Correlation between chemical composition and 90Sr concentrations in groundwater of the Chornobyl NPP industrial site.

The volumetric activity of the divalent 90Sr ion in groundwater at the Chornobyl NPP industrial site ranges from 1 to 2 to 400-3800 Bq/l. The increase in groundwater radionuclides concentrations is associated with the reduced sorption properties of local sediments, which affect the migration capacity of radionuclides in the environment. The decrease of the 90Sr sorption properties of sediments is caused by changes in the chemical composition of groundwater. A new statistical method has been performed. Method based on the Monte Carlo method in order to evaluate the correlations between the 90Sr volumetric activity and the groundwater chemical composition components. Simulation results using this method suggest a correlation between the volumetric activity of 90Sr, the concentrations cations, the pH, and the oxidation index (organic contents). A direct correlation was established between the volumetric activity of 90Sr, Ca2+ concentrations and the pH of groundwater in the range from 7 to 12.4. It was revealed that the concentrations of Na+ and K+ do not affect the conditions of 90Sr migration with groundwater. There is an inverse correlation between the concentration of 90Sr and the oxidation index, which is an indirect indicator of the organic substances content in water. Thus, the presence of organic substances in the groundwater effectively promotes sorption of 90Sr. The proposed method of geochemical statistics enables a quantitative assessment of groundwater monitoring results.

Expanding indications for laparoscopic parenchyma-sparing resection of posterosuperior liver segments in patients with colorectal metastases: comparison with open hepatectomy for immediate and long-term outcomes.

BACKGROUND: Laparoscopic liver resection (LLR) of posterosuperior segments (PSS) is still technically demanding procedure for highly selective patients. There is no long-term survival comparative estimation after LLR and open liver resection (OLR) for colorectal liver metastases (CRLM) located in PSS. We aimed to compare long-term overall (OS) and disease-free survival (DFS) after parenchyma-sparing LLR with expanding indications and open liver resection (OLR) of liver PSS in patients with CRLM. METHODS: Two Russian centers took part in the study. Patients with missing data, hemihepatectomy and extrahepatic tumors were excluded. One of contraindications for LLR was suspicion for tumor invasion in large hepatic vessels. Logistic regression was used for 1:1 propensity score matching (PSM). RESULTS: PSS were resected in 77 patients, which accounted for 42% of the total number of liver resections for CRLM. LLR were performed in 51 (66%) patients. Before and after matching, no differences were found between groups in the following factors: median size of the largest metastatic tumor; proximity to the large liver vessels; the rate of anatomical parenchyma sparing resection of PSS; a positive response to chemotherapy before and after surgery. Regardless of matching, the size of the largest metastases was above 50 mm in more than one-third of patients who received LLR. Before matching, intraoperative blood loss, ICU stay and hospital stay were significantly greater in the group of OLR. No 90-day mortality was observed within both groups. There were no differences in long-term oncological outcomes: 5-year OS after PSM was 78% and 63% after LLR and OLR, respectively; 4-year DFS after PSM was 27% in both groups. CONCLUSION: Laparoscopic parenchyma-sparing resection of PSS for CRLM are justified in majority of patients who have an indication for OLR if performed in high volume specialized centers expertized in laparoscopic liver surgery.

Dynamic regime of coherent population trapping and optimization of frequency modulation parameters in atomic clocks.

We theoretically investigate the dynamic regime of coherent population trapping (CPT) in the presence of frequency modulation (FM). We have formulated the criteria for quasi-stationary (adiabatic) and dynamic (non-adiabatic) responses of atomic system driven by this FM. Using the density matrix formalism for Λ system, the error signal is exactly calculated and optimized. It is shown that the optimal FM parameters correspond to the dynamic regime of atomic-field interaction, which significantly differs from conventional description of CPT resonances in the frame of quasi-stationary approach (under small modulation frequency). Obtained theoretical results are in good qualitative agreement with different experiments. Also we have found CPT-analogue of Pound-Driver-Hall regime of frequency stabilization.

[Surgical treatment of multiple isolated intrapulmonary metastases].

An analysis of treatment results was made in 226 patients with multiple isolated intrapulmonary metastases of solid tumors. It appears that surgical removal of metastases was possible in patients with satisfactory functional resources and accurate evaluation in order to validate the indications for surgery. The operation shouldn't result in considerable reduction of quality of life and didn't prevent using other methods of treatment such as medicamental and radiation therapy. The indications to surgical intervention have to be set as individual in consideration of the number of metastases and potential of the patient to undergo the surgery.

[Additional evidence for the species composition of mosquitoes (Diptera, Psichodidae, Phlebotominae) in the visceral leishmaniasis foci of Uzbekistan].

The species composition of mosquitoes was studied in the foci of visceral leishmaniasis in the Navoiy and Samarkand Provinces of Uzbekistan. The human settlements where these observations were made were located at 1000-1200 m above sea level. Seven species: Phlebotomus sergenti, P. caucasicus, P. longiductus, P. papatasi, P. alexandri, Sergetomyia sumbarica, and S. grecovi were found. The predominant species was P. sergenti; P. longiductus was a vector for visceral leishmaniasis, which was present in all the collected samples. Bovine animal and small cattle yards were ascertained to be the hatching of mosquito eggs.

[The species composition and epidemiological significance of mosquitoes (Diptera, Psychodidae, Phlebotominae) in the foci of visceral leishmaniasis in the Papsky District, Namangan Region, Uzbekistan].

In 2008, mosquito observations were made in 4 populated areas of the Papsky District, Namangan Region, Uzbekistan (Fergana Valley), where visceral leishmaniasis cases had been registered. The mosquitoes were caught in Oltinkan, Gulistan, Chodak, and Chorkesar in July and in Oltinkan in September. A total of 7245 mosquitoes were caught in the living and utility premises during the observation period. The mosquito fauna of this focus was found to represent 10 species: P. papatasi, P. sergenti, P. alexandri, P. caucasicus, P. nuri, P. keshishiani, P. angustus, P. longiductus, S. grecovi, and S. sumbarica. It also contained P. papatasi, a vehicle for transmission of zoonotic cutaneous leishmaniasis, P. sergenti, an anthroponotic cutaneous leishmaniasis vehicle, and P. longiductus, a visceral leishmaniasis one. The major site of hatching and habitat for mosquitoes were utility premises for large and small cattle. A polymerase chain reaction was used to determine mosquito infestation with L. infantum. A total of 38 female pools of 5 species: P. papatasi, P. sergenti, P. keshishiani, P. angustus, and P. longiductus were tested. Testing of female mosquitoes for L. infantum yielded a negative result.

[The epidemiological features of visceral leishmaniasis, revealed on examination of children by polymerase chain reaction, in the Papsky District, Namangan Region, Uzbekistan].

Patients with visceral leishmaniasis (VL) have been registered in the Papsky District, Namangan Region, Uzbekistan, over the past 23 years. A total of 95 patients were notified in 1987 to 2009. In 2007-2008, a mass survey using the polymerase chain reaction (PCR) within the international INTAS project 05-100006-8043 was conducted in 5 population aggregates of the Papsky District, Namangan Region, Uzbekistan, where VL cases had been regularly registered in the last years. Bone marrow and venous and peripheral blood smears were used as a test material. A total of 234 samples, including 3 bone marrow biopsy specimens, 9 venous blood samples and 222 peripheral blood ones, were tested. All the samples were on the glass slides. Three groups were identified among the examinees. Group 1 consisted of 13 subjects who had been ill at different times. Group 2 comprised 27 children treated at hospital for various diagnoses. Group 3 (the largest one, n=190) included apparently healthy children. All the children of this group felt well and had no symptoms of any illnesses at the examination. In this group, 85 (44.7%) subjects were PCR-positive. Twenty-four (55.8%) of 43 children in the age group of 0-3 years were PCR-positive; the 4-7-year age group comprised 66 subjects and 33 (50%) of them were PCR-positive. Group over 7 years of age included 81 subjects; 45 (55.5%) were PCR-positive. The results of the mass survey with PCR, which covered the 5 population aggregates in the Papsky District, Namangan Region, Uzbekistan, suggest the epidemic activity of a synathropic focus of VL and make us look at many fixed notions of its epidemiology in new contexts.

[Human and canine visceral leishmaniasis in the Papsky District, Namangan Region, Uzbekistan: seroepidemiological and seroepizootological surveys].

In 2007 - 2008, four (Chodak, Oltinkan, Gulistan, and Chorkesar) of 9 population aggregates in the Papsky District, Namangan Region, Uzbekistan, where visceral leishmaniasis (VL) cases had been registered in the last years were selected to make seroepidemiological and seroepizootological surveys within the international project funded by INTAS grant 05-100006-8043. The surveys of the populations were conducted visiting their homesteads. These additionally included children's and health care facilities where all children aged less than 14 years were examined. On examining the children, their peripheral blood (approximately 0.1 ml) was taken on filter paper for serological assays. Canine blood was sampled from the vein. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect antibodies to VL pathogens. A total of 521 children were examined for two years, by applying ELISA. Five hundred and fourteen blood samples from children younger than 14 years, 162 dogs, 4 foxes, and 1 cat were tested. Testing 514 children's blood samples for VL pathogen antigen ascertained that in the 4 population aggregates there was an average of 10% VL-seropositive children, including those who were ill with VL at the moment of the examination and had been ill. The highest number of VL-seropositive samples (14.9%) was found in the settlement of Chodak. VL pathogen antibodies were detected in 26 (61.9%) of 42 dogs with the clinical signs of VL. VL-positive tests were found in 26 (21.6%) of 120 apparently healthy dogs. The samples from 4 foxes and 1 cat were negative. Immunological findings indicated that 0-3-year-old children were a group that is most susceptible to VL in the study focus of this disease. The high proportion of dogs with VL may account for the rise in infant morbidity and suggests the epizootic strain in the focus of VL in the Papsky District.

Identification of the agent causing visceral leishmaniasis in Uzbeki and Tajiki foci by analysing parasite DNA extracted from patients' Giemsa-stained tissue preparations.

Our present study is the first attempt to characterize Leishmania parasites from foci in Uzbekistan and Tajikistan endemic for visceral leishmaniasis (VL). PCR-sequencing of the ribosomal internal transcribed spacer 1 and multilocus microsatellite typing (MLMT) were applied to DNA extracted from preparations of Giemsa-stained bone marrow aspirates from 13 cases of VL. L. infantum was shown to cause VL currently occurring in this area. MLMT applying 14 microsatellite markers, previously shown to be polymorphic for strains of the L. donovani complex, revealed that microsatellite profiles of parasites causing human VL in the Namangan and Jizzakh regions in Uzbekistan, and Penjikent region in Tajikistan, basically coincide with those of strains of L. infantum MON-1. Furthermore, these parasites were assigned to a distinct cluster genetically clearly separated from the populations of L. infantum MON-1 from Europe, the Middle East and North Africa. The existence of a genetically homogeneous but distinct group of L. infantum MON-1 indicates that the parasites circulating in the Uzbeki and Tajiki foci studied have been restricted there for a long time rather than having been recently introduced from elsewhere by human or animal reservoir migration.

[The comparative analysis of two methods of an estimation a butter's quality at its long storage and influence of a thistle spotty extracts on a period of storage].

In of the comparative analysis of definition of butter's quality--method of peroxide number and a method of definition of aldehydes maintenance are received. Data of peroxide number received by the first method, for 7 and 28 days of storage are practically identical, that does not reflect the valid condition of butter quality. Results of the second method adequately reflect a condition of butter's quality and give the chance to confirm about expediency of its use. Entering as an antioxidant of a thistle spotty seeds extract of 0,001% silybin in butter structure which contains 82,5% of fat prolongs term of its storage on 21 days.

[The estimation of biological value and quality of propolis and propolis based food products and food dietary supplements].

The method of determination of indicative flavonoids of propolis has been developed. The method is applicable for the standardization and estimation of quality and origin of raw propolis and propolis-containing food products, food dietary supplements (FDS) and drugs. The method allows to determine the concentration and composition of individual flavonoids on the background of complicated matrix of food products and FDS. The detection limit amounted 0, 1% (for chrysin). 20 samples of propolis from different regions and 12 samples of propolis-enriched food products and FDS were investigated by proposed method.

Sprouty genes are expressed in osteoblasts and inhibit fibroblast growth factor-mediated osteoblast responses.

Fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) are major regulators of skeletal growth and development. Signal transduction via FGFRs is complex and mediates proliferation, differentiation, or migration depending upon the cellular context. Members of the Spry gene family antagonize the FGFR signal transduction pathway and inhibit lung morphogenesis, angiogenesis, and chondrogenesis. We examined the expression of Spry2 in the osteoblastic MC3T3-E1 cell line. MC3T3-E1 cells express Spry2 in response to FGF1 stimulation. Treatment of MC3T3-E1 cells with FGF1 results in the expression of Spry2 in a manner consistent with an early response gene. Pharmacological inhibitors of mitogen-activated protein kinase activation inhibit FGF1-induced expression of Spry2 mRNA. Transient overexpression of Spry2 in MC3T3-E1 resulted in decreased FGF1-mediated extracellular signal-regulated kinase phosphorylation and FGF1-stimulated osteopontin promoter activity. Furthermore, we show that Spry2 interacts with Raf-1 in a glutathione-S-transferase pulldown assay and that this interaction may involve multiple sites. Finally, Spry2 expression precedes the onset of the expression of osteoblast differentiation markers in an in vitro assay of primary osteoblast differentiation. Taken together, these results indicate that Spry2 expression is an early response to stimulation by FGF1 in MC3T3-E1 cells and acts as a feedback inhibitor of FGF1-induced osteoblast responses, possibly through interaction with Raf1.

Soluble Jagged 1 represses the function of its transmembrane form to induce the formation of the Src-dependent chord-like phenotype.

We have previously demonstrated that the expression of the soluble extracellular domain of the transmembrane ligand for Notch receptors, Jagged 1 (sJ1), in NIH 3T3 cells results in the formation of a matrix-dependent chord-like phenotype, the loss of contact inhibition of growth, and an inhibition of pro-alpha 1(I) collagen expression. In an effort to define the mechanism by which sJ1 induces this phenotype, we report that sJ1 transfectants display biochemical and cytoskeletal alterations consistent with the activation of Src. Indeed, cotransfection of sJ1 transfectants with a dominant-negative mutant of Src resulted in the loss of matrix-dependent chord formation and correlated with the restoration of type I collagen expression and contact inhibition of growth. We also report that the sJ1-mediated induction of Src activity and related phenotypes, including chord formation, may result from the inhibition of endogenous Jagged 1-mediated Notch signaling since it was not possible to detect an sJ1-dependent induction of CSL-dependent transcription in these cells. Interestingly, NIH 3T3 cells transfected with dominant-negative (but not constitutively active) mutants of either Notch 1 or Notch 2 displayed a similar Src-related phenotype as the sJ1 transfectants. These data suggest that the ability of sJ1 to mediate chord formation is Src-dependent and requires the repression of endogenous Jagged 1-mediated Notch signaling, which is tolerant to the destabilization of the actin cytoskeleton, a mediator of cell migration.

Differential induction of cellular responses by live and dead Leishmania promastigotes in healthy donors.

The most effective protection against human leishmaniasis has been achieved following vaccination with live promastigotes. Killed promastigotes + BCG can protect, albeit to a lower degree. To explore what mechanisms may be involved in these differences, the ability of live and dead promastigotes to induce immune responses were evaluated in vitro. The data showed that live and dead promastigotes differ in their ability to induce proliferation and cytokine production. Cytokine gene expression of Th1 related cytokines (IL-12, IFNgamma and TNFalpha) in adult PBMC was more evident to live than to heat killed promastigotes. This was coupled with significantly higher number of IFNgamma secreting cells induced by live than killed promastigotes. However, alpha-IL-12 antibodies did not block the IFNgamma response induced by live promastigotes. Proliferative responses were variable. In contrast to adult PBMC no IFNgamma secreting MNC could be detected in cord blood. However, in these cells the live promastigotes consistently induced higher proliferative response compared to dead. Implications of these findings are discussed.

Apoptosis provoked by the oxidative stress inducer menadione (Vitamin K(3)) is mediated by the Fas/Fas ligand system.

Menadione, or vitamin K(3) (VK(3)), a potent oxidative stress inducer, has been recently used as an effective and remarkably safe cytotoxic drug for treatment of several human tumors. VK(3) induces apoptotic cell death through a poorly understood mechanism. Here we show for the first time that VK(3)-induced apoptosis requires the Fas/FasL system. Spleen cells from both Fas- and FasL-deficient mice (C57BL/6-lpr and C57BL/6-gld, respectively) had much lower levels of VK(3) apoptosis in vitro compared to cells from control C57BL/6 mice. VK(3) cytotoxicity toward mouse splenocytes was also blocked with a Fas-Fc fusion protein. VK(3) induced apoptosis in Jurkat cells, coincident with an increase in both Fas and FasL expression. A FasL-resistant variant of these Jurkat cells was also resistant to VK(3)-induced apoptosis. Furthermore, because VK(3) effects were inhibited by glutathione, a potent antioxidant, oxidative stress was linked to the Fas/FasL system. Moreover, since the Jurkat cell lines were p53 null, the activation of Fas/FasL system after oxidative stress apparently acted through a p53-independent pathway. The therapeutic relevance of the K vitamins has been growing in recent years; our findings offer new insight for improving and expanding their applications.

Molecular mechanisms of the antiproliferative effect of vitamin K3 on Jurkat cells.

Molecular mechanisms of the antiproliferative effect of vitamin K3 (sodium 2,3-dihydro-2-methyl-1,4-naphthoquinone-2-sulfonate) were studied on a human T-lymphoma model (Jurkat cell line). It is shown that a short-term treatment of the cells with vitamin K3 damages their genomic DNA. Further culturing of the cells in the presence of vitamin K3 decreases the expression of the c-myc gene, inhibits the activity of DNA-dependent DNA-polymerases, and leads to the subsequent development of apoptosis. Combined exposure to vitamin K3 and azidothymidine has a synergistic antiproliferative effect.

NF-kappaB activation provides the potential link between inflammation and hyperplasia in the arthritic joint.

The transcription factor NF-kappaB is a pivotal regulator of inflammatory responses. While the activation of NF-kappaB in the arthritic joint has been associated with rheumatoid arthritis (RA), its significance is poorly understood. Here, we examine the role of NF-kappaB in animal models of RA. We demonstrate that in vitro, NF-kappaB controlled expression of numerous inflammatory molecules in synoviocytes and protected cells against tumor necrosis factor alpha (TNFalpha) and Fas ligand (FasL) cytotoxicity. Similar to that observed in human RA, NF-kappaB was found to be activated in the synovium of rats with streptococcal cell wall (SCW)-induced arthritis. In vivo suppression of NF-kappaB by either proteasomal inhibitors or intraarticular adenoviral gene transfer of super-repressor IkappaBalpha profoundly enhanced apoptosis in the synovium of rats with SCW- and pristane-induced arthritis. This indicated that the activation of NF-kappaB protected the cells in the synovium against apoptosis and thus provided the potential link between inflammation and hyperplasia. Intraarticular administration of NF-kB decoys prevented the recurrence of SCW arthritis in treated joints. Unexpectedly, the severity of arthritis also was inhibited significantly in the contralateral, untreated joints, indicating beneficial systemic effects of local suppression of NF-kappaB. These results establish a mechanism regulating apoptosis in the arthritic joint and indicate the feasibility of therapeutic approaches to RA based on the specific suppression of NF-kappaB.

Bacterial beta-galactosidase and human dystrophin genes are expressed in mouse skeletal muscle fibers after ballistic transfection.

Ballistic transfection, based on cell and tissue bombardment by the tungsten and gold microparticles covered with the gene DNA, was used for the delivery of a bacterial beta-galactosidase and a full-length cDNA copy of the human dystrophin genes into mouse skeletal muscles. CMV-lacZ, SV40-lacZ, LTR-lacZneo and full-length cDNA dystrophin (pDMD-1, approximately 16 kb) in eukaryotic expression vector pJ OMEGA driven by mouse leukaemia virus promotor (pMLVDy) were used throughout the studies. Musculus glutaeus superficialis of C57BL/6J and quadriceps femoris of mdx male mice were opened surgically under anesthesia and bombarded by means of the gene-gun technique originally developed by us. Different mixtures of gold and tungsten particles at ratios of 4:1, 1:1, 1:4 were applied. X-gal assay revealed marked beta-gal activity, both in total muscles and whole muscle fibers on histological sections, up to three months after transfection. The most intensive staining was observed after SV40-lacZ delivery. No staining was detected with LTR-lacZneo DNA as well as in untreated muscles. The higher tungsten particle concentration in the bombardment mixture correlated with more intense X-gal staining. At the gold/tungsten ratio of 1:4 the microparticles penetrated the musculus glutaeus superficialis and transfected the underlying musculus glutaeus medius as well. Immuno-cytochemical assay for human dystrophin revealed dystrophin positive myofibers (DPM) in the bombarded area up to two months after transfection. The proportion of DMP varied from 2.5% on day 17 up two 5% on day 60 after bombardment compared to only 0.5% in the control mdx mice. These results suggest the applicability of particle bombardment for gene delivery into muscle fibers.