[Management of the patient with renal artery fibromuscular dysplasia: clinical case].

Fibromuscular dysplasia (FMD) is a rare disease that affects small and medium-sized arteries. Clinical manifestations of FMD depend on its localization. In many cases, FMD of renal arteries (RA) is associated with arterial hypertension. Young age, particularly of female patients, suspected RA dissection or kidney infarction, absence of atherosclerosis or presence of FMD in other arteries of such patients evidence for RA FMD. In invasive treatment of hemodynamically significant stenoses, transluminal balloon angioplasty (TBA) of renal arteries is preferrable. Taking into account initial alterations of the vascular wall and unevenness of the lumen of the affected blood vessel, stent implantation is associated with an increased risk of complications and is recommended only if ballooning complications develop. An open reconstructive surgery is indicated in complicated narrowing anatomy, a high risk of the endovascular treatment, or after failure of the endovascular intervention. This article presents a clinical case of a young female patient with RA FMD and renovascular arterial hypertension who successfully underwent renal TBA with a drug-coated balloon.

Clinical and prognostic significance of the soluble form of the VISTA immunity control point in patients with primary bone tumors.

The data of a comparative enzyme-linked immunosorbent assay of the content of the soluble form of the immunity checkpoint VISTA in the blood serum of 30 healthy donors (control group), 79 patients with primary malignant (osteosarcoma - 30, chondrosarcoma - 31, chordoma - 14) and 14 borderline (giant cell tumor) bone neoplasms are presented. In the general group of patients with malignant neoplasms of bones, the median sVISTA content in blood serum is statistically significant lower than in the control (p = 0.040). In patients with bone tumors and healthy donors over 18 years of age, there was a decrease with age in serum sVISTA levels. There were no significant differences in sVISTA concentration between patients with osteosarcoma, chondrosarcoma and healthy donors. Only in patients with chordoma were sVISTA levels statistically significant lower than in controls (p = 0.013). In the groups of patients with chondrosarcoma and osteosarcoma of the bone, there were no significant associations between the serum sVISTA content and the main clinical and morphological characteristics of the disease. In patients with osteosarcoma, no relationship was found between sVISTA levels and overall survival rates, while in patients with bone chondrosarcoma, there was a tendency towards a favorable prognosis with a high content of the marker in the blood serum.

[Developmental dysphasia and epileptiform EEG activity in children]. / Narusheniia razvitiia rechi u detei i épileptiformnaia aktivnost' na ÉÉG.

Objective. To study the electrical activity of the brain in children with developmental dysphasia (alalia). Material and methods. We analyzed the EEGs of 65 children with developmental dysphasia, including 48 boys and 17 girls, aged from 3 to 4 years 11 months. General speech underdevelopment (GSU) of the 1st level (with active vocabulary less than 15-20 words) was found in 31 children and GSU of the 2nd level (with active vocabulary of 20-50 words) - in 34 children. To specify the changes in the brain electrical activity, we conducted video-EEG-monitoring during sleep and waking states in 27 patients. Results. Focal epileptiform EEG changes with no concomitant paroxysmal symptoms were recorded in 12,3% of children with dysphasia. The epileptiform activity was more frequent in GSU of the 1st level (5 (16.1%) patients) than in GSU of the 2nd level (3 (8.8%) patients). Benign epileptiform discharges of childhood with low index were identified in 2 (6,5%) children with GSU of the 1st level and in1 (2,9%) child with GSU of the 2nd level; low index spike-waves were recorded in 3 (9,7%) children with GSU of the 1st level and in 2 (5,9%) with GSU of the 2nd level. Conclusion. The data allow to clarify the frequency of epileptiform EEG activity in those children with developmental dysphasia, who do not have autism or history of seizures. The differential diagnosis with rare epileptic encephalopathies is needed, such as epilepsy with electrical status epilepticus during slow sleep (ESES) and Landau-Kleffner syndrome.

[Developmental dysphasia in children: perspectives of neurotrophic therapy].

Developmental dysphasia (alalia) represents a severe speech and language disorder in children. To assess the efficacy of treatment with cerebrolysin, we have examined 60 children with developmental dysphasia, aged from 3 to 4 years. Group 1 (30 patients) received cerebrolysin (monotherapy, daily dosage 0.1 ml/kg, in the morning hours, on each other day, i.m., 30 injections in total) during 2 months. Group 2 (controls, 30 patients) did not receive pharmacotherapy. A significant improvement of expressive, impressive speech and speech attention was observed in group 1 after the treatment. The active vocabulary increased by a factor of 3.5 and phrases number in colloquial speech by a factor of 5, versus 1.5 in the control group. According to parents' questionnaires, the treatment resulted in the decrease of psychasthenic, psychosomatic problems, motor clumsiness and hyperactivity along with the improvement of attention, emotional control and behavioral measures. The positive effect of cerebrolysin on the motor development was demonstrated by the assessment of motor milestones.

[Developmental dysphasia: assessment of the drug treatment efficacy].

To assess the efficacy of treatment with encephabol, we examined 40 children, aged from 3 to 5 years, with developmental dysphasia. All patients were randomized into two equal groups: group 1 received encephabol (suspension form, daily dosage 200-250 mg, or 12-15 mg/kg) during 2 months; group 2 did not receive this medication. In the first group, there was a significant improvement of expressive and impressive speech and speech attention; the active vocabulary and a number of phrases in colloquial speech increased by a factor of 3 versus 1.5 in the control group. After the treatment with encephabol, the parents reported the decrease in motor disturbances, psychosomatic disorders, the improvement of attention and the emotional state of the children.

[The effect of 2,4-dinitrophenol on the intensity of oxidative processes in the rat liver during prolonged experiment].

The effect of uncoupler 2,4-dinitrophenol on the oxidative processes intensity in liver biomembranes of different age and sex of rats during longitudinal experiment was studied. It was established that 2,4-dinitrophenol in the used concentration hadn't essential negative effect on the organism of females and their posterity. On the young, 3-3,5-month old males it was shown that long-term xenobiotic administration had been accompanied by intensification of the rate of oxygen consumption, decrease of the rate of reactive oxygen species formation in microsomal redox-chain, decline in lipid hydroperoxides and protein carbonils levels in blood serum and liver microsomes, and also by increase of their mean lifespan. The obtained results may testify the possibility of correction of oxidative processes intensity in tissues of mammals and their lifespan by means of modulation of membrane electron transport chains activity.

Comparative Global Gene Expression Profiles of Wild-Type Yersinia pestis CO92 and Its Braun Lipoprotein Mutant at Flea and Human Body Temperatures.

Braun/murein lipoprotein (Lpp) is involved in inflammatory responses and septic shock. We previously characterized a Deltalpp mutant of Yersinia pestis CO92 and found that this mutant was defective in surviving in macrophages and was attenuated in a mouse inhalation model of plague when compared to the highly virulent wild-type (WT) bacterium. We performed global transcriptional profiling of WT Y. pestis and its Deltalpp mutant using microarrays. The organisms were cultured at 26 and 37 degrees Celsius to simulate the flea vector and mammalian host environments, respectively. Our data revealed vastly different effects of lpp mutation on the transcriptomes of Y. pestis grown at 37 versus 26 degrees C. While the absence of Lpp resulted mainly in the downregulation of metabolic genes at 26 degrees C, the Y. pestis Deltalpp mutant cultured at 37 degrees C exhibited profound alterations in stress response and virulence genes, compared to WT bacteria. We investigated one of the stress-related genes (htrA) downregulated in the Deltalpp mutant relative to WT Y. pestis. Indeed, complementation of the Deltalpp mutant with the htrA gene restored intracellular survival of the Y. pestis Deltalpp mutant. Our results support a role for Lpp in Y. pestis adaptation to the host environment, possibly via transcriptional activation of htrA.

[Formation of plasma cell infiltrates in gingiva of patients with chronic apical periodontitis].

The structure of leukocyte infiltrates in gingiva of 80 patients of various ages and gender with chronic apical periodontitis was studied using light microscopy with the application of monoclonal antibodies detecting CD38 antigen. Gingival tissues of practically of all the patients with periodontitis contained 2 types of leukocyte infiltrates: infiltrates with the low plasma cell content and high numbers of neutrophils and structures with high number of plasmocytes and low concentration of neutrophilic granulocytes. Within the gingival epithelium in patients with chronic apical periodontitis CD38 + cells were absent. The histogenesis of gingival leukocyte infiltrates in chronic apical periodontitis is discussed with the special emphasis on the role of plasma cells in the development of the pathological process.

[Gingival tissues age- and gender-specific peculiarities in healthy conditions and in cases of chronic apical periodontitis].

By light microscopy there was studied gingival tissues structure depending upon age and gender in 96 relatively healthy persons and 80 patients with chronic apical periodontitis. It was disclosed that in gingival mucosa of patients with chronic apical periodontitis the interstitial space volumetric density and numerical density of tissue leucocytes increased in the first place due to neutrophils. Between the healthy men and women there was no significant difference in structural organization of the gum as well as between the patients of different gender. The only sign was that in healthy men and women with age progressing only lymphatic vessels area decreased on gingival mucosa microscopic section. In patients with chronic apical periodontitis both blood and lymphatic vessels were involved through decrease of relative capillary density.

[B-cellular lymphoid follicles of gingival mucous membrane in cases of chronic apical periodontitis].

The structure of gingival mucous membrane leukocytal infiltration of 80 patients with chronic apical periodontitis of different age groups was studied by the light microscopy with the use of monoclonal antibodies to CD38. It was disclosed that in gingival tissues of practically all patients 2 types of leukocytal infiltration were present with low number of plasmatic cells and high number of neutrophils (true leukocytal infiltration) and structures with high number of plasmatic cells and low number of neutrophils - most likely lymphoid follicle resultant in mucous membranes of different organs in cases of chronic inflammation. In epithelial gingival paving in cases of chronic apical periodontitis CD38(+)-cells were absent.

[The protein oxidative damage level and lifespan modulation by xenobiotics in Drosophila melanogaster].

The effect of xenobiotics on protein oxidative damage and lifespan of Drosophila melanogaster Meig., line Oregon-R, was studied. Addition of the uncoupler 2,4-dinitrophenol (DNP) to the nutritional mixture results in an induction of synthesis of heat shock proteins and increase of lifespan of insects, whereas sodium nitroprusside (SNP) has negative effect on flies viability connected, probably, with activation of processes of proteins oxidative damage. It is shown that DNP essentially corrects the SNP negative action on insects' survival rates and this "normalizing" action is revealed both at a level of sensitivity of flies to exogenic stresses and protein carbonils level and at a level of insects lifespan as a whole. It is supposed that DNP protects from SNP negative action on flies viability by reduction of intensity of free radicals production and/or induction of heat shock proteins synthesis. Consequence of that is reduction of oxidative proteins damage degree and increase of survival rate (life span) of flies.

Molecular characterization of a glucose-inhibited division gene, gidA, that regulates cytotoxic enterotoxin of Aeromonas hydrophila.

By using a mini-transposon, we obtained two mutated strains of a diarrheal isolate, SSU, of Aeromonas hydrophila that exhibited a 50 to 53% reduction in the hemolytic activity and 83 to 87% less cytotoxic activity associated with the cytotoxic enterotoxin (Act). Act is a potent virulence factor of A. hydrophila and has been shown to contribute significantly to the development of both diarrhea and septicemia in animal models. Subsequent cloning and DNA sequence analysis revealed that transposon insertion occurred at different locations in these two mutants within the same 1,890-bp open reading frame for the glucose-inhibited division gene (gidA). A similar reduction in hemolytic (46%) and cytotoxic (81%) activity of Act was noted in the gidA isogenic mutant of A. hydrophila that was generated by marker exchange mutagenesis. Northern blot analysis revealed that the transcription of the cytotoxic enterotoxin gene (act) was not altered in the gidA transposon and isogenic mutants. However, by generating a chromosomal act::alkaline phosphatase gene (phoA) reporter construct, we demonstrated significantly reduced phosphatase activity in these mutants, indicating the effect of glucose-inhibited division (GidA) protein in modulating act gene expression at the translational level. The biological effects of Act in the gidA mutants were restored by complementation. The virulence of the gidA mutants in mice was dramatically reduced compared to the those of the wild-type (WT) and complemented strains of A. hydrophila. The histopathological examination of lungs, in particular, indicated severe congestion, alveolar hemorrhage, and acute inflammatory infiltrate in the interstitial compartment and the alveolar spaces when mice were infected with the WT and complemented strains. Minimal-to-mild changes were noted in the lungs with the gidA mutants. Taken together, our data indicate for the first time that GidA regulates the most-potent virulence factor of A. hydrophila, Act.

Role of various enterotoxins in Aeromonas hydrophila-induced gastroenteritis: generation of enterotoxin gene-deficient mutants and evaluation of their enterotoxic activity.

Three enterotoxins from the Aeromonas hydrophila diarrheal isolate SSU have been molecularly characterized in our laboratory. One of these enterotoxins is cytotoxic in nature, whereas the other two are cytotonic enterotoxins, one of them heat labile and the other heat stable. Earlier, by developing an isogenic mutant, we demonstrated the role of a cytotoxic enterotoxin in causing systemic infection in mice. In the present study, we evaluated the role of these three enterotoxins in evoking diarrhea in a murine model by developing various combinations of enterotoxin gene-deficient mutants by marker-exchange mutagenesis. A total of six isogenic mutants were prepared in a cytotoxic enterotoxin gene (act)-positive or -negative background strain of A. hydrophila. We developed two single knockouts with truncation in either the heat-labile (alt) or the heat-stable (ast) cytotonic enterotoxin gene; three double knockouts with truncations of genes encoding (i) alt and ast, (ii) act and alt, and (iii) act and ast genes; and a triple-knockout mutant with truncation in all three genes, act, alt, and ast. The identity of these isogenic mutants developed by double-crossover homologous recombination was confirmed by Southern blot analysis. Northern and Western blot analyses revealed that the expression of different enterotoxin genes in the mutants was correspondingly abrogated. We tested the biological activity of these mutants in a diet-restricted and antibiotic-treated mouse model with a ligated ileal loop assay. Our data indicated that all of these mutants had significantly reduced capacity to evoke fluid secretion compared to that of wild-type A. hydrophila; the triple-knockout mutant failed to induce any detectable level of fluid secretion. The biological activity of selected A. hydrophila mutants was restored after complementation. Taken together, we have established a role for three enterotoxins in A. hydrophila-induced gastroenteritis in a mouse model with the greatest contribution from the cytotoxic enterotoxin Act, followed by the Alt and Ast cytotonic enterotoxins.

[Effect of arsenite on the physiological and cytological properties of Pseudomonas putida strains capable of degrading polycyclic aromatic hydrocarbons]. / Vliianie arsenita na fiziologicheskie i tsitologicheskie svoistva shtammov Pseudomonas putida, destruktorov politsiklicheskikh aromaticheskikh uglevodorodov.

Some physiological and cytological properties of Pseudomonas putida strains resistant to arsenite and capable of degrading polycyclic aromatic hydrocarbons were studied. The resistance of P. putida BS202 (NPL-1) to arsenite proved to be determined by chromosomal genes, while the arsenite resistance of P. putida BS238 (pBS2; pBS3031) was by plasmid-borne genes. Arsenite affected the pattern and rate of growth of strain BS202 (NPL-1) in media with naphthalene or salicylate as carbon sources; particularly, it lengthened the lag phase. Electron-microscope analysis of the strains studied did not reveal any arsenite-induced destructive changes in the cell envelope. At the same time, arsenite in the growth medium induced some alterations in the structure of the outer membrane of strain BS202 (NPL-1) and the cytoplasmic membrane of strain BS238 (pBS2; pBS3031) and, in both strains, led to an increase in the density of intramembrane particles on the EF face of the freeze-fractured cytoplasmic membrane. Arsenite resistance probably evidently protects cells of both strains from greater damage. Physiological and cytological data suggest that the mechanisms of arsenite resistance in the strains studied are different.

[Effect of paracetamol on the microsomal oxidation, oxidative phosphorylation and liver mitochondria swelling in rats of various ages]. / Vliianie paratsetamola na mikrosomal'noe okislenie, okislitel'noe fosforilirovanie i nabukhanie mitokhondrii pecheni krys raznogo vozrasta.

The effect of hepatotoxic dose of paracetamol (800 mg per kg, intraperitoneally, once a day during two days) on the system of microsomal oxidation, respiration, oxidative phosphorylation and high amplitude swelling of liver mitochondria was studied on 1-, 4- and 30-months old Wistar male rats. It has been shown, that paracetamol injection leads to the decrease of content of cytochrome P-450, to disorders of the function of monooxygenase system (the aminopyrine-N-demethylase and aniline hydroxylase activities were diminished), mitochondria macrostructure (the mitochondria high amplitude swelling time was decreased) and function (the respiratory control was decreased). These alterations have been observed to manifest to more extent in the liver of young rats as compared with old ones.

[Cloning and expression of a plasmid pBS195 gene, determining oxygenase activity, in Escherichia coli cells]. / Klonirovanie i ékspressiia v kletkakh Escherichia coli gena plazmida pBS195, determiniruiushchego oksigenaznuiu aktivnost'.

Plasmid pBS195, detected in a strain of Lactobacillus sp. isolated from long-living persons, has a broad host range, including Gram-positive and Gram-negative microorganisms [1]. Plasmid-harboring colonies of the strain Escherichia coli HB101 give a color reaction with catechol. This indicates that genes mediating the activity of oxygenase are present in this plasmid. The high activity level of this enzyme, mediated by pBS195, and substrate specificity, which has not bee detected in any known metapyrocatechases, were found in cells of E. coli. Hybridization with a 32P-labeled fragment containing the NahC gene revealed a region of homology with a 1.6-kb EcoR I- BamH I fragment of plasmid pBS195. Deletion variants of this plasmid that lost oxygenase activity confirmed the location of the oxygenase gene in this region. The gene responsible for oxygenase activity in the plasmid was cloned on the pUC19 vector in E. coli cells. The expression of the cloned gene is controlled by the lac promoter of this vector. Physical, hybridization, and deletion analyses as well as analysis of polypeptides, which are synthesized in E. coli mini-cells, showed that this activity requires the participation of a polypeptide with molecular mass of 34 kDa.

[Structure-functional characteristics of pBS195 plasmids from a broad range of gram-positive and gram-negative hosts]. / Strukturno-funktsional'naia kharakteristika plazmidy pBS195 s shirokim krugom grampolozhitel'nykh i gramotritsatel'nykh khoziaev.

The ability of plasmid pBS195 to be inherited by a broad host range including both gram-positive and gram-negative bacteria attracts special attention to its molecular genetic organization. Physical map of the plasmid has been constructed and the gene for kanamycin resistance and oriV homologous to the one of pUC19 have been localized. The determinants for kanamycin-resistance have been shown to share no homology with the genes for the I and II type phosphotransferases and type II nucleotide-transferase. The minicells of Escherichia coli x925 harboring pBS195 produce two plasmid-encoded proteins with mol. masses 26 and 34 kD found in SDS-PAGE. The plasmid determines an oxygenase activity and shares homology with a nahC gene in the EcoRI-BamHI region (0 bp-1.6 kbp). The enzyme was identified as a methylpyrocatehase possessing high activity in Escherichia coli cells and substrate specificity uncharacteristic of this type enzymes.

[Genetic control of tetracycline resistance in bacteria]. / Geneticheskii kontrol' ustoichivosti k tetratsiklinam u bakterii.

Modern data on prevalence, structural and functional organization of the tetracycline resistance determinants in bacteria are reviewed. The three mechanisms of the antibiotic resistance are the tetracycline efflux, the ribosomal protection and the antibiotic modification. The problems of evolution of tetracycline resistance genes are discussed.

[Regulation of the catalytic activity and supermolecular structure of penicillin acylase from Escherichia coli in an aerosol OT reversed micelle system in octane]. / Reguliatsiia kataliticheskoi aktivnosti i nadmolekuliarnoi struktury penitsillinatsilazy iz Escherichia coli v sistem obrashchennykh mitsell aérozolia OT v oktane.

The properties of penicillin acylase from E. coli solubilized by hydrated reversed micelles of Aerozol OT (AOT) in octane were studied. The catalytic activity dependence on the hydration degree, a parameter which determines the size of the micelle inner cavity, represents a curve with three optima, each corresponding to the enzyme functioning either in a dimer form (omega 0 = 23) or in the form of separate subunits--heavy, beta, and light, alpha, at omega 0 = 20 and 14, respectively. Reversible dissociation of the enzyme was confirmed by ultracentrifugation followed by electrophoresis. Preparative isolation of penicillin acylase subunits, their catalytic activity being retained, was shown to be possible.

How to predict product yield in kinetically controlled enzymatic peptide synthesis.

The published theory of kinetically controlled enzymatic peptide synthesis needed experimental verification. We carried out the measurement of the peptide yield and estimation of the key parameters alpha and beta for papain-catalyzed synthesis of Mal-L-Phe-L-Ala-LLeuNH(2) from Mal-L-Phe-L-AlaOMe and L-LeuNH(2). The experimental results demonstrate that this theory adequately describes the real process.