Chemical Composition of Bottom Sediments in Small Mountain Rivers (Altai, the Russian Federation)

The article deals with the chemical composition of bottom sediments in the small mountain rivers Aktru, Tyute, and Uznezya (Altai, Russia). It is established that as compared to small and middle plain rivers in Taiga zone, Siberia bottom sediments of the Aktru River contain less amount of K, Na, V, Cr, Mn, Ni, Al, Si, Ti, Sr, approximately the same - Fe, Co, Cu, Zn, Pb and more - As, Ca, Mg. It is suggested that there is a sharp increase of relative Al, Na, K and Si shares from the upland to lowland due to both weathering products accumulation of primary alumosilicates in bottom sediments and export of Ca and Mg from them when dissolving carbonate minerals. Composition transformations of bottom sediments is non-linear and considerably depends on composition of underlying and water-bearing rocks and water exchange intensity that manages time, conditions, and stages of interactions in "water - organic matter - rock" system

Sulfur Mustard Toxicity Following Dermal Exposure: Role of Oxidative Stress, and Antioxidant Therapy

Objective: Sulfur mustard (bis-2-(chloroethyl) sulfide) is a chemical warfare agent (military code: HD) causing extensive skin injury. The mechanisms underlying HD-induced skin damage are not fully elucidated. This review will critically evaluate the evidence showing that oxidative stress is an important factor in HD skin toxicity. Oxidative stress results when the production of reactive oxygen (ROS) and/or reactive nitrogen oxide species (RNOS) exceeds the capacity of antioxidant defense mechanisms. Methods: This review will discuss the role of oxidative stress in the pathophysiology of HD skin toxicity in both in vivo and in vitro model systems with emphasis on the limitations of the various model systems. Evidence supporting the therapeutic potential of antioxidants and antioxidant liposomes will be evaluated. Antioxidant liposomes are effective vehicles for delivering both lipophilic (incorporated into the lipid bilayers) and water-soluble (encapsulated in the aqueous inner-spaces) antioxidants to skin. The molecular mechanisms interconnecting oxidative stress to HD skin toxicity are also detailed. Results: DNA repair and inflammation, in association with oxidative stress, induce intracellular events leading to apoptosis or to a programmable form of necrosis. The free radical, nitric oxide (NO), is of considerable interest with respect to the mechanisms of HD toxicity. NO signaling pathways are important in modulating inflammation, cell death, and wound healing in skin cells. Conclusions: Potential future directions are summarized with emphasis on a systems biology approach to studying sulfur mustard toxicity to skin as well as the newly emerging area of redox proteomics

Climate of West Siberia during the slowing phase of warming (1986–2015) and prediction of hydro-climatic resources for 2021–2030

The relevance of the study. The most visible affect of the present climate change is the rise of surface air temperature. Regional and local indicators of climate change differ from the global characteristics. Transformation of the hydrological cycle, water balance, river runoff in its turn affects climate processes. In order to predict the response of geosystems and their hydro-climatic resources to climate change it is necessary to have a clear vision of contemporary climate change and its projections for the coming decades in specific geographical localities. The aim of the study is (1) to assess the climate change over West Siberia on the basis of statistical analysis of monthly air temperature and precipitation time series up to 2015, (2) predict the average air temperature and precipitation fields for the 2021-2030, and (3) determine the climate-driven changes in water balance and water flow regime over the study area. The methods used in the study. Analysis and forecasting of spatial and temporal variability of surface air temperature and precipitation rates at meteorological stations in the region are made by statistical methods in the StatSoft STATISTICA package (regression analysis, trend analysis, cluster analysis to classify objects, exponential smoothing and forecasting). The averaged monthly land water balance constituents are determined for the base (1966-1985), current (1986-2015) and forecast (2021-2030) using the method of hydrological and climatical calculations developed by V.S. Mezentsev. The results. It is shown that the modern 30yrs climatic period differs from the previous one in higher energy level (air temperature). Against this background, not only upward but downward temperature trends in some months are observed. The authors have predicted the average temperatures and precipitation rates in a cold season and monthly temperatures and precipitation in a warm season of the year at 31 meteorological stations for 2021-2030. The estimates for the current and forecast periods made it possible to compute the average regime parametres of precipitation, evapotranspiration, runoff and moisture of soil active layer at the meteorological stations located in different lanscape zones and regions of West Siberian plain. The projected increase in temperature and evapotranspiration does not lead to the expected decrease in flow even in the southern dry regions. At the same time, soil moisture in summer will decrease everywher

The influence of N-acetyl-L-cysteine on oxidative stress and nitric oxide synthesis in stimulated macrophages treated with a mustard gas analogue

Background: Sulphur mustard gas, 2, 2′-dichlorodiethyl sulphide (HD), is a chemical warfare agent. Both mustard gas and its monofunctional analogue, 2-chloroethyl ethyl sulphide (CEES), are alkylating agents that react with and diminish cellular thiols and are highly toxic. Previously, we reported that lipopolysaccharide (LPS) significantly enhances the cytotoxicity of CEES in murine RAW 264.7 macrophages and that CEES transiently inhibits nitric oxide (NO) production via suppression of inducible NO synthase (iNOS) protein expression. NO generation is an important factor in wound healing. In this paper, we explored the hypotheses that LPS increases CEES toxicity by increasing oxidative stress and that treatment with N-acetyl-L-cysteine (NAC) would block LPS induced oxidative stress and protect against loss of NO production. NAC stimulates glutathione (GSH) synthesis and also acts directly as a free radical scavenger. The potential therapeutic use of the antibiotic, polymyxin B, was also evaluated since it binds to LPS and could thereby block the enhancement of CEES toxicity by LPS and also inhibit the secondary infections characteristic of HD/CEES wounds. Results: We found that 10 mM NAC, when administered simultaneously or prior to treatment with 500 μM CEES, increased the viability of LPS stimulated macrophages. Surprisingly, NAC failed to protect LPS stimulated macrophages from CEES induced loss of NO production. Macrophages treated with both LPS and CEES show increased oxidative stress parameters (cellular thiol depletion and increased protein carbonyl levels). NAC effectively protected RAW 264.7 cells simultaneously treated with CEES and LPS from GSH loss and oxidative stress. Polymyxin B was found to partially block nitric oxide production and diminish CEES toxicity in LPS-treated macrophages. Conclusion: The present study shows that oxidative stress is an important mechanism contributing to CEES toxicity in LPS stimulated macrophages and supports the notion that antioxidants could play a therapeutic role in preventing mustard gas toxicity. Although NAC reduced oxidative stress in LPS stimulated macrophages treated with CEES, it did not reverse CEES-induced loss of NO production. NAC and polymyxin B were found to help prevent CEES toxicity in LPS-treated macrophages

Inhibition of Inducible Nitric Oxide Synthase by a Mustard Gas Analog in Murine Macrophages

Background: 2-Chloroethyl ethyl sulphide (CEES) is a sulphur vesicating agent and an analogue of the chemical warfare agent 2,2′-dichlorodiethyl sulphide, or sulphur mustard gas (HD). Both CEES and HD are alkylating agents that influence cellular thiols and are highly toxic. In a previous publication, we reported that lipopolysaccharide (LPS) enhances the cytotoxicity of CEES in murine RAW264.7 macrophages. In the present investigation, we studied the influence of CEES on nitric oxide (NO) production in LPS stimulated RAW264.7 cells since NO signalling affects inflammation, cell death, and wound healing. Murine macrophages stimulated with LPS produce NO almost exclusively via inducible nitric oxide synthase (iNOS) activity. We suggest that the influence of CEES or HD on the cellular production of NO could play an important role in the pathophysiological responses of tissues to these toxicants. In particular, it is known that macrophage generated NO synthesised by iNOS plays a critical role in wound healing. Results: We initially confirmed that in LPS stimulated RAW264.7 macrophages NO is exclusively generated by the iNOS form of nitric oxide synthase. CEES treatment inhibited the synthesis of NO (after 24 hours) in viable LPS-stimulated RAW264.7 macrophages as measured by either nitrite secretion into the culture medium or the intracellular conversion of 4,5-diaminofluorescein diacetate (DAF-2DA) or dichlorofluorescin diacetate (DCFH-DA). Western blots showed that CEES transiently decreased the expression of iNOS protein; however, treatment of active iNOS with CEES in vitro did not inhibit its enzymatic activity. Conclusion: CEES inhibits NO production in LPS stimulated macrophages by decreasing iNOS protein expression. Decreased iNOS expression is likely the result of CEES induced alteration in the nuclear factor kappa B (NF-κB) signalling pathway. Since NO can act as an antioxidant, the CEES induced down-regulation of iNOS in LPS-stimulated macrophages could elevate oxidative stress. Since macrophage generated NO is known to play a key role in cutaneous wound healing, it is possible that this work has physiological relevance with respect to the healing of HD induced skin blisters

Inhibition of inducible Nitric Oxide Synthase by a mustard gas analog in murine macrophages

BACKGROUND: 2-Chloroethyl ethyl sulphide (CEES) is a sulphur vesicating agent and an analogue of the chemical warfare agent 2,2'-dichlorodiethyl sulphide, or sulphur mustard gas (HD). Both CEES and HD are alkylating agents that influence cellular thiols and are highly toxic. In a previous publication, we reported that lipopolysaccharide (LPS) enhances the cytotoxicity of CEES in murine RAW264.7 macrophages. In the present investigation, we studied the influence of CEES on nitric oxide (NO) production in LPS stimulated RAW264.7 cells since NO signalling affects inflammation, cell death, and wound healing. Murine macrophages stimulated with LPS produce NO almost exclusively via inducible nitric oxide synthase (iNOS) activity. We suggest that the influence of CEES or HD on the cellular production of NO could play an important role in the pathophysiological responses of tissues to these toxicants. In particular, it is known that macrophage generated NO synthesised by iNOS plays a critical role in wound healing. RESULTS: We initially confirmed that in LPS stimulated RAW264.7 macrophages NO is exclusively generated by the iNOS form of nitric oxide synthase. CEES treatment inhibited the synthesis of NO (after 24 hours) in viable LPS-stimulated RAW264.7 macrophages as measured by either nitrite secretion into the culture medium or the intracellular conversion of 4,5-diaminofluorescein diacetate (DAF-2DA) or dichlorofluorescin diacetate (DCFH-DA). Western blots showed that CEES transiently decreased the expression of iNOS protein; however, treatment of active iNOS with CEES in vitro did not inhibit its enzymatic activity CONCLUSION: CEES inhibits NO production in LPS stimulated macrophages by decreasing iNOS protein expression. Decreased iNOS expression is likely the result of CEES induced alteration in the nuclear factor kappa B (NF-κB) signalling pathway. Since NO can act as an antioxidant, the CEES induced down-regulation of iNOS in LPS-stimulated macrophages could elevate oxidative stress. Since macrophage generated NO is known to play a key role in cutaneous wound healing, it is possible that this work has physiological relevance with respect to the healing of HD induced skin blisters

Assessment of Education Quality Assurance Conditions During Public Accreditation of Educational Organization

The article proposes to evaluate the conditions of educational activities, which ensure the quality of education, during public accreditation of an educational organization. The approach is based on the use of the mechanism of external independent evaluation, conducted by a public organization, to determine the level of an educational organization in order to promote consistent improvement in the quality of the processes of providing and implementing educational activities. A number of indicators that can be expressed quantitatively are proposed. The work of the educational organization to ensure the quality of education in this case can be evaluated on the basis of the proposed indicators

Lipid Transfer Inhibitor Protein (Apolipoprotein F) Concentration in Normolipidemic and Hyperlipidemic Subjects

Lipid transfer inhibitor protein (LTIP) is an important regulator of cholesteryl ester transfer protein function. We report the development of an immunoassay for LTIP and its use to quantify LTIP in plasma of varying lipid contents. A rabbit antibody against bacterially produced recombinant LTIP detected two LTIP isoforms in plasma differing in carbohydrate content. This antibody was used in a competitive, enzyme-linked immunoassay that uses partially purified LTIP bound to microtiter plates. To optimize LTIP immunoreactivity, plasma samples required preincubation in 1% Tween-20 and 0.5% Nonidet P-40. In normolipidemic plasma, LTIP averaged 83.5 mg/ml. LTIP was 31% higher in males than in females. LTIP was positively associated with HDL cholesterol in normolipidemic males but not in females. In hypertriglyceridemic males, LTIP was only 56% of control values, whereas in hypertriglyceridemic females, LTIP tended to increase. Additionally, in males with normal cholesterol and triglyceride (TG) ≤ 200 mg/dl, LTIP varied inversely with plasma TG. Overall, we have confirmed the negative association between plasma TG levels and LTIP previously suggested by a small data set, but now we demonstrate that this effect is seen only in males. The mechanisms underlying this gender-specific response to TG, and why LTIP and HDL levels correlate in males but not in females, remain to be determined

Identification of Oxidized Protein Hydrolase as a Potential Prodrug Target in Prostate Cancer

Background: Esterases are often overexpressed in cancer cells and can have chiral specificities different from that of the corresponding normal tissues. For this reason, ester prodrugs could be a promising approach in chemotherapy. In this study, we focused on the identification and characterization of differentially expressed esterases between non-tumorigenic and tumorigenic prostate epithelial cells.Methods: Cellular lysates from LNCaP, DU 145, and PC3 prostate cancer cell lines, tumorigenic RWPE-2 prostate epithelial cells, and non-tumorigenic RWPE-1 prostate epithelial cells were separated by native polyacrylamide gel electrophoresis (n-PAGE) and the esterase activity bands visualized using α-naphthyl acetate or α-naphthyl-N-acetylalaninate (ANAA) chiral esters and Fast Blue RR salt. The esterases were identified using nanospray LC/MS-MS tandem mass spectrometry and confirmed by Western blotting, native electroblotting, inhibition assays, and activity towards a known specific substrate. The serine protease/esterase oxidized protein hydrolase (OPH) was overexpressed in COS-7 cells to verify our results.Results: The major esterase observed with the ANAA substrates within the n-PAGE activity bands was identified as OPH. OPH (EC 3.4.19.1) is a serine protease/esterase and a member of the prolyl oligopeptidase family. We found that LNCaP lysates contained approximately 40% more OPH compared to RWPE-1 lysates. RWPE-2, DU145 and PC3 cell lysates had similar levels of OPH activity. OPH within all of the cell lysates tested had a chiral preference for the S-isomer of ANAA. LNCaP cells were stained more intensely with ANAA substrates than RWPE-1 cells and COS-7 cells overexpressing OPH were found to have a higher activity towards the ANAA and AcApNA than parent COS-7 cells.Conclusions: These data suggest that prodrug derivatives of ANAA and AcApNA could have potential as chemotherapeutic agents for the treatment of prostate cancer tumors that overexpress OPH

Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog

Sulfur mustard or mustard gas (HD) and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES), or “half-mustard gas,” are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated using in vitro model systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes) increased cell viability and attenuated production of reactive oxygen species (ROS) in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM) increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously described in vivo protective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD