administration of the agents into the ischemic area allowed the stores of glycogen and ATP to be preserved, by lowering the activity of glucose-6-phosphate dehydrogenase and lactate dehydrogenase fraction V in the skeletal muscle of rats with extremity ischemia. The intraperitoneal administration of the agents produced no positive metabolic effect.

[The efficacy of using alpha-tocopherol during ftorotan anesthesia]. / Effektivnost' primeneniia al'fa-tokoferola pri anestezii ftorotanom.

Halothane monoanesthesia in hypoxia leads to activation of lipolysis with increase in the content of NEFA and POL products. The administration of alpha-tocopherol in a dose of 50 mg/liter in such cases was conductive to a statistically significant decrease in the content of peroxidation products in the blood.

[Effect of lactate on the effectiveness of glucose and succinate oxidation by myocardium homogenates]. / Vliianie laktata na éffektivnost' okisleniia gliukozy i suktsinata gomogenatami miokarda.

Lactate (20 mM) was studied for its effect on the intensity of [1-6-14C] glucose and [1,4-14C] succinate oxidation by the rat myocardial homogenates. It is established that lactate induces specific suppression of aerobic glucose oxidation. A moderate reduction of the succinate and lactate oxidation in their combined incubation is of a non-specific character.