Dimeric Disintegrins from the Steppe Viper V. ursinii Venom.

Four dimeric disintegrins were isolated from the venom of the steppe viper V. ursinii using liquid chromatography. Disintegrins prevented adhesion of MCF7 cells to fibronectin, which indicates their interaction with integrin receptors of the αVß1 type. According to mass spectrometry data, the molar masses of disintegrins are about 14 kDa. The method of peptide mapping established the structure of a new heterodimeric disintegrin weighing 13 995.5 Da and shows that it belongs to the class of RGD/KGD-containing disintegrins.

Polyarginine Peptides As a New Class of Ligands of Nicotinic Acetylcholine Receptors.

Arginine-containing peptides R3, R8, and R16 were obtained by solid-phase peptide synthesis, and their binding to nicotinic acetylcholine receptors (nAChRs) of muscle and neuronal (α7) types was studied by competitive radioligand assay with the use of 125I-α-bungarotoxin. The resulting peptides exhibited a significantly greater binding activity with respect to the muscle-type nAChRs than to the α7 receptor. Thus, we have discovered a new class of nAChR ligands. The affinity of the synthesized oligoarginines for nAChR depended on the number of amino acid residues in the chain. The highest affinity was exhibited by the R16 peptide, which contained 16 arginine residues.

Low-molecular-weight compounds with anticoagulant activity from the scorpion Heterometrus laoticus venom.

Low-molecular-weight compounds with anticoagulant activity were isolated from the scorpion Heterometrus laoticus venom. The determination of the structure of the isolated compounds by nuclear magnetic resonance and mass spectrometry showed that one of the isolated compounds is adenosine, and the other two are dipeptides leucyl-tryptophan and isoleucyl-tryptophan. The anticoagulant properties of adenosine, which is an inhibitor of platelet aggregation, is well known, but its presence in scorpion venom is shown for the first time. The ability of leucyl-tryptophan and isoleucyl-tryptophan to slow down blood clotting and their presence in scorpion venom are also established for the first time.

α-conotoxins revealed different roles of nicotinic cholinergic receptor subtypes in oncogenesis of Ehrlich tumor and in the associated inflammation.

Multiple injections of conotoxin MII, a blocker of alfa3-ß2 and alfa6-containing subtypes of nicotinic acetylcholine receptors (n-AChRs), as well as conotoxin ArIB11L16D, a blocker of alfa7 subtype n-AChR, at a dose of 1 nmol/kg reduce both the lactate dehydrogenase level in tumor cells and the inflammatory leukocyte infiltration in tumor tissue in mice bearing Ehrlich carcinoma. The first stage of pathomorphism was detected in the tumor tissue after the treatment with the ArIB11L16D conotoxin, whereas the second stage was observed after the treatment with conotoxins RgIA and MII. Only MII injections led to a significant reduction in tumor growth. Our results show the involvement of n-AChRs in the regulation of metabolic processes and cell-cell interactions related to carcinogenesis and tumor-associated inflammation.

[Pathology diagnostics by human breath analyze].

Modern medicine experiences deficit of inexpensive rapid screening technologies despite progress in the development of diagnostic methods for various diseases. A promising approach is the analysis of exhaled air known to contain thousands of volatile organic substances whose composition differs considerably in health and disease. We isolated certain compounds that may be used as biomarkers of cardiovascular pathology (nitric oxide, carbon monoxide, pentane, isoprene, acetone). There is a variety of methods for the detection of substances in the exhaled air; such as gas spectrography, mass spectrometry, etc. However, ion mobility spectrometry appears the most suitable technique for the purpose of screening studies due to its high speed and sensitivity, small size of the apparatus, and possibility to measure trace amounts of the substances of interest. Possibilities to diagnose lung cancer based on exhaled air composition are considered.

[Assessment of radiation exposure level for hydrobionts in some special industrial ponds at the "Mayak" PA].

Evaluation of the radionuclide content in the ecosystem components (water, sediments, aquatic organisms) of industrial reservoirs-storages of liquid radioactive waste of the "Mayak" PA (reservoirs R-4, R-10, R-11, R-17, R-9) and the estimation of the absorbed dose rate in aquatic organisms of these reservoirs using the software package ERICA Assessment Tool 1.0 May 2009 have been performed. Gradient of the absorbed dose rate for the detected taxonomic groups of hydrobionts in the series of the studied reservoirs R-11 --> R-10 --> R-4 --> R-17 --> R-9 was almost equal to one order of magnitude. The estimated absorbed dose rate for phytoplankton ranged from 5.4 x 10(0) mGy/day (R-11) to 4.0 x 10(4) mGy/day (R-9), for zooplankton--from 6.4 x 10(-1) mGy/day (R-11) to 3.8 x 10(3) mGy/day (R-9), for zoobenthos (chironomids)--from 5.6 x 10(0) mGy/day (R-11) to 1.1 x 10(3) mGy/day (R-17), for fish (roach)--from 8.0 x 10(-1) mGy/day (R-11) to 1.9 x 10(1) mGy/day (R-4).

[Non-viral gene therapy approach for regenerative recovery of skin wounds in mammals].

The rate and character of skin tissue regeneration after wounds, burns and other traumas depend on the cell proliferation within damaged area. Acceleration of healing by stimulation of cell proliferation and extracellular matrix synthesis is one of the most important tasks of modern medicine. There are gene therapy approaches to wound treatment consisting in the transfer of genes encoding mitogenic growth factors to wound area. The most important step in the development of gene therapy approaches is the design of gene delivery tools. In spite of high efficacy of viral vectors, the non-viral means have some preferences (low toxicity, low immunogenity, safety and the absence of backside effects). Among non-viral gene delivery tools, molecular conjugates are the most popular because of their efficacy, simplicity, and the capacity to the targeted gene transfer. In the present work we have developed two molecular conjugates--NLS-TSF7 and NLS-TSF12 consisting of the modified signal of nuclear localization of T-antigen of SV40 virus (cationic part) and the peptide ligands of mammalian transferrin receptor (ligand part). These conjugates bind to plasmid DNA with formation of polyelectrolytic complexes and are capable to deliver plasmid DNA into cells expressing transferrin receptors by receptor-mediated endocytosis. Transfer of the expression vector of luciferase gene in the complex with molecular conjugate NLS-TSF7 to murine surface tissues led to about 100 fold increasing of luciferase activity in comparison with the transfer of free expression vector. Treatment of slash wounds in mice with the complexes of expression vector of synthetic human gene encoding insulin-like growth factor 1 with molecular conjugates NLS-TSF7 led to acceleration of healing in comparison with mice treated with free expression vector. The results obtained confirm the high efficiency of the developed regenerative gene therapy approach for the treatment of damaged skin tissues in mammals.

[Malignant tumors in patients with kidney transplants ]. / Zlokachestvennye opukholi u bol'nykh s peresazhennoi pochkoi..

In this retrospective study we evaluated incidence of malignancies observed among 718 renal transplant recipients with at least 6 months of follow-up. A total of 461 men and 257 women (mean age at transplantation 36.3 +/- 8.3 years) were included. Thirty three out of 718 recipients (4.6%) developed malignant neoplasia: 45.4% of these were Kaposi's sarcomas, 12.1%--cancers of the uterine cervix, 12.1% cancers of the stomach, 12.1%--basal cell carcinomas, 6.06%--posttransplant lymphoproliferative disorder. There was no significant effect of either cyclosporin A doses or OKT3/ATG on the incidence of the tumors. Mean age of transplant recipients with malignancies was statistically higher as compared to those without malignancies (45.5 +/- 8.2 years versus 36.1 +/- 8.4 years, p < 0.00001). The median time from onset of end-stage renal failure (dialysis start) and from the transplantation to the diagnosis of the tumor make up 32 (16-161) and 23 (5-158) months, respectively. One renal transplant patient suffered from multiple myeloma with aggressive course.

[The status of the gastric and duodenal mucosa, biopsied from those who worked in the cleanup of the aftermath of the accident at the Chernobyl Atomic Electric Power Station, in an organotypic tissue culture]. / Sostoianie slizistoi obolochki zheludka i dvenadtsatipertsnoi kishki likvidatorov posledstvii avarii na Chernobyl'skoi AES v organotipicheskoi kul'ture tkani.

Biopsies of stomach and duodenum different regions mucosa obtained from patients with gastroduodenitis (liquidators of consequences of accident in Chernobyl nuclear station--LCA CNS-- and control patients) were studied cultured in vitro. The following are the differences found. Mononuclear cells, differentiating into macrophages were exposed from control biopsies. Mononuclear cells exposed from LCA CNS biopsies formed rosette-like accumulations after mitotic dividing on a distance from the explant. Part of cells within the rosettes acquired processes and formed syncytial structure.

[Clinical x-ray criteria for a differential approach to the surgical treatment of uremic osteodystrophy]. / Kliniko-rentgenologicheskie kriterii differentsirovannogo podkhoda k operativnomu lecheniiu uremicheskoi osteodistrofii.

To define the criteria for a differential approach to operative treatment of uremic osteodystrophy arising in hemodialysis 51 patients were examined clinically, biochemically and roentgenologically before and after parathyroidectomy. Basing on the X-ray picture, the patients were divided into 3 groups: patients with fibrous osteodystrophy seen at X-ray examination (group 1); patients with fibrous osteodystrophy, osteomalacia in predominance of secondary hyperthyroidism (group 2); patients with osteodystrophy and osteomalacia in predominance of osteomalacia syndrome (group 3); patients with uremic osteodystrophy diagnosed only biochemically. Parathyroidectomy proved most effective in group 1 patients. For group 2 patients it is indicated in a subtotal or partial form in a failure of the conservative treatment. In group 3 patients parathyroidectomy is not recommended to avoid a drastic progress of osteomalacia.

[A comparative evaluation of the clinical x-ray picture of uremic osteodystrophy before and after parathyroidectomy]. / Sravitel'naia otsenka kliniko-rentgenologicheskoi kartiny uremicheskoi osteodistrofii do i posle paratireoidéktomii.

The authors present the results of clinical, x-ray, and biochemical studies carried out in 51 patients with uremic osteodystrophy, treated with hemodialysis, before and after parathyroidectomy. The patients were divided into 4 groups with various patterns of x-ray symptoms. Patients with x-ray signs of fibrous osteodystrophy made up group 1, the second group consisted of patients with a combination of fibrous osteodystrophy and osteomalacia with secondary hyperparathyrosis predominance; the third group, like the second one, included patients with the mixed form of uremic osteodystrophy, but with the predominance of the osteomalacic syndrome; Group 4 patients had no x-ray signs of bone changes, and the diagnosis of uremic osteodystrophy was confirmed by clinical laboratory evidence. Analysis of the clinical and x-ray data before and after parathyroidectomy has brought the authors to a conclusion that such an intervention was effective only in cases with manifest clinical and x-ray symptoms of fibrous osteodystrophy. In Group 2 patients with the mixed form of uremic osteodystrophy and less manifest osteomalacia as against fibrous osteodystrophy, subtotal or partial parathyroidectomy is advisable only in cases when conservative therapy is of no avail and fibrous dystrophy is progressing. Surgical treatment is contraindicated to patients in whom x-ray signs of osteomalacia predominate over fibrous osteodystrophy in the total picture of uremic osteodystrophy; it may result in a rapid progress of osteomalacia.

[Risk factors and results in kidney transplantation]. / Faktory riska i rezul'taty transplantatsii pochki.

The authors analyzed the results of 139 kidney transplantations in 115 patients with chronic renal failure depending on a degree of risk. The most frequent risk factors were poor compatibility, high arterial hypertension, myocardial and valvular lesions and retransplantation. As to the combination of various risk factors 4 types of risk were defined. It was proved that in the 4th type of risk kidney transplantation was inappropriate. In the 2nd and 3rd types of risk sparing immunodepression was indicated.