Interaction of hydrocortisone with ATP and adenosine on nerve-mediated contractions of frog skeletal muscle

The inhibitory effects of ATP and adenosine on the nerve-mediated contractile responses of isolated sartorius muscle of the frog, Rana ridibunda, evoked by electrical field stimulation (EFS) were studied using pharmacological organ-bath technique. The effects of hydrocortisone applied in vitro and in vivo on contractility of sartorius muscle were also examined. ATP (100 μM) significantly reduced the amplitude of contraction to EFS of sartorius muscle, while pyridoxalphosphate-6-azonphenyl-2′,4′-disulfonic acid (PPADS; 10 μM), a P2 receptor antagonist, abolished inhibitory effect of ATP. A similar inhibitory effect of adenosine (100 μM) was fully antagonized by 8-(p-sulfophenyl)-theophylline (8-SPT, 100 μM), a P1 receptor antagonist. Incubation of the tissue with hydrocortisone (10 μM) caused a slight, but significant, decrease of muscle contractions. After incubation of muscle preparations with both hydrocortisone and ATP, no inhibition of muscle contractility was registered. A single injection of hydrocortisone (100 mg/kg) 12 h prior to experiments to frogs did not significantly change the nerve-mediated contractility of isolated sartorius muscle; however, it abolished the inhibitory action of ATP without changing inhibitory activity of adenosine. After treatment of frogs with hydrocortisone for 14 days (100 mg/kg/day), both ATP and adenosine retained their inhibitory action on EFS-induced contractions of the muscle, and their effects were antagonized by PPADS and 8-SPT, respectively. It is concluded that hydrocortisone has antagonistic actions against the inhibitory effects of ATP at the frog neuromuscular junction, although this effect is lost following long-term treatment with hydrocortisone. © 2009 Elsevier B.V

Registration, insurance, and medical application of biotechnological drugs in Russia

Existing approaches to the registration, insurance, and application of biotechnological drugs in Russia were analyzed using monoclonal antibody drugs and those produced using recombinant DNAtechnology as examples. Pharmacoeconomic aspects of using these drugs in the RF were described and compared with WHO recommendations for their use. © 2013 Springer Science+Business Media New York

The role of P2 receptor-mediated component in neurogenic tone control of human great saphenous vein

© 2017, Nizhny Novgorod State Medical Academy. All rights reserved.The aim of the investigation was to evaluate experimentally the role of the P2 receptor-mediated component in neurogenic tone control of human varicose-affected and healthy great saphenous vein (GSV). Materials and Methods. The material for the study were segments of GSV obtained from two groups of patients: group 1 (n=14) included patients with varicose vein disease, in whom GSV was removed during surgical treatment; group 2 (n=21) comprised patients with coronary artery disease who underwent coronary artery bypass grafting using GSV as an autograft. Mechanical activity of the isolated veins was studied in vitro by electrical stimulation before and after incubation with atropine and phentolamine, pyridoxal-phosphate-6-azophenyl- 2’,4’-disulfonate (PPADS) and suramin (both nonselective antagonists of P2 receptors), and also after desensitization of P2X receptors by a,ß-methylene ATP. Results. Atropine and phentolamine did not completely inhibit the contractile responses evoked by electric field stimulation of the varicose and non-varicose GSV. PPADS (10 and 30 µM) and suramin (100 and 300 µM) significantly reduced the contractile amplitude of GSV response in both groups of veins (p0.05). Atropine, phentolamine and PPADS inhibited the contractile responses to a lesser extent in the varicose-affected veins compared to the veins unaffected by varicose disease. Conclusion. These experimental results suggest the presence of the P2 receptor-mediated component in the neurogenic control of human GSV tone. Further studies of the P2 receptor mechanism of action is promising for the development of drugs both for treating varicose veins and for preventing spasm of the venous grafts after aortocoronary bypass surgery

Aerobic degradation of 2,4,6-trinitrotoluene by the yeast strain Geotrichum candidum AN-Z4

The yeast strain Geotrichum candidum AN-Z4 isolated from an anthropogenically polluted site was able to transform 2,4,6-trinitrotoluene (TNT) via the formation of unstable intermediate hydride Meisenheimer complexes with their subsequent destruction and accumulation of nitrite and nitrate ions as the end mineral forms of nitrogen. Aeration of the medium promoted more profound destruction of this xenobiotic by the strain G. candidum AN-Z4 than static conditions. The yeast strain was shown to produce citrate, succinate, and isocitrate, which sharply acidified the medium and influenced the TNT destruction. Two possible pathways of TNT biodegradation were confirmed experimentally: (1) via the destruction of the TNT-monohydride complex (3-H--TNT) and (2) via the destruction of one protonated TNT-dihydride complex (3,5-2H--TNT · H+). The strain G. candidum AN-Z4, due to its ability for TNT degradation, may be promising for bioremediation of TNT-contaminated soil and water. © Pleiades Publishing, Ltd., 2010

Influence of pH on 2,4,6-trinitrotoluene degradation by Yarrowia lipolytica

The microbial reduction of the aromatic ring of 2,4,6-trinitrotoluene (TNT) can lead to its complete destruction. The acid-tolerant yeast Yarrowia lipolytica AN-L15 transformed TNT through hydride ion-mediated reduction of the aromatic ring (as the main pathway), resulting in the accumulation of nitrite and nitrate ions, as well as through nitro group reduction (as minor pathway), resulting in hydroxylamino- and aminoaromatics. TNT transformation depended on the yeasts' ability to acidify the culture medium through the production of organic acids. Aeration and a low medium buffer capacity favored yeast growth and resulted in rapid acidification of the medium, which influenced the rate and extent of TNT transformation. This is the first time that nitrate has been detected as a major product of microbial TNT degradation, and this work demonstrates the importance of pH on TNT biotransformation. The ability of Y. lipolytica AN-L15 to reduce the TNT aromatic ring to form TNT-hydride complexes, followed by their denitration, makes this strain a potential candidate for bioremediation of sites contaminated with explosives. © 2010 Elsevier Ltd. All rights reserved

Study of reservoir properties of carbonate rocks based on analysis of reservoir quality index

The article presents the reservoir properties of carbonate rocks by analyzing the factors that characterize the filtration cell reservoir rocks: reservoir quality index, free fluid index, flow zone indicator. These factors are usually used for clastic reservoirs in order to isolate the flow units - rock volume has certain geological and petrophysical properties, as well as a unified hydraulics. It was believed that such a definition for the carbonate rocks is problematic. However, studies have shown the possibility of allocating the flow units in the carbonate deposits subject to the provision of good reservoir rocks and determination of litho-genetic type of carbonate rocks. For the analysis considered several litho-genetic types. It was found that the best collectors are limestone bioclastic-zoogene type. The coefficients revealed the Flow Units in all productive carbonate deposits considered deposits. Allocation of volumes of rocks possessing common hydraulics allows more correctly carry out operational activities

Effect of ferrihydrite on 2,4,6-trinitrotoluene biotransformation by an aerobic yeast

This study investigated the impact of ferrihydrite on the pathway and rate of 2,4,6-trinitrotoluene (TNT) transformation by Yarrowia lipolytica AN-L15. The presence of ferrihydrite in the culture medium decreased the rate of TNT biotransformation but resulted in the accumulation of the same TNT metabolites as in the absence of ferrihydrite, albeit at slightly different concentrations. Transformation products observed included aromatic ring reduction products, such as hydride-Meisenheimer complexes, and nitro group reduction products, such as hydroxylamino- and amino-dinitrotoluenes. Independently of the presence of ferrihydrite the subsequent degradation of the hydride complex(es) resulted in the release of nitrite followed by its conversion to nitrate and nitric oxide at the low pH values observed during yeast cultivation. Nitric oxide generation was ascertained by electron spin resonance spectroscopy. In addition, increased Fe3+-reduction was observed in the presence of TNT and Y. lipolytica. This study demonstrates that in the presence of yeast cells, TNT-hydride complexes were formed at approximately the same level as in the presence of ferrihydrite, opening up the possibility of aromatic ring cleavage, instead of promoting the production of potentially toxic nitro group reduction products in the presence of iron minerals. © 2012 Springer Science+Business Media Dordrecht

Production of eight different hydride complexes and nitrite release from 2,4,6-trinitrotoluene by Yarrowia lipolytica

2,4,6-Trinitrotoluene (TNT) transformation by the yeast strain Yarrowia lipolytica AN-L15 was shown to occur via two different pathways. Direct aromatic ring reduction was the predominant mechanism of TNT transformation, while nitro group reduction was observed to be a minor pathway. Although growth of Y. lipolytica AN-L15 was inhibited initially in the presence of TNT, TNT transformation was observed, indicating that the enzymes necessary for TNT reduction were present initially. Aromatic ring reduction resulted in the transient accumulation of eight different TNT-hydride complexes, which were characterized using high-performance liquid chromatography, UV-visible diode array detection, and negative-mode atmospheric pressure chemical ionization mass spectrometry (APCI-MS). APCI-MS analysis revealed three different groups of TNT-hydride complexes with molecular ions at m/z 227, 228, and 230, which correspond to TNT-mono- and dihydride complexes and protonated dihydride isomers, respectively. One of the three protonated dihydride complex isomers detected appears to release nitrite in the presence of strain AN-L15. This release of nitrite is of particular interest since it can provide a pathway towards complete degradation and detoxification of TNT. Copyright © 2007, American Society for Microbiology. All Rights Reserved

Hydride-mediated reduction of 2,4,6-trinitrotoluene by yeasts as the way to its deep degradation

Broad screening of microorganisms from natural and anthropogenic ecological niches has revealed strains Candida sp. AN-L15 and Geotrichum sp. AN-Z4 which transform, 2,4,6-trinitrotoluene (TNT) via alternative pathways (with the domination of hydride ion-mediated reduction of the aromatic ring) and produce relatively high amounts of nitrites. According to the spectrophotometry data, the hydride attack of TNT by Candida sp. AN-L15 and Geotrichum sp. AN-Z4 grown at pH 5.0-8.0 leads to the mono-and dihydride complexes of TNT (H --TNT and 2H--TNT, respectively) and to protonated forms of the latter. Analysis by HPLC, GC-mass spectrometry, and ion chromatography revealed the products of deep conversion of TNT. The growth of the yeast strains in a weakly acidic medium with TNT (440 μM) is accompanied by formation of 2,4-dinitrotoluene (2,4-DNT, up to 18.2 μM). Together with accumulation of nitrites (up to 76.0 μM, depending on pH of the medium), these findings demonstrate the capacity of both strains for TNT denitration. Formation of 2,4-DNT reflects the realization of one of the possible mechanisms of TNT ortho-nitro group elimination and switching over to the pathways of metabolism of dinitrotoluenes, which are much more easily biodegradable than TNT. Simultaneously with the dominating TNT hydride attack, the mechanism of 4-and 6-electron reduction of the nitro group also functions in Candida sp. AN-L15 and Geotrichum sp. AN-Z4. Realization of the studied mechanisms of TNT transformation under growth of Candida sp. AN-L15 on n-alkane is important for bioremediation in the cases of combined pollution by oil products and explosives. © 2007 Pleiades Publishing, Ltd

Molecular recognition of organic compounds by the data on polymorphic and pseudo-polymorphic transformations of tert-butylthiacalix[4]arene derivative

The receptor properties of metastable polymorphic forms of 5,11,17,23-tetra(tert-butyl)-25,26,27,28-tetrakis[N-(2-ethoxycarbonyl(methyl) carbamoylmethoxy]-2,8,14,20-tetrathiacalix[4]arene in the cone and partial cone configurations obtained by the crystallization of their solutions in an organic solvent were studied. The ability of the studied calixarenes to "remember" the history of interaction with individual vaporous organic guests and their mixtures was discovered. The observed different effects of methanol and ethanol vapors on the phase state of the studied calixarene in the cone configuration can be used for qualitative and quantitative analyses of ethanol in binary mixtures. Calixarene in the partial cone configuration can remember the earlier bound methanol. The "memory" effect appears as a specific polymorphic transition in the receptor phase after bound methanol leaving on heating the clathrate. This effect is not observed for other studied guests. © 2014 Springer Science+Business Media, Inc