[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.

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.

[Effect of propofol anesthesia on the serum level of lipid peroxidation products]. / Vliianie anestezii propofolom na soderzhanie produktov perekisnogo okisleniia lipidov v syvorotke krovi.

The propophol anesthesia induced the lipid peroxidation and inhibits the body antioxidation activity, which manifests itself by a reduced total antioxidation activity of the blood serum. However, the propophol effect, related with peroxidation activation, is not long and the mentioned parameters of lipid metabolism go down to the original values in 17-18 hour after the preparation was administered.

[Analysis of mutations in ATP7B gene and experience with direct DNA-diagnosis in hepato-lenticular degeneration]. / Analiz mutatsii v gene ATP7B i opyt priamoi DNK-diagnostiki pri gepatolentikuliarnoi degeneratsii.

Hepatolenticular degeneration (HLD) is a severe autosomal-recessive disorder of the copper metabolism. It is characterized by excessive accumulation of copper in the brain and in viscera and is conditioned by the damage in the gene of copper ATP-ase (ATP7B). The paper presents the results of screening of ATP7B gene mutation in 42 patients with HLD from Russian population. The regions of ATP7B gene that are the most frequently exposed to the mutation have been studied (the exzones 14, 15, 16, 18). It is demonstrated that A-->C mutation in the 14-th exzone that led to the change of histidine1069 amino acid for glutamine, was found in more than 60% of patients--Slavs from the European Russia. This mutation was observed in both homo- and heterozygous states. The deletion of (CCC-->CC) nucleotide in the 15-th exzone of the gene was observed in 2 cases. The detailed analysis of the clinical-genetic correlations was performed in patients with the determined damages of ATP7B gene. In Russia the experience of the direct DNA-diagnosis of HLD is described for the first time. It is significant for early evaluation of the patients in preclinical state and for prescription of the preventive copper-eliminating therapy.

Different phenotypes of Friedreich's ataxia within one 'pseudo-dominant' genealogy: relationships between trinucleotide (GAA) repeat lengths and clinical features.

We examined a large Turkmen family with 'pseudo-dominant' inheritance of Friedreich's ataxia resulting from consanguineous marriage of a Friedreich's ataxia patient to a heterozygote carrying an ancestral mutated allele. Two distinct phenotypes of the disease co-segregated within this genealogy. Two brothers from the younger generation exhibited 'classical' Friedreich's ataxia with onset of symptoms before 10 years and a rapidly progressive course. In contrast, three patients (two sisters from the younger generation and their father) had a more benign phenotype of late-onset Friedreich's ataxia with the onset at 26, 45 and 48 years and slow progression over decades. The patients with 'classical' Friedreich's ataxia were homozygous for a common ancestral expanded allele of the X25 gene containing 700-800 GAA repeats, while the patients with late-onset Friedreich's ataxia had two different mutated alleles, the shorter 250-repeat expansion of paternal origin and the longer 700-repeat expansion of maternal origin. One may conclude that clinical variability of Friedreich's ataxia in our patients is accounted for predominantly by a modifying effect of one of the two (shorter or longer) expanded alleles inherited from their affected father. Our observation clearly demonstrates the significance of variable-sized alleles for the phenotypic expression of the disease.

Benzodifuroxan as an NO-dependent activator of soluble guanylate cyclase and a novel highly effective inhibitor of platelet aggregation.

The ability of benzodifuroxan (BDF) to activate human platelet guanylate cyclase was investigated. The maximal stimulatory effect (1160 +/- 86%) was observed at 0.01 mM concentration. Sodium nitroprusside produced the same stimulatory effect (1220 +/- 100%) but at a higher concentration (0.1 mM). 1-H-[1,2,4,]-Oxadiazolo[4, 3-alpha]quinoxalin-1-one (ODQ), an inhibitor of NO-dependent guanylate cyclase activation, attenuated the stimulatory effect of BDF (0.01 mM) by 75% and that of sodium nitroprusside (0.1 mM) by 80%. Increasing dithiothreitol concentration in the sample from 2. 10-6 to 2.10-4 M increased the stimulatory effect of BDF 2.7-fold. The possible involvement of sulfhydryl groups of low-molecular-weight thiols and guanylate cyclase in thiol-dependent activation of the enzyme is discussed. We have also found that BDF is a highly effective inhibitor of ADP-induced human platelet aggregation with IC50 of 6.10-8 M. The effect of sodium nitroprusside was much weaker (IC50, 5.10-5 M).

Molecular analysis of Neanderthal DNA from the northern Caucasus.

The expansion of premodern humans into western and eastern Europe approximately 40,000 years before the present led to the eventual replacement of the Neanderthals by modern humans approximately 28,000 years ago. Here we report the second mitochondrial DNA (mtDNA) analysis of a Neanderthal, and the first such analysis on clearly dated Neanderthal remains. The specimen is from one of the eastern-most Neanderthal populations, recovered from Mezmaiskaya Cave in the northern Caucasus. Radiocarbon dating estimated the specimen to be approximately 29,000 years old and therefore from one of the latest living Neanderthals. The sequence shows 3.48% divergence from the Feldhofer Neanderthal. Phylogenetic analysis places the two Neanderthals from the Caucasus and western Germany together in a clade that is distinct from modern humans, suggesting that their mtDNA types have not contributed to the modern human mtDNA pool. Comparison with modern populations provides no evidence for the multiregional hypothesis of modern human evolution.

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.

[Friedreich's disease: a real spectrum of clinical manifestations in terms of direct DNA diagnosis]. / Bolezn' Fridreikha: istinnyi spektr klinicheskikh proiavlenii v svete vozmozhnostei priamoi DNK-diagnostiki.

Friedreich's disease (FD) is autosomal-recessive form of hereditary ataxias conditioned by expansion of the trinucleotide GAA-repetitions in a new X25 gene. The study was performed in 20 patients from 13 families of different ethnic origin (Slavs, Turkmen, Moldavians, etc) with a suspicion to FD as well as in their 24 relatives who were clinically healthy. Direct DNA-diagnosis confirmed FD diagnosis in patients from 11 families; besides, a number of GAA-repetitions in the patients was in the range from 100 till 1200 (680 +/- 350). A molecular analysis revealed that FD severity was determined by a character of the mutation in each case: a classic form of the disease was characterized by the highest degree of the expansion of GAA-repetitions (more than 400), meanwhile atypic FD cases with late debut and slow progression were conditioned by either a small degree of the expansion of GAA-repetitions or by the presence of point mutations in one of the gene's alleles. A direct DNA-diagnosis permitted to determine a heterozygous carriage of the mutation in 3 clinically healthy individuals. Such cases are necessary to take into consideration in medico-genetic consultations.

Polymorphism of dopamine D2 and D4 receptor genes and Slavic-surnamed alcoholic patients.

The association between alcoholism and the Taq1 "A" and "B" polymorphic alleles at the DRD2 gene and 48-bp tandem repeat in exon 3 of dopamine D4 receptor (DRD4) gene in 42 unrelated Slavic-surnamed patients and 76 normal controls was examined. The frequency of the A1 allele was higher in alcoholic patients and in alcoholic patients with a family history of alcoholism than in controls (χ²= 3.45, p < 0.001 and χ²)= 3.97, p < 0.001, respectively). Moreover, the frequency of the A1 allele was higher in alcoholics with a family history of alcoholism than in alcoholics without a family history (χ²= 3.33, p < 0.001).The results of association analysis for both the Taq1 "B" and DRD4 alleles were negative for alcoholics in general, subgroups of alcoholics and normal controls. However, the 7-repeat allele (DRD4*7R) of DRD4 gene occurred at significantly higher frequency in alcoholics with a family history of alcoholism compared with those without a family history (χ²= 3.42, p < 0.01).The results indicate that the A1 allele of the DRD2 gene is associated with susceptibility to alcoholism in general.The A1 allele, as well as the DRD4*7R allele, is significantly prevalent among alcoholics with a family history, in comparison with alcoholics without a family history, reflecting different roles of genetic factors in development of alcoholism.