[Main causes of poor efficacy of outpatient and hospital medical help to patients with septic forms of the diabetic foot syndrome].

The treatment results of 2431 patients with the septic forms of the diabetic foot syndrome were analyzed. The first group of patients (n=1356) were treated in specialized hospital departments, where as the second group (n=1066) received help in general "septic" departments of city hospitals. Certain organizational, diagnostic and treatment mistakes were registered predominately among patients of the second group. The obtained results vividly indicate the economic efficacy of the development and creation of the specialized departments or centers for the adequate treatment of such patients. It would allow the decrease of amputation rates from 36,9 to 12,0% and lethality rate from 9,8 to 4,3% in specialized departments and general hospitals, relatively.

[Genetic control of metabolism of mutagenic purine base analogs 6-hydroxylaminopurine and 2-amino-6-hydroxylaminopurine in yeast Saccharomyces cerevisiae].

The influence of inactivation of genes, which control biosynthesis of inosine monophosphate (IMP) de novo and the purine utilization and interconversion pathway, on sensitivity of yeast Saccharomyces cerevisiae cells to the mutagenic and toxic action of 6-hydroxylaminopurine (HAP) and 2-amino-6-hydroxylaminopurine (AHA) was studied. It was shown that the manifestation of HAP and AHA mutagenic properties involves the action of enzyme adenine phosphoribosyltransferase encoded in yeast by APT1 gene. A blockade of each stage of IMP biosynthesis, with the exception of the block mediated by inactivation of genes ADE16 and ADE17 leading to the accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), was shown to enhance yeast cell sensitivity to the HAP mutagenic effect; however, it does not affect the sensitivity to AHA. A blockade of conversion of IMP into adenosine monophosphate (AMP) causes hypersensitivity of yeast cells to the mutagenic action of HAP and to the toxic effect of HAP, AHA, and hypoxanthine. It is fully probable that this enhancement of sensitivity to HAP and AHA is conditioned by changes in the pool of purines. This indicates that genes ADE12, ADE13, AAH1, and HAM1 controlling processes of purine utilization and interconversion in yeast make the greatest contribution to the system of protection against the toxic and mutagenic action of the examined analogs. Possible mechanisms of HAP detoxication in bacteria, yeast, and humans are considered.

[Vertebrate immunity: mutator proteins and their evolution].

M.E. Lobashev has brilliantly postulated in 1947 that error-prone repair contribute to mutations in cells. This was shown to be true once the mechanisms of UV mutagenesis in Escherichia coli were deciphered. Induced mutations are generated during error-prone SOS DNA repair with the involvement of inaccurate DNA polymerases belonging to the Y family. Currently, several distinct mutator enzymes participating in spontaneous and induced mutagenesis have been identified. Upon induction of these proteins, mutation rates increase by several orders of magnitude. These proteins regulate the mutation rates in evolution and in ontogeny during immune response. In jawed vertebrates, somatic hypermutagenesis occurs in the variable regions of immunoglobulin genes, leading to affinity maturation of antibodies. The process is initiated by cytidine deamination in DNA to uracil by AID (Activation-Induced Deaminase). Further repair of uracil-containing DNA through proteins that include the Y family DNA polymerases causes mutations, induce gene conversion, and class switch recombination. In jawless vertebrates, the variable lymphocyte receptors (VLR) serve as the primary molecules for adaptive immunity. Generation of mature VLRs most likely depends on agnathan AID-like deaminases. AID and its orthologs in lamprey (PmCDA1 and PMCDA2) belong to the AID/APOBEC family of RNA/DNA editing cytidine deaminases. This family includes enzymes with different functions: APOBEC1 edits RNA, APOBEC3 restricts retroviruses. The functions of APOBEC2 and APOBEC4 have not been yet determined. Here, we report a new member of the AID/APOBEC family, APOBEC5, in the bacterium Xanthomonas oryzae. The widespread presence of RNA/DNA editing deaminases suggests that they are an ancient means of generating genetic diversity.

[An analysis of main causes of low efficiency of rendering care for pyo-necrotic complications of syndrome of the diabetic foot].

In the city of Chelyabinsk during 1996 through 2003 there was growing incidence of necrotic complications of syndrome of the diabetic foot (SDF) from 26.0 up to 50.5 per 100 000 adults (p < or = 0.001). According to prognosis the incidence of SDF will grow by 2010 more than two times (R2 = 0.9849). Comparison of effectiveness of surgical treatment on Diabetological centers (1st group) and non-specialized institutions (2nd group) has shown that lethality in the first group was 4.2%, in the second group--9.7%. In the first group the frequency of high amputations decreased from 31.3% in 1996 to 12.3% in 2005 (p < 0.05). As a whole, organizational, diagnostic and medical defects of treatment were noted in 89.5 out of 100 patients in both groups, the errors in specialized institutions being made 5.7 times more rarely than in non-specialized ones, that speaks well to specialized Diabetological centers.

[Incidence of pyo-necrotic complications of the diabetic foot syndrome and preferences of specialized care].

Total retrospective clinical-social investigation of 2431 patients with pyo-necrotic complications of the diabetic foot syndrome (DFS) has revealed a considerably increased incidence of pyo-necrotic complications of DFS, mainly at the expense of patients with type II diabetes mellitus. Most of these patients (87.8%) are elderly and senile patients with a middle or severe degree of diabetes (98.2%) and signs of subcompensation or decompensation (87.2%). In 98.0% of the patients there were coexisting diseases. 87.9% of the patients were urgently admitted to hospital with acute pyo-inflammatory processes. A comparison of the results has shown that treatment and interdisciplinary observation in specialized institutions allowed to reduce lethality and number of high amputations more than two times.

[Characterization of blood flow in different forms of diabetic foot syndrome].

The lowering of the mean blood flow velocity (Vmean), pulsation index (PI), resistance index (RI) revealed by Doppler ultrasonography is most characteristic of patients with the ischemic form (IF) and mixed form (MF) of diabetic foot syndrome (DFS). The IF is marked by the high degree damping of the pulse wave in limb segments (damping factor). These changes are less significant in the MF of DFS and are in fact lacking in patients with the neuropathic form (NF). In health, the ankle brachial index (ABI) is equal to 1.0. The rise of the index up to 1.1-1.3 is common to patients with the NF of DFS. Occlusion and stenotic lesions of the arteries are associated with the index lowering to 0.7-0.8. The decrease of the index to 0.5 is recorded in critical ischemia. Nevertheless in 10.3% of cases with clinically manifest ischemia, the ABI remains within normal which is determined by arterial wall rigidity in the presence of Menkenberg' s atherosclerosis. Laser Doppler flowmetry provided to patients with the IF of DFS revealed a decrease in the level of the basic and postischemic flow in the feet and legs. The maintenance of the high parameters of the micro-circulatory flow in patients with the NF and MF of DFS is regarded as a consequence of blood shunting in arteriolo-venulat anastomoses. Analysis of thermograms (Thermovision 400, AGEMA) has demonstrated that circulatory deterioration is associated with a decrease in the intensity of infrared irradiation of the legs. Patients with the IF and MF of DFS are characterized by the "amputation" type tomograms This stems from the lowering of the temperature of the distal segments in the presence of ischemia whereas the NF is marked by the "hot feet" symptom. In patients with the IF of DFS, .TcpO2 is 1.3 times lower than in those with the MF and 1.7 times lower in the NF of DFS (p<0.05). In the MF of DFS, the level of oxygenation is 1.3 times lower versus patients with the NF (p<0.05), in which it does not differ from normal. Thus, the hemodynamic parameters in different forms of DFS are significantly different which is especially noticeable in the distal segments of the legs.

[Genetic control of metabolism of a mutagenic analog of 6-N-hydroxylaminopurine bases in Saccharomyces cerevisiae yeasts]. / Izuchenie geneticheskogo kontrolia metabolizma mutagennogo analoga osnovanii 6-N-gidroksilaminopurina u drozhzhei Saccharomyces cerevisiae.

Yeasts were shown to utilize 6-substituted adenine analogues as a purine source via the reutilization pathway leading to the formation of inosine monophosphate (IMP). This occurs because the ade12 strains with blocked conversion of IMP into adenosine monophosphate (AMP) cannot grow on media containing the above analogues as a sole purine source. Haploid strains with the double mutation ham1 ade2 or ham1 ade5 were also incapable of growing on a medium with 6-N-hydroxylaminopurine (HAP) as a sole purine source. However, in this case, this inability was caused by the occurrence of recessive lethal mutations rather than by a defect in purine reutilization. Yeast adenine aminohydrolase (AAH) can deaminate HAP to hypoxanthine. Adenine aminohydrolase (AAH) was uniformly active both in strains with a mutation in the HAMI gene and in strains wild-type with respect to this trait.

[Genetic activity of aminofluorene and 2-acetylaminofluorene in strains of Saccharomycetes under conditions of in vitro metabolic activation: influence of rad 1-5 mutation]. / Geneticheskaia aktivnost' 2-aminofliuorena i 2-atsetilaminofliuorena u shtammov drozhzhei sakharomitsetov v usloviiakh metabolicheskoi aktivatsii i vitro: vliianie mutatsii rad 1-5.

It has been shown that the rad1-5 mutation which alters excision repair in Saccharomyces cerevisiae yeast increased reversion frequency of the ochre mutation his7-1 and the frequency of intragenic mitotic recombination in the LYS2 gene induced by 2-aminofluorene and 2-acetylaminofluorene, as compared with the wild type strains activated in vitro by 39 mix from chicken liver.

[Development of a system of intragenic mapping for molecular genetic analysis of mutations in the gene LYS2 of Saccharomyces yeasts]. / Razrabotka sistemy vnutrigennogo kartirovaniia dlia molekuliarno- geneticheskogo analiza mutatsii v gene LYS2 u drozhzhei sakharomitsetov.

The collection of overlapping lys2 deletions (five in the chromosomal and seven in the plasmid LYS2 gene) is constructed in this work. The deletions overlap the whole coding region of the gene and provide the system for intragenic recombinational mapping of lys2 mutations in one of 14 controlled regions. A portion of these regions can be correlated with the regions on the physical map of LYS2. Mutations in two regions can be easily cloned. The system constructed gives the possibility for the study of intragenic and molecular specificity of mutagenesis.

[Genetic analysis of spontaneous and 6-N-hydroxylaminopurine and propiolactone induced Adp+ mutants in Saccharomyces yeasts]. / Geneticheskii analiz spontannykh i indutsirovannykh 6-N-gidroksilaminpurinom i propiolaktonom mutantov Adp+ u drozhzhei sakharomitsetov.

652 spontaneous and 6-N-hydroxylaminopurine and propiolactone-induced mutants were obtained in yeast. 598 of them were LYS2 mutants. Detailed genetic analysis of the mutants was performed, including analysis of growth pattern on lysineless medium, suppressibility by nonsense suppressors of three types and localization on the recombination map of the LYS2 gene. Mutants induced by different agents were different for all these criteria, except for distribution among the map regions.

[Effect of low- and moderate-frequency ultrasonic waves on the course of suppurative wound process]. / Vliianie u'ltrazvukovykh kolebanii nizkoi i srednei chastoty na techenie gnoinogo ranevogo protsessa.

The author conducted a clinico-laboratory and morphological evaluation of the effect of low- and moderate-frequency ultrasonics on the course of a purulent wound process. He found that ultrasonic waves of different frequency subbands differ in their effect on wound healing. The use of low-frequency ultrasonics is most expedient in phase 1, preference is given to ultrasonics of the moderate-frequency subband in phase 2.

[Mutability of LYS2 gene in diploid Saccharomyces yeasts. II. Frequency of mutants induced by 6-N-hydroxylaminopurine and propiolactone]. / Izuchenie mutabil'nosti gena LES2 u diploidov drozhzhei sakharomitsetov. Soobshchenie II. Vozniknovenie mutantov, indutsirovannykh 6-N-gidroksilaminopurinom i propiolaktonom.

Chemical mutagens 6-N-hydroxylaminopurine (HAP) and propiolactone (PRO) induce Lys2 mutants with high frequency in diploid yeast Saccharomyces cerevisiae. HAP induces such mutants even in tetraploid strains. The genetic analysis of mutants was performed. It is shown that PRO induces mutants by means of "mutation-mitotic segregation" mechanism, while HAP induces mutants through novel mechanism "both allele mutation". Manifestation of such mechanism is the null fertility after meiosis of diploid mutants induced by HAP.

[Effect of hyperbaric oxygenation on the survivability, mutagenesis and recombinogenesis of single-cell organisms]. / Vliianie giperbaricheskoi oksigenatsii na vyzhivaemost', mutagenez i rekombinogenez odnokletochnykh organizmov.

The hyperbaric oxygenation (HBO) has been studied for its ability to induce the cell death and different genetic variations in normal and repair defective strains of bacteria (Escherichia coli and Salmonella typhimurium) and of yeast (Saccharomyces cerevisiae) strains with different ploidy. HBO is shown to induce an increase in the mutability of excision-repair defective strains and a decrease in the survival rate of error-prone repair defective strains of the procaryote. HBO is a weak recombinogen for yeast and induces no mutations of the haploid strain. The results obtained reflect doubt on the community of the mechanisms of radiation and HBO actions on the cell.

[Mutants of Saccharomyces cerevisiae supersensitive to the mutagenic effect of 6-N-hydroxylaminopurine]. / Mutanty drozhzhei Saccharomyces cerevisiae, sverkhchuvstvitel'nye k mutagennomu deistviiu 6-N-gidroksilaminopurina.

Yeast mutants hypersensitive to the mutagenic action of 6-N-hydroxylaminopurine (HAP) were obtained by EMS mutagenesis. One of the mutants segregated monogenically and possessed reduced capacity to utilize HAP as a purine source. A set of diploids suitable for parallel study of mutagenesis and induction of recombination, and differing in the trait of mutability after exposure to HAP ("hm" trait or HAP mutability), were constructed. It was shown that a weak recombinogenic effect of HAP is not enhanced in "hm" mutants when HAP mutability increases.

[Isolation and characteristics of Saccharomyces cerevisiae strains with increased sensitivity to detergents]. / Poluchenie i kharakteristika shtammov drozhzhei Saccharomyces cerevisiae s povyshennoi chuvstvitel'nost'iu k detergentam.

The yeast mutants possessing enhanced sensitivity to detergents were obtained after treatment with ethyl methanesulfonate. The whole set of mutants may be divided into three groups, according to sensitivity to: cetylthreemethylammonium chloride detergents and dyes of the ethidium bromide type, detergents, dyes and antibiotics (gramycidin C and actinomycin D). The genetic analysis performed indicated that more than one gene are responsible for sensitivity. On the basis of the test for allelism mutants were distributed into three groups. It was shown that ethidium bromide is far more potent inducer of cytoplasmic petites in detergent-sensitive than in wild-type strains.

[Genetic activity of base analogs in Salmonella typhimurium and Escherichia coli and Saccharomyces cerevisiae]. / Geneticheskaia aktivnost' analogov osnovanii u bakterii Salmonella typhimurium, Escherichia coli i drozhzhei Saccharomyces cerevisiae.

The study of 6-N-hydroxylaminopurine (HAP) and 2-amino-6-N-hydroxylaminopurine (AHAP) activity in bacteria and the yeast was undertaken. AHAP was found to be more effective as a mutagen in bacteria and HAP--in the yeast. Mutagenic and lethal effects or analogues were independent of excision and mutagenic repair both in bacteria and the yeast. Deletion in uvrB region of Salmonella genome leads to hypersensitivity to lethal and mutagenic action of analogues. Both of the latter only cause reversions of base-substitution but not frameshift mutations. Considering the data obtained and the information from published papers, we proposed that HAP and AHAP exert their mutagenic action, like classical analogues, by means of incorporation into DNA and disturbing the regular replication laws.