Pub Date : 2019-12-05DOI: 10.35825/2587-5728-2019-3-4-319-328
Th is review is dedicated to the peculiarities of pathogenesis of the experimental Bolivian hemorrhagic fever (BHF) – the disease, caused by Machupo virus (Arenaviridae family). Th e authors come to the conclusion that for carrying out preclinical researches of the medical means of protection (MMP) in vivo on small laboratory animals it is expedient to use guinea pigs, infected with a strain of Chicava or with a variant of Carvallo strain, adapted for these animals. Th e use of guinea pigs as small laboratory animals when studying pathogenesis of the disease caused by Machupo virus allows to carry out statistically reliable defi nition of quantitative indices of an experimental infection and to select medicines for the fi nal stage of preclinical assessment. As arenaviruses block the process of formation of interferon (IFN) in the infected organism, mice, defective by IFN formation, are the perspective animal models for the study of BHF pathogenesis and may be used for the study of attenuated variants of Machupo virus. Th e Javanese macaques (Macaca fascicularis) are the laboratory animals, modeling the pathogenetic manifestations of BHF in humans. Th ey can be used when carrying out the fi nal stages of preclinical assessment of means of medical protection
{"title":"Validation of Сhoice of Laboratory Model for Preclinical Estimation of Medical Protectors Against Bolivian Hemorrhagic Fever","authors":"","doi":"10.35825/2587-5728-2019-3-4-319-328","DOIUrl":"https://doi.org/10.35825/2587-5728-2019-3-4-319-328","url":null,"abstract":"Th is review is dedicated to the peculiarities of pathogenesis of the experimental Bolivian hemorrhagic fever (BHF) – the disease, caused by Machupo virus (Arenaviridae family). Th e authors come to the conclusion that for carrying out preclinical researches of the medical means of protection (MMP) in vivo on small laboratory animals it is expedient to use guinea pigs, infected with a strain of Chicava or with a variant of Carvallo strain, adapted for these animals. Th e use of guinea pigs as small laboratory animals when studying pathogenesis of the disease caused by Machupo virus allows to carry out statistically reliable defi nition of quantitative indices of an experimental infection and to select medicines for the fi nal stage of preclinical assessment. As arenaviruses block the process of formation of interferon (IFN) in the infected organism, mice, defective by IFN formation, are the perspective animal models for the study of BHF pathogenesis and may be used for the study of attenuated variants of Machupo virus. Th e Javanese macaques (Macaca fascicularis) are the laboratory animals, modeling the pathogenetic manifestations of BHF in humans. Th ey can be used when carrying out the fi nal stages of\u0000preclinical assessment of means of medical protection","PeriodicalId":16578,"journal":{"name":"Journal of NBC Protection Corps","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75981257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-05DOI: 10.35825/2587-5728-2019-3-4-381-393
Patenting of inventions is the basis of the independence of the Russian Federation in the sphere of high technologies, including dual-use ones. Th e purpose of this work is to review the main approaches to the legal protection of inventions in the Russian Federation. Th e ignorance of these approaches becomes one of the main obstacles to the eff ective patenting of inventions created at the scientifi c research institutes of the NBC Protection Troops. Th e paper is dedicated to the detailed consideration of particular problems, such as the correctness of the title of invention, the importance of clear indication of the purpose of the invention and its closest analogue, the danger of the confusion between technical problems and technical results ect. Th e ignorance of these aspects oft en leads to the delay in the substantive examination of patent applications. Special attention is paid to the procedure of patenting secret inventions and their status. Th e internal logic of the creation of intellectual property objects that should be taken into account during the patenting is shown at the example of patenting antidotes for organophosphorus toxic substances, based on hexahistidine-containing organophosphorus hydrolase. Th e Russian patent system is modern, incorporated into existing international agreements and provides Russian inventors and patent owners all the opportunities for competition in the Russian and world high technology markets. Th e reasons for delays in the substantive examination of patent applications, as well as for the ineffi ciency of patenting inventions in the NBC Protection Troops are purely subjective – poor knowledge of the Russian patent system and MoD orders, and the lack of motivation in opposing patent colonization of Russia
{"title":"Preparation of Applications for Inventions Created in the Nuclear, Biological and Chemical Protection Troops","authors":"","doi":"10.35825/2587-5728-2019-3-4-381-393","DOIUrl":"https://doi.org/10.35825/2587-5728-2019-3-4-381-393","url":null,"abstract":"Patenting of inventions is the basis of the independence of the Russian Federation in the sphere of high technologies, including dual-use ones. Th e purpose of this work is to review the main approaches to the legal protection of inventions in the Russian Federation. Th e ignorance of these approaches becomes one of the main obstacles to the eff ective patenting of inventions created at the scientifi c research institutes of the NBC Protection Troops. Th e paper is dedicated to the detailed consideration of particular problems, such as the correctness of the title of invention, the importance of clear indication of the purpose of the invention and its closest analogue, the danger of the confusion between technical problems and technical results ect. Th e ignorance of these aspects oft en leads to the delay in the substantive examination of patent applications. Special attention is paid to the procedure of patenting secret inventions and their status. Th e internal logic of the creation of intellectual property objects that should be taken into account during the patenting is shown at the example of patenting antidotes for organophosphorus toxic substances, based on hexahistidine-containing organophosphorus hydrolase. Th e Russian patent system is modern, incorporated into existing international agreements and provides Russian inventors and patent owners all the opportunities for competition in the Russian and world high technology markets. Th e reasons for delays in the substantive examination of patent applications, as well as for the ineffi ciency of patenting inventions in the NBC Protection Troops are purely subjective – poor knowledge of the Russian patent system and MoD orders, and the lack of motivation in opposing patent colonization of Russia","PeriodicalId":16578,"journal":{"name":"Journal of NBC Protection Corps","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77016280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-05DOI: 10.35825/2587-5728-2019-3-4-329-336
The purpose of the work is to analyze the distribution, natural reservoirs and potential epidemic hazard of new members of the Filoviridae family – Bombali viruses (genus Ebolavirus), Lloviu (genus Cuevavirus), Mengla (genus Dianlovirus), Xylang (genus Striavirus), and Hungjiao (genus Th amnovirus). New filoviruses were detected in Africa (Bombali virus), Europe (Llovi virus) and in Southeast Asia (Mengla, Xylang and Hungjiao viruses). Bats are a natural reservoir for all known fi loviruses. Th is fact is confi rmed by the information about the detection of genomic RNA and virus-specifi c antibodies in them. Th e isolation of the genomic RNA of fi loviruses from bats with the subsequent sequencing and phylogenetic analysis made it possible to identify the Bombali, Lloviu, Mengla, Xylang and Hungjiao viruses as new representatives of the Filoviridae family and to establish their position on the phylogenetic tree of the Filoviridae family. Despite the current lack of information about the isolation of biologically active virus from bats, as well as in spite of lack of established connection between new fi loviruses and human diseases, the information that newly identifi ed fi loviruses use the same receptors (Neumann-Peak protein) to enter sensitive cells, as the Ebola and Marburg viruses, that are pathogenic for humans, the possible pathogenetic potential of new fi loviruses poses a great threat to people living in the territories, inhabited by bats. Th e possibility of the emergence of new emergent fi lovirus infections on the territory of Russia necessitates an in-depth study of bats as a natural reservoir of fi loviruses in nature
{"title":"The New Members of Filoviridae Family: Distribution, Natural Reservoirs, Potential Epidemic Danger","authors":"","doi":"10.35825/2587-5728-2019-3-4-329-336","DOIUrl":"https://doi.org/10.35825/2587-5728-2019-3-4-329-336","url":null,"abstract":"The purpose of the work is to analyze the distribution, natural reservoirs and potential epidemic hazard of new members of the Filoviridae family – Bombali viruses (genus Ebolavirus), Lloviu (genus Cuevavirus), Mengla (genus Dianlovirus), Xylang (genus Striavirus), and Hungjiao (genus Th amnovirus). New filoviruses were detected in Africa (Bombali virus), Europe (Llovi virus) and in Southeast Asia (Mengla, Xylang and Hungjiao viruses). Bats are a natural reservoir for all known fi loviruses. Th is fact is confi rmed by the information about the detection of genomic RNA and virus-specifi c antibodies in them. Th e isolation of the genomic RNA of\u0000fi loviruses from bats with the subsequent sequencing and phylogenetic analysis made it possible to identify the Bombali, Lloviu, Mengla, Xylang and Hungjiao viruses as new representatives of the Filoviridae family\u0000and to establish their position on the phylogenetic tree of the Filoviridae family. Despite the current lack of information about the isolation of biologically active virus from bats, as well as in spite of lack of established\u0000connection between new fi loviruses and human diseases, the information that newly identifi ed fi loviruses use the same receptors (Neumann-Peak protein) to enter sensitive cells, as the Ebola and Marburg viruses, that are\u0000pathogenic for humans, the possible pathogenetic potential of new fi loviruses poses a great threat to people living in the territories, inhabited by bats. Th e possibility of the emergence of new emergent fi lovirus infections on the territory of Russia necessitates an in-depth study of bats as a natural reservoir of fi loviruses in nature","PeriodicalId":16578,"journal":{"name":"Journal of NBC Protection Corps","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90083990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-05DOI: 10.35825/2587-5728-2019-3-4-337-349
Th e purpose of the work is to show the possibilities of vaccine prophylaxis of anthrax in the Russian Federation and its immediate prospects. Th e article is dedicated to the vaccine preparations, available in Russia and abroad in the arsenal of medical remedies at present, to the history of their creation, to the eff ectiveness of their use and to the main directions of the improving of the vaccine prevention. Th e eff orts to develop a new generation of vaccines are aimed mainly at the increasing of the safety of vaccines, reducing the frequency of their administration and improving their production technologies. Th e combined anthrax vaccine developed in the USSR can be used in the emergency prophylaxis of anthrax along with antibiotics. The development of vaccines based on immunogenic antigens synthesized by recombinant producers solves the problem of residual virulence and reactogenicity, as well as the problem of increasing stability and reduction of doses of modern anthrax vaccines. In the nearest future it is necessary: to develop an industrial technology of the production of anthrax vaccines based on recombinant strains – hyperproducers of protective antigen and include them in the prophylaxis and treatment regimens of anthrax infection; to develop scientifi c and methodological approaches and vaccines for mass immunization against anthrax; to evaluate the possibility of using new adjuvants for the construction of anthrax vaccines, more eff ective and safer than the existing ones
{"title":"Vaccinal Preventon of Anthrax in the Russian Federation and Its Immediate Prospects","authors":"","doi":"10.35825/2587-5728-2019-3-4-337-349","DOIUrl":"https://doi.org/10.35825/2587-5728-2019-3-4-337-349","url":null,"abstract":"Th e purpose of the work is to show the possibilities of vaccine prophylaxis of anthrax in the Russian Federation and its immediate prospects. Th e article is dedicated to the vaccine preparations, available\u0000in Russia and abroad in the arsenal of medical remedies at present, to the history of their creation, to the eff ectiveness of their use and to the main directions of the improving of the vaccine prevention. Th e eff orts to develop a new generation of vaccines are aimed mainly at the increasing of the safety of vaccines, reducing the frequency of their administration and improving their production technologies. Th e combined anthrax vaccine developed in the USSR can be used in the emergency prophylaxis of anthrax along with antibiotics. The development of vaccines based on immunogenic antigens synthesized by recombinant producers solves the problem of residual virulence and reactogenicity, as well as the problem of increasing stability and reduction of doses of modern anthrax vaccines. In the nearest future it is necessary: to develop an industrial technology of the production of anthrax vaccines based on recombinant strains – hyperproducers of protective antigen and include them in the prophylaxis\u0000and treatment regimens of anthrax infection; to develop scientifi c and methodological approaches and vaccines for mass immunization against anthrax; to evaluate the possibility of using new adjuvants for the construction of anthrax vaccines, more eff ective and safer than the existing ones","PeriodicalId":16578,"journal":{"name":"Journal of NBC Protection Corps","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88448007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-30DOI: 10.35825/2587-5728-2019-3-2-111-116
E. Efremenko, I. Lyagin
The advanced biocatalysts based on hexahistidine-tagged organophosphorus hydrolase (His6-OPH) were recently developed for the detoxification of various organophosphorus compounds and degradation of N-acyl homoserine lactones. Due to enzyme immobilization, some of obtained biocatalysts are quite stable, easy to use and very effective/active (e.g. tens of millions of substrate solution volumes appeared to be treated with column cartridges containing immobilized His6-OPH). Recently, the possible bioengineering of different stabilized nanocomplexes of His6-OPH due to its non-covalent binding with different compounds (polymers, antioxidants, antimicrobials, etc.) was demonstrated. Firstly, it was realized by computer modeling via molecular docking. Polymers of amino acids (polyglutamic and polyasparctic acids) were established to be the most effective stabilizers of the enzyme that enabled effective preservation of the enzyme activity. Up to 100 %-retention of initial catalytic characteristics of the enzyme was reached in obtained enzymatic complexes. Such nanobiocatalysts were stabilized against inactivating effects of solvents, temperatures and were able to circulate in vivo for at least 25 hours. It appeared that different antioxidants can be applied as partners of the enzyme in the nanocomplexing. Thus, a new set of original enzymatic antidotes were developed possessing dual action: both hydrolytic activity against organophosphorus neurotoxins and improved antioxidant activity. Additionally, it was shown that different organophosphorus compounds and N-acyl homoserine lactones could be molecularly docked directly to the active centers of His6 -OPH dimer, thus allowing to theoretically clarify some new prospective substrates for the enzymatic hydrolysis. It appeared that new type of nanocomplexes of the enzyme with antibiotics also can be prepared. In this case the combination of antibiotics with enzyme quenching the quorum of the pathogenic gram-negative bacteria was performed. The enzyme being stabilized by the various antibiotics (especially those containing β-lactame ring) played the role of a carrier for the antimicrobial compounds significantly improving their efficiency of the action. Such biocatalysts and/or method of their design have a great potential and can be very useful for both chemical and biological defense
{"title":"Advanced Biocatalysts Based on Hexahistidine-Containing organophosphorus Hydrolase for Chemical and Biological Defense","authors":"E. Efremenko, I. Lyagin","doi":"10.35825/2587-5728-2019-3-2-111-116","DOIUrl":"https://doi.org/10.35825/2587-5728-2019-3-2-111-116","url":null,"abstract":"The advanced biocatalysts based on hexahistidine-tagged organophosphorus hydrolase (His6-OPH) were recently developed for the detoxification of various organophosphorus compounds and degradation of N-acyl homoserine lactones. Due to enzyme immobilization, some of obtained biocatalysts are quite stable, easy to use and very effective/active (e.g. tens of millions of substrate solution volumes appeared to be treated with column cartridges containing immobilized His6-OPH). Recently, the possible bioengineering of different stabilized nanocomplexes of His6-OPH due to its non-covalent binding with different compounds (polymers, antioxidants, antimicrobials, etc.) was demonstrated. Firstly, it was realized by computer modeling via molecular docking. Polymers of amino acids (polyglutamic and polyasparctic acids) were established to be the most effective stabilizers of the enzyme that enabled effective preservation of the enzyme activity. Up to 100 %-retention of initial catalytic characteristics of the enzyme was reached in obtained enzymatic complexes. Such nanobiocatalysts were stabilized against inactivating \u0000effects of solvents, temperatures and were able to circulate in vivo for at least 25 hours. It appeared that different antioxidants can be applied as partners of the enzyme in the nanocomplexing. Thus, a new set \u0000of original enzymatic antidotes were developed possessing dual action: both hydrolytic activity against organophosphorus neurotoxins and improved antioxidant activity. Additionally, it was shown that different \u0000organophosphorus compounds and N-acyl homoserine lactones could be molecularly docked directly to the active centers of His6 -OPH dimer, thus allowing to theoretically clarify some new prospective substrates for the enzymatic hydrolysis. It appeared that new type of nanocomplexes of the enzyme with antibiotics also can be prepared. In this case the combination of antibiotics with enzyme quenching the quorum of the pathogenic gram-negative bacteria was performed. The enzyme being stabilized by the various antibiotics (especially those containing β-lactame ring) played the role of a carrier for the antimicrobial compounds significantly improving their efficiency of the action. Such biocatalysts and/or method of their design have a great potential and can be very useful for both chemical and biological defense","PeriodicalId":16578,"journal":{"name":"Journal of NBC Protection Corps","volume":"119 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88441594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-03-30DOI: 10.35825/2587-5728-2019-3-1-4-14
V. A. A. I. Soloshin
The contemporary level of the development of the theory of laser location and technical possibilities of lidar systems allows not only to solve certain problems of remote control of the optical properties of aerosol formations, but also to measure their concentrational characteristics and the parameters of the distribution function of the aerosol particles, using multi-frequency laser sensing. Because of that the remote means of chemical reconnaissance of active type with the function of measuring the parameters of aerosols of toxic substances and highly active toxic substances represent a new generation of such technologies. It is possible to give certain promising mobile lidar complexes of remote chemical reconnaissance special functions of measuring systems by introducing modern software and special algorithms for reversing lidar sensing data into macro- and microstructural characteristics of clouds of physiologically active substances (PhAS) in the atmosphere. This ensures control of the concentrations of multicomponental mixtures of PhAS, the parameters of the distribution function of the aerosol of PhAS by dispersion with the overlapping of isolines of the concentrations of the displayed PhAS on the terrain map. Mathematical studies allows us to formulate basic requirements for multi-frequency lidar measurements – optical measurement error for all λi should not exceed 5% - the imaginary part of the complex index of refraction of the substance of the aerosol of PhAS should be χ ≤ 0, 005 the error in specifying the real part of the complex refractive index must be within +_0,02. If these requirements are met, this sensing method becomes an effective tool for the study of the disperse composition of aerosols
{"title":"Main \u0000Trends in the Improvement of Software of Mobile Laser Remote Chemical Reconnaissance Complexes","authors":"V. A. A. I. Soloshin","doi":"10.35825/2587-5728-2019-3-1-4-14","DOIUrl":"https://doi.org/10.35825/2587-5728-2019-3-1-4-14","url":null,"abstract":"The contemporary level of the development of the theory of laser location and technical possibilities \u0000of lidar systems allows not only to solve certain problems of remote control of the optical properties \u0000of aerosol formations, but also to measure their concentrational characteristics and the parameters \u0000of the distribution function of the aerosol particles, using multi-frequency laser sensing. Because \u0000of that the remote means of chemical reconnaissance of active type with the function of measuring \u0000the parameters of aerosols of toxic substances and highly active toxic substances represent a new \u0000generation of such technologies. It is possible to give certain promising mobile lidar complexes of \u0000remote chemical reconnaissance special functions of measuring systems by introducing modern \u0000software and special algorithms for reversing lidar sensing data into macro- and microstructural \u0000characteristics of clouds of physiologically active substances (PhAS) in the atmosphere. This \u0000ensures control of the concentrations of multicomponental mixtures of PhAS, the parameters of \u0000the distribution function of the aerosol of PhAS by dispersion with the overlapping of isolines of \u0000the concentrations of the displayed PhAS on the terrain map. Mathematical studies allows us to \u0000formulate basic requirements for multi-frequency lidar measurements – optical measurement \u0000error for all λi should not exceed 5% - the imaginary part of the complex index of refraction of the \u0000substance of the aerosol of PhAS should be χ ≤ 0, 005 the error in specifying the real part of the \u0000complex refractive index must be within +_0,02. If these requirements are met, this sensing method \u0000becomes an effective tool for the study of the disperse composition of aerosols","PeriodicalId":16578,"journal":{"name":"Journal of NBC Protection Corps","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85761702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01DOI: 10.35825/2587-5728-2019-3-2-103-110
Krylov V.I. Rybalchenko I.V.
Organophosphorus chemical agents are included in the 1st List of the Annex on Chemicals of the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on Their Destruction (Chemical Weapons Convention, CWC). For the purposes of verification of compliance with the provisions of the CWC, special methods, which are considered the most informative at determining the retrospective effects of organophosphorus toxicants on the body, are necessary. Typical long-lived biomarkers of organophosphate toxic agents are tyrosine phosphorylation products, the presence of which in biomedical samples clearly indicates the exposure to sarin, soman, tabun and V-series agents. We have elaborated methods for the synthesis and isolation of tyrosine adducts derivatives of methylphosphonic and phosphoric acids, used as reference samples. The synthesis scheme included the consecutive protection of carboxyl and amino groups of tyrosine, its O-phosphorylation by the corresponding alkylphosphonates and phosphates, the removal of protective groups with the release of corresponding O-phosphorylated tyrosine adducts. Their purification from im purities was carried out, using column chromatography (SiO2, eluent: dichloromethane/ethyl acetate 1:1). The purity of the obtained products was more than 90 %, so it was possible to involve them in further transformations with the use of catalyst without the threat of its «poisoning». Benzyl and carboxybenzyl protection of phosphorylated L-tyrosines (12–17) was removed by means of catalytic hydrogenation by molecular hydrogen under atmospheric pressure. Target adducts of phosphorylated reagents and L-tyrosin were obtained (63–82 %) in form of crystal white substances, readily soluble in water and ethanol, and poorly – in dichloromethane and acetonitrile
{"title":"Synthesis of O-tyrosine Phosphorylated Adducts of Methylphosphonic and Phosphoric Acid Derivatives as Reference Compounds for the Analysis of Biomedical Samples","authors":"Krylov V.I. Rybalchenko I.V.","doi":"10.35825/2587-5728-2019-3-2-103-110","DOIUrl":"https://doi.org/10.35825/2587-5728-2019-3-2-103-110","url":null,"abstract":"Organophosphorus chemical agents are included in the 1st List of the Annex on Chemicals of the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on Their Destruction (Chemical Weapons Convention, CWC). For the purposes of verification of compliance with the provisions of the CWC, special methods, which are considered the most informative at determining the retrospective effects of organophosphorus toxicants on the body, are necessary. Typical long-lived biomarkers of organophosphate toxic agents are tyrosine phosphorylation products, the presence of which in biomedical samples clearly indicates the exposure to sarin, soman, tabun and V-series agents. We have elaborated methods for the synthesis and isolation of tyrosine adducts derivatives of methylphosphonic and phosphoric acids, used as reference samples. The synthesis scheme included the consecutive protection of carboxyl and amino groups of tyrosine, its O-phosphorylation by the corresponding alkylphosphonates and phosphates, the removal of protective groups with the release of corresponding O-phosphorylated tyrosine adducts. Their purification from im purities was carried out, using column chromatography (SiO2, eluent: dichloromethane/ethyl acetate 1:1). The purity of the obtained products was more than 90 %, so it was possible to involve them in further transformations with the use of catalyst without the threat of its «poisoning». Benzyl and carboxybenzyl protection of phosphorylated L-tyrosines (12–17) was removed by means of catalytic hydrogenation by molecular hydrogen under atmospheric pressure. Target adducts of phosphorylated reagents and L-tyrosin were obtained (63–82 %) in form of crystal white substances, readily soluble in water and ethanol, and poorly – in dichloromethane and acetonitrile","PeriodicalId":16578,"journal":{"name":"Journal of NBC Protection Corps","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84577981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01DOI: 10.35825/2587-5728-2019-3-1-40-64
Supotnitskiy M.V. Kovtun V.A.
The Iraqis became the first nation to use chemical weapons on the modern battlefield during the Iran-Iraq War (1980-1988). There are no general reviews and research available on this issue in Russian. It also puts the Russian researchers in an unequal position in comparison with their Western and Middle Eastern colleagues, who have such information from a wide range of sources. This lack of knowledge limits our ability to understand the secret mechanisms that trigger modern chemical wars in the Middle East. The analysis in the present study is based on different Western sources, UN and CIA materials. The article shows that Iraq – a third world country with the population of 16,3 million people in 1980-ies and relatively low educational level – could start its chemical weapons program only due to the Western aid and assistance (supplies of the precursors, technologies and technical documentation, education of specialists, diplomatic support ect). Only due to this assistance the Iraqi`s chemical weapons program could become successful. The industrial production of chemical agents and chemical munitions of various tactical purposes was established by the Iraqis in less than 10 years. By the end of the 1980-ies, the Iraqi chemists laid the foundations of the future research in the sphere of toxic chemicals. The industrial base for the production of CW have also been established. For Russia, the success of the Iraq`s chemical weapons program is a warning. It means that technically backward, but oil rich quasi-state can acquire chemical weapons in a few years with the clandestine support of the same «sponsors», and use it both for provocations and for conducting combat operations in the regions, vital for Russia`s interests.
{"title":"Chemical Weapons in the Iran-Iraq War (1980-1988). 1. Iraq Preparing for Chemical War","authors":"Supotnitskiy M.V. Kovtun V.A.","doi":"10.35825/2587-5728-2019-3-1-40-64","DOIUrl":"https://doi.org/10.35825/2587-5728-2019-3-1-40-64","url":null,"abstract":"The Iraqis became the first nation to use chemical weapons on the modern battlefield during the Iran-Iraq War (1980-1988). There are no general reviews and research available on this issue in Russian. It also puts the Russian researchers in an unequal position in comparison with their Western and Middle Eastern colleagues, who have such information from a wide range of sources. This lack of knowledge limits our ability to understand the secret mechanisms that trigger modern chemical wars in the Middle East. The analysis in the present study is based on different Western sources, UN and CIA materials. The article shows that Iraq – a third world country with the population of 16,3 million people in 1980-ies and relatively low educational level – could start its chemical weapons program only due to the Western aid and assistance (supplies of the precursors, technologies and technical documentation, education of specialists, diplomatic support ect). Only due to this assistance the Iraqi`s chemical weapons program could become successful. The industrial production of chemical agents and chemical munitions of various tactical purposes was established by the Iraqis in less than 10 years. By the end of the 1980-ies, the Iraqi chemists laid the foundations of the future research in the sphere of toxic chemicals. The industrial base for the production of CW have also been established. For Russia, the success of the Iraq`s chemical weapons program is a warning. It means that technically backward, but oil rich quasi-state can acquire chemical weapons in a few years with the clandestine support of the same «sponsors», and use it both for provocations and for conducting combat operations in the regions, vital for Russia`s interests.","PeriodicalId":16578,"journal":{"name":"Journal of NBC Protection Corps","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82127786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01DOI: 10.35825/2587-5728-2019-3-1-23-39
Aminin D.L. alinin V.I. T
Holothurians (or sea cucumbers) are echinoderms and are found in all areas of the world oceans. These animals produce special low-molecular metabolites - triterpene glycosides, which are a means of chemical protection of holothurians from predators. The content of triterpene glycosides in the tissues of holothurians can reach a significant amount of up to 1 g/kg, and especially many of these compounds are localized in the Cuvierian tubules - special protection organ presents in a number of tropical holothurians. Tritirepene glycosides of holothurians are quite toxic, they exhibit hemohttp://journal.ofhim.ru/index.php/vestnik/article/view/86lytic, cytotoxic and neurotoxic activity at a concentration range of 1×104–1×106 M. The toxic properties of glycosides are based on the ability of these compounds to interact with ∆ 5-sterols (mainly cholesterol) of plasma membranes and form ion-conducting complexes. In turn, this leads to a change in the ion permeability and selectivity of biomembranes, disruption of barrier properties, ion homeostasis and osmolarity of cells, and further to cell lysis and death. Contact with holoturias when diving in shallow water, which is fraught with damage to the eyes and mucous membranes by triterpene glycosides, may be of some danger to humans. Excessive consumption of commercial edible holothurians in food, especially without prior heat treatment, as is customary in some South-East Asia countries, can lead to diarrhea and dyspepsia. Triterpene glycosides in the bloodstream can lead to blood lysis and serious consequences up to death. The holothurians are animals commercially harvested in Russia. They are used in food and for the preparation of medicinal supplements and preparations. Excessive consumption of commercial edible holothurians for food, especially without long-term boiling, as is customary in Southeast Asia, can lead to diarrhea and dyspepsia. Triterpene glycosides in the bloodstream can lead to blood lysis and serious consequences up to death. The use of dietary supplements with an uncontrolled glycoside content is fraught with similar consequences, and the presence of immunosuppressants among glycosides that have fallen into such additives and drugs can worsen the condition of patients or sick animals. Control of the qualitative and quantitative content of glycosides in food and medicinal products from holothurians should be an integral part of measures to improve the biological safety of citizens of the Russian Federation
{"title":"Toxic Properties of Holothurian’s Triterpene Glycosides","authors":"Aminin D.L. alinin V.I. T","doi":"10.35825/2587-5728-2019-3-1-23-39","DOIUrl":"https://doi.org/10.35825/2587-5728-2019-3-1-23-39","url":null,"abstract":"Holothurians (or sea cucumbers) are echinoderms and are found in all areas of the world oceans. These animals produce special low-molecular metabolites - triterpene glycosides, which are a means of chemical protection of holothurians from predators. The content of triterpene glycosides in the tissues of holothurians can reach a significant amount of up to 1 g/kg, and especially many of these compounds are localized in the Cuvierian tubules - special protection organ presents in a number of tropical holothurians. Tritirepene glycosides of holothurians are quite toxic, they exhibit hemohttp://journal.ofhim.ru/index.php/vestnik/article/view/86lytic, cytotoxic and neurotoxic activity at a concentration range of 1×104–1×106 M. The toxic properties of glycosides are based on the ability of these compounds to interact with ∆ 5-sterols (mainly cholesterol) of plasma membranes and form ion-conducting complexes. In turn, this leads to a change in the ion permeability and selectivity of biomembranes, disruption of barrier properties, ion homeostasis and osmolarity of cells, and further to cell lysis and death. Contact with holoturias when diving in shallow water, which is fraught with damage to the eyes and mucous membranes by triterpene glycosides, may be of some danger to humans. Excessive consumption of commercial edible holothurians in food, especially without prior heat treatment, as is customary in some South-East Asia countries, can lead to diarrhea and dyspepsia. Triterpene glycosides in the bloodstream can lead to blood lysis and serious consequences up to death. The holothurians are animals commercially harvested in Russia. They are used in food and for the preparation of medicinal supplements and preparations. Excessive consumption of commercial edible holothurians for food, especially without long-term boiling, as is customary in Southeast Asia, can lead to diarrhea and dyspepsia. Triterpene glycosides in the bloodstream can lead to blood lysis and serious consequences up to death. The use of dietary supplements with an uncontrolled glycoside content is fraught with similar consequences, and the presence of immunosuppressants among glycosides that have fallen into such additives and drugs can worsen the condition of patients or sick animals. Control of the qualitative and quantitative content of glycosides in food and medicinal products from holothurians should be an integral part of measures to improve the biological safety of citizens of the Russian Federation","PeriodicalId":16578,"journal":{"name":"Journal of NBC Protection Corps","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84751771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01DOI: 10.35825/2587-5728-2019-3-2-117-136
R S M M Kalina Monastyrnaya
Sea anemones are well-spread everywhere in the World Ocean and represent the most ancient active poisonous organisms. Their main instrument of attack on other animals are the nematocysts – stinging organelles with the curtailed hollow thread with poisonous edge on the end. In order to attract their potential victims, they use fluorescent proteins. These proteins became a separate object of research as genetically coded markers for the observation of activity of promotors of genes. The poisonous secret of sea anemones is characterized by the presence of maximum number of peptides of various structural classes and spatial structures among the studied land and marine organisms (bees, spiders, scorpions, snakes ect.). This fact complicates the identification of sea anemones' secret and its differentiation from poisons of animals of other taxons, if the concrete source of its origin is unknown. The toxicity of some biologically active sea anemone peptides (RpI, RpIII) at intravenous administration to experimental animals is comparable with that of the most well-known and dangerous representatives of natural toxins with the similar mechanism of action (an alpha-hemolysine and tetrodotoxin), or chemical warfare agents, such as sarin and hydrogen cyanide. Based on their toxic effect, the biologically active sea anemone peptides generally can be classified as neurotoxins due to their impact on the functioning of sodium channels in the cells of the nervous system of animals. cardiotoxic effect of sea anemone secret is caused by the specificity of interaction between its separate neurotoxins and one of the sub-types of sodium channels of muscle cells, characteristic for heart tissues. The main ways of identification of sea anemone neurotoxins in samples (for example, during the investigation of biological crimes) can be sequence by Edman`s method or tandem mass spectrometry (the analysis of fragments of toxin molecule for the establishment of its structure). Further study on the mechanisms of interaction between the sea anemone neurotoxins and the ion channels of the cells of nervous and muscular systems may result in the creation of medicines for treatment of channelopathy, as well as pluripotential antidotes, blocking the toxins, that influence on sodium channels
{"title":"Neuro- and Cardiotoxins from Sea Anemones: Structure, Function and Potential of Application in Research and Medical Practice","authors":"R S M M Kalina Monastyrnaya","doi":"10.35825/2587-5728-2019-3-2-117-136","DOIUrl":"https://doi.org/10.35825/2587-5728-2019-3-2-117-136","url":null,"abstract":"Sea anemones are well-spread everywhere in the World Ocean and represent the most ancient active poisonous organisms. Their main instrument of attack on other animals are the nematocysts – stinging organelles with the curtailed hollow thread with poisonous edge on the end. In order to attract their potential victims, they use fluorescent proteins. These proteins became a separate object of research as genetically coded markers for the observation of activity of promotors of genes. The poisonous secret of sea anemones is characterized by the presence of maximum number of peptides of various structural classes and spatial structures among the studied land and marine organisms (bees, spiders, scorpions, snakes ect.). This fact complicates the identification of sea anemones' secret and its differentiation from poisons of animals of other taxons, if the concrete source of its origin is unknown. The toxicity of some biologically active sea anemone peptides (RpI, RpIII) at intravenous administration to experimental animals is comparable with that of the most well-known and dangerous representatives of natural toxins with the similar mechanism of action (an alpha-hemolysine and tetrodotoxin), or chemical warfare agents, such as sarin and hydrogen cyanide. Based on their toxic effect, the biologically active sea anemone peptides generally can be classified as neurotoxins due to their impact on the functioning of sodium channels in the cells of the nervous system of animals. cardiotoxic effect of sea anemone secret is caused by the specificity of interaction between its separate neurotoxins and one of the sub-types of sodium channels of muscle cells, characteristic for heart tissues. The main ways of identification of sea anemone neurotoxins in samples (for example, during the investigation of biological crimes) can be sequence by Edman`s method or tandem mass spectrometry (the analysis of fragments of toxin molecule for the establishment of its structure). Further study on the mechanisms of interaction between the sea anemone neurotoxins and the ion channels of the cells of nervous and muscular systems may result in the creation of medicines for treatment of channelopathy, as well as pluripotential antidotes, blocking the toxins, that influence on sodium channels","PeriodicalId":16578,"journal":{"name":"Journal of NBC Protection Corps","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85704885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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