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Sample records for agents sulfur mustard

  1. Sulfur Mustard

    MedlinePlus

    ... the environment. Sulfur mustard was introduced in World War I as a chemical warfare agent. Historically it ... fatal. When sulfur mustard was used during World War I, it killed fewer than 5% of the ...

  2. Surface decontamination for blister agents Lewisite, sulfur mustard and agent yellow, a Lewisite and sulfur mustard mixture.

    PubMed

    Stone, Harry; See, David; Smiley, Autumn; Ellingson, Anthony; Schimmoeller, Jessica; Oudejans, Lukas

    2016-08-15

    Sulfur mustard (HD) and Lewisite (L) are blister agents that have a high potential for terrorist use; Agent Yellow (HL) is the eutectic mixture of HD and L. Bench-scale testing was used to determine the residual amount of these chemical warfare agents remaining on three building materials (wood, metal and glass) after application of various decontaminants (household bleach, full strength and dilute; hydrogen peroxide 3% solution; and EasyDECON(®) DF200). All decontaminants reduced the amount of L recovered from coupons. Application of dilute bleach showed little or no difference compared to natural attenuation in the amount of HD recovered from coupons. Full-strength bleach was the most effective of four decontaminants at reducing the amount of HD from coupons. Hydrogen peroxide (3% solution) and DF200 did decrease the amount of HD recovered from coupons more than natural attenuation (except DF200 against HD on metal), but substantial amounts of HD remained on some materials. Toxic HD by-products were generated by hydrogen peroxide treatment. The effectiveness of decontaminants was found to depend on agent, material, and decontaminant. Increased decontaminant reaction time (60min rather than 30min) did not significantly increase effectiveness. PMID:27107236

  3. Surface decontamination for blister agents Lewisite, sulfur mustard and agent yellow, a Lewisite and sulfur mustard mixture.

    PubMed

    Stone, Harry; See, David; Smiley, Autumn; Ellingson, Anthony; Schimmoeller, Jessica; Oudejans, Lukas

    2016-08-15

    Sulfur mustard (HD) and Lewisite (L) are blister agents that have a high potential for terrorist use; Agent Yellow (HL) is the eutectic mixture of HD and L. Bench-scale testing was used to determine the residual amount of these chemical warfare agents remaining on three building materials (wood, metal and glass) after application of various decontaminants (household bleach, full strength and dilute; hydrogen peroxide 3% solution; and EasyDECON(®) DF200). All decontaminants reduced the amount of L recovered from coupons. Application of dilute bleach showed little or no difference compared to natural attenuation in the amount of HD recovered from coupons. Full-strength bleach was the most effective of four decontaminants at reducing the amount of HD from coupons. Hydrogen peroxide (3% solution) and DF200 did decrease the amount of HD recovered from coupons more than natural attenuation (except DF200 against HD on metal), but substantial amounts of HD remained on some materials. Toxic HD by-products were generated by hydrogen peroxide treatment. The effectiveness of decontaminants was found to depend on agent, material, and decontaminant. Increased decontaminant reaction time (60min rather than 30min) did not significantly increase effectiveness.

  4. Teratology Studies on Lewisite and Sulfur Mustard Agents: Effects of Sulfur Mustard in Rats and Rabbits

    SciTech Connect

    Hackett, P. L.; Rommereim, R. L.; Burton, F. G.; Buschbom, R. L.; Sasser, L . B.

    1987-09-30

    Sulfur mustard (HD) was administered to rats and rabbits by intragastric intubation. Rats were dosed daily from 6 through 15 days of gestation (dg) with 0. 0.5, 1.0 or 2.0 mg of HD/kg; rabbits were dosed with 0, 0.4, 0.6 or 0.8 mg/kg on 6 through 19 dg. Maternal animals were weighed periodically and, at necropsy, were examined for gross lesions of major organs and reproductive performance; live fetuses were weighed and examined for external, internal and skeletal defects. In rats, reductions in body weights were observed in maternal animals and their female fetuses at the lowest administered dose (0.5 mg/kg), but the incidence of fetal malformations was not increased. In rabbits the highest administered dose (0.8 mg/kg) induced maternal mortality and depressed body weight measures but did not affect fetal development. These results suggest that orally administered HD is not teratogenic in rats and rabbits since fetal effects were observed only at dose levels that induced frank maternal toxicity. Estimations of dose ranges for "no observable effects levels" in rats and rabbits, respectively, were: < 0.5 and < 0.4 mg/kg in maternal animals and < 0.5 and > 0.8 mg/kg in their fetuses.

  5. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity of Sulfur Mustard (HD) In Rats Final Report

    SciTech Connect

    Sasser, L. B.; Miller, R. A.; Kalkwarf, D, R.; Buschbom, R. L.; Cushing, J. A.

    1989-06-30

    Occupational health standards have not been established for sulfur mustard [bis(2- chlorethyl)-sulfide], a strong alkylating agent with known mutagenic properties. Seventytwo Sprague-Dawley rats of each sex, 6-7 weeks old, were divided into six groups (12/group/ sex) and gavaged with either 0, 0.003 , 0.01 , 0.03 , 0.1 or 0.3 mg/kg of sulfur mustard in sesame oil 5 days/week for 13 weeks. No dose-related mortality was observed. A significant decrease (P ( 0.05) in body weight was observed in both sexes of rats only in the 0.3 mg/kg group. Hematological evaluations and clinical chemistry measurements found no consistent treatment-related effects at the doses studied. The only treatment-related lesion associated with gavage exposure upon histopathologic evaluation was epithelial hyperplasia of the forestomach of both sexes at 0.3 mg/kg and males at 0.1 mg/kg. The hyperplastic change was minimal and characterized by cellular disorganization of the basilar layer, an apparent increase in mitotic activity of the basilar epithelial cells, and thickening of the epithelial layer due to the apparent increase in cellularity. The estimated NOEL for HD in this 90-day study is 0.1 mg/kg/day when administered orally.

  6. Degradation of the blister agent sulfur mustard, bis(2-chloroethyl) sulfide, on concrete.

    PubMed

    Brevett, Carol A S; Sumpter, Kenneth B; Wagner, George W; Rice, Jeffrey S

    2007-02-01

    The products formed from the degradation of the blister agent sulfur mustard [bis(2-chloroethyl) sulfide] on concrete were identified using gas chromatography with mass spectrometry detection (GC/MSD), (1)H NMR, 2D (1)H-(13)C NMR and (13)C solid state magic angle spinning (SSMAS) NMR. In situ and extraction experiments were performed. Sulfur mustard was detected in the in situ (13)C SSMAS samples for 12 weeks, whereas less than 5% of the sulfur mustard was detected in extracts from the concrete monoliths after 8 days. Sulfonium ions and (2-chloroethylthio)ethyl ether (T) were observed on the in situ samples after a period of 12 weeks, whereas vinyl species and bis(2-chloroethyl) sulfoxide were observed in the extracts of the concrete monoliths within 24h. The differences between the extraction and the SSMAS data indicated that the sulfur mustard existed in the concrete in a non-extractable form prior to its degradation. Extraction methods alone were not sufficient to identify the products; methods to identify the presence of non-extractable degradation products were also required. PMID:17049727

  7. Degradation of the blister agent sulfur mustard, bis(2-chloroethyl) sulfide, on concrete.

    PubMed

    Brevett, Carol A S; Sumpter, Kenneth B; Wagner, George W; Rice, Jeffrey S

    2007-02-01

    The products formed from the degradation of the blister agent sulfur mustard [bis(2-chloroethyl) sulfide] on concrete were identified using gas chromatography with mass spectrometry detection (GC/MSD), (1)H NMR, 2D (1)H-(13)C NMR and (13)C solid state magic angle spinning (SSMAS) NMR. In situ and extraction experiments were performed. Sulfur mustard was detected in the in situ (13)C SSMAS samples for 12 weeks, whereas less than 5% of the sulfur mustard was detected in extracts from the concrete monoliths after 8 days. Sulfonium ions and (2-chloroethylthio)ethyl ether (T) were observed on the in situ samples after a period of 12 weeks, whereas vinyl species and bis(2-chloroethyl) sulfoxide were observed in the extracts of the concrete monoliths within 24h. The differences between the extraction and the SSMAS data indicated that the sulfur mustard existed in the concrete in a non-extractable form prior to its degradation. Extraction methods alone were not sufficient to identify the products; methods to identify the presence of non-extractable degradation products were also required.

  8. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Modified Dominant Lethal Study of Sulfur Mustard in Rats Final Report

    SciTech Connect

    Sasser, L. B.; Cushing, J. A.; Kalkwarf, D. R.; Buschbom, R. L.

    1989-05-01

    Occupational health standards have not been established for sulfur mustard (HD) [bis{2-chloroethyl)-sulfide) ' a strong alkylating agent with known mutagenic properties. Little, however, is known about the mutagenic activity of HD in mammalian species and data regarding the dominant lethal effects of HD are ambiguous. The purpose of this study was to determine the dominant lethal effect in male and female rats orally exposed to HD. The study was conducted in two phases; a female dominant lethal phase and a male dominant lethal phase. Sprague-Dawley rats of each sex were administered 0.08, 0.20, or 0.50 mg/kg HD in sesame oil 5 days/week for 10 weeks. For the female phase, treated or untreated males were mated with treated females and their fetuses were evaluated at approximately 14 days after copulation. For the male dominant lethal phase, treated males cohabited with untreated femal (during 5 days of each week for 10 weeks) and females were sacrificed for fetal evaluation 14 days after the midweek of cohabitation during each of the 10 weeks. The appearance and behavior of the rats were unremarkable throughout the experiment and there were no treatment-related deaths. Growth rates were reduced in both female and male rats treated with 0.50 mg/kg HD. Indicators of reproductive performance did not demonstrate significant female dominant lethal effects, although significant male dominant lethal effects were observed at 2 and 3 week post-exposure. These effects included increases of early fetal resorptions and preimplantation losses and decreases of total live embryo implants. These effects were most consistently observed at a dose of 0.50 mg/kg, but frequently occurred at the lower doses. Although no treatment-related effects on male reproductive organ weights or sperm motility were found, a significant increase in the percentage of abnormal sperm was detected in males exposed to 0. 50 mg/kg HD. The timing of these effects is consistent with an effect during the

  9. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Mutagenicity of Sulfur Mustard in the Salmonella Histidine Reversion Assay Final Report

    SciTech Connect

    Stewart, D. L.; Sass, E. J.; Fritz, L. K.; Sasser, L. B.

    1989-07-31

    The mutagenic potential of bis 2-chloroethyl sulfide (HD} a bifunctional sulfur mustard was evaluated in the standard plate incorporation version and the preincubation modification of the Salmonella/microsomal assay with tester strains TA97, TA98, TA100 and TA102, with and without 59 activation. HD-induced point mutations in strain TA102 and frameshift mutations in TA97 but showed little or no mutagenicity against strains TA98 and TA100. Extensive HD-induced cell killing was observed with the excision repair deficient strains (TA100, TA98 and TA97) but not with strain TA102, which is wild-activation by Aroc1or induced rat liver microsomes (S9).

  10. Teratology Studies on Lewisite and Sulfur Mustard Agents: Effects of Sulfur Mustard in Rats and Rabbits - Part 2, Appendices

    SciTech Connect

    Hackett, P L; Rommereim, R L; Burton, F G; Buschbom, R L; Sasser, L B

    1987-09-30

    Sulfur mustard (HD) was administered to rats and rabbits by intragastric intubation. Rats were dosed daily from 6 through 15 days of gestation (dg) with o. 0.5, 1 .0 or 2.0 mg of HD/kg; rabbits were dosed with 0, 0.4, 0.6 or 0.8 mg/kg on 6 through 19 dg. Maternal animals were weighed periodically and, at necropsy, were examined for gross lesions of major organs and reproductive performance; live fetuses were weighed and examined for external, internal and skeletal defects. In rats, reductions in body weights were observed in maternal animals and their female fetuses at the lowest administered dose (0.5 mg/kg), but the incidence of fetal malformations was not increased. In rabbits the highest administered dose (0.8 mg/kg) induced maternal mortality and depressed body weight measures but did not affect fetal development These results suggest that orally administered HD is not teratogenic in rats • and rabbits since fetal effects were obs~rved only at dose levels that induced frank maternal toxicity. Estimations of dose ranges for •no observable effects levers· in rats and rabbits, respectively, were: < 0.5 and < 0.4 mg/kg in maternal animals and < 0.5 and > 0.8 mg/kg in their fetuses.

  11. Sulfur mustard as a carcinogen: application of relative potency analysis to the chemical warfare agents H, HD, and HT.

    PubMed

    Watson, A P; Jones, T D; Griffin, G D

    1989-08-01

    A relative potency method for assessing potential human health effects from exposures to relatively untested chemicals is presented and documented. The need for such a method in evaluating the carcinogenic potential of the chemical warfare agent sulfur mustard (agent HD) from a limited data base is specifically addressed. The best-estimate potency factor for sulfur mustard relative to benzo[a]pyrene is 1.3, with an interquartile range of 0.6 to 2.9. The method is applied to (1) the estimated fence-boundary air concentrations of mustard during operation of a proposed agent incinerator at Aberdeen Proving Ground (APG), Maryland, and (2) the current approved general population exposure level of 1 X 10(-4) mg HD/m3 and the occupational exposure level of 3 X 10(-3) mg HD/m3. Maximum estimates of excess lifetime cancer risk for individuals at sites along the APG boundary range between 3 X 10(-8) and 1 X 10(-7). Lifetime cancer risk estimates less than or equal to 10(-6) are not now regulated by the U.S. Environmental Protection Agency or the Food and Drug Administration. Maximum estimates of excess lifetime cancer risk assuming daily exposure to the approved standards during the proposed 5 years of incinerator operation are on the order of 10(-5) for the general public and 10(-4) for the worker population. These values are considered upper limit estimates.

  12. Decontamination of chemical warfare sulfur mustard agent simulant by ZnO nanoparticles

    NASA Astrophysics Data System (ADS)

    Sadeghi, Meysam; Yekta, Sina; Ghaedi, Hamed

    2016-07-01

    In this study, zinc oxide nanoparticles (ZnO NPs) have been surveyed to decontaminate the chloroethyl phenyl sulfide as a sulfur mustard agent simulant. Prior to the reaction, ZnO NPs were successfully prepared through sol-gel method in the absence and presence of polyvinyl alcohol (PVA). PVA was utilized as a capping agent to control the agglomeration of the nanoparticles. The formation, morphology, elemental component, and crystalline size of nanoscale ZnO were certified and characterized by SEM/EDX, XRD, and FT-IR techniques. The decontamination (adsorption and destruction) was tracked by the GC-FID analysis, in which the effects of polarity of the media, such as isopropanol, acetone and n-hexane, reaction time intervals from 1 up to 18 h, and different temperatures, including 25, 35, 45, and 55 °C, on the catalytic/decontaminative capability of the surface of ZnO NPs/PVA were investigated and discussed, respectively. Results demonstrated that maximum decontamination (100 %) occurred in n-hexane solvent at 55 °C after 1 h. On the other hand, the obtained results for the acetone and isopropanol solvents were lower than expected. GC-MS chromatograms confirmed the formation of hydroxyl ethyl phenyl sulfide and phenyl vinyl sulfide as the destruction reaction products. Furthermore, these chromatograms proved the role of hydrolysis and elimination mechanisms on the catalyst considering its surface Bronsted and Lewis acid sites. A non-polar solvent aids material transfer to the reactive surface acid sites without blocking these sites.

  13. Toxicology and pharmacology of the chemical warfare agent sulfur mustard - a review. Final technical report, 29 September 1994-31 January 1995

    SciTech Connect

    Dacre, J.C.; Beers, R.; Goldman, M.

    1995-04-05

    Sulfur mustard is a poisonous chemical agent which exerts a local action on the eyes, skin and respiratory tissue with subsequent systemic action on the nervous, cardiac, and digestive and endocrine systems in man and laboratory animals causing lacrimation, malaise, anorexia, salivation, respiratory distress, vomiting, hyperexcitability, cardiac distress, and death. Sulfur mustard is a cell poison which causes disumption and impairment of a variety of cellular activities which are dependent upon a very specific integral relationship. These cytotoxic effects are manifested in widespread metabolic disturbances whose variable characteristics are observed in enzymatic deficiencies, vesicant action, abnormal mitotic activity and cell division, bone marrow disruption, disturbances in hematopoietic activity and systemic poisoning. Indeed, mustard gas readily combines with various components of the cell such as amino acids, amines and proteins. Sulfur mustard has been shown to be mainly a lung carcinogen in various test animal species; this effect is highly dependent of size of the dose and the route of exposure. In the human, there is evidence of cancers of the respiratory tract in men exposed to mustard gas. Mutagenicity of sulfur mustard, due to the strong alkylating activity, has been reported to occur in many different species of animals, plants, bacteria, and fungi. There is no strong evidence that sulfur mustard is a teratogen but much further research, with particular emphasis on maternal and fetal toxicity, is needed and recommended.

  14. Wound Healing of Cutaneous Sulfur Mustard Injuries

    PubMed Central

    Graham, John S.; Chilcott, Robert P.; Rice, Paul; Milner, Stephen M.; Hurst, Charles G.; Maliner, Beverly I.

    2005-01-01

    Sulfur mustard is an alkylating chemical warfare agent that primarily affects the eyes, skin, and airways. Sulfur mustard injuries can take several months to heal, necessitate lengthy hospitalizations, and result in significant cosmetic and/or functional deficits. Historically, blister aspiration and/or deroofing (epidermal removal), physical debridement, irrigation, topical antibiotics, and sterile dressings have been the main courses of action in the medical management of cutaneous sulfur mustard injuries. Current treatment strategy consists of symptomatic management and is designed to relieve symptoms, prevent infections, and promote healing. There are currently no standardized or optimized methods of casualty management that prevent or minimize deficits and provide for speedy wound healing. Several laboratories are actively searching for improved therapies for cutaneous vesicant injury, with the aim of returning damaged skin to optimal appearance and normal function in the shortest time. Improved treatment will result in a better cosmetic and functional outcome for the patient, and will enable the casualty to return to normal activities sooner. This editorial gives brief overviews of sulfur mustard use, its toxicity, concepts for medical countermeasures, current treatments, and strategies for the development of improved therapies. PMID:16921406

  15. Effects of Exposure to Sulfur Mustard on Speech Aerodynamics

    ERIC Educational Resources Information Center

    Heydari, Fatemeh; Ghanei, Mostafa

    2011-01-01

    Sulfur mustard is an alkylating agent with highly cytotoxic properties even at low exposure. It was used widely against both military and civilian population by Iraqi forces in the Iraq-Iran war (1983-1988). Although various aspects of mustard gas effects on patients with chemical injury have been relatively well characterized, its effects on…

  16. Antioxidants countermeasures against sulfur mustard.

    PubMed

    Pohanka, M

    2012-07-01

    Sulfur mustard (SM) is a vesicant chemical warfare agent that persists as a serious menace from the viewpoint of acute and chronic toxicity, simple synthesis and no effective treatment currently being available. The two most deleterious basic molecular mechanisms in SM poisoning are: inflammation and over-activation of poly(ADP-ribose) polymerase and the resulting DNA alkylation. Oxidative stress is the common consequence of these pathway activations. In the present review, the significance of oxidative stress in SM poisoning is discussed along with research on antioxidant therapy as a suitable antidote. The temporal dynamics of the redox imbalance, the antioxidant depletion and impact this has on tissues are described as the pathologies induced by SM. Special attention is paid to ameliorating the damage using low molecular weight antioxidants. Melatonin, epigallocatechin gallate and flavone derivatives, in particular, have been studied in recent experiments. The suitability of these antioxidants for therapy purposes is considered in a separate chapter. The review concludes with a view to the future and the studies needed on antioxidant therapy as a countermeasure to SM poisoning.

  17. Development and Application of Acute Exposure Guideline Levels (AEGLs) for Chemical Warfare Nerve and Sulfur Mustard Agents.

    SciTech Connect

    Watson, Annetta Paule; Opresko, Dennis M; Young, Robert A; Hauschild, Veronique

    2006-01-01

    Acute exposure guideline levels (AEGLs) have been developed for the chemical warfare agents GB, GA, GD, GF, VX, and sulfur mustard. These AEGLs were approved by the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances after Federal Register publication and comment, and judged as scientifically valid by the National Research Council Committee on Toxicology Subcommittee on AEGLs. AEGLs represent general public exposure limits for durations ranging from 10 min to 8 h, and for three levels of severity (AEGL-1, AEGL-2, AEGL-3). Mild effects are possible at concentrations greater than AEGL-1, while life-threatening effects are expected at concentrations greater than AEGL-3. AEGLs can be applied to various civilian and national defense purposes, including evacuation and shelter-in-place protocols, reentry levels, protective clothing specifications, and analytical monitoring requirements. This report documents development and derivation of AEGL values for six key chemical warfare agents, and makes recommendations for their application to various potential exposure scenarios.

  18. Domestic swine model for the assessment of chemical warfare agent-anesthetic interactions: some effects of sulfur mustard.

    PubMed

    Conley, J; Hunter, K; Lundy, P; Hamilton, M; Sawyer, T W

    2000-08-01

    A domestic swine model was developed to examine the interaction of chemical warfare agents with anesthetics and other drugs used during general anesthesia. Animals were fully instrumented, and clinically relevant physiological parameters were monitored throughout the experimental procedures. Exposure of animals under halothane anesthesia to the chemical warfare agent sulfur mustard (HD; 1 mg/kg intravenous) produced mild signs of systemic intoxication during the subsequent 5 hours. Induction doses of ketamine 1 hour after HD exposure resulted in periods of profound apnea, with continued respiratory distress for the next 2 hours. When animals were treated with HD 1 hour after the initiation of ketamine anesthesia, severe and persistent convulsion-like muscular activity was observed within 45 minutes of HD administration. This nonpurposeful activity was not ameliorated by diazepam but was dramatically reduced or eliminated by resumption of halothane anesthesia. Treatment of HD-intoxicated pigs with succinylcholine produced a prolonged apnea resulting in death. In these apparently mildly HD-intoxicated animals, the introduction of ketamine or succinylcholine can rapidly induce potentially life-threatening situations.

  19. Understanding evaporation characteristics of a drop of distilled sulfur mustard (HD) chemical agent from stainless steel and aluminum substrates.

    PubMed

    Jung, H; Lee, H W

    2014-05-30

    We report herein the evaporation rates and mechanism of a drop of distilled sulfur mustard (HD) agent from stainless steel and aluminum substrates. For systematic analysis, we used a laboratory-sized wind tunnel, thermal desorption (TD) connected to gas chromatograph/mass spectrometry (GC/MS) and drop shape analysis (DSA). We found that the evaporation rates of HD from stainless steel and aluminum increased with temperature. The rates were also linearly proportional to drop size. The time-dependent contact angle measurement showed that the evaporation of the drop of HD proceeded only by constant contact area mechanism from stainless steel surface. On the other hand, the evaporation of HD from aluminum proceeded by a combined mechanism of constant contact area mode and constant contact angle mode. Our experimental data sets and analysis could be used to predict vapor and contact hazard persistence of chemical warfare agents (CWAs) in the air and on exterior surfaces with chemical releases, which assists the military decision influencing personnel safety and decontamination of the site upon a chemical attack event.

  20. Putative roles of inflammation in the dermatopathology or sulfur mustard

    SciTech Connect

    Cowan, F.M.; Broomfield, C.A.

    1993-12-31

    Sulfur mustard (2,2`-dichlorodiethyl sulfide), a radiomimetic agent with mutagenic (Cappizzi et al., 1973; Fox and Scott, 1983), cytotoxic (Wheeler, 1962; Papirmeister and Davison, 1965), and vesicant (Anslow and Houck, 1946; Renshaw, 1946) properties, is also a chemical-warfare blistering agent with no known antidote. Sulfur mustard predominantly effects exposed epithelial tissues of the skin, the eye, and the respiratory tract, although higher doses can produce systemic toxicity (reviewed by Papirmeister et al., 1991). The severity of sulfur mustard toxicity is dose dependent, causing irritation, edema, necrosis and ulceration; characteristic symptoms are unique to the site of exposure, e.g., vesication, conjunctivitis, bronchopneumonia (reviewed by Papirmeister et al., 1991). The basic histopathology of mustard-induced cutaneous lesions has been reviewed by Papirmeister et al. (1985, 1991) and includes degeneration of epidermal cells, especially in the basal layer, followed by the formation of vesicles (and, in man, bullae) that have been variously characterized as intraepidermal or subcorneal but that appear in most cases to result from cleavage at the dermal-epidermal junction. However, despite general agreement concerning the morphologic changes caused by mustard and despite more than 50 years of research, the pathogenesis of mustard injury is still incompletely understood.

  1. Neutralization and biodegradation of sulfur mustard

    SciTech Connect

    Harvey, S.P.; Beaudry, W.T.; Szafraniec, L.L.

    1995-12-31

    One technology recommended for consideration for the disposal of the U.S. Chemical Stockpile is chemical neutralization followed by biodegradation. In the case of sulfur mustard ({open_quotes}mustard gas{close_quotes}, 2,2{prime}-dichlorodiethyl sulfide), alkaline hydrolysis yields a detoxified and biodegradable product. The hydrolysis reaction was studied with respect to the effects of temperature and sulfur mustard concentration on the rate and products of the reaction. A 28-fold overall rate enhancement was observed at 70{degrees}C vs. 30{degrees}C corresponding to an enthalpy of activation value of 17.9 Kcal/mole. Material balance studies conducted by {sup 1}H Nuclear Magnetic Resonance analysis showed that the products of the reaction consisted of thiodiglycol was relatively greater at lower sulfur mustard concentrations and higher temperatures. As temperatures were decreased or sulfur mustard concentrations was increased, the proportion of ether-type compounds increased accordingly. Conditions of 1% (vol//vol) sulfur mustard, 5% stoichiometric excess of NaOH and 90{degrees}C were selected for generation of the hydrolyzed bioreactor influent material. The bioreactor was seeded with activated sludge and was initially operated as 5 liter sequencing batch reactor with a hydraulic residence time of approximately days. Early results show total organic carbon removal of greater than 90%.

  2. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Genetic Toxicity of Sulfur Mustard (HD) in Chinese Hamster Ovary Cells Final Report

    SciTech Connect

    Jostes, Jr., R. F.; Sasser, L. B.; Rausch, R. J.

    1989-05-01

    The cytotoxic, clastogenic and mutagenic effects of sulfur nustard in Chinese hamster ovary cells are described in this reoort. The cytotoxicity data indicate that micromolar amounts of HC are highly toxic in microrolar amounts. Chromosone aberration frequencies increased in a dose-dependent manner over a dose range of 0. 5 to 1.0 {micro}m and SCE increased in a dose-dependent fashion in the dose range of 0.0625 to 0.25 {micro}M. Mutation induction at the HGPRT locus was sporadic, but the majority of the exoosures resulted in mutation frequencies which were 1.2 to 4.3 fold higher than the spontaneous frequencies.

  3. Cytometric analysis of DNA changes induced by sulfur mustard

    SciTech Connect

    Smith, W.J.; Sanders, K.M.; Ruddle, S.E.; Gross, C.L.

    1993-05-13

    Sulfur mustard is an alkylating agent which causes severe, potentially debilitating blisters following cutaneous exposure. Its mechanism of pathogenesis is unknown and no antidote exists to prevent its pathology. The biochemical basis of sulfur mustard's vesicating activity has been hypothesized to be a cascade of events beginning with alkylation of DNA. Using human cells in culture, we have assessed the effects of sulfur mustard on cell cycle activity using flow cytometry with propidium iodide. Two distinct patterns emerged, a Gl/S interface block at concentrations equivalent to vesicating doses (>50-micronM) and a G2 block at 10-fold lower concentrations. In addition, noticeable increases in amount of dye uptake were observed at 4 and 24 hours after sulfur mustard exposure. These increases are believed to be related to DNA repair activities and can be prevented by treatment of the cells with niacinamide, which inhibits DNA repair. Other drugs which provide alternate alkylating sites or inhibit cell cycle progression were shown to lower the cytotoxicity of sulfur mustard and to protect against its direct DNA damaging effects.

  4. Comparison of latex body paint with wetted gauze wipes for sampling the chemical warfare agents VX and sulfur mustard from common indoor surfaces.

    PubMed

    Hernon-Kenny, Laura A; Behringer, Deborah L; Crenshaw, Michael D

    2016-05-01

    Comparison of solvent-wetted gauze with body paint, a peelable surface sampling media, for the sampling of the chemical warfare agents VX and sulfur mustard from nine surfaces was performed. The nine surfaces sampled are those typical of interior public venues and include smooth, rough, porous, and non-porous surfaces. Overall, solvent-wetted gauze (wipes) performed better for the recovery of VX from non-porous surfaces while body paint (BP) performed better for the porous surfaces. The average percent VX recoveries using wipes and BP, respectively, are: finished wood flooring, 86.2%, 71.4%; escalator handrail, 47.3%, 26.7%; stainless steel, 80.5%, 56.1%; glazed ceramic tile, 81.8%, 44.9%; ceiling tile, 1.77%, 13.1%; painted drywall 7.83%, 21.1%; smooth cement, 0.64%, 10.3%; upholstery fabric, 24.6%, 23.1%; unfinished wood flooring, 9.37%, 13.1%. Solvent-wetted gauze performed better for the recovery of sulfur mustard from three of the relatively non-porous surfaces while body paint performed better for the more porous surfaces. The average percent sulfur mustard recoveries using wipes and BP, respectively, are: finished wood flooring, 30.2%, 2.97%; escalator handrail, 4.40%, 4.09%; stainless steel, 21.2%, 3.30%; glazed ceramic tile, 49.7%, 16.7%; ceiling tile, 0.33%, 11.1%; painted drywall 2.05%, 10.6%; smooth cement, 1.20%, 35.2%; upholstery fabric, 7.63%, 6.03%; unfinished wood flooring, 0.90%, 1.74%.

  5. Comparison of latex body paint with wetted gauze wipes for sampling the chemical warfare agents VX and sulfur mustard from common indoor surfaces.

    PubMed

    Hernon-Kenny, Laura A; Behringer, Deborah L; Crenshaw, Michael D

    2016-05-01

    Comparison of solvent-wetted gauze with body paint, a peelable surface sampling media, for the sampling of the chemical warfare agents VX and sulfur mustard from nine surfaces was performed. The nine surfaces sampled are those typical of interior public venues and include smooth, rough, porous, and non-porous surfaces. Overall, solvent-wetted gauze (wipes) performed better for the recovery of VX from non-porous surfaces while body paint (BP) performed better for the porous surfaces. The average percent VX recoveries using wipes and BP, respectively, are: finished wood flooring, 86.2%, 71.4%; escalator handrail, 47.3%, 26.7%; stainless steel, 80.5%, 56.1%; glazed ceramic tile, 81.8%, 44.9%; ceiling tile, 1.77%, 13.1%; painted drywall 7.83%, 21.1%; smooth cement, 0.64%, 10.3%; upholstery fabric, 24.6%, 23.1%; unfinished wood flooring, 9.37%, 13.1%. Solvent-wetted gauze performed better for the recovery of sulfur mustard from three of the relatively non-porous surfaces while body paint performed better for the more porous surfaces. The average percent sulfur mustard recoveries using wipes and BP, respectively, are: finished wood flooring, 30.2%, 2.97%; escalator handrail, 4.40%, 4.09%; stainless steel, 21.2%, 3.30%; glazed ceramic tile, 49.7%, 16.7%; ceiling tile, 0.33%, 11.1%; painted drywall 2.05%, 10.6%; smooth cement, 1.20%, 35.2%; upholstery fabric, 7.63%, 6.03%; unfinished wood flooring, 0.90%, 1.74%. PMID:26990562

  6. Sulfur mustard-induced ocular surface disorders.

    PubMed

    Baradaran-Rafii, Alireza; Eslani, Medi; Tseng, Scheffer C G

    2011-07-01

    Sulfur mustard is a vesicant agent with severe irritating effects on living tissues, including skin, mucous membranes, eyes, and respiratory tract. The eyes are the most susceptible tissue to mustard gas effects, and varying degrees of ocular involvement are seen in 75% to 90% of exposed individuals. Most cases resolve uneventfully; however, a minority of exposed patients will have a continuous process, which manifests clinically either as a persistent smoldering inflammation (chronic form) or late-onset lesions appearing many years after a variable "silent" period (delayed form). Distinctive features common to most cases with chronic involvement include chronic blepharitis, meibomian gland dysfunction, dry eye, limbal ischemia, limbal stem cell deficiency, aberrant conjunctival vessels, corneal neovascularization, and secondary degenerative changes, including lipid and amyloid deposition and corneal irregularity, thinning and scarring. Most cases can be managed with conservative measures, eg, preservative-free artificial tears, lubricants, and topical steroids. Punctal plugs or punctal cauterization is helpful in moderate and severe forms of injury. Surgical modalities, including lateral or medial tarsorrhaphies, amniotic membrane transplantation, lamellar or penetrating keratoplasty, and stem cell transplantation have been used.

  7. Detoxication of sulfur half-mustards by nucleophilic scavengers: robust activity of thiopurines.

    PubMed

    Liu, Jinyun; Powell, K Leslie; Thames, Howard D; MacLeod, Michael C

    2010-03-15

    Sulfur mustard (bis-(2-chloroethyl)sulfide) has been used in chemical warfare since World War I and is well known as an acutely toxic vesicant. It has been implicated as a carcinogen after chronic low-level exposure and is known to form interstrand cross-links in DNA. Sulfur and nitrogen mustards are currently of interest as potential chemical threat agents for terrorists because of ease of synthesis. Sulfur mustard and monofunctional analogues (half-mustards, 2-[chloroethyl] alkyl sulfides) react as electrophiles, damaging cellular macromolecules, and thus are potentially subject to scavenging by nucleophilic agents. We have determined rate constants for the reaction of four purine derivatives that contain nucleophilic thiol moieties with several sulfur-half-mustards. Three of these compounds, 2,6-dithiopurine, 2,6-dithiouric acid, and 9-methyl-6-mercaptopurine, exhibit facile reaction with the electrophilic mustard compounds. At near neutral pH, these thiopurines are much better nucleophilic scavengers of mustard electrophiles than other low molecular weight thiols such as N-acetyl cysteine and glutathione. Progress curves calculated by numerical integration techniques indicate that equimolar concentrations of thiopurine provide significant reductions in the overall exposure to the episulfonium ions, which are the major reactive, electrophiles produced when sulfur mustards are dissolved in aqueous solution.

  8. Sulfur mustard toxicity: history, chemistry, pharmacokinetics, and pharmacodynamics.

    PubMed

    Ghabili, Kamyar; Agutter, Paul S; Ghanei, Mostafa; Ansarin, Khalil; Panahi, Yunes; Shoja, Mohammadali M

    2011-05-01

    Sulfur mustard (SM) and similar bifunctional agents have been used as chemical weapons for almost 100 years. Victims of high-dose exposure, both combatants and civilians, may die within hours or weeks, but low-dose exposure causes both acute injury to the eyes, skin, respiratory tract and other parts of the body, and chronic sequelae in these organs are often debilitating and have a serious impact on quality of life. Ever since they were first used in warfare in 1917, SM and other mustard agents have been the subjects of intensive research, and their chemistry, pharmacokinetics and mechanisms of toxic action are now fairly well understood. In the present article we review this knowledge and relate the molecular-biological basis of SM toxicity, as far as it has been elucidated, to the pathological effects on exposure victims.

  9. Capsaicinoids, chloropicrin and sulfur mustard: possibilities for exposure biomarkers.

    PubMed

    Pesonen, Maija; Vähäkangas, Kirsi; Halme, Mia; Vanninen, Paula; Seulanto, Heikki; Hemmilä, Matti; Pasanen, Markku; Kuitunen, Tapio

    2010-01-01

    Incapacitating and irritating agents produce temporary disability persisting for hours to days after the exposure. One can be exposed to these agents occupationally in industrial or other working environments. Also general public can be exposed in special circumstances, like industrial accidents or riots. Incapacitating and irritating agents discussed in this review are chloropicrin and capsaicinoids. In addition, we include sulfur mustard, which is an old chemical warfare agent and known to cause severe long-lasting injuries or even death. Chloropicrin that was used as a warfare agent in the World War I is currently used mainly as a pesticide. Capsaicinoids, components of hot pepper plants, are used by police and other law enforcement personnel as riot control agents. Toxicity of these chemicals is associated particularly with the respiratory tract, eyes, and skin. Their acute effects are relatively well known but the knowledge of putative long-term effects is almost non-existent. Also, mechanisms of effects at cellular level are not fully understood. There is a need for further research to get better idea of health risks, particularly of long-term and low-level exposures to these chemicals. For this, exposure biomarkers are essential. Validated exposure biomarkers for capsaicinoids, chloropicrin, and sulfur mustard do not exist so far. Metabolites and macromolecular adducts have been suggested biomarkers for sulfur mustard and these can already be measured qualitatively, but quantitative biomarkers await further development and validation. The purpose of this review is, based on the existing mechanistic and toxicokinetic information, to shed light on the possibilities for developing biomarkers for exposure biomonitoring of these compounds. It is also of interest to find ideas for early effect biomarkers considering the need for studies on subchronic and chronic toxicity. PMID:21833179

  10. Capsaicinoids, Chloropicrin and Sulfur Mustard: Possibilities for Exposure Biomarkers

    PubMed Central

    Pesonen, Maija; Vähäkangas, Kirsi; Halme, Mia; Vanninen, Paula; Seulanto, Heikki; Hemmilä, Matti; Pasanen, Markku; Kuitunen, Tapio

    2010-01-01

    Incapacitating and irritating agents produce temporary disability persisting for hours to days after the exposure. One can be exposed to these agents occupationally in industrial or other working environments. Also general public can be exposed in special circumstances, like industrial accidents or riots. Incapacitating and irritating agents discussed in this review are chloropicrin and capsaicinoids. In addition, we include sulfur mustard, which is an old chemical warfare agent and known to cause severe long-lasting injuries or even death. Chloropicrin that was used as a warfare agent in the World War I is currently used mainly as a pesticide. Capsaicinoids, components of hot pepper plants, are used by police and other law enforcement personnel as riot control agents. Toxicity of these chemicals is associated particularly with the respiratory tract, eyes, and skin. Their acute effects are relatively well known but the knowledge of putative long-term effects is almost non-existent. Also, mechanisms of effects at cellular level are not fully understood. There is a need for further research to get better idea of health risks, particularly of long-term and low-level exposures to these chemicals. For this, exposure biomarkers are essential. Validated exposure biomarkers for capsaicinoids, chloropicrin, and sulfur mustard do not exist so far. Metabolites and macromolecular adducts have been suggested biomarkers for sulfur mustard and these can already be measured qualitatively, but quantitative biomarkers await further development and validation. The purpose of this review is, based on the existing mechanistic and toxicokinetic information, to shed light on the possibilities for developing biomarkers for exposure biomonitoring of these compounds. It is also of interest to find ideas for early effect biomarkers considering the need for studies on subchronic and chronic toxicity. PMID:21833179

  11. Sulfur, oxygen, and nitrogen mustards: stability and reactivity.

    PubMed

    Wang, Qi-Qiang; Begum, Rowshan Ara; Day, Victor W; Bowman-James, Kristin

    2012-11-28

    Mustard gas, bis(β-chloroethyl) sulfide (HD), is highly toxic and harmful to humans and the environment. It comprises one class of chemical warfare agents (CWAs) that was used in both World Wars I and II. The three basic analogues or surrogates are: the monochloro derivative, known as the half mustard, 2-chloroethyl ethyl sulfide (CEES); an oxygen analogue, bis(β-chloroethyl) ether (BCEE); and several nitrogen analogues based on the 2,2'-dichlorodiethylamine framework (e.g., HN1, HN2, and HN3). The origin of their toxicity is considered to be from the formation of three-membered heterocyclic ions, a reaction that is especially accelerated in aqueous solution. The reaction of these cyclic ion intermediates with a number of important biological species such as DNA, RNA and proteins causes cell toxicity and is responsible for the deleterious effects of the mustards. While a number of studies have been performed over the last century to determine the chemistry of these compounds, early studies suffered from a lack of more sophisticated NMR and X-ray techniques. It is now well-established that the sulfur and nitrogen mustards are highly reactive in water, while the oxygen analog is much more stable. In this study, we review and summarize results from previous studies, and add results of our own studies of the reactivity of these mustards toward various nonaqueous solvents and nucleophiles. In this manner a more comprehensive evaluation of the stability and reactivity of these related mustard compounds is achieved. PMID:23070251

  12. Interaction of sulfur mustard with rat liver salt fractionated chromatin.

    PubMed

    Jafari, Mahvash; Nateghi, M; Rabbani, A

    2010-01-01

    In this study, the interaction of an alkylating agent, sulfur mustard (SM) with rat liver active (S1 and S2) and inactive (P2) chromatin was investigated employing UV/vis spectroscopy and gel electrophoreses. The results show that SM affects the chromatin structure in a dose-dependent manner. The binding of SM to fractions is different. At lower concentrations (<500 microM), SM seems to unfold the structure and at higher concentrations, it induces aggregation and condensation of chromatin possibly via forming cross-links between the chromatin components. The extent of condensation in S2 is higher when compared to the P2 fraction.

  13. Emerging targets for treating sulfur mustard-induced injuries.

    PubMed

    Ahmad, Shama; Ahmad, Aftab

    2016-06-01

    Sulfur mustard (SM; bis-(2-chlororethyl) sulfide) is a highly reactive, potent warfare agent that has recently reemerged as a major threat to military and civilians. Exposure to SM is often fatal, primarily due to pulmonary injuries and complications caused by its inhalation. Profound inflammation, hypercoagulation, and oxidative stress are the hallmarks that define SM-induced pulmonary toxicities. Despite advances, effective therapies are still limited. This current review focuses on inflammatory and coagulation pathways that influence the airway pathophysiology of SM poisoning and highlights the complexity of developing an effective therapeutic target. PMID:27285828

  14. Sulfur mustard induces the formation of keratin aggregates in human epidermal keratinocytes.

    PubMed

    Dillman, James F; McGary, Kriston L; Schlager, John J

    2003-12-01

    The vesicant sulfur mustard is an alkylating agent that has the capacity to cross-link biological molecules. We are interested in identifying specific proteins that are altered upon sulfur mustard exposure. Keratins are particularly important for the structural integrity of skin, and several genetically inherited blistering diseases have been linked to mutations in keratin 5 and keratin 14. We examined whether sulfur mustard exposure alters keratin biochemistry in cultured human epidermal keratinocytes. Western blotting with specific monoclonal antibodies revealed the formation of stable high-molecular-weight "aggregates" containing keratin 14 and/or keratin 5. These aggregates begin to form within 15 min after sulfur mustard exposure. These aggregates display a complex gel electrophoresis pattern between approximately 100 and approximately 200 kDa. Purification and analysis of these aggregates by one- and two-dimensional gel electrophoresis and mass spectrometry confirmed the presence of keratin 14 and keratin 5 and indicate that at least some of the aggregates are composed of keratin 14-keratin 14, keratin 14-keratin 5, or keratin 5-keratin 5 dimers. These studies demonstrate that sulfur mustard induces keratin aggregation in keratinocytes and support further investigation into the role of keratin aggregation in sulfur mustard-induced vesication. PMID:14644625

  15. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

    SciTech Connect

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B.; Heck, Diane E.; Heindel, Ned D.; Young, Sherri C.; Sinko, Patrick J.; Casillas, Robert P.; Laskin, Jeffrey D.; Laskin, Debra L.; Gerecke, Donald R.

    2014-10-15

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

  16. Therapeutic Potential of a Non-Steroidal Bifunctional Anti-Inflammatory and Anti-Cholinergic Agent against Skin Injury Induced by Sulfur Mustard

    PubMed Central

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B.; Heck, Diane E.; Heindel, Ned D.; Young, Sherri C.; Sinko, Patrick J.; Casillas, Robert P.; Laskin, Jeffrey D.; Laskin, Debra L.; Gerecke, Donald R.

    2014-01-01

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 hr post-SM exposure. After 96 hr, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermalepidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. PMID:25127551

  17. Multiphoton imaging the disruptive nature of sulfur mustard lesions

    NASA Astrophysics Data System (ADS)

    Werrlein, Robert J.; Braue, Catherine R.; Dillman, James F.

    2005-03-01

    Sulfur mustard [bis-2-chloroethyl sulfide] is a vesicating agent first used as a weapon of war in WWI. It causes debilitating blisters at the epidermal-dermal junction and involves molecules that are also disrupted by junctional epidermolysis bullosa (JEB) and other blistering skin diseases. Despite its recurring use in global conflicts, there is still no completely effective treatment. We have shown by imaging human keratinocytes in cell culture and in intact epidermal tissues that the basal cells of skin contain well-organized molecules (keratins K5/K14, α6β4 integrin, laminin 5 and α3β1 integrin) that are early targets of sulfur mustard. Disruption and collapse of these molecules is coincident with nuclear displacement, loss of functional asymmetry, and loss of polarized mobility. The progression of this pathology precedes basal cell detachment by 8-24 h, a time equivalent to the "clinical latent phase" that defines the extant period between agent exposure and vesication. Our images indicate that disruption of adhesion-complex molecules also impairs cytoskeletal proteins and the integration of structures required for signal transduction and tissue repair. We have recently developed an optical system to test this hypothesis, i.e., to determine whether and how the early disruption of target molecules alters signal transduction. This environmentally controlled on-line system provides a nexus for real-time correlation of imaged lesions with DNA microarray analysis, and for using multiphoton microscopy to facilitate development of more effective treatment strategies.

  18. A review on delayed toxic effects of sulfur mustard in Iranian veterans.

    PubMed

    Mansour Razavi, Seyed; Salamati, Payman; Saghafinia, Masoud; Abdollahi, Mohammad

    2012-01-01

    Iranian soldiers were attacked with chemical bombs, rockets and artillery shells 387 times during the 8-years war by Iraq (1980-1988). More than 1,000 tons of sulfur mustard gas was used in the battlefields by the Iraqis against Iranian people. A high rate of morbidities occurred as the result of these attacks. This study aimed to evaluate the delayed toxic effects of sulfur mustard gas on Iranian victims. During a systematic search, a total of 193 (109 more relevant to the main aim) articles on sulfur mustard gas were reviewed using known international and national databases. No special evaluation was conducted on the quality of the articles and their publication in accredited journals was considered sufficient. High rate of morbidities as the result of chemical attacks by sulfur mustard among Iranian people occurred. Iranian researchers found a numerous late complications among the victims which we be listed as wide range of respiratory, ocular, dermatological, psychological, hematological, immunological, gastrointestinal and endocrine complications, all influenced the quality of life of exposed victims. The mortality rate due to this agent was 3%. Although, mortality rate induced by sulfur mustard among Iranian people was low, variety and chronicity of toxic effects and complications of this chemical agent were dramatic. PMID:23351810

  19. A review on delayed toxic effects of sulfur mustard in Iranian veterans

    PubMed Central

    2012-01-01

    Iranian soldiers were attacked with chemical bombs, rockets and artillery shells 387 times during the 8-years war by Iraq (1980–1988). More than 1,000 tons of sulfur mustard gas was used in the battlefields by the Iraqis against Iranian people. A high rate of morbidities occurred as the result of these attacks. This study aimed to evaluate the delayed toxic effects of sulfur mustard gas on Iranian victims. During a systematic search, a total of 193 (109 more relevant to the main aim) articles on sulfur mustard gas were reviewed using known international and national databases. No special evaluation was conducted on the quality of the articles and their publication in accredited journals was considered sufficient. High rate of morbidities as the result of chemical attacks by sulfur mustard among Iranian people occurred. Iranian researchers found a numerous late complications among the victims which we be listed as wide range of respiratory, ocular, dermatological, psychological, hematological, immunological, gastrointestinal and endocrine complications, all influenced the quality of life of exposed victims. The mortality rate due to this agent was 3%. Although, mortality rate induced by sulfur mustard among Iranian people was low, variety and chronicity of toxic effects and complications of this chemical agent were dramatic. PMID:23351810

  20. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Two-Generation Reproduction Study of Lewisite in Rats Final Report

    SciTech Connect

    Sasser, L. B.; Cushing, J. A.; Kalkwarf, D. R.; Mellick, P. W.; Buschbom, R. L.

    1989-07-15

    Occupational health standards have not been established for Lewisite [bis(2-chlorethyl)arsine], a potent toxic vesicant which reacts with the sulfhydryl groups of proteins through its arsenic group. The purposes of this study were to determine the reproductive consequences and dose~response of continuing Lewisite exposure of parental males and females and their offspring in a 42-week two-generation study. Solutions of Lewisite were prepared for administration by diluting the neat agent with sesame oil. Rats were administered Lewisite (0, 0.10, 0.25 or 0.60 mg/kg/day for 5 days a week) via intragastric intubation prior to mating, during mating and after mating until the birth of their offspring. The dams continued to receive Lewisite during lactation. At weaning, male and female offspring of each group were selected to continue on the study; rece1v1ng Lewisite during adolescence, mating and throughout gestation. Again, the dams continued to receive Lewisite until weaning of the offspring. Lewisite had no adverse effect on reproduction performance, fertility or reproductive organ weights of male or female rats through two consecutive generations. No adverse effect to offspring were attributed to Lewisite exposure. Minor changes in growth was the only maternal effect observed. Lewisite exposure of parental rats caused no gross or microscopic lesions in testes, epididymis, prostrate, seminal vesicles, ovaries, uterus or vagina. Severe inflammation of the lung was observed at necropsy in cases in which Lewisite gained access to the respiratory system from accidental dosing or reflux and aspiration; this usually caused early death of the animal. The NOEL for reproductive effects in this study was greater than 0.60 mg/kg/day.

  1. Determination and prevention of cytotoxic effects induced in human lymphocytes by the alkylating agent 2,2`-dichlorodiethyl sulfide (sulfur mustard, HD). (Reannouncement with new availability information)

    SciTech Connect

    Meier, H.L.; Johnson, J.B.

    1992-12-31

    2,2`-Dichlorodiethyl sulfide (sulfur mustard), HD, 1,1`thiobis(2-chloroethane) is a potent vesicant which can cause severe lesions to skin, lung, and eyes. There is no convenient in vitro or in vivo method(s) to objectively measure the damage induced by HD; therefore, a simple in vitro method was developed using human peripheral lymphocytes to study HD-induced cytotoxicity. The cytotoxicity of HD was measured using dye exclusion as an indicator of human lymphocyte viability. Exposure to HD resulted in both a time- and a concentration-dependent cytotoxic effect on human lymphocytes. Using this in vitro assay, the effectiveness of various therapeutics (niacin, niacinamide, and 3-aminobenzamide) in preventing HD-induced cytotoxicity was studied. Niacinamide and 3-aminobenzamide prevented the cytotoxic effects of HD for up to 2 days.

  2. Nucleophilic substitution by grignard reagents on sulfur mustards.

    PubMed

    Converso, Antonella; Saaidi, Pierre-Loïc; Sharpless, K Barry; Finn, M G

    2004-10-15

    With proper activation of the leaving group, sulfur mustards react with Grignard reagents with neighboring group participation of the sulfur atom. 2,6-Dichloro-9-thiabicyclo[3.3.1]nonane is especially useful in this regard, providing clean reactivity with organomagnesium nucleophiles on a topologically constrained scaffold.

  3. A serious skin sulfur mustard burn from an artillery shell.

    PubMed

    Ruhl, C M; Park, S J; Danisa, O; Morgan, R F; Papirmeister, B; Sidell, F R; Edlich, R F; Anthony, L S; Himel, H N

    1994-01-01

    Despite the Geneva Protocol of 1925 and the Paris Conference on Prohibition of Chemical Weapons in 1989, sulfur mustard and other chemical weapons continue to pose a hazard to both civilians and soldiers. The presence of artillery shells containing sulfur mustard, both in waters where these shells were dumped and in old battlefields, presents a problem in times of peace, especially for those who collect wartime memorabilia. Past literature has reported several hundred incidents involving fishermen who inadvertently pulled leaking shells aboard their fishing vessels, thereby exposing themselves to the vesicant chemical. Other literature reports exposure to children who found the chemical shells in old battlefields. The purpose of this article is to report the first case of a serious sulfur mustard burn that occurred after removing the detonator from an old artillery shell in a historic battle field near Verdun, France. The circumstances surrounding the injury, the diagnosis and management of injuries secondary to sulfur mustard, and the long-term consequences to the patient are presented and discussed. Although skin grafting has been used in the management of other chemical burn injuries, this report is the first to describe the need for split-thickness skin grafts in the management of a patient with sulfur mustard burns.

  4. Respiratory Complications Due to Sulfur Mustard Exposure

    PubMed Central

    Rahmani, Hossein; Shirali, Saeed

    2016-01-01

    Sulfur mustard (SM) or bis (2-chloroethyl) sulfide is a vesicant and alkylating chemical weapon. SM was used in the 1980s against Iran by Iraqi forces. After exposure to SM in initial acute phase the greatest damage is incurred by the eyes, skin and lungs and the highest damage is caused to the lungs. This injury not only in the acute phase but also in the long-term has the highest prevalence among these patients. Clinical symptoms of people after exposure to SM start with irritation of the nose and sinuses in the mild doses to the runny nose and pain at higher doses and even irritation of the airways and bronchial engagement in very high doses. Respiratory complications in patients exposed to SM have been associated with long-term symptoms and these symptoms add to the intensity of the complication. Bloody sputum, feeling of tightness in the chest and shortness of breath over nights are among common symptoms; also the main respiratory symptoms including generalized wheezing, rale (crackle), decreased breath sounds and cyanosis and Apparently FEV1 is reduced by 50 mL/year. In these patients there are changes in blood cells especially in white blood cells and neutrophils and systemic inflammation and systemic changes with other comorbidities are observed. Although SM pulmonary patients’ treatment is based on bronchodilators and long-acting–β2 agonists, paying attention to the comorbidities with prior systemic changes in these patients is a reason for the need to change treatment strategies of these patients with systemic and extra-pulmonary therapy. PMID:27668271

  5. Respiratory Complications Due to Sulfur Mustard Exposure

    PubMed Central

    Rahmani, Hossein; Shirali, Saeed

    2016-01-01

    Sulfur mustard (SM) or bis (2-chloroethyl) sulfide is a vesicant and alkylating chemical weapon. SM was used in the 1980s against Iran by Iraqi forces. After exposure to SM in initial acute phase the greatest damage is incurred by the eyes, skin and lungs and the highest damage is caused to the lungs. This injury not only in the acute phase but also in the long-term has the highest prevalence among these patients. Clinical symptoms of people after exposure to SM start with irritation of the nose and sinuses in the mild doses to the runny nose and pain at higher doses and even irritation of the airways and bronchial engagement in very high doses. Respiratory complications in patients exposed to SM have been associated with long-term symptoms and these symptoms add to the intensity of the complication. Bloody sputum, feeling of tightness in the chest and shortness of breath over nights are among common symptoms; also the main respiratory symptoms including generalized wheezing, rale (crackle), decreased breath sounds and cyanosis and Apparently FEV1 is reduced by 50 mL/year. In these patients there are changes in blood cells especially in white blood cells and neutrophils and systemic inflammation and systemic changes with other comorbidities are observed. Although SM pulmonary patients’ treatment is based on bronchodilators and long-acting–β2 agonists, paying attention to the comorbidities with prior systemic changes in these patients is a reason for the need to change treatment strategies of these patients with systemic and extra-pulmonary therapy.

  6. Pathogenesis of skin lesions caused by sulfur mustard.

    PubMed

    Vogt, R F; Dannenberg, A M; Schofield, B H; Hynes, N A; Papirmeister, B

    1984-04-01

    Sulfur mustard (SM) (di-2-chlorethyl sulfide), used for chemical warfare in World War I, is a highly reactive radiomimetic alkylating agent. When applied to the skin of rabbits and guinea pigs, it produced vascular leakage, leukocyte infiltration, and slow death of basal epidermal cells. Thirty to sixty minutes after exposure to SM, injury to the superficial microvasculature (beneath the SM application site) was detected by measuring vascular leakage with Evans blue dye and also with horseradish peroxidase. At this same time, injury to the superficial fibroblasts was observed ultrastructurally; and an unexpectedly high percentage of basophils was found among the early infiltrating granulocytes. At 2 to 4 hr, the vascular leakage ceased, and had resumed by 8 hr in a more diffuse form. At this time, the basal epidermal cells showed pyknotic nuclei, an increase in their lysosomal enzymes (observed histochemically), and autophagic vacuoles (observed ultrastructurally). Leukocyte infiltration was marked, consisting mostly of heterophils (PMN) with a reduced percentage of basophils. During the next 24 to 72 hr, the entire inflammatory reaction reached its peak; and a superficial, crust-covered ulcer developed. Then, over the next 10 days, the lesion gradually subsided with concomitant repair and healing. Glucocorticosteroids decreased the early edematous phase, but did not affect the rate of healing. These findings suggest that the skin response to sulfur mustard has an immediate and a delayed phase. The immediate phase, i.e., within the first hour, was characterized by injury to the superficial fibroblasts and to the endothelium of superficial capillaries and venules, possibly because of direct damage to their cell membranes. At this time, a restricted vascular leakage and a selective granulocyte infiltration containing many basophils occurred. The delayed phase, which became evident after 8 hr, was characterized by the death of basal epidermal cells, probably because

  7. Kinetics of the degradation of sulfur mustard on ambient and moist concrete.

    PubMed

    Brevett, Carol A S; Sumpter, Kenneth B; Nickol, Robert G

    2009-02-15

    The rate of degradation of the chemical warfare agent sulfur mustard, bis(2-chloroethyl) sulfide, was measured on ambient and moist concrete using (13)C Solid State Magic Angle Spinning Nuclear Magnetic Resonance (SSMAS NMR). Three samples of concrete made by the same formulation, but differing in age and alkalinity were used. The sulfur mustard eventually degraded to thiodiglycol and 1,4-oxathiane via the intermediate sulfonium ions CH-TG, H-TG, H-2TG and O(CH(2)CH(2))(2)S(+)CH(2)CH(2)OH on all of the concrete samples, and in addition formed 8-31% vinyl moieties on the newer, more alkaline concrete samples. This is the first observation of the formation of O(CH(2)CH(2))(2)S(+)CH(2)CH(2)OH on a solid substrate. The addition of 2-chloroethanol to concrete on which mustard had fully degraded to thiodiglycol and 1,4-oxathiane resulted in the formation of O(CH(2)CH(2))(2)S(+)CH(2)CH(2)OH, thus demonstrating the reversibility of sulfur mustard degradation pathways. The sulfur mustard degradation half-lives on ambient concrete at 22 degrees C ranged from 3.5 to 54 weeks. When the substrates were moistened, the degradation half-lives at 22 degrees C ranged from 75 to 350h. The degradation of sulfur mustard occurred more quickly at elevated temperatures and with added water. The non-volatile toxic sulfonium ions persisted for months to years on concrete at 22 degrees C and weeks to months on concrete at 35 degrees C, before decomposing to the relatively non-toxic compounds thiodiglycol and 1,4-oxathiane. PMID:18584953

  8. Kinetics of the degradation of sulfur mustard on ambient and moist concrete.

    PubMed

    Brevett, Carol A S; Sumpter, Kenneth B; Nickol, Robert G

    2009-02-15

    The rate of degradation of the chemical warfare agent sulfur mustard, bis(2-chloroethyl) sulfide, was measured on ambient and moist concrete using (13)C Solid State Magic Angle Spinning Nuclear Magnetic Resonance (SSMAS NMR). Three samples of concrete made by the same formulation, but differing in age and alkalinity were used. The sulfur mustard eventually degraded to thiodiglycol and 1,4-oxathiane via the intermediate sulfonium ions CH-TG, H-TG, H-2TG and O(CH(2)CH(2))(2)S(+)CH(2)CH(2)OH on all of the concrete samples, and in addition formed 8-31% vinyl moieties on the newer, more alkaline concrete samples. This is the first observation of the formation of O(CH(2)CH(2))(2)S(+)CH(2)CH(2)OH on a solid substrate. The addition of 2-chloroethanol to concrete on which mustard had fully degraded to thiodiglycol and 1,4-oxathiane resulted in the formation of O(CH(2)CH(2))(2)S(+)CH(2)CH(2)OH, thus demonstrating the reversibility of sulfur mustard degradation pathways. The sulfur mustard degradation half-lives on ambient concrete at 22 degrees C ranged from 3.5 to 54 weeks. When the substrates were moistened, the degradation half-lives at 22 degrees C ranged from 75 to 350h. The degradation of sulfur mustard occurred more quickly at elevated temperatures and with added water. The non-volatile toxic sulfonium ions persisted for months to years on concrete at 22 degrees C and weeks to months on concrete at 35 degrees C, before decomposing to the relatively non-toxic compounds thiodiglycol and 1,4-oxathiane.

  9. Molecular and cellular mechanism of lung injuries due to exposure to sulfur mustard: a review.

    PubMed

    Ghanei, Mostafa; Harandi, Ali Amini

    2011-06-01

    Sulfur mustard (SM), a potent chemical weapon agent, was used by Iraqi forces against Iranian in the Iraq-Iran war (1981-1989). Chronic obstructive pulmonary disease (COPD) is a late toxic pulmonary consequence after SM exposure. The COPD observed in these patients is unique (described as Mustard Lung) and to some extent different from COPD resulted from other well-known causes. Several mechanisms have been hypothesized to contribute to the pathogenesis of COPD including oxidative stress, disruption of the balance between apoptosis and replenishment, proteinase-antiproteinase imbalance and inflammation. However, it is not obvious which of these pathways are relevant to the pathogenesis of mustard lung. In this paper, we reviewed studies addressing the pathogenicity of mustard lung, and reduced some recent ambiguities in this field. There is ample evidence in favor of crucial role of both oxidative stress and apoptosis as two known mechanisms that are more involved in pathogenesis of mustard lung comparing to COPD. However, according to available evidences there are no such considerable data supporting neither proteolytic activity nor inflammation mechanism as the main underlying pathogenesis in Mustard Lung. PMID:21639706

  10. Cleft Palate induced by Sulfur Mustard in mice fetus

    PubMed Central

    Hassanzadeh-Nazarabadi, Mohammad; Sanjarmoosavi, Nasrin; Sanjarmoosavi, Naser; Shekouhi, Sahar

    2012-01-01

    Sulfur Mustard (SM) is a chemical warfare agent which was widely used in the World War I and more recently during Gulf war in the early 1980s'. SM is a strong alkylating agent with known mutagenic and carcinogenic effects; but only few studies have been published on its teratogenicity. Since SM has been widely used as a chemical weapon by the Iraqi regime against the Iranian soldiers as well as the civilian population particularly pregnant women in the border area; therefore, the investigation of SM adverse effects on cleft malformations which is one of the most frequent congenital anomalies is considered in this study. An experimental work has been carried out in embryopathy in mouse with intraperitoneal injection of 0.75 and 1.5 mg/kg SM at different periods of gestation. Cleft lip and palate were examined by stereomicroscopy. Current data demonstrate that exposure with SM on the 11th day of gestation can increase the incidence of cleft defects in comparison with control group (P<0.001). These results also show that SM treatment in GD 11 and 13 can lead to more anomalies compared with GD 14 (P<0.001). They also show that the teratogenic effects of SM are restrictively under the influence of the threshold dose and time of gestation. The present results suggest that exposure to sufficient doses of SM on critical days of gestation may increase the risk of congenital cleft malformations. PMID:24551757

  11. Sulfur Mustard Induces Immune Sensitization in Hairless Guinea Pigs

    PubMed Central

    Mishra, Neerad C.; Rir-sima-ah, Jules; March, Thomas; Weber, Waylon; Benson, Janet; Jaramillo, Richard; Seagrave, Jean-Clare; Schultz, Gregory; Grotendorst, Gary; Sopori, Mohan

    2009-01-01

    Sulfur mustard (SM, bis-(2-chloroethyl) sulfide) is a well known chemical warfare agent that may cause long-term debilitating injury. Because of the ease of production and storage, it has a strong potential for chemical terrorism; however, the mechanism by which SM causes chronic tissue damage is essentially unknown. SM is a potent protein alkylating agent, and we tested the possibility that SM modifies cellular antigens, leading to an immunological response to “altered self” and a potential long-term injury. To that end, in this communication, we show that dermal exposure of euthymic hairless guinea pigs induced infiltration of both CD4+ and CD8+ T cells into the SM-exposed skin and strong upregulated expression of proinflammatory cytokines and chemokines (TNF-α, IFN-γ, and IL-8) in distal tissues such as the lung and the lymph nodes. Moreover, we present evidence for the first time that SM induces a specific delayed-type hypersensitivity response that is associated with splenomegaly, lymphadenopathy, and proliferation of cells in these tissues. These results clearly suggest that dermal exposure to SM leads to immune activation, infiltration of T cells into the SM-exposed skin, delayed-type hypersensitivity response, and molecular imprints of inflammation in tissues distal from the site of SM exposure. These immunological responses may contribute to the long-term sequelae of SM toxicity. PMID:19887117

  12. Degradation of sulfur mustard on KF/Al2O3 supports: insights into the products and the reactions mechanisms.

    PubMed

    Zafrani, Yossi; Goldvaser, Michael; Dagan, Shai; Feldberg, Liron; Mizrahi, Dana; Waysbort, Daniel; Gershonov, Eytan; Columbus, Ishay

    2009-11-01

    The degradation of the warfare agent sulfur mustard (HD) adsorbed onto KF/Al(2)O(3) sorbents is described. These processes were explored by MAS NMR, using (13)C-labeled sulfur mustard (HD*) and LC-MS techniques. Our study on the detoxification of this blister agent showed the formation of nontoxic substitution and less-toxic elimination products (t(1/2) = 3.5-355 h). Interestingly, the reaction rates were found to be affected by MAS conditions, i.e., by a centrifugation effect. The products and the mechanisms of these processes are discussed.

  13. Sulfur mustard gas exposure: case report and review of the literature

    PubMed Central

    Goverman, J.; Montecino, R.; Ibrahim, A.; Sarhane, K.A.; Tompkins, R.G.; Fagan, S.P.

    2014-01-01

    Summary This report describes a case of burn injury following exposure to sulfur mustard, a chemical agent used in war. A review of the diagnostic characteristics, clinical manifestations, and therapeutic measures used to treat this uncommon, yet extremely toxic, entity is presented. The aim of this report is to highlight the importance of considering this diagnosis in any war victim, especially during these unfortunate times of rising terrorist activities. PMID:26170794

  14. Biochemical manipulation of intracellular glutathione levels influences cytotoxicity to isolated human lymphocytes by sulfur mustard

    SciTech Connect

    Gross, C.L.; Innace, J.K.; Hovatter, R.C.; Meier, H.L.; Smith, W.J.

    1993-12-31

    Glutathione (GSH) is the major nonprotein thiol that can protect cells from damage due to electrophilic alkylating agents by forming conjugates with the agent. Sulfur mustard (HD) is an electrophilic alkylating agent that has potent mutagenic, carcinogenic, cytotoxic, and vesicant properties. Compounds that elevate or reduce intracellular levels of GSH may produce changes in cytotoxicity induced by sulfur mustard. Pretreatment of human peripheral blood lymphocytes (PBL) for 72 hr with 1 mM buthionine sulfoximine (BSO), which reduces intracellular GSH content to approximately 26% of control, appears to sensitize these in vitro cells to the cytotoxic effects of 10 AM HD but not to higher HD concentrations. Pretreatment of PBL for 48 hr with 10 mM N-acetyl cysteine (NA C), which elevates intracellular glutathione levels to 122% of control, appears to partially protect these in vitro cells from the cytotoxic effects of 10 LAIHD but not to higher HD concentrations. Augmentation of intracellular levels of glutathione may provide partial protection against cytotoxicity of sulfur mustard.

  15. Assessment of sulfur mustard interaction with basement membrane components

    SciTech Connect

    Zhang, Z.; Peters, B.P.; Monteiro-Rivier, N.A.

    1995-08-01

    Bis-2-chloroethyl sulfide (sulfur mustard, RD) is a bifunctional alkylating agent which causes severe vesication characterized by slow wound healing. Our previous studies have shown that the vesicant RD disrupts the epidermal-dermal junction at the lamina lucida of the basement membrane. The purpose of this study was to examine whether RD directly modifies basement membrane components (BMCs), and to evaluate the effect of RD on the cell adhesive activity of BMCs. EHS laminin was incubated with (14C)HRD, and extracted by gel filtration. Analysis of the (14C)HRD-conjugated laminin fraction by a reduced sodium dodecyl sulfate-polyacrylaminde gel electrophoresis (SD S-PAGE) revealed the incorporation of radioactivity into both laminin subunits and a laminin trimer resistant to dissociation in reduced SDS-PAGE sample buffer, suggesting direct alkylation and cross-linking of EHS laminin by (14C)HD. Normal human foreskin epidermal keratinocytes were biosynthetically labeled with (35S)cysteine. (35S)-labeled laminin isoforms, Ae.Ble.B2e. laminin and K.Ble.B2e. laminin (using the nomenclature of Engel), fibronectin, and heparan sulfate proteoglycan were isolated by irnmunoprecipitation from the cell culture medium, treated with RD or ethanol as control, and then analyzed by SDS-PAGE.

  16. NMR- and GC/MS-based metabolomics of sulfur mustard exposed individuals: a pilot study.

    PubMed

    Nobakht, B Fatemeh; Aliannejad, Rasoul; Rezaei-Tavirani, Mostafa; Arefi Oskouie, Afsaneh; Naseri, Mohammad Taghi; Parastar, Hadi; Aliakbarzadeh, Ghazaleh; Fathi, Fariba; Taheri, Salman

    2016-09-01

    Sulfur mustard (SM) is a potent alkylating agent and its effects on cells and tissues are varied and complex. Due to limitations in the diagnostics of sulfur mustard exposed individuals (SMEIs) by noninvasive approaches, there is a great necessity to develop novel techniques and biomarkers for this condition. We present here the first nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC/MS) metabolic profiling of serum from and healthy controls to identify novel biomarkers in blood serum for better diagnostics. Of note, SMEIs were exposed to SM 30 years ago and that differences between two groups could still be found. Pathways in which differences between SMEIs and healthy controls are observed are related to lipid metabolism, ketogenesis, tricarboxylic acid (TCA) cycle and amino acid metabolism. PMID:26984270

  17. NMR- and GC/MS-based metabolomics of sulfur mustard exposed individuals: a pilot study.

    PubMed

    Nobakht, B Fatemeh; Aliannejad, Rasoul; Rezaei-Tavirani, Mostafa; Arefi Oskouie, Afsaneh; Naseri, Mohammad Taghi; Parastar, Hadi; Aliakbarzadeh, Ghazaleh; Fathi, Fariba; Taheri, Salman

    2016-09-01

    Sulfur mustard (SM) is a potent alkylating agent and its effects on cells and tissues are varied and complex. Due to limitations in the diagnostics of sulfur mustard exposed individuals (SMEIs) by noninvasive approaches, there is a great necessity to develop novel techniques and biomarkers for this condition. We present here the first nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC/MS) metabolic profiling of serum from and healthy controls to identify novel biomarkers in blood serum for better diagnostics. Of note, SMEIs were exposed to SM 30 years ago and that differences between two groups could still be found. Pathways in which differences between SMEIs and healthy controls are observed are related to lipid metabolism, ketogenesis, tricarboxylic acid (TCA) cycle and amino acid metabolism.

  18. Mass spectral studies on vinylic degradation products of sulfur mustards under gas chromatography/mass spectrometry conditions.

    PubMed

    Sai Sachin, L; Karthikraj, R; Kalyan Kumar, K; Sony, T; Prasada Raju, N; Prabhakar, S

    2015-01-01

    Sulfur mustards are a class of vesicant chemical warfare agents that rapidly degrade in environmental samples. The most feasible degradation products of sulfur mustards are chloroethyl vinylic compounds and divinylic compounds, which are formed by the elimination of one and two HCl molecules from sulfur mustards, respectively. The detection and characterization of these degradation products in environmental samples are an important proof for the verification of sulfur mustard usage. In this study, we synthesized a set of sulfur mustard degradation products, i.e., divinylic compounds (1-7) and chloroethyl vinylic compounds (8-14), and characterized using gas chromatography/mass spectrometry (GC/MS) under electron ionization (EI) and chemical ionization (CI) (methane) conditions. The EI mass spectra of the studied compounds mainly included the fragment ions that resulted from homolytic cleavages with or without hydrogen migrations. The divinylic compounds (1-7) showed [M-SH](+) ions, whereas the chloroethylvinyl compounds (8-14) showed [M-Cl](+) and [M-CH2CH2Cl](+) ions. Methane/CI mass spectra showed [M+H](+) ions and provided molecular weight information. The GC retention index (RI) values were also calculated for the studied compounds. The EI and CI mass spectral data together with RI values are extremely useful for off-site analysis for the verification of the chemical weapons convention and also to participate in official Organization for the Prohibition of Chemical Weapons proficiency tests. PMID:26764309

  19. Teratogenic Effects of Sulfur Mustard on Mice Fetuses

    PubMed Central

    Sanjarmoosavi, Nasrin; Sanjarmoosavi, Naser; Shahsavan, Marziyeh; Hassanzadeh-Nazarabadi, Mohammad

    2012-01-01

    Introduction Sulfur Mustard (SM) has been used as a chemical warfare agent, in the World War I and more recently during Iraq-Iran war in early 1980s’. Its biological poisoning effect could be local or systemic and its effect depends on environmental conditions, exposed organs, and the extent and duration of exposure. It is considered as a strong alkylating agent with known mutagenic, carcinogenic effects; although a few studies have been performed on its teratogenicity so far. Materials and Methods Mice were administered with SM intraperitoneally with a dose of 0.75 and 1.5 mg/kg in different periods of their gestation (gestational age of 11, 13 and 14 weeks). Control mice groups were included. Between 5 and 9 mice were used in each group. Dams underwent cesarean section on day 19 of their gestation. External examination was performed on the animals investigating craniofacial and septal defects and limb malformations such as adactyly and syndactyly. All data were analyzed by Chi-Square test and Fisher's exact test. The P- value less than 0.05 was considered significant. Results Craniofacial and septal defects as well as the limb malformations were the most common types of birth defects, displaying an extremely complex biomedical problem. Conclusion This study confirms a significant correlation between SM exposure and its teratogenic effect. We postulated that the malformations could be caused by an uncontrolled migration of neural crest cells, causing developmental disorders. In addition to environmental factors, modifying genes could play an important role in the pathogenesis of the defects. PMID:23493485

  20. Silibinin as a potential therapeutic for sulfur mustard injuries.

    PubMed

    Balszuweit, Frank; John, Harald; Schmidt, Annette; Kehe, Kai; Thiermann, Horst; Steinritz, Dirk

    2013-12-01

    Sulfur mustard (SM) is a vesicating chemical warfare agent causing skin blistering, ulceration, impaired wound healing, prolonged hospitalization and permanent lesions. Silibinin, the lead compound from Silybum marianum, has also been discussed as a potential antidote to SM poisoning. However, its efficacy has been demonstrated only with regard to nitrogen mustards. Moreover, there are no data on the efficacy of the water-soluble prodrug silibinin-bis-succinat (silibinin-BS). We investigated the effect of SIL-BS treatment against SM toxicity in HaCaT cells with regard to potential reduction of necrosis, apoptosis and inflammation including dose-dependency of any protective effects. We also demonstrated the biotransformation of the prodrug into free silibinin. HaCaT cells were exposed to SM (30, 100, and 300μM) for 30min and treated thereafter with SIL-BS (10, 50, and 100μM) for 24h. Necrosis and apoptosis were quantified using the ToxiLight BioAssay and the nucleosome ELISA (CDDE). Pro-inflammatory interleukins-6 and -8 were determined by ELISA. HaCaT cells, incubated with silibinin-BS were lysed and investigated by LC-ESI MS/MS. LC-ESI MS/MS results suggest that SIL-BS is absorbed by HaCaT cells and biotransformed into free silibinin. SIL-BS dose-dependently reduced SM cytotoxicity, even after 300μM exposure. Doses of 50-100μM silibinin-BS were required for significant protection. Apoptosis and interleukin production remained largely unchanged by 10-50μM silibinin-BS but increased after 100μM treatment. Observed reductions of SM cytotoxicity by post-exposure treatment with SIL-BS suggest this as a promising approach for treatment of SM injuries. While 100μM SIL-BS is most effective to reduce necrosis, 50μM may be safer to avoid pro-inflammatory effects. Pro-apoptotic effects after high doses of SIL-BS are in agreement with findings in literature and might even be useful to eliminate cells irreversibly damaged by SM. Further investigations will focus on the

  1. Hematological profile of the euthymic hairless guinea pig following sulfur mustard vesicant exposure.

    PubMed

    Gold, M B; Scharf, B A

    1995-01-01

    Sulfur mustard (HD) is a potent vesicating agent of military importance, with known radiomimetic properties. The euthymic hairless guinea pig (EHGP) (Cavia porcellus) is emerging as the animal model of choice for cutaneous HD study. With elucidation of the systemic effects, we may better utilize this animal for all HD toxicity work. To this end, studies were conducted to determine the definitive median lethal dose (MLD) of subcutaneously applied sulfur mustard (HD) in the EHGP, and to correlate the induced hematological changes. Eight groups of two animals each were dosed at 0.3 log intervals from an extrapolated expected dose, deriving a tentative mean around which five groups of six animals each were dosed at 0.1 log intervals, resulting in a definitive MLD of 48.17 mg kg(-1). Sulfur mustard was then administered to seven groups of six animals each at a dose of 30 mg kg(-1) and hematology performed. Significant leukocyte count suppression was found to occur on days 4, 5 and 6, following a leukocyte elevation on day 1 after exposure. Serum potassium levels were found to be elevated all 7 days after HD exposure. Establishing the MLD for subcutaneously applied HD and the pattern of induced leukocyte suppression allows for more definitive evaluation of successful toxicity counter-measures.

  2. Temporal and spatial features of the formation of DNA adducts in sulfur mustard-exposed skin

    SciTech Connect

    Batal, Mohamed; Boudry, Isabelle; Mouret, Stéphane; Wartelle, Julien; Emorine, Sandy; Bertoni, Marine; Bérard, Izabel; and others

    2013-12-15

    Sulfur mustard (SM) is a chemical warfare agent that targets skin where it induces large blisters. DNA alkylation is a critical step to explain SM-induced cutaneous symptoms. We determined the kinetics of formation of main SM–DNA adducts and compare it with the development of the SM-induced pathogenesis in skin. SKH-1 mice were exposed to 2, 6 and 60 mg/kg of SM and treated skin was biopsied between 6 h and 21 days. Formation of SM DNA adducts was dose-dependent with a maximum immediately after exposure. However, adducts were persistent and still detectable 21 days post-exposure. The time-dependent formation of DNA adducts was also found to be correlated with the appearance of apoptotic cells. This temporal correlation suggests that these two early events are responsible for the severity of the damage to the skin. Besides, SM–DNA adducts were also detected in areas located next to contaminated zone, thus suggesting that SM diffuses in skin. Altogether, this work provides for the first time a clear picture of SM-induced genotoxicity using DNA adducts as a marker. - Highlights: • Sulfur mustard adducts are formed in DNA after skin exposure. • DNA damage formation is an early event in the pathological process of skin burn. • The amount of SM–DNA adducts is maximal at the earliest time point investigated. • Adducts are still detected 3 weeks after exposure. • Sulfur mustard diffuses in skin especially when large doses are applied.

  3. Historical perspective on effects and treatment of sulfur mustard injuries.

    PubMed

    Graham, John S; Schoneboom, Bruce A

    2013-12-01

    Sulfur mustard (2,2'-dichlorodiethyl sulfide; SM) is a potent vesicating chemical warfare agent that poses a continuing threat to both military and civilian populations. Significant SM injuries can take several months to heal, necessitate lengthy hospitalizations, and result in long-term complications affecting the skin, eyes, and lungs. This report summarizes initial and ongoing (chronic) clinical findings from SM casualties from the Iran-Iraq War (1980-1988), with an emphasis on cutaneous injury. In addition, we describe the cutaneous manifestations and treatment of several men recently and accidentally exposed to SM in the United States. Common, chronic cutaneous problems being reported in the Iranian casualties include pruritis (the primary complaint), burning, pain, redness, desquamation, hyperpigmentation, hypopigmentation, erythematous papular rash, xerosis, multiple cherry angiomas, atrophy, dermal scarring, hypertrophy, and sensitivity to mechanical injury with recurrent blistering and ulceration. Chronic ocular problems include keratitis, photophobia, persistent tearing, sensation of foreign body, corneal thinning and ulceration, vasculitis of the cornea and conjunctiva, and limbal stem cell deficiency. Chronic pulmonary problems include decreases in lung function, bronchitis with hyper-reactive airways, bronchiolitis, bronchiectasis, stenosis of the trachea and other large airways, emphysema, pulmonary fibrosis, decreased total lung capacity, and increased incidences of lung cancer, pulmonary infections, and tuberculosis. There are currently no standardized or optimized methods of casualty management; current treatment strategy consists of symptomatic management and is designed to relieve symptoms, prevent infections, and promote healing. New strategies are needed to provide for optimal and rapid healing, with the goals of (a) returning damaged tissue to optimal appearance and normal function in the shortest period of time, and (b) ameliorating chronic

  4. Acute effects of sulfur mustard injury--Munich experiences.

    PubMed

    Kehe, K; Thiermann, H; Balszuweit, F; Eyer, F; Steinritz, D; Zilker, T

    2009-09-01

    Sulfur mustard (SM) is a strong vesicant agent which has been used in several military conflicts. Large stockpiles still exist to the present day. SM is believed to be a major threat to civilian populations because of the persistent asymmetric threat by non-state actors, such as terrorist groups, its easy synthesis and handling and the risk of theft from stockpiles. Following an asymptomatic interval of several hours, acute SM exposure produces subepidermal skin blisters, respiratory tract damage, eye lesions and bone marrow depression. Iranian victims of SM exposure during the Iran-Iraq (1984-1988) war were treated at intensive care units of 3 Munich hospitals. All 12 patients were injured following aerial attacks with SM filled bombs, which exploded in a distance between 5 and 30m. All patients soon noted an offensive smell of garlic, addle eggs or oil roasted vegetables. No individual protective equipment was used. Eye itching and skin blistering started 2h after SM exposure. Some patients complained of nausea, dizziness and hoarseness. 4h after exposure, most patients started vomiting. Eye symptoms worsened and most patients suffered from temporary blindness due to blepharospasm and lid oedema. Additionally, pulmonary symptoms such as productive cough occurred. Patients were transferred to Munich 4-17 days after SM exposure. On admission all patients showed significant skin blistering and pigmentation. Conjunctivitis and photophobia were the major eye symptoms. Pulmonary symptoms, including productive cough were persistent. Bronchoscopy revealed massive inflammation of the trachea with signs of necrosis. 3 patients needed tracheotomy. Chest X-ray did not yield abnormal observations. This presentation summarizes the experience of treating SM victims in Munich and discusses therapeutic implications. PMID:19482056

  5. Inflammatory effects of inhaled sulfur mustard in rat lung

    SciTech Connect

    Malaviya, Rama; Sunil, Vasanthi R.; Cervelli, Jessica; Anderson, Dana R.; Holmes, Wesley W.; Conti, Michele L.; Gordon, Ronald E.; Laskin, Jeffrey D.; Laskin, Debra L.

    2010-10-15

    Inhalation of sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating its cytotoxic effects are unknown and were investigated in the present studies. Male rats Crl:CD(SD) were anesthetized, and then intratracheally intubated and exposed to 0.7-1.4 mg/kg SM by vapor inhalation. Animals were euthanized 6, 24, 48 h or 7 days post-exposure and bronchoalveolar lavage fluid (BAL) and lung tissue collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including focal ulceration and detachment of the trachea and bronchial epithelia from underlying mucosa, thickening of alveolar septal walls and increased numbers of inflammatory cells in the tissue. There was also evidence of autophagy and apoptosis in the tissue. This was correlated with increased BAL protein content, a marker of injury to the alveolar epithelial lining. SM exposure also resulted in increased expression of markers of inflammation including cyclooxygenase-2 (COX-2), tumor necrosis factor-{alpha} (TNF{alpha}), inducible nitric oxide synthase (iNOS), and matrix metalloproteinase-9 (MMP-9), each of which has been implicated in pulmonary toxicity. Whereas COX-2, TNF{alpha} and iNOS were mainly localized in alveolar regions, MMP-9 was prominent in bronchial epithelium. In contrast, expression of the anti-oxidant hemeoxygenase, and the anti-inflammatory collectin, surfactant protein-D, decreased in the lung after SM exposure. These data demonstrate that SM-induced oxidative stress and injury are associated with the generation of cytotoxic inflammatory proteins which may contribute to the pathogenic response to this vesicant.

  6. Inflammatory effects of inhaled sulfur mustard in rat lung

    PubMed Central

    Malaviya, Rama; Sunil, Vasanthi R.; Cervelli, Jessica; Anderson, Dana R.; Holmes, Wesley W.; Conti, Michele L.; Gordon, Ronald E.; Laskin, Jeffrey D.; Laskin, Debra L.

    2013-01-01

    Inhalation of sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating its cytotoxic effects are unknown and were investigated in the present studies. Male rats Crl:CD(SD) were anesthetized, and then intratracheally intubated and exposed to 0.7–1.4 mg/kg SM by vapor inhalation. Animals were euthanized 6, 24, 48 h or 7 days post-exposure and bronchoalveolar lavage fluid (BAL) and lung tissue collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including focal ulceration and detachment of the trachea and bronchial epithelia from underlying mucosa, thickening of alveolar septal walls and increased numbers of inflammatory cells in the tissue. There was also evidence of autophagy and apoptosis in the tissue. This was correlated with increased BAL protein content, a marker of injury to the alveolar epithelial lining. SM exposure also resulted in increased expression of markers of inflammation including cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNFα), inducible nitric oxide synthase (iNOS), and matrix metalloproteinase-9 (MMP-9), each of which has been implicated in pulmonary toxicity. Whereas COX-2, TNFα and iNOS were mainly localized in alveolar regions, MMP-9 was prominent in bronchial epithelium. In contrast, expression of the anti-oxidant hemeoxygenase, and the anti-inflammatory collectin, surfactant protein-D, decreased in the lung after SM exposure. These data demonstrate that SM-induced oxidative stress and injury are associated with the generation of cytotoxic inflammatory proteins which may contribute to the pathogenic response to this vesicant. PMID:20659490

  7. Evaluation of miR-9 and miR-143 expression in urine specimens of sulfur mustard exposed patients

    PubMed Central

    Khafaei, Mostafa; Samie, Shahram; Mowla, Seyed Javad; Alvanegh, Akbar Ghorbani; Mirzaei, Behnaz; Chavoshei, Somaye; Dorraj, Ghamar Soltan; Esmailnejad, Mostafa; Nourani, Mohammadreza

    2015-01-01

    Sulfur mustard (SM) or mustard gas is a chemical alkylating agent that causes blisters in the skin (blister gas), burns the eyes and causes lung injury. Some major cellular pathways are involved in the damage caused by mustard gas such as NF-κb signaling, TGF-β signaling, WNT pathway, inflammation, DNA repair and apoptosis. MicroRNAs are non-coding small RNAs (19–25 nucleotides) that are involved in the regulation of gene expression and are found in two forms, extracellular and intracellular. Changes in the levels of extracellular microRNAs are directly associated with many diseases, it is thus common to study the level of extracellular microRNAs as a biomarker to determine the pathophysiologic status. In this study, 32 mustard gas injured patients and 32healthy subjects participated. Comparative evaluation of miR-9 and miR-143 expression in urine samples was performed by Real Time PCR and Graph Pad software. The Mann Whitney t-test analysis of data showed that the expression level of miR-143 and miR-9 had a significant decrease in sulfur mustard individuals with the respective p-value of 0.0480 and 0.0272 compared to normal samples, with an imbalance of several above mentioned pathways. It seems that reducing the expression level of these genes has a very important role in the pathogenicity of mustard gas injured patients. PMID:27486378

  8. Evaluation of miR-9 and miR-143 expression in urine specimens of sulfur mustard exposed patients.

    PubMed

    Khafaei, Mostafa; Samie, Shahram; Mowla, Seyed Javad; Alvanegh, Akbar Ghorbani; Mirzaei, Behnaz; Chavoshei, Somaye; Dorraj, Ghamar Soltan; Esmailnejad, Mostafa; Tavallaie, Mahmood; Nourani, Mohammadreza

    2015-12-01

    Sulfur mustard (SM) or mustard gas is a chemical alkylating agent that causes blisters in the skin (blister gas), burns the eyes and causes lung injury. Some major cellular pathways are involved in the damage caused by mustard gas such as NF-κb signaling, TGF-β signaling, WNT pathway, inflammation, DNA repair and apoptosis. MicroRNAs are non-coding small RNAs (19-25 nucleotides) that are involved in the regulation of gene expression and are found in two forms, extracellular and intracellular. Changes in the levels of extracellular microRNAs are directly associated with many diseases, it is thus common to study the level of extracellular microRNAs as a biomarker to determine the pathophysiologic status. In this study, 32 mustard gas injured patients and 32healthy subjects participated. Comparative evaluation of miR-9 and miR-143 expression in urine samples was performed by Real Time PCR and Graph Pad software. The Mann Whitney t-test analysis of data showed that the expression level of miR-143 and miR-9 had a significant decrease in sulfur mustard individuals with the respective p-value of 0.0480 and 0.0272 compared to normal samples, with an imbalance of several above mentioned pathways. It seems that reducing the expression level of these genes has a very important role in the pathogenicity of mustard gas injured patients. PMID:27486378

  9. Induction and repair of DNA cross-links induced by sulfur mustard in the A-549 cell line followed by a comet assay.

    PubMed

    Jost, Petr; Svobodova, Hana; Stetina, Rudolf

    2015-07-25

    Sulfur mustard is a highly toxic chemical warfare agent with devastating impact on intoxicated tissues. DNA cross-links are probably the most toxic DNA lesions induced in the cell by sulfur mustard. The comet assay is a very sensitive method for measuring DNA damage. In the present study using the A-549 lung cell line, the comet assay protocol was optimized for indirect detection of DNA cross-links induced by sulfur mustard. The method is based on the additional treatment of the assayed cells containing cross-links with the chemical mutagen, styrene oxide. Alkali-labile adducts of styrene oxide cause DNA breaks leading to the formation of comets. A significant dose-dependent reduction of DNA migration of the comet's tail was found after exposing cells to sulfur mustard, indicative of the amount of sulfur mustard induced cross-links. The remarkable decrease of % tail DNA could be observed as early as 5min following exposure to sulfur mustard and the maximal effect was found after 30min, when DNA migration was reduced to the minimum. Sulfur mustard preincubated in culture medium without cells lost its ability to induce cross-links and had a half-life of about 15min. Pre-incubation longer than 30min does not lead to a significant increase in cross-links when applied to cells. However, the amount of cross-links is decreased during further incubation due to repair. The current modification of the comet assay provides a useful tool for detecting DNA cross-links induced by sulfur mustard and could be used for detection of other DNA cross-linking agents such as chemotherapeutic drugs. PMID:25986970

  10. Induction and repair of DNA cross-links induced by sulfur mustard in the A-549 cell line followed by a comet assay.

    PubMed

    Jost, Petr; Svobodova, Hana; Stetina, Rudolf

    2015-07-25

    Sulfur mustard is a highly toxic chemical warfare agent with devastating impact on intoxicated tissues. DNA cross-links are probably the most toxic DNA lesions induced in the cell by sulfur mustard. The comet assay is a very sensitive method for measuring DNA damage. In the present study using the A-549 lung cell line, the comet assay protocol was optimized for indirect detection of DNA cross-links induced by sulfur mustard. The method is based on the additional treatment of the assayed cells containing cross-links with the chemical mutagen, styrene oxide. Alkali-labile adducts of styrene oxide cause DNA breaks leading to the formation of comets. A significant dose-dependent reduction of DNA migration of the comet's tail was found after exposing cells to sulfur mustard, indicative of the amount of sulfur mustard induced cross-links. The remarkable decrease of % tail DNA could be observed as early as 5min following exposure to sulfur mustard and the maximal effect was found after 30min, when DNA migration was reduced to the minimum. Sulfur mustard preincubated in culture medium without cells lost its ability to induce cross-links and had a half-life of about 15min. Pre-incubation longer than 30min does not lead to a significant increase in cross-links when applied to cells. However, the amount of cross-links is decreased during further incubation due to repair. The current modification of the comet assay provides a useful tool for detecting DNA cross-links induced by sulfur mustard and could be used for detection of other DNA cross-linking agents such as chemotherapeutic drugs.

  11. FTIR-ATR evaluation of topical skin protectants useful for sulfur mustard and related compounds

    NASA Astrophysics Data System (ADS)

    Braue, Ernest H., Jr.; Litchfield, Marty R.; Bangledorf, Catherine R.; Rieder, Robert G.

    1992-03-01

    The US Army has a need to develop topical protectants that can decrease the effects of cutaneous exposure to chemical warfare (CW) agents. Such materials would enhance a soldier's ability to carry out the mission in a chemically hostile environment, would lessen the burden on medical personnel, and may allow the casualties to return to duty in a shorter period of time than might otherwise be possible. In a preliminary report (E. H. Braue, Jr. and M. G. Pannella, Applied Spectrosc., 44, 1061 (1990)), we described a unique analytical method using FT-IR spectroscopy and the horizontal attenuated total reflectance (ATR) accessory for evaluating the effectiveness of topical skin protectants (TSPs) against penetration by chemical agents. We now describe the application of this method to the chemical warfare agent sulfur mustard (HD).

  12. Sulfur mustard induced nuclear translocation of glyceraldehyde-3-phosphate-dehydrogenase (GAPDH).

    PubMed

    Steinritz, Dirk; Weber, Jana; Balszuweit, Frank; Thiermann, Horst; Schmidt, Annette

    2013-12-01

    Sulfur Mustard (SM) is a vesicant chemical warfare agent, which is acutely toxic to a variety of organ systems including skin, eyes, respiratory system and bone marrow. The underlying molecular pathomechanism was mainly attributed to the alkylating properties of SM. However, recent studies have revealed that cellular responses to SM exposure are of more complex nature and include increased protein expression and protein modifications that can be used as biomarkers. In order to confirm already known biomarkers, to detect potential new ones and to further elucidate the pathomechanism of SM, we conducted large-scale proteomic experiments based on a human keratinocyte cell line (HaCaT) exposed to SM. Surprisingly, our analysis identified glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) as one of the up-regulated proteins after exposure of HaCaT cells to SM. In this paper we demonstrate the sulfur mustard induced nuclear translocation of GAPDH in HaCaT cells by 2D gel-electrophoresis (2D GE), immunocytochemistry (ICC), Western Blot (WB) and a combination thereof. 2D GE in combination with MALDI-TOF MS/MS analysis identified GAPDH as an up-regulated protein after SM exposure. Immunocytochemistry revealed a distinct nuclear translocation of GAPDH after exposure to 300μM SM. This finding was confirmed by fractionated WB analysis. 2D GE and subsequent immunoblot staining of GAPDH demonstrated two different spot locations of GAPH (pI 7.0 and pI 8.5) that are related to cytosolic or nuclear GAPDH respectively. After exposure to 300μM SM a significant increase of nuclear GAPDH at pI 8.5 occurred. Nuclear GAPDH has been associated with apoptosis, detection of structural DNA alterations, DNA repair and regulation of genomic integrity and telomere structure. The results of our study add new aspects to the pathophysiology of sulfur mustard toxicity, yet further studies will be necessary to reveal the specific function of nuclear GAPDH in the pathomechanism of sulfur mustard

  13. Prevention and Treatment of Respiratory Consequences Induced by Sulfur Mustard in Iranian Casualties

    PubMed Central

    Razavi, Seyed M.; Salamati, Payman; Harandi, Ali Amini; Ghanei, Mostafa

    2013-01-01

    Background: About 100,000 Iranian have been exposed to chemical weapons during Iraq-Iran conflict (1980-88). After being spent of more than two decades, still about 30,000 of them are under follow-up treatment. The main aim of this study was to review various preventive and therapeutic methods for injured patients with sulfur mustard in different phases. Methods: For gathering information, we have used the electronic databases including Scopus, Medline, ISI, IranMedex, Irandoc sites. According to this search strategy, 104 published articles associated to respiratory problems and among them 50 articles related to prevention and treatment of respiratory problems were found and reviewed. Results: There is not any curative treatment for sulfur mustard induced lung injuries, but some valuable experienced measures for prevention and palliative treatments are available. Some useful measures in acute phase include: Symptomatic management, oxygen supplementation, tracheostomy in laryngospasm, use of moist air, respiratory physical therapy, mucolytic agents and bronchodilators. In the chronic phases, these measures include: Periodic clinical examinations, administration of inhaled corticosteroids alone or with long-acting beta 2 agonists, use of antioxidants, magnesium ions, long term oxygen supplement, therapeutic bronchoscopy, laser therapy, and use of respiratory tract stents. Conclusions: Most treatments are symptomatic but using preventive points immediately after exposure could improve following outcomes. PMID:23671768

  14. Mechanisms of sulfur mustard-induced metabolic injury

    SciTech Connect

    Martens, M.E.; Smith, W.J.

    1993-05-13

    Studies on the mechanism of metabolic injury induced by sulfur mustard (2, 2'- dichlorodiethyl sulfide, HD) have demonstrated that exposure of human epidermal keratinocytes in culture to HD induces time- and dose-dependent NAD+ depletion and inhibition of glucose metabolism (Martens, Biochem. Pharmacol., in press). Both occurred relatively early after alkylation, preceding the loss of membrane integrity that is indicative of metabolic cell death. The inhibition of glycolysis induced by HD was only partially correlated with the depletion of NAD+ and, thus, was not simply of changes in the NAD+ level. Rather, HD appeared to induce complex shifts in the pattern of glucose metabolism that paralleled both the timing and degree of injury. In line with these findings, recent experiments have shown that partial protection against HD-induced NAD+ depletion by 1 mM niacinamide did not protect against the inhibition of glycolysis. In preliminary experiments examining the effect of HD-induced metabolic changes on the cellular energy state, dose-dependent depletion of ATP was seen at 24 hours after exposure, but not at 4 or 8 hours. As seen for glucose metabolism, 1 mM niacinamide did not prevent the loss of high-energy intermediate (ATP). We conclude from these studies that relationships among HD exposure, glucose metabolism, and intracellular NAD and ATP are more complex than originally proposed (Papirmeister et al, Fund. Appl. Toxicol. 5:S134, 1985).

  15. Multiphoton imaging: a view to understanding sulfur mustard lesions

    NASA Astrophysics Data System (ADS)

    Werrlein, Robert J. S.; Madren-Whalley, Janna S.

    2003-07-01

    It is well known that topical exposure to sulfur mustard (SM) produces persistent, incapacitating blisters of the skin. However, the primary lesions effecting epidermal-dermal separation and disabling of mechanisms for cutaneous repair remain uncertain. Immunofluorescent staining plus multiphoton imaging of human epidermal tissues and keratinocytes exposed to SM (400 μM x 5 min)have revealed that SM disrupts adhesion-complex molecules which are also disrupted by epidermolysis bullosa-type blistering diseases of the skin. Images of keratin-14 showed early, progressive, postexposure collapse of the K5/K14 cytoskeleton that resulted in ventral displacement of the nuclei beneath its collapsing filaments. This effectively corrupted the dynamic filament assemblies that link basal-cell nuclei to the extracellular matrix via α6β4-integrin and laminin-5. At 1 h postexposure, there was disruption in the surface organization of α6β4 integrins, associated displacement of laminin-5 anchoring sites and a concomitant loss of functional asymmetry. Accordingly, our multiphoton images are providing compelling evidence that SM induces prevesicating lesions that disrupt the receptor-ligand organization and cytoskeletal systems required for maintaining dermal-epidermal attachment, signal transduction, and polarized mobility.

  16. Degradation of sulfur mustard and sarin over hardened cement paste.

    PubMed

    Tang, Hairong; Cheng, Zhenxing; Zhou, Liming; Zuo, Guomin; Kong, Lingce

    2009-03-01

    A study has been done to examine the degradation of sulfur mustard (HD) and sarin (GB) over hardened cement paste (HCP). The HCP behaved as a typical base like CaO and Ca(OH)2. The base sites over the HCP were not entirely poisoned by H2O and CO2 in air, and about 0.47 mmol/g base sites could still be evidenced by chemisorption of CO2. A large amount of water irreversibly adsorbed by HCP was experimentally demonstrated. Ten kinds of products through hydrolysis S(N)1 (C-Cl), elimination E1 or E2 (C-Cl, C-H), and addition-elimination (A-E) under the action of base sites and water from the degradation of HD over HCP were detected and identified by GC-FPD, GC-MS, and NMR approaches. Their distribution and kinds varied with time of degradation and water content Both degradation activity and distribution of products from HD were strongly determined by the strength and density of base sites and the water content in HCP. The molecules of GB adsorbed over HCP in comparison with HD could be more quickly and completely degraded into hydrolyzed products such as isopropyl methylphosphonic acid and methylphosphonic acid by adsorbed water, in comparison with HD. PMID:19350934

  17. Sulfur mustard induced oxidative stress and its alteration using asoxime (HI-6).

    PubMed

    Pohanka, Miroslav; Sobotka, Jakub; Svobodova, Hana; Stetina, Rudolf

    2013-12-01

    Sulfur mustard (SM) is a blister agent with cytotoxic mechanism of action. There is no suitable treatment based on administration of an antidote. In this study, Wistar rats were exposed to SM in doses of 0-40 mg/kg body weight and treated with the compound HI-6. The treatment provided no significant effect on ferric reducing antioxidant power of blood and plasma. However, HI-6 caused an increase in the level of thiobarbituric acid reactive substances. This stressogenic response was presumably the cause of the significant elevation of the blood level of both glutathione reductase and reduced glutathione. HI-6 appears to be suitable for enhancing prophylactically oxidative stress protection from small oxidative insult.

  18. Sulfur mustard-induced increase in intracellular calcium: A mechanism of mustard toxicity

    SciTech Connect

    Ray, R.; Majerus, B.J.; Munavalli, G.S.; Petrali, J.P.

    1993-05-13

    The effect of sulfur mustard SM, bis-(2-chloroethyl) sulfide on intracellular free Ca2+ concentration (Ca2+)i was studied in vitro using the clonal mouse neuroblastoma-rat glioma hybrid NG108-15 and primary normal human epidermal keratinocyte (NHEK) cell culture models. SM depletes cellular glutathione (GSH) and thus may inhibit GSH-dependent Ca2+-ATPase (Ca2+ pump), leading to a high (Ca2+) and consequent cellular toxicity. Following 0.3 mM SM exposure, GSH levels decreased 20-34% between 1-6 hr in NG108-15 cells. SM increased (Ca2+)i, measured using the Ca2+-specific fluorescent probe Fluo-3 AM, in both NG108-15 cells (1030% between 2-6 hr) and NHEK (23-30% between 0.5-3 hr) . Depletion of cellular GSH by buthionine sulfoximine (1 mM), a specific GSH biosynthesis inhibitor, also increased Ca2+, (88% at 1 hr) in NHEK, suggesting that GSH depletion may lead to increased (Ca2+)i. Calcium, localized cytochemically with antimony, accumulated in increased amounts around mitochondria and endoplasmic reticula, in the cytosol, and in particular in the euchromatin regions of the nucleus beginning at 6 hr after 0.3 mM SM exposure of NG108-15 cells. Cell membrane integrity examined with the fluorescent membrane probe calcein AM was unaffected through 6 hr following 1 mM SM exposure; and cell viability (NG108-15 cells) measured by trypan blue exclusion was >80% of control through 9 hr following 0.3 mM SM exposure.

  19. Gene expression profile of oxidative stress and antioxidant defense in lung tissue of patients exposed to sulfur mustard.

    PubMed

    Tahmasbpour, Eisa; Ghanei, Mostafa; Qazvini, Ali; Vahedi, Ensieh; Panahi, Yunes

    2016-04-01

    Sulfur mustard (SM) is a potent alkylating agent that targets several organs, especially lung tissue. Although pathological effects of SM on mustard lung have been widely considered, molecular and cellular mechanisms for these pathologies are poorly understood. We investigated changes in expression of genes related to oxidative stress (OS) and antioxidant defense caused by SM in lung tissue of patients. We performed gene expression profiling of OS and antioxidant defense in lung tissue samples from healthy controls (n=5) and SM-exposed patients (n=6). Changes in gene expression were measured using a 96-well RT(2) Profiler ™PCR Array: Human Oxidative Stress and Antioxidant Defense, which arrayed 84 genes functionally involved in cellular OS response. 47 (55.95%) genes were found to be significantly upregulated in patients with mustard lung compared with controls (p<0.05), whereas 7 (8.33%) genes were significantly downregulated (p<0.05). Among the most upregulated genes were OS responsive-1 (OXSR1), forkhead box M1 (FOXM1), and glutathione peroxidase-2 (GPX2), while metallothionein-3 (MT3) and glutathione reductase (GSR) were the most downregulated genes. Expression of hypoxia-induced genes (CYGB and MB), antioxidants and reactive oxygen species (ROS)-producing genes were significantly altered, suggesting an increased oxidative damage in mustard lungs. Mustard lungs were characterized by hypoxia, massive production of ROS, OS, disruption of epithelial cells, surfactant dysfunction, as well as increased risk of lung cancer and pulmonary fibrosis. Oxidative stress induced by ROS is the major mechanism for direct effect of SM exposure on respiratory system. Antioxidant treatment may improve the main features of mustard lungs.

  20. Gene expression profile of oxidative stress and antioxidant defense in lung tissue of patients exposed to sulfur mustard.

    PubMed

    Tahmasbpour, Eisa; Ghanei, Mostafa; Qazvini, Ali; Vahedi, Ensieh; Panahi, Yunes

    2016-04-01

    Sulfur mustard (SM) is a potent alkylating agent that targets several organs, especially lung tissue. Although pathological effects of SM on mustard lung have been widely considered, molecular and cellular mechanisms for these pathologies are poorly understood. We investigated changes in expression of genes related to oxidative stress (OS) and antioxidant defense caused by SM in lung tissue of patients. We performed gene expression profiling of OS and antioxidant defense in lung tissue samples from healthy controls (n=5) and SM-exposed patients (n=6). Changes in gene expression were measured using a 96-well RT(2) Profiler ™PCR Array: Human Oxidative Stress and Antioxidant Defense, which arrayed 84 genes functionally involved in cellular OS response. 47 (55.95%) genes were found to be significantly upregulated in patients with mustard lung compared with controls (p<0.05), whereas 7 (8.33%) genes were significantly downregulated (p<0.05). Among the most upregulated genes were OS responsive-1 (OXSR1), forkhead box M1 (FOXM1), and glutathione peroxidase-2 (GPX2), while metallothionein-3 (MT3) and glutathione reductase (GSR) were the most downregulated genes. Expression of hypoxia-induced genes (CYGB and MB), antioxidants and reactive oxygen species (ROS)-producing genes were significantly altered, suggesting an increased oxidative damage in mustard lungs. Mustard lungs were characterized by hypoxia, massive production of ROS, OS, disruption of epithelial cells, surfactant dysfunction, as well as increased risk of lung cancer and pulmonary fibrosis. Oxidative stress induced by ROS is the major mechanism for direct effect of SM exposure on respiratory system. Antioxidant treatment may improve the main features of mustard lungs. PMID:27085470

  1. Inhibition of sulfur mustard-increased protease activity by niacinamide, N-acetyl-L-cysteine or dexamethasone

    SciTech Connect

    Cowan, F.M.; Broomfield, C.A.; Smith, W.J.

    1991-03-11

    The pathologic mechanism of sulfur mustard-induced skin vesication is as yet undefined. Papirmeister et al. have postulated a biochemical mechanism for sulfur mustard-induced cutaneous injury involving sequelae of DNA alkylation, metabolic disruption resulting in NAD+ depletion and activation of protease. The authors have utilized a chromogenic peptide substrate assay to establish that human peripheral blood lymphocytes exposed 24 hr previously to sulfur mustard exhibited an increase in proteolytic activity. Doses of compounds known to alter the biochemical events associated with sulfur mustard exposure or reduce protease activity were tested in this system for their ability to block the sulfur mustard-induced protease activity. Treatment with niacinamide 1 hr after or with N-acetyl-L-cysteine or dexamethasone 24 hr prior to sulfur mustard exposure resulted in a decrease of 39%, 33% and 42% respectively of sulfur mustard-increased protease activity. These data suggest that therapeutic intervention into the biochemical pathways that culminate in protease activation might serve as an approach to treatment of sulfur mustard-induced pathology.

  2. Acute and chronic effects of sulfur mustard on the skin: a comprehensive review.

    PubMed

    Ghanei, Mostafa; Poursaleh, Zohreh; Harandi, Ali Amini; Emadi, Seyed Emad; Emadi, Seyed Naser

    2010-12-01

    Sulfur mustard (2,2-dichlorodiethyl sulfide, SM) is one of the vesicant classes of chemical warfare agents that causes blistering in the skin and mucous membranes, where it can have lingering long-term effects for up to ten years (1). SM was employed extensively by the Iraqi army against not only Iranian soldiers but also civilians between 1983 and 1988, resulting in over 100,000 chemical casualties. Approximately 45,000 victims are still suffering from long-term effects of exposure (2,3). More than 90% of the patients exposed to SM exhibit various cutaneous lesions in the affected area. The human skin can absorb approximately 20% of the SM through exposure. Up to 70% of the chemical is concentrated in the epidermis and the remainder in the basement membrane and in the dermis (4).Sulfur mustard exists in different physical states. The liquid form of SM evaporates slowly in cold weather and can penetrate through the clothing, thereby increasing exposure. However, the gas form readily diffuses in the air and it can be inhaled, leading to systemic absorption. In addition, warm temperatures are ideal conditions that liquid SM present in the clothing of the exposed individual could be converted to gas form. SM-induced clinical cutaneous symptoms include itching and burning. Other clinical findings include erythema or painless sunburn, bulla, hypo- and hyper pigmentation in both exposed and unexposed areas (5,6) The mechanism and biochemical cascade of SM-induced cutaneous manifestations are not completely understood but several published pathways support many of the know facts. Our current understanding fails to explain the time interval between the acute chemical exposure and the late-onset and delayed tissue damage (7,8). The aim of this article is to review the acute and long-term cutaneous findings resulting from SM exposure. Also, cellular and molecular mechanism involved in SM-induced skin pathology have been discussed. PMID:20868209

  3. A Simplified Method for Quantifying Sulfur Mustard Adducts to Blood Proteins by Ultra-High Pressure Liquid Chromatography-Isotope Dilution Tandem Mass Spectrometry

    PubMed Central

    Pantazides, Brooke G.; Crow, Brian S.; Garton, Joshua W.; Quiñones-González, Jennifer A.; Blake, Thomas A.; Thomas, Jerry D.; Johnson, Rudolph C.

    2016-01-01

    Sulfur mustard binds to reactive cysteine residues, forming a stable sulfur-hydroxyethylthioethyl [S-HETE] adduct that can be used as a long-term biomarker of sulfur mustard exposure in humans. The digestion of sulfur mustard-exposed blood samples with proteinase K following total protein precipitation with acetone produces the tripeptide biomarker [S-HETE]-Cys-Pro-Phe. The adducted tripeptide is purified by solid phase extraction, separated by ultra-high pressure liquid chromatography, and detected by isotope dilution tandem mass spectrometry. This approach was thoroughly validated and characterized in our laboratory. The average interday relative standard deviation was ≤ 9.49%, and the range of accuracy was between 96.1-109% over a concentration range of 3.00 to 250. ng/mL with a calculated limit of detection of 1.74 ng/mL. A full 96-well plate can be processed and analyzed in 8 h which is five times faster than our previous 96-well plate method and only requires 50 µL of serum, plasma, or whole blood. Extensive ruggedness and stability studies and matrix comparisons were conducted to create a robust, easily transferrable method. As a result, a simple and high-throughput method has been developed and validated for the quantitation of sulfur mustard blood protein adducts in low volume blood specimens which should be readily adaptable for quantifying human exposures to other alkylating agents. PMID:25622494

  4. Epigenetic: A missing paradigm in cellular and molecular pathways of sulfur mustard lung: a prospective and comparative study.

    PubMed

    Imani, Saber; Panahi, Yunes; Salimian, Jafar; Fu, Junjiang; Ghanei, Mostafa

    2015-08-01

    Sulfur mustard (SM, bis- (2-chloroethyl) sulphide) is a chemical warfare agent that causes DNA alkylation, protein modification and membrane damage. SM can trigger several molecular pathways involved in inflammation and oxidative stress, which cause cell necrosis and apoptosis, and loss of cells integrity and function. Epigenetic regulation of gene expression is a growing research topic and is addressed by DNA methylation, histone modification, chromatin remodeling, and noncoding RNAs expression. It seems SM can induce the epigenetic modifications that are translated into change in gene expression. Classification of epigenetic modifications long after exposure to SM would clarify its mechanism and paves a better strategy for the treatment of SM-affected patients. In this study, we review the key aberrant epigenetic modifications that have important roles in chronic obstructive pulmonary disease (COPD) and compared with mustard lung.

  5. Epigenetic: A missing paradigm in cellular and molecular pathways of sulfur mustard lung: a prospective and comparative study

    PubMed Central

    Imani, Saber; Panahi, Yunes; Salimian, Jafar; Fu, Junjiang; Ghanei, Mostafa

    2015-01-01

    Sulfur mustard (SM, bis- (2-chloroethyl) sulphide) is a chemical warfare agent that causes DNA alkylation, protein modification and membrane damage. SM can trigger several molecular pathways involved in inflammation and oxidative stress, which cause cell necrosis and apoptosis, and loss of cells integrity and function. Epigenetic regulation of gene expression is a growing research topic and is addressed by DNA methylation, histone modification, chromatin remodeling, and noncoding RNAs expression. It seems SM can induce the epigenetic modifications that are translated into change in gene expression. Classification of epigenetic modifications long after exposure to SM would clarify its mechanism and paves a better strategy for the treatment of SM-affected patients. In this study, we review the key aberrant epigenetic modifications that have important roles in chronic obstructive pulmonary disease (COPD) and compared with mustard lung. PMID:26557960

  6. Epigenetic: A missing paradigm in cellular and molecular pathways of sulfur mustard lung: a prospective and comparative study.

    PubMed

    Imani, Saber; Panahi, Yunes; Salimian, Jafar; Fu, Junjiang; Ghanei, Mostafa

    2015-08-01

    Sulfur mustard (SM, bis- (2-chloroethyl) sulphide) is a chemical warfare agent that causes DNA alkylation, protein modification and membrane damage. SM can trigger several molecular pathways involved in inflammation and oxidative stress, which cause cell necrosis and apoptosis, and loss of cells integrity and function. Epigenetic regulation of gene expression is a growing research topic and is addressed by DNA methylation, histone modification, chromatin remodeling, and noncoding RNAs expression. It seems SM can induce the epigenetic modifications that are translated into change in gene expression. Classification of epigenetic modifications long after exposure to SM would clarify its mechanism and paves a better strategy for the treatment of SM-affected patients. In this study, we review the key aberrant epigenetic modifications that have important roles in chronic obstructive pulmonary disease (COPD) and compared with mustard lung. PMID:26557960

  7. Spinach and mustard greens response to soil type, sulfur addition and lithium level

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A greenhouse experiment was conducted near Weslaco, Texas (Lat. 26o 8' N, Long. 97o 57' W) between Dec. 2006 and Feb 2007 to evaluate the effect of soil type, added sulfur and lithium level on the growth and leaf nutrients, particularly biofortified levels of Li and S, in spinach and mustard gree...

  8. The quantitation of sulfur mustard by-products, sulfur-containing herbicides, and organophosphonates in soil and concrete

    SciTech Connect

    Tomkins, B.A.; Sega, G.A.; Macnaughton, S.J.

    1998-07-01

    For approximately thirty years, the facilities at Rocky Mountain Arsenal were used for producing, packaging, and shipping sulfur- and phosphorus-containing mustard, Sarin, and pesticides. Degradation and manufacturing by-products related to these species are analyzed quickly using a combination of accelerated solvent extraction and gas chromatography (flame photometric detector) to determine exactly how specific waste structure materials should be handled, treated, and landfilled. These by-products are extracted rapidly from heated samples of soil or crushed concrete using acetonitrile at 100 C and 1500 psi, then analyzed using a gas chromatograph equipped with a flame photometric detector in its phosphorus- or sulfur-selective mode. Thiodiglycol, the major hydrolysis product of sulfur mustard, must be converted to a trimethylsilyl ether prior to quantitation. Detection limits, calculated using two statistically-unbiased protocols, ranged between 2--13 {micro}g analyte/g soil or concrete.

  9. The Quantitation of Sulfur Mustard By-Products, Sulfur-Containing Herbicides, and Organophosphonates in Soil and Concrete

    SciTech Connect

    Tomkins, B.A., Sega, G.A. , Macnaughton, S.J.

    1997-12-31

    Over the past fifty years, the facilities at Rocky Mountain Arsenal have been used for the manufacturing, bottling, and shipping sulfur- containing herbicides, sulfur mustard, and Sarin. There is a need for analytical methods capable of determining these constituents quickly to determine exactly how specific waste structural materials should be handled, treated, and landfilled.These species are extracted rapidly from heated samples of soil or crushed concrete using acetonitrile at elevated pressure, then analyzed using a gas chromatograph equipped with a flame photometric detector. Thiodiglycol, the major hydrolysis product of sulfur mustard, must be converted to a silylated derivative prior to quantitation. Detection limits, calculated using two statistically-unbiased protocols, ranged between 2-13 micrograms analyte/g soil or concrete.

  10. Calmodulin mediates sulfur mustard toxicity in human keratinocytes.

    PubMed

    Simbulan-Rosenthal, Cynthia M; Ray, Radharaman; Benton, Betty; Soeda, Emiko; Daher, Ahmad; Anderson, Dana; Smith, William J; Rosenthal, Dean S

    2006-10-01

    Sulfur mustard (SM) causes blisters in the skin through a series of cellular changes that we are beginning to identify. We earlier demonstrated that SM toxicity is the result of induction of both death receptor and mitochondrial pathways of apoptosis in human keratinocytes (KC). Because of its importance in apoptosis in the skin, we tested whether calmodulin (CaM) mediates the mitochondrial apoptotic pathway induced by SM. Of the three human CaM genes, the predominant form expressed in KC was CaM1. RT-PCR and immunoblot analysis revealed upregulation of CaM expression following SM treatment. To delineate the potential role of CaM1 in the regulation of SM-induced apoptosis, retroviral vectors expressing CaM1 RNA in the antisense (AS) orientation were used to transduce and derive stable CaM1 AS cells, which were then exposed to SM and subjected to immunoblot analysis for expression of apoptotic markers. Proteolytic activation of executioner caspases-3, -6, -7, and the upstream caspase-9, as well as caspase-mediated PARP cleavage were markedly inhibited by CaM1 AS expression. CaM1 AS depletion attenuated SM-induced, but not Fas-induced, proteolytic processing and activation of caspase-3. Whereas control KC exhibited a marked increase in apoptotic nuclear fragmentation after SM, CaM1 AS cells exhibited normal nuclear morphology up to 48h after SM, indicating that suppression of apoptosis in CaM1 AS cells increases survival and does not shift to a necrotic death. CaM has been shown to activate the phosphatase calcineurin, which can induce apoptosis by Bad dephosphorylation. Interestingly, whereas SM-treated CaM1-depleted KC expressed the phosphorylated non-apoptotic sequestered form of Bad, Bad was present in the hypophosphorylated apoptotic form in SM-exposed control KC. To determine if pharmacological CaM inhibitors could attenuate SM-induced apoptosis via Bad dephosphorylation, KC were pretreated with the CaM-specific antagonist W-13 or its less active structural

  11. Comparative transcriptional and translational analysis of heme oxygenase expression in response to sulfur mustard.

    PubMed

    Nourani, Mohammad Reza; Mahmoodzadeh Hosseini, Hamideh; Imani Fooladi, Abbas Ali

    2015-01-01

    Sulfur mustard (SM) is a potent alkylating agent which reacts with nucleophilic groups on DNA, RNA and proteins. It is capable of inducing cellular toxicity and oxidative stress via production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The accumulation of high amounts of the reactive species causes harmful effects such as DNA damage, lipid peroxidation, protein oxidation, inflammation and apoptosis. Although SM (also known as mustard gas) and its derivatives are rapidly removed from the body, long-term damages are much more serious than the short-term effects and may be correlated with the subsequent changes occurred on the genome. In order to defend against oxidative properties of this toxic molecule, cells trigger several anti-oxidant pathways through up-regulating the corresponding genes. Enzymes like heme oxygenase-1, superoxide dismutase and glutathione-S-transferase are the examples of such genes. These enzymes produce anti-oxidant substances that are able to scavenge the reactive species, alleviate their noxious effects and protect the cells. Following SM gas exposure, gene transcription (mRNA levels) of these enzymes are ramped up to help detoxify the cells. Yet, some studies have reported that the up-regulated transcription does not necessarily translate into higher protein expression levels. The exact reason why this phenomenon happens is not clear. Creation of mutations in the genome sequence may lead to protein structure changes. Phosphorylation or other post-translational alterations of proteins upon SM exposure are also considered as possible causes. In addition, alterations in some microRNAs responsible for regulating post-translation events may inhibit the expression of the anti-oxidant proteins in the poisoned cells at translational level. PMID:26096165

  12. Photoassisted and photocatalytic degradation of sulfur mustard using TiO2 nanoparticles and polyoxometalates.

    PubMed

    Naseri, Mohammad Taghi; Sarabadani, Mansour; Ashrafi, Davood; Saeidian, Hamdollah; Babri, Mehran

    2013-02-01

    The decomposition of highly toxic chemical warfare agent, sulfur mustard (bis(2-chloroethyl) sulfide or HD), has been studied by homogeneous photolysis and heterogeneous photocatalytic degradation on titania nanoparticles. Direct photolysis degradation of HD with irradiation system was investigated. The photocatalytic degradation of HD was investigated in the presence of TiO(2) nanoparticles and polyoxometalates embedded in titania nanoparticles in liquid phase at room temperature (33 ± 2 °C). Degradation products during the treatment were identified by gas chromatography-mass spectrometry. Whereas apparent first-order kinetics of ultraviolet (UV) photolysis were slow (0.0091 min(-1)), the highest degradation rate is obtained in the presence of TiO(2) nanoparticles as nanophotocatalyst. Simultaneous photolysis and photocatalysis under the full UV radiation leads to HD complete destruction in 3 h. No degradation products observed in the presence of nanophotocatalyst without irradiation in 3 h. It was found that up to 90 % of agent was decomposed under of UV irradiation without TiO(2), in 6 h. The decontamination mechanisms are often quite complex and multiple mechanisms can be operable such as hydrolysis, oxidation, and elimination. By simultaneously carrying out photolysis and photocatalysis in hexane, we have succeeded in achieving faster HD decontamination after 90 min with low catalyst loading. TiO(2) nanoparticles proved to be a superior photocatalyst under UV irradiation for HD decontamination. PMID:22707206

  13. Sulfur mustard medical countermeasures in a nuclear environment.

    PubMed

    Smith, William J; Gross, Clark L

    2002-02-01

    The possibility of chemical warfare occurring on a nuclear battlefield exists, given the increased proliferation of both types of weapons in small nations during the last two decades. Antidotes to mustard "gas" have not yet been fielded because its mechanism of action is not fully understood. Researchers at the U.S. Army Medical Research Institute of Chemical Defense have been addressing this dilemma and have developed six intervention strategies that may have efficacy for both chemical and nuclear weapons. These strategies include intracellular scavengers, DNA cell cycle modulators, poly(ADP-ribose) polymerase inhibitors, calcium modulators, anti-proteases, and anti-inflammatories. Because mustard and radiation may produce synergistic effects that could impair the efficacy of individual therapies, studies have been proposed to evaluate the combined effects of nuclear and chemical exposures. Once models for these studies have been established, the safety and efficacy of the intervention strategies can be evaluated.

  14. A Choline Oxidase Amperometric Bioassay for the Detection of Mustard Agents Based on Screen-Printed Electrodes Modified with Prussian Blue Nanoparticles

    PubMed Central

    Arduini, Fabiana; Scognamiglio, Viviana; Covaia, Corrado; Amine, Aziz; Moscone, Danila; Palleschi, Giuseppe

    2015-01-01

    In this work a novel bioassay for mustard agent detection was proposed. The bioassay is based on the capability of these compounds to inhibit the enzyme choline oxidase. The enzymatic activity, which is correlated to the mustard agents, was electrochemically monitored measuring the enzymatic product, hydrogen peroxide, by means of a screen-printed electrode modified with Prussian Blue nanoparticles. Prussian Blue nanoparticles are able to electrocatalyse the hydrogen peroxide concentration reduction at low applied potential (−50 mV vs. Ag/AgCl), thus allowing the detection of the mustard agents with no electrochemical interferences. The suitability of this novel bioassay was tested with the nitrogen mustard simulant bis(2-chloroethyl)amine and the sulfur mustard simulants 2-chloroethyl ethyl sulfide and 2-chloroethyl phenyl sulfide. The bioassay proposed in this work allowed the detection of mustard agent simulants with good sensitivity and fast response, which are excellent premises for the development of a miniaturised sensor well suited for an alarm system in case of terrorist attacks. PMID:25688587

  15. Airway Tissue Plasminogen Activator Prevents Acute Mortality Due to Lethal Sulfur Mustard Inhalation

    PubMed Central

    Veress, Livia A.; Anderson, Dana R.; Hendry-Hofer, Tara B.; Houin, Paul R.; Rioux, Jacqueline S.; Garlick, Rhonda B.; Loader, Joan E.; Paradiso, Danielle C.; Smith, Russell W.; Rancourt, Raymond C.; Holmes, Wesley W.; White, Carl W.

    2015-01-01

    Rationale: Sulfur mustard (SM) is a chemical weapon stockpiled today in volatile regions of the world. SM inhalation causes a life-threatening airway injury characterized by airway obstruction from fibrin casts, which can lead to respiratory failure and death. Mortality in those requiring intubation is more than 80%. No therapy exists to prevent mortality after SM exposure. Our previous work using the less toxic analog of SM, 2-chloroethyl ethyl sulfide, identified tissue plasminogen activator (tPA) an effective rescue therapy for airway cast obstruction (Veress, L. A., Hendry-Hofer, T. B., Loader, J. E., Rioux, J. S., Garlick, R. B., and White, C. W. (2013). Tissue plasminogen activator prevents mortality from sulfur mustard analog-induced airway obstruction. Am. J. Respir. Cell Mol. Biol. 48, 439–447). It is not known if exposure to neat SM vapor, the primary agent used in chemical warfare, will also cause death due to airway casts, and if tPA could be used to improve outcome. Methods: Adult rats were exposed to SM, and when oxygen saturation reached less than 85% (median: 6.5 h), intratracheal tPA or placebo was given under isoflurane anesthesia every 4 h for 48 h. Oxygen saturation, clinical distress, and arterial blood gases were assessed. Microdissection was done to assess airway obstruction by casts. Results: Intratracheal tPA treatment eliminated mortality (0% at 48 h) and greatly improved morbidity after lethal SM inhalation (100% death in controls). tPA normalized SM-associated hypoxemia, hypercarbia, and lactic acidosis, and improved respiratory distress. Moreover, tPA treatment resulted in greatly diminished airway casts, preventing respiratory failure from airway obstruction. Conclusions: tPA given via airway more than 6 h after exposure prevented death from lethal SM inhalation, and normalized oxygenation and ventilation defects, thereby rescuing from respiratory distress and failure. Intra-airway tPA should be considered as a life

  16. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    PubMed Central

    2012-01-01

    Objective Sulfur mustard (SM) is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988). It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments. PMID:23351279

  17. Comparative Proteomic Study Reveals the Molecular Aspects of Delayed Ocular Symptoms Induced by Sulfur Mustard

    PubMed Central

    Pashandi, Zaiddodine; Saraygord-Afshari, Neda; Naderi-Manesh, Hossein; Naderi, Mostafa

    2015-01-01

    Objective. Sulfur mustard (SM) is a highly reactive alkylating agent which produces ocular, respiratory, and skin damages. Eyes are the most sensitive organ to SM due to high intrinsic metabolic and rapid turnover rate of corneal epithelium and aqueous-mucous interfaces of the cornea and conjunctiva. Here we investigate underlying molecular mechanism of SM exposure delayed effects which is still a controversial issue after about 30 years. Materials and Methods. Following ethical approval, we have analyzed serum proteome of ten severe SM exposed male patients with delayed eye symptoms with two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. The western blotting was used to confirm the proteins that have been identified. Results. We have identified thirteen proteins including albumin, haptoglobin, and keratin isoforms as well as immunoglobulin kappa chain which showed upregulation while transferrin and alpha 1 antitrypsin revealed downregulation in these patients in comparison with healthy control group. Conclusions. Our results elevated participation of free iron circulatory imbalance and local matrix-metalloproteinase activity in development of delayed ocular symptoms induced by SM. It demonstrates that SM induced systemic toxicity leads to some serum protein changes that continually and gradually exacerbate the ocular surface injuries. PMID:25685557

  18. Sulfur mustard induced oxidative stress and its alteration by epigallocatechin gallate.

    PubMed

    Pohanka, Miroslav; Sobotka, Jakub; Stetina, Rudolf

    2011-03-01

    Sulfur mustard (bis(2-chloroethyl)sulfide; CAS: 505-60-2; abbreviated as HD) is a chemical warfare agent with not well understood mechanism of toxic effect. Deprivation of energy in cells and arising of oxidative stress appears during the exposure. Our experiment is based on investigation of 10mg or 20mg epigallocatechin gallate (EGCG) dose prophylactic effect (1h before HD) in rats exposed to either 20mg or 80 mg of HD. Blood mass, plasma and liver were sampled. Ferric reducing antioxidant power (FRAP), reduced glutathione, thiobarbuturic acid reactive substances (TBARSs), glutathione reductase, glutathione S-transferase and caspase 3 were assessed. Animals were sacrificed one day after exposure. We found significant deprivation of low molecular weight antioxidants due to EGCG but not due to HD. However, HD depleted reduced glutathione. EGCG has no effect to influence TBARS level. EGCG and HD up-regulated glutathione reductase and EGCG down regulated glutathione S-transferase in liver tissue. Regarding caspase, EGCG had anti apoptotic potency. We discuss potency to use EGCG to ameliorate redox balance after HD exposure. The data also appoints at difficulty in antioxidant therapy as prophylaxis to the oxidative stress related toxins exposure and ambivalent modulation of oxidative stress.

  19. Imaging sulfur mustard lesions in human epidermal tissues and keratinocytes by confocal and multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Werrlein, Robert; Madren-Whalley, Janna S.

    2002-06-01

    Topical exposure to sulfur mustard (HD), a known theat agent, produces persistent and debilitating cutaneous blisters. The blisters occur at the dermal-epidermal junction following a dose-dependent latent period of 8-24 h, however, the primary lesions causing vesication remain uncertain. Immunofluorescent images reveal that a 5-min exposure to 400 (mu) M HD disrupts molecules that are also disrupted by epidermolysis bullosa-type blistering diseases of the skin. Using keratinocyte cultures and fluorochomes conjugated to two different keratin-14 (K14) antibodies (clones CKB1 and LL002), results have shown a statistically significant (p<0.1) 1-h decrease of 29.2% in expression of the CKB1 epitope, a nearly complete loss of CKB1 expression within 2 h, and progressive cytoskeletal (K14) collapse without loss in expression of the LL002 epitope. With human epidermal tissues, multi-photon images of (alpha) 6 integrin and laminin 5 showed disruptive changes in the cell-surface organization and integrity of these adhesion molecules. At 1 H postexposure, analyses showed a statistically significant (p<0.1) decrease of 27.3% in (alpha) 6 integrin emissions, and a 32% decrease in laminin 5 volume. Multi-photon imaging indicates that molecules essential for epidermal-dermal attachment are early targets in the alkylating events leading to HD-induced vesication.

  20. Lack of FLT3-TKD835 gene mutation in toxicity of sulfur mustard in Iranian veterans

    PubMed Central

    Ayatollahi, Hossein; Rafiee, Mohammad; Keramati, Mohammad-Reza; Balali-Mood, Mahdi; Asgharzadeh, Ali; Sadeghian, Mohammad Hadi; Sheikhi, Maryam; Amini, Nafiseh; Zarmehri, Azam Moradi

    2015-01-01

    Objective(s): Sulfur mustard (SM) was used by the Iraqi army against the Iranian troops in the Iran-Iraq war from 1983–1988. This chemical gas affects different organs including the skin, lungs and the hematopoietic system. Any exposure to SM increases the risk of chromosomal breaking, hyperdiploidy and hypodiploidy. Studies have shown that the risk for acute myeloblastic and lymphoblastic leukemia increases in veterans exposed to SM. FLT3 mutations including ITD and TKD mutations had been observed in some cases of leukemia. Therefore, we aimed to investigate the frequency of FLT3-TKD835 mutations in the veterans exposed to SM agent. Materials and Methods: We studied 42 patients who were exposed to SM during the war in Khorasan Razavi province, Mashhad, Iran in 2012. As control group, 30 healthy males were selected from first-degree relatives of the patients. For assessment of TKD835 mutation, DNA was extracted and RFLP-PCR was performed. Results: Analysis of RFLP-PCR data showed no FLT-3 TKD mutation in any of the patients. Conclusion: Although contact with SM can increase the risk of malignancy especially hematologic neoplasms, results of the study show that another mechanism of leukemogenesis, other than FLT3-TKD mutation, may be the reason for increased risk of leukemia in SM toxicity. PMID:26523218

  1. Thiodiglycol, the hydrolysis product of sulfur mustard: Analysis of in vitro biotransformation by mammalian alcohol dehydrogenases using nuclear magnetic resonance

    SciTech Connect

    Brimfield, A.A.; Hodgson, Ernest

    2006-06-15

    Thiodiglycol (2,2'-bis-hydroxyethylsulfide, TDG), the hydrolysis product of the chemical warfare agent sulfur mustard, has been implicated in the toxicity of sulfur mustard through the inhibition of protein phosphatases in mouse liver cytosol. The absence of any inhibitory activity when TDG was present in assays of pure enzymes, however, led us to investigate the possibility for metabolic activation of TDG to inhibitory compound(s) by cytosolic enzymes. We have successfully shown that mammalian alcohol dehydrogenases (ADH) rapidly oxidize TDG in vitro, but the classic spectrophotometric techniques for following this reaction provided no information on the identity of TDG intermediates and products. The use of proton NMR to monitor the oxidative reaction with structural confirmation by independent synthesis allowed us to establish the ultimate product, 2-hydroxyethylthioacetic acid, and to identify an intermediate equilibrium mixture consisting of 2-hydroxyethylthioacetaldehyde, 2-hydroxyethylthioacetaldehyde hydrate and the cyclic 1,4-oxathian-2-ol. The intermediate nature of this mixture was determined spectrophotometrically when it was shown to drive the production of NADH when added to ADH and NAD.

  2. Solid-Phase Extraction of Sulfur Mustard Metabolites Using an Activated Carbon Fiber Sorbent.

    PubMed

    Lee, Jin Young; Lee, Yong Han

    2016-01-01

    A novel solid-phase extraction method using activated carbon fiber (ACF) was developed and validated. ACF has a vast network of pores of varying sizes and microporous structures that result in rapid adsorption and selective extraction of sulfur mustard metabolites according to the pH of eluting solvents. ACF could not only selectively extract thiodiglycol and 1-methylsulfinyl-2-[2-(methylthio)-ethylsulfonyl]ethane eluting a 9:1 ratio of dichloromethane to acetone, and 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] and 1,1'-sulfonylbis- [2-S-(N-acetylcysteinyl)ethane] eluting 3% hydrogen chloride in methanol, but could also eliminate most interference without loss of analytes during the loading and washing steps. A sample preparation method has been optimized for the extraction of sulfur mustard metabolites from human urine using an ACF sorbent. The newly developed extraction method was applied to the trace analysis of metabolites of sulfur mustard in human urine matrices in a confidence-building exercise for the analysis of biomedical samples provided by the Organisation for the Prohibition of Chemical Weapons. PMID:26364317

  3. Synthesis and alkylation activity of a nitrogen mustard agent to penetrate the blood-brain barrier.

    PubMed

    Bartzatt, Ronald L

    2004-01-01

    Nitrogen mustard agents are widely used for the clinical treatment of cancers. A nitrogen mustard (N-mustard) agent was synthesized utilizing nicotinic acid as the carrier of the alkylating substituent (-OCH2CH2N(CH2CH2Cl)2) that forms an ester group (R-C(O)-OR) on a heterocyclic ring. The N-mustard agent is a solid at room temperature and is stable for more than 6 weeks when stored at -10 degrees C. To determine the kinetics of alkylation activity a nucleophilic primary amine compound (4-chloroaniline) was placed in aqueous solution with the mustard agent at physiological pH 7.4 (pH of blood) and 37 degrees C. The alkylation reaction was found to be second-order with rate equation: rate = k2[N-mustard][Nu], where Nu = nucleophile and k2 = 0.0415 L/(mol x min). Pharmacological descriptors calculated showed values indicating a strong potential of penetrating the blood-brain barrier. The partition coefficient (Log P) of the mustard agent is 1.95 compared with 0.58 for nicotinic acid. Values of descriptors such as dipole, polar surface area, Log BB, molar refractivity, parachor, and violations of Rule of 5 were found to be 5.057 Debye, 42.44 A2, 0.662, 72.7 cm3, 607.7 cm3, and 0.0 for the N-mustard agent. Value of polar surface area for the mustard agent (42.44 A2) predicts that >90% of any amount present in the intestinal tract will be absorbed.

  4. Protective effects of amifostine and its analogues on sulfur mustard toxicity in vitro and in vivo.

    PubMed

    Bhattacharya, R; Rao, P V; Pant, S C; Kumar, P; Tulsawani, R K; Pathak, U; Kulkarni, A; Vijayaraghavan, R

    2001-10-01

    Sulfur mustard (bis(2-chloroethyl)sulfide, SM) is a highly reactive bifunctional alkylating agent that forms sulfonium ions in the body. SM alkylates DNA, leading to DNA strand breaks and cell death in a variety of cell types and tissues. Although several approaches have been proposed to challenge the toxic action(s) of SM, no satisfactory treatment regimen has evolved. The synthetic aminothiol amifostine, earlier known as WR-2721 (S-2-(3-aminopropylamino)ethyl phosphorothioate), has been extensively used as a chemical radioprotector for the normal tissues in cancer radiotherapy and chemotherapy. SM is known as a radiomimetic agent and this prompted us to evaluate the protective efficacy of amifostine (2.5 mM) and three of its analogues, DRDE-06 (S-2 (3-aminopropylamino) ethyl phenyl sulfide), DRDE-07 (S-2 (2-aminoethylamino) ethyl phenyl sulfide), and DRDE-08 (S-2 (4-aminobutylamino) ethyl phenyl sulfide), against SM toxicity in rat liver slices. Of the four agents tested, a 30-min pretreatment of amifostine and DRDE-07 enhanced the LC50 (a concentration producing 50% leakage of lactate dehydrogenase (LDH) or alanine aminotransferase (ALT)) of SM by 5.9- and 3.3-fold for LDH and 10.2- and 5.5-fold for ALT, respectively. Except DNA fragmentation, both these agents significantly attenuated the loss of intracellular K(+) and mitochondrial integrity (MTT assay), depletion of GSH levels, and histopathology produced by a toxic concentration (80 microM) of SM. However, when amifostine and DRDE-07 were introduced 2 h after SM, no significant protection was observed. SM (77.5 or 155 mg/kg) was also applied dermally on female albino mice and challenged by 0.20 LD50 (po) of amifostine, DRDE-06, DRDE-07, or DRDE-08 at -30 min, 0 min, or +6 h. Protection was observed only when the agents were administered at -30 min or 0 min; posttreatment (+6 h) did not offer any protection. The magnitude of in vivo protection was in the following order: DRDE-07 >or= amifostine > DRDE-08

  5. DNA-directed alkylating agents. 1. Structure-activity relationships for acridine-linked aniline mustards: consequences of varying the reactivity of the mustard.

    PubMed

    Gourdie, T A; Valu, K K; Gravatt, G L; Boritzki, T J; Baguley, B C; Wakelin, L P; Wilson, W R; Woodgate, P D; Denny, W A

    1990-04-01

    A series of DNA-targeted aniline mustards have been prepared, and their chemical reactivity and in vitro and in vivo cytotoxicity have been evaluated and compared with that of the corresponding simple aniline mustards. The alkylating groups were anchored to the DNA-intercalating 9-aminoacridine chromophore by an alkyl chain of fixed length attached at the mustard 4-position through a link group X, while the corresponding simple mustards possessed an electronically identical small group at this position. The link group was varied to provide a series of compounds of similar geometry but widely differing mustard reactivity. Variation in biological activity should then largely be a consequence of this varying reactivity. Rates of mustard hydrolysis in the two series related only to the electronic properties of the link group, with attachment of the intercalating chromophore having no effect. The cytotoxicities of the simple mustards correlated well with group electronic properties (with a 200-300-fold range in IC50S). The corresponding DNA-targeted mustards were much more potent (up to 100-fold), but their IC50 values varied much less with linker group electronic properties. Most of the DNA-targeted mustards showed in vivo antitumor activity, being both more active and more dose-potent than either the corresponding untargeted mustards and chlorambucil. These results show that targeting alkylating agents to DNA by attachment to DNA-affinic units may be a useful strategy.

  6. DNA-directed alkylating agents. 4. 4-anilinoquinoline-based minor groove directed aniline mustards.

    PubMed

    Gravatt, G L; Baguley, B C; Wilson, W R; Denny, W A

    1991-05-01

    A series of 4-anilinoquinoline-linked aniline mustards of widely varying mustard reactivity were prepared and evaluated for their antitumor activity. The compounds were designed as minor grove binding agents, where the aniline mustard ring is itself part of the DNA-binding ligand. While there was a general trend for cytotoxicity to correlate with mustard reactivity, this was much less pronounced than with untargeted mustards. The compounds were much more cytotoxic than the parent diols, and were also at least 10-fold more cytotoxic than the corresponding aniline mustards themselves. Comparative cell line studies suggested that the mechanism of cytotoxicity varied with mustard reactivity. The most reactive mustards cross-linked DNA, while cell killing by the less reactive compounds appeared to be by the formation of bulky monoadducts. The compounds were active but not particularly dose-potent against P388 leukemia in vivo. The modest potency may be related to their poor aqueous solubility, since the more soluble methyl quaternary salts were equally active at much lower doses.

  7. Long-term evaluation of the fate of sulfur mustard on dry and humid soils, asphalt, and concrete.

    PubMed

    Mizrahi, Dana M; Goldvaser, Michael; Columbus, Ishay

    2011-04-15

    The long-term fate of the blister agent sulfur mustard (HD, bis(2-chloroethyl)sulfide) was determined in a variety of commercial and natural matrices. HD was found to be extremely stable in dry matrices for over a year. The addition of 5% water to the matrices induced slow degradation of HD, which lasted several months. The major degradation product in sands and asphalt was found to be a sulfonium salt, S[CH(2)CH(2)S(+)(CH(2)CH(2)OH)(2)](2) (H-2TG). Red loam soil, which has not been examined before, exhibited strong interaction with HD, both in dry form and in the presence of water. Humid red loam soil gave rise to unique oxidative degradation products. On humid concrete HD degraded to a complex mixture of products, including vinyls. This may be attributed to the basic sites incorporated in concrete.

  8. Long-term evaluation of the fate of sulfur mustard on dry and humid soils, asphalt, and concrete.

    PubMed

    Mizrahi, Dana M; Goldvaser, Michael; Columbus, Ishay

    2011-04-15

    The long-term fate of the blister agent sulfur mustard (HD, bis(2-chloroethyl)sulfide) was determined in a variety of commercial and natural matrices. HD was found to be extremely stable in dry matrices for over a year. The addition of 5% water to the matrices induced slow degradation of HD, which lasted several months. The major degradation product in sands and asphalt was found to be a sulfonium salt, S[CH(2)CH(2)S(+)(CH(2)CH(2)OH)(2)](2) (H-2TG). Red loam soil, which has not been examined before, exhibited strong interaction with HD, both in dry form and in the presence of water. Humid red loam soil gave rise to unique oxidative degradation products. On humid concrete HD degraded to a complex mixture of products, including vinyls. This may be attributed to the basic sites incorporated in concrete. PMID:21438603

  9. Long-term effects of sulfur mustard on civilians’ mental health 20 years after exposure (The Sardasht-Iran Cohort Study)

    PubMed Central

    2013-01-01

    Background Sulfur mustard (SM) is an alkylating agent that induces short and long term toxicity on various organs. The aim of this study was to assess the long-term psychological symptoms among samples of exposed to sulfur mustard gas compared with unexposed civilians 20 years after exposure. Methods This historical cohort study was conducted on 495 civilians of Sardasht and Rabat in two age matched groups, including 367 sulfur mustard exposed participants from Sardasht and 128 unexposed subjects from Rabat. Psychological symptoms was assessed using the Symptom Check List-90 Revised (SCL-90-R) including measures of somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism providing three global distress indices namely: Global Severity Index (GSI), Positive Symptom Total (PST) and Positive Symptom Distress Index (PSDI). Comparison was made between exposed and unexposed civilians. Results There were significant differences in somatization (P = 0.002), obsessive-compulsive (P = 0.031), depression (P = 0.007), anxiety (P = 0.042), and hostility (P = 0.002), between the exposed and unexposed groups. In addition there were significant differences between two groups concerning the GSI (P = 0.045) and the PSDI (P < 0.001). The differences between two groups in other subscales were not significant. Conclusions The findings from this study showed that civilians who exposed to sulfur mustard gas were suffering from a number of psychological symptoms even 20 years after exposure. Providing mental health services and more resource allocation for this community are highly recommended. PMID:23618038

  10. Structural changes in hair follicles and sebaceous glands of hairless mice following exposure to sulfur mustard.

    PubMed

    Joseph, Laurie B; Heck, Diane E; Cervelli, Jessica A; Composto, Gabriella M; Babin, Michael C; Casillas, Robert P; Sinko, Patrick J; Gerecke, Donald R; Laskin, Debra L; Laskin, Jeffrey D

    2014-06-01

    Sulfur mustard (SM) is a bifunctional alkylating agent causing skin inflammation, edema and blistering. A hallmark of SM-induced toxicity is follicular and interfollicular epithelial damage. In the present studies we determined if SM-induced structural alterations in hair follicles and sebaceous glands were correlated with cell damage, inflammation and wound healing. The dorsal skin of hairless mice was treated with saturated SM vapor. One to seven days later, epithelial cell karyolysis within the hair root sheath, infundibulum and isthmus was apparent, along with reduced numbers of sebocytes. Increased numbers of utriculi, some with connections to the skin surface, and engorged dermal cysts were also evident. This was associated with marked changes in expression of markers of DNA damage (phospho-H2A.X), apoptosis (cleaved caspase-3), and wound healing (FGFR2 and galectin-3) throughout pilosebaceous units. Conversely, fatty acid synthase and galectin-3 were down-regulated in sebocytes after SM. Decreased numbers of hair follicles and increased numbers of inflammatory cells surrounding the utriculi and follicular cysts were noted within the wound 3-7 days post-SM exposure. Expression of phospho-H2A.X, cleaved caspase-3, FGFR2 and galectin-3 was decreased in dysplastic follicular epidermis. Fourteen days after SM, engorged follicular cysts which expressed galectin-3 were noted within hyperplastic epidermis. Galectin-3 was also expressed in basal keratinocytes and in the first few layers of suprabasal keratinocytes in neoepidermis formed during wound healing indicating that this lectin is important in the early stages of keratinocyte differentiation. These data indicate that hair follicles and sebaceous glands are targets for SM in the skin.

  11. Nuclear magnetic resonance analysis of the solution and solvolysis of sulfur mustard in deuterium oxide.

    PubMed

    Logan, Thomas P; Sartori, David A

    2003-01-01

    Our laboratory performs in vitro experiments in which cell cultures are exposed to sulfur mustard (HD) to investigate the toxicity of this agent of chemical warfare. To perform these experiments, it is important to know the rate of hydrolysis of HD in order to calculate the concentrations of HD and its hydrolysis products during the experiment. Researchers have previously investigated the kinetics and mechanism of the hydrolysis of HD using a variety of methods. In the present study, we used nuclear magnetic resonance (NMR) spectroscopy and gas chromatography/mass spectrometry (GC/MS) to investigate HD's dissolution and solvolysis in deuterium oxide (D 2 O) at 2 mM. We followed activity in proton spectrums and determined the half-life (t 1/2) of HD to be 7.0 +/- 0.5 min in four experiments performed at 22 degrees C. In addition, we determined the t 1/2 of HD in D 2 O containing 0.17 M sodium chloride to be 24 +/- 1 min in three experiments performed at 22 degrees C. As further proof of the existence of HD dissolved into D 2 O, deutero-hexane was used to extract the D 2 O HD solution. The resulting deutero-hexane solution was studied by 1 H NMR and GC/MS. The results obtained match those received from a standard deutero-hexane HD solution. These results demonstrate that HD can be identified in D 2 O with proton NMR and that proton NMR data can be used to monitor the subsequent solvolysis of HD. PMID:20021164

  12. Medical documentation, bioanalytical evidence of an accidental human exposure to sulfur mustard and general therapy recommendations.

    PubMed

    Steinritz, Dirk; Striepling, Enno; Rudolf, Klaus-Dieter; Schröder-Kraft, Claudia; Püschel, Klaus; Hullard-Pulstinger, Andreas; Koller, Marianne; Thiermann, Horst; Gandor, Felix; Gawlik, Michael; John, Harald

    2016-02-26

    Sulfur mustard (SM) is a chemical warfare agent (CWA) that was first used in World War I and in several military conflicts afterwards. The threat by SM is still present even today due to remaining stockpiles, old and abandoned remainders all over the world as well as to its ease of synthesis. CWA are banned by the Chemical Weapons Convention (CWC) interdicting their development, production, transport, stockpiling and use and are subjected to controlled destruction. The present case report describes an accidental exposure of three workers that occurred during the destruction of SM. All exposed workers presented a characteristic SM-related clinical picture that started about 4h after exposure with erythema and feeling of tension of the skin at the upper part of the body. Later on, superficial blister and a burning phenomenon of the affected skin areas developed. Similar symptoms occurred in all three patients differing severity. One patient presented sustained skin affections at the gluteal region while another patient came up with affections of the axilla and genital region. Fortunately, full recovery was observed on day 56 after exposure except some little pigmentation changes that were evident even on day 154 in two of the patients. SM-exposure was verified for all three patients using bioanalytical GC MS and LC MS/MS based methods applied to urine and plasma. Urinary biotransformation products of the β-lyase pathway were detected until 5 days after poisoning whereas albumin-SM adducts could be found until day 29 underlining the beneficial role of adduct detection for post-exposure verification. In addition, we provide general recommendations for management and therapy in case of SM poisoning.

  13. Medical documentation, bioanalytical evidence of an accidental human exposure to sulfur mustard and general therapy recommendations.

    PubMed

    Steinritz, Dirk; Striepling, Enno; Rudolf, Klaus-Dieter; Schröder-Kraft, Claudia; Püschel, Klaus; Hullard-Pulstinger, Andreas; Koller, Marianne; Thiermann, Horst; Gandor, Felix; Gawlik, Michael; John, Harald

    2016-02-26

    Sulfur mustard (SM) is a chemical warfare agent (CWA) that was first used in World War I and in several military conflicts afterwards. The threat by SM is still present even today due to remaining stockpiles, old and abandoned remainders all over the world as well as to its ease of synthesis. CWA are banned by the Chemical Weapons Convention (CWC) interdicting their development, production, transport, stockpiling and use and are subjected to controlled destruction. The present case report describes an accidental exposure of three workers that occurred during the destruction of SM. All exposed workers presented a characteristic SM-related clinical picture that started about 4h after exposure with erythema and feeling of tension of the skin at the upper part of the body. Later on, superficial blister and a burning phenomenon of the affected skin areas developed. Similar symptoms occurred in all three patients differing severity. One patient presented sustained skin affections at the gluteal region while another patient came up with affections of the axilla and genital region. Fortunately, full recovery was observed on day 56 after exposure except some little pigmentation changes that were evident even on day 154 in two of the patients. SM-exposure was verified for all three patients using bioanalytical GC MS and LC MS/MS based methods applied to urine and plasma. Urinary biotransformation products of the β-lyase pathway were detected until 5 days after poisoning whereas albumin-SM adducts could be found until day 29 underlining the beneficial role of adduct detection for post-exposure verification. In addition, we provide general recommendations for management and therapy in case of SM poisoning. PMID:26321678

  14. Downregulation of super oxide dismutase level in protein might be due to sulfur mustard induced toxicity in lung.

    PubMed

    Mirbagheri, Leila; Habibi Roudkenar, Mehryar; Imani Fooladi, Abbas Ali; Ghanei, Mostafa; Nourani, Mohammad Reza

    2013-05-15

    Sulfur mustard (SM) has been identified as an important chemical weapon. During the Iran-Iraq war of 1980-88, the extensive usage of SM against Iranian civilians and military forces was proven. This agent has been shown to cause severe damage mainly in the skin, eyes, lungs, and respiratory tract in Iranian veterans. The most common disease is bronchiolitis obliterans (BO)). SM increases the endogenous production of reactive oxygen species (ROS). Superoxide dismutases (SODs) are known as protective antioxidants against the harmful effects of ROS. Twenty exposed SM individuals (43.2±6.4 years), and 10 normal controls (41.3±2.5 years) were enrolled in this study. Evaluation of SODs was performed by semiquantitative RT-PCR and immunohistochemistry. Our results demonstrated that CuZnSOD and MnSOD mRNA were up-regulated 2.79±1.09 and 2.49±1.11 folds, respectively in SM-injured patients in comparison with control levels. In contrast, Immunohistochemistry results showed downregulation of CuZnSOD protein expression in SM injured patients. Our results revealed that SODs may play an important role in cellular protection against oxidative stress due to mustard gas toxicity in airway wall of SM exposed patients.

  15. Loss of expression of TGF-βs and their receptors in chronic skin lesions induced by sulfur mustard as compared with chronic contact dermatitis patients

    PubMed Central

    2011-01-01

    Background Sulfur mustard (SM) is a blister-forming agent that has been used as a chemical weapon. Sulfur mustard can cause damage in various organs, especially the skin, respiratory system, and eyes. Generally, the multiple complications of mustard gas result from its alkalizing potency; it reacts with cellular components like DNA, RNA, proteins, and lipid membranes. TGF-β is a multi-functional cytokine with multiple biological effects ranging from cell differentiation and growth inhibition to extracellular matrix stimulation, immunosuppression, and immunomodulation. TGF-β has 3 isoforms (TGF-β 1, 2, 3) and its signaling is mediated by its receptors: R1, R2 and intracellular Smads molecules. TGF-β has been shown to have anti-inflammatory effects. TGF-βs and their receptors also have an important role in modulation of skin inflammation, proliferation of epidermal cells, and wound healing, and they have been implicated in different types of skin inflammatory disorders. Methods Seventeen exposed SM individuals (48.47 ± 9.3 years), 17 chronic dermatitis patients (46.52 ± 14.6 years), and 5 normal controls (44.00 ± 14.6 years) were enrolled in this study. Evaluation of TGF-βs and their receptors expressions was performed by semiquantitative RT-PCR. Only TGF1was analyzed immunohistochemically. Results Our results showed significant decreases in the expression percentages of TGF-β 1, 2 and R1, R2 in chemical victims in comparison with chronic dermatitis and normal subjects and significant decreases in the intensity of R1 and R2 expressions in chemical victims in comparison with chronic dermatitis and normal controls. (P value < 0.05) Conclusions TGF-βs and their receptors appear to have a noticeable role in chronic inflammatory skin lesions caused by sulfur mustard. PMID:21235789

  16. Influence of sulfur and cadmium on antioxidants, phytochelatins and growth in Indian mustard

    PubMed Central

    Bashir, Humayra; Ibrahim, Mohamed M.; Bagheri, Rita; Ahmad, Javed; Arif, Ibrahim A.; Baig, M. Affan; Qureshi, M. Irfan

    2015-01-01

    Soils in many parts of the world are contaminated with heavy metals, leading to multiple, deleterious effects on plants and threats to world food production efficiency. Cadmium (Cd) is one such metal, being toxic at relatively low concentrations as it is readily absorbed and translocated in plants. Sulfur-rich compounds are critical to the impact of Cd toxicity, enabling plants to increase their cellular defence and/or sequester Cd into vacuoles mediated by phytochelatins (PCs). The influence of sulfur on Cd-induced stress was studied in the hyperaccumulator plant Indian mustard (Brassica juncea) using two sulfur concentrations (+S, 300 µM SO42− and S-deficient −S, 30μMSO42−) with and without the addition of Cd (100 µM CdCl2) at two different time intervals (7 and 14 days after treatment). Compared with control plants (+S/−Cd), levels of oxidative stress were higher in S-deficient (−S/−Cd) plants, and greatest in S-deficient Cd-treated (−S/+Cd) plants. However, additional S (+S/+Cd) helped plants cope with oxidative stress. Superoxide dismutase emerged as a key player against Cd stress under both −S and +S conditions. The activity of ascorbate peroxidase, glutathione reductase and catalase declined in Cd-treated and S-deficient plants, but was up-regulated in the presence of sulfur. Sulfur deficiency mediated a decrease in ascorbate and glutathione (GSH) content but changes in ascorbate (reduced : oxidized) and GSH (reduced : oxidized) ratios were alleviated by sulfur. Our data clearly indicate that a sulfur pool is needed for synthesis of GSH, non-protein thiols and PCs and is also important for growth. Sulfur-based defence mechanisms and the cellular antioxidant pathway, which are critical for tolerance and growth, collapsed as a result of a decline in the sulfur pool. PMID:25587194

  17. Influence of sulfur and cadmium on antioxidants, phytochelatins and growth in Indian mustard.

    PubMed

    Bashir, Humayra; Ibrahim, Mohamed M; Bagheri, Rita; Ahmad, Javed; Arif, Ibrahim A; Baig, M Affan; Qureshi, M Irfan

    2015-01-01

    Soils in many parts of the world are contaminated with heavy metals, leading to multiple, deleterious effects on plants and threats to world food production efficiency. Cadmium (Cd) is one such metal, being toxic at relatively low concentrations as it is readily absorbed and translocated in plants. Sulfur-rich compounds are critical to the impact of Cd toxicity, enabling plants to increase their cellular defence and/or sequester Cd into vacuoles mediated by phytochelatins (PCs). The influence of sulfur on Cd-induced stress was studied in the hyperaccumulator plant Indian mustard (Brassica juncea) using two sulfur concentrations (+S, 300 µM [Formula: see text] and S-deficient -S, [Formula: see text]) with and without the addition of Cd (100 µM CdCl2) at two different time intervals (7 and 14 days after treatment). Compared with control plants (+S/-Cd), levels of oxidative stress were higher in S-deficient (-S/-Cd) plants, and greatest in S-deficient Cd-treated (-S/+Cd) plants. However, additional S (+S/+Cd) helped plants cope with oxidative stress. Superoxide dismutase emerged as a key player against Cd stress under both -S and +S conditions. The activity of ascorbate peroxidase, glutathione reductase and catalase declined in Cd-treated and S-deficient plants, but was up-regulated in the presence of sulfur. Sulfur deficiency mediated a decrease in ascorbate and glutathione (GSH) content but changes in ascorbate (reduced : oxidized) and GSH (reduced : oxidized) ratios were alleviated by sulfur. Our data clearly indicate that a sulfur pool is needed for synthesis of GSH, non-protein thiols and PCs and is also important for growth. Sulfur-based defence mechanisms and the cellular antioxidant pathway, which are critical for tolerance and growth, collapsed as a result of a decline in the sulfur pool. PMID:25587194

  18. Influence of sulfur and cadmium on antioxidants, phytochelatins and growth in Indian mustard.

    PubMed

    Bashir, Humayra; Ibrahim, Mohamed M; Bagheri, Rita; Ahmad, Javed; Arif, Ibrahim A; Baig, M Affan; Qureshi, M Irfan

    2015-01-12

    Soils in many parts of the world are contaminated with heavy metals, leading to multiple, deleterious effects on plants and threats to world food production efficiency. Cadmium (Cd) is one such metal, being toxic at relatively low concentrations as it is readily absorbed and translocated in plants. Sulfur-rich compounds are critical to the impact of Cd toxicity, enabling plants to increase their cellular defence and/or sequester Cd into vacuoles mediated by phytochelatins (PCs). The influence of sulfur on Cd-induced stress was studied in the hyperaccumulator plant Indian mustard (Brassica juncea) using two sulfur concentrations (+S, 300 µM [Formula: see text] and S-deficient -S, [Formula: see text]) with and without the addition of Cd (100 µM CdCl2) at two different time intervals (7 and 14 days after treatment). Compared with control plants (+S/-Cd), levels of oxidative stress were higher in S-deficient (-S/-Cd) plants, and greatest in S-deficient Cd-treated (-S/+Cd) plants. However, additional S (+S/+Cd) helped plants cope with oxidative stress. Superoxide dismutase emerged as a key player against Cd stress under both -S and +S conditions. The activity of ascorbate peroxidase, glutathione reductase and catalase declined in Cd-treated and S-deficient plants, but was up-regulated in the presence of sulfur. Sulfur deficiency mediated a decrease in ascorbate and glutathione (GSH) content but changes in ascorbate (reduced : oxidized) and GSH (reduced : oxidized) ratios were alleviated by sulfur. Our data clearly indicate that a sulfur pool is needed for synthesis of GSH, non-protein thiols and PCs and is also important for growth. Sulfur-based defence mechanisms and the cellular antioxidant pathway, which are critical for tolerance and growth, collapsed as a result of a decline in the sulfur pool.

  19. Comparison of fixation and processing methods for hairless guinea pig skin following sulfur mustard exposure. (Reannouncement with new availability information)

    SciTech Connect

    Bryant, M.A.; Braue Jr, E.H.

    1992-12-31

    Ten anesthetized hairless guinea pigs Crl:IAF(HA)BR were exposed to 10 pi of neat sulfur mustard (HD) in a vapor cup on their skin for 7 min. At 24 h postexposure, the guinea pigs were euthanatized and skin sections taken for histologic evaluation. The skin was fixed using either 10% neutral buffered formalin (NBF), McDowell Trump fixative (4CF-IG), Zenker`s formol-saline (Helly`s fluid), or Zenker`s fluid. Fixed skin sections were cut in half: one half was embedded in paraffin and the other half in plastic (glycol methacrylate). Paraffin-embedded tissue was stained with hematoxylin and eosin; plastic-embedded tissue was stained with Lee`s methylene blue basic fuchsin. Skin was also frozen unfixed, sectioned by cryostat, and stained with pinacyanole. HD-exposed skin was evaluated histologically for the presence of epidermal and follicular necrosis, microblister formation, epidermitis, and intracellular edema to determine the optimal fixation and embedding method for lesion preservation. The percentage of histologic sections with lesions varied little between fixatives and was similar for both paraffin and plastic embedding material. Plastic-embedded sections were thinner, allowing better histologic evaluation, but were more difficult to stain. Plastic embedding material did not infiltrate tissue fixed in Zenker`s fluid or Zenker`s formol-saline. Frozen tissue sections were prepared in the least processing time and lesion preservation was comparable to fixed tissue. It was concluded that standard histologic processing using formalin fixation and paraffin embedding is adequate for routine histopathological evaluation of HD skin lesions in the hairless guinea pig.... Sulfur mustard, Vesicating agents, Pathology, Hairless guinea pig model, Fixation.

  20. Development of the sulfur mustard resistant keratinocyte cell line HaCaT/SM.

    PubMed

    Schmidt, Annette; Steinritz, Dirk; Thiermann, Horst

    2016-02-26

    Pairs of corresponding cytotoxic drug sensitive and resistant cell lines are powerful tools to develop treatment strategies. Developing cytotoxic drug resistant cell lines is a well-established method in cancer research. In more than fifty years of sulfur mustard (SM) resistant research such a cell pair has never been produced. Hereinafter we describe the first successful approach to develop a SM resistant keratinocyte cell line. Starting with the SM sensitive keratinocyte cell line HaCaT we used a strategy of continuous exposure with gradually increased concentrations. Cells were cultured in total for more than 40 months starting with an initial concentration of 0.07μM SM twice a week up to a final concentration of 7.2μM SM. The achieved cell line HaCaT/SM had an LC50 resistance increase of 4.7-fold and an LC90 increase of 8.2-fold. Hereinafter we demonstrate the production of the first sulfur mustard (SM) resistant cell line. The new achieved cell line called HaCaT/SM is able to tolerate a continuous exposure of an SM concentration, which is associated with an inhibitory effect of 93% within the original HaCaT cells, which were used as starting point.

  1. Phenidone and hydroxyurea reduce sulfur mustard-increased proteolysis in hairless guinea pig skin

    SciTech Connect

    Cowan, F.M.; Bongiovanni, R.; Broomfield, C.A.; Schulz, S.M.; Smith, W.J.

    1995-12-31

    Increased proteolytic activity at the dermal-epidermal junction is postulated as being involved in sulfur-mustard-induced cutaneous injury. Homogenates of skin punch biopsy specimens from the skin of hairless guinea pig at 6, 9, 12, and 24 h after a 7 min vapor cup exposure to sulfur mustard (HD) demonstrated enhanced proteolytic activity. Homogenates from the biopsy specimens of exposed animals produced from 3 to 10 times the hydrolysis of the chromogenic peptide substrate Chromzym TH (tosyl-gly-pro-arg-p-nitrani-lide) and human elastase substrate N-methoxysuccinyl-ala- ala-pro-val-p-nitranilide than did the homogenates from control samples. In this study HD-increased proteolysis of the TH substrate by extracts of hairless guinea pig skin biopsies was nearly eliminated by systemic treatment with hydroxyurea and greatly reduced by topical application of the anti-inflammatory compound phenidone. Compounds that reduce HD-increased proteolytic activity, such as phenidone and hydroxyurea, can serve as probes to examine the role of proteolysis in HD-induced pathology. HD-increased proteolysis provides a biochemical correlate for investigating cutaneous exposure to HD. Increased proteolysis may therefore serve as a biomarker for HD-induced pathology that might be used as an index of efficacy for potential treatment compounds.

  2. Effect of sulfur mustard on mast cells in hairless guinea pig skin

    SciTech Connect

    Graham, J.S.; Bryant, M.A.; Braue, E.H.

    1993-05-13

    The skin of 24 anesthetized hairless guinea pigs was exposed to saturated sulfur mustard (bis-2-chloroethyl sulfide; HD) for 5 and 7 minutes using 14-mm diameter vapor cups. Animals were euthanatized 24 hours after exposure and skin specimens taken for morphometric evaluation of granulated mast cells with an image analysis system (IAS). Tissue specimens were processed in paraffin, sectioned at 5 microns and stained with Unna's stain for mast cells. The number of granulated mast cells and the area occupied by mast cell granules was determined. There were significantly fewer mast cells (p < 0.05) in either HD exposure group than in sham-exposed animals, with significantly fewer mast cells in the 7-minute than the 5-minute HD group. There were also significantly smaller areas occupied by granules in either HD exposure group than in sham-exposed animals. HD-induced lesions in the hairless guinea pig have shown signs of an inflammatory response, and with their granules of vasoactive histamine, mast cells might be expected to play a role in HD-induced injury. Changes in mast cells exposed to low sulfur mustard levels, as detected by an IAS, may serve as an early marker for cutaneous damage, which might not be as easily determined with routine light microscopy.

  3. Mutagenicity and antimutagenicity studies of DRDE-07 and its analogs against sulfur mustard in the in vitro Ames Salmonella/microsome assay.

    PubMed

    Vijayan, Vinod; Pathak, Uma; Meshram, Ghansham Pundilikji

    2014-10-01

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM), a chemical warfare agent, is classified as a class I human carcinogen by IARC. No effective antidote against this agent is available. The synthetic aminothiol, amifostine, earlier known as WR-2721, has been extensively used as a chemical radioprotector for normal tissues in cancer radiotherapy and chemotherapy. SM is a radiomimetic agent; this prompted us to evaluate the protective efficacy of amifostine and three of its analogs, DRDE-07 [S-2(2-aminoethylamino) ethyl phenyl sulphide], DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide] and DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide], against sulfur mustard-induced mutagenicity in the Ames Salmonella/microsome assay. The antidotes were also evaluated for possible mutagenic activity. DRDE-07 was mutagenic in strain TA104 in the absence of S9; DRDE-30 was mutagenic in strain TA100; amifostine and DRDE-35 did not show mutagenic activity in any of the five tester strains used. SM is mutagenic in strains TA97a and TA102, with or without S9 activation. In the antimutagenicity studies, DRDE-07 and DRDE-35 showed promising antimutagenic activity against SM in the absence of S9, in comparison to amifostine. DRDE-07 and DRDE-35 are promising protective agents against SM-induced mutagenicity.

  4. Macromolecular metabolism of a differentiated rat keratinocyte culture system following exposure to sulfur mustard

    SciTech Connect

    Vaughan, F.L.; Zaman, S.; Scavarelli, R.; Bernstein, I.A.

    1988-01-01

    A method for producing a stratified, squamous epithelium in vitro by cultivating rat keratinocytes on nylon membranes has been developed in this laboratory. This epidermal-like culture is being used to obtain a better understanding of the mechanism of skin vesication after topical exposure to the sulfur mustard bis(beta-chloroethyl) sulfide (BCES) dissolved in a selected solvent. Radiolabeled macromolecular precursors (thymidine, uridine, and leucine) have been used to study the effect of BCES on the synthesis of DNA, RNA, and protein, respectively, after topical exposure to the mustard at concentrations of 0.01-500 nmol/cm2 dissolved in 70% dimethyl sulfoxide (DMSO). From these and other studies it has been determined that exposure to even the low concentration of 0.01 nmol BCES/cm2 for 30 min results in significant inhibition of (/sup 3/H)thymidine incorporation, although complete recovery occurs by 24 h. Significant inhibition of (/sup 3/H)uridine and (/sup 14/C)leucine incorporation is observed only after exposure to much higher concentrations of BCES (10-500 nmol/cm2). This suggests a very early lesion in macromolecular metabolism with DNA being the primary target.

  5. Cancer Events After Acute or Chronic Exposure to Sulfur Mustard: A Review of the Literature

    PubMed Central

    Razavi, Seyed Mansour; Abdollahi, Mohammad; Salamati, Payman

    2016-01-01

    Background: Sulfur mustard (SM) has been considered as a carcinogen in the laboratory studies. However, its carcinogenic effects on human beings were not well discussed. The main purpose of our study is to assess carcinogenesis of SM following acute and/or chronic exposures in human beings. Methods: The valid scientific English and Persian databases including PubMed, Web of Science, Scopus, IranMedex, and Irandoc were searched and the collected papers reviewed. The used keywords were in two languages: English and Persian. The inclusion criteria were the published original articles indexed in above-mentioned databases. Eleven full-texts out of 296 articles were found relevant and then assessed. Results: Studies on the workers of the SM factories during the World Wars showed that the long-term chronic exposure to mustards can cause a variety of cancers in the organs such as oral cavity, larynx, lung, and skin. Respiratory system was the most important affected system. Acute single exposure to SM was assumed as the carcinogenic inducer in the lung and blood and for few cancers including basal cell carcinoma and squamous cell carcinoma. Conclusions: SM is a proven carcinogen in chronic situations although data are not enough to strongly conclude in acute exposure. PMID:27280012

  6. Evidence of VX nerve agent use from contaminated white mustard plants

    PubMed Central

    Gravett, Matthew R.; Hopkins, Farrha B.; Self, Adam J.; Webb, Andrew J.; Timperley, Christopher M.; Baker, Matthew J.

    2014-01-01

    The Chemical Weapons Convention prohibits the development, production, acquisition, stockpiling, retention, transfer or use of chemical weapons by Member States. Verification of compliance and investigations into allegations of use require accurate detection of chemical warfare agents (CWAs) and their degradation products. Detection of CWAs such as organophosphorus nerve agents in the environment relies mainly upon the analysis of soil. We now present a method for the detection of the nerve agent VX and its hydrolysis products by gas chromatography and liquid chromatography mass spectrometry of ethanol extracts of contaminated white mustard plants (Sinapis alba) which retained the compounds of interest for up to 45 days. VX is hydrolysed by the plants to ethyl methylphosphonic acid and then to methylphosphonic acid. The utility of white mustard as a nerve agent detector and remediator of nerve agent-polluted sites is discussed. The work described will help deter the employment of VX in conflict. PMID:25104906

  7. Zinc oxide nanocubes as a destructive nanoadsorbent for the neutralization chemistry of 2-chloroethyl phenyl sulfide: A sulfur mustard simulant.

    PubMed

    Kiani, Armin; Dastafkan, Kamran

    2016-09-15

    Zinc oxide nanocubes were surveyed for their destructive turn-over to decontaminate 2-chloro ethyl phenyl sulfide, a sulfur mustard simulant. Prior to the reaction, nanocubes were prepared through sol-gel method using monoethanolamine, diethylene glycol, and anhydrous citric acid as the stabilizing, cross linking/structure directing agents, respectively. The formation of nanoscale ZnO, the cubic morphology, crystalline structure, and chemical-adsorptive characteristics were certified by FESEM-EDS, TEM-SAED, XRD, FTIR, BET-BJH, H2-TPR, and ESR techniques. Adsorption and destruction reactions were tracked by GC-FID analysis in which the effects of polarity of the media, reaction time, and temperature on the destructive capability of the surface of nanocubes were investigated and discussed. Results demonstrated that maximum neutralization occurred in n-heptane solvent after 1/2h at 55°C. Kinetic study construed that the neutralization reaction followed the pseudo-second order model with a squared correlation coefficient and rate constant of 0.9904 and 0.00004gmg(-1)s(-1), respectively. Furthermore, GC-MS measurement confirmed the formation of 2-hydroxy ethyl phenyl sulfide (2-HEPS) and phenyl vinyl sulfide (PVS) as neutralization products that together with Bronsted and Lewis acid/base approaches exemplify the role of hydrolysis and elimination mechanisms on the surface of zinc oxide nanocubes.

  8. Nitrogen mustard hydrochloride-induced acute respiratory failure and myelosuppression: A case report

    PubMed Central

    ZHANG, XIAOJUAN; ZHANG, ZHIDAN; CHEN, SONG; ZHAO, DONGMEI; ZHANG, FANGXIAO; HU, ZIWEI; XIAO, FENG; MA, XIAOCHUN

    2015-01-01

    Nitrogen mustards are chemical agents that are similar to sulfur mustards, with similar toxicities. The present study describes a case of nitrogen mustard-induced acute respiratory failure and myelosuppression in a 33-year-old man. The patient, who was accidentally exposed to nitrogen mustard hydrochloride in a pharmaceutical factory, exhibited severe inhalation injury and respiratory symptoms. Laboratory tests revealed reduced white blood cell counts and lowered platelet levels during the first 6 days after the skin exposure to nitrogen mustard. Following treatment with mechanical ventilation, immunity-enhancing agents and nutritional supplements for 1 month, the patient successfully recovered and was released from hospital. PMID:26622480

  9. The Role of Fas-FasL Signaling Pathway in Induction of Apoptosis in Patients with Sulfur Mustard-Induced Chronic Bronchiolitis

    PubMed Central

    Pirzad, Gila; Jafari, Mahvash; Tavana, Sasan; Sadrayee, Homayoon; Ghavami, Saeid; Shajiei, Arezoo; Ghanei, Mostafa

    2010-01-01

    Sulfur mustard (SM) is an alkylating agent that induces apoptosis and necrosis in cells. Fas-Fas ligand (FasL) interaction could induce apoptosis as well. In this study, it was hypothesized that apoptosis might play an important role in the pathogenesis of SM-induced lung injury via Fas-FasL signaling pathway. In a case-control study, Fas and FasL levels, caspase-3 activity and percent of apoptotic cells were measured in bronchoalveolar lavage (BAL) fluid of patients 20 years after exposure to sulfur mustard and compared with the control group. Results show that Fas and FasL levels were significantly higher in BAL fluid cells in patients group compared with the control (P = .001). No significant differences were observed between mild and moderate-severe groups. BAL fluid cells caspase-3 activity was not significantly different among the mild, moderate-severe, and control groups. The data suggest that Fas-FasL-induced apoptosis was impaired in BAL fluid cells of SM-exposed patients which might be one of the initiators of pathogenesis in SM-induced lung injury in these patients. PMID:21317984

  10. Atopic dermatitis-associated protein interaction network lead to new insights in chronic sulfur mustard skin lesion mechanisms.

    PubMed

    Amiri, Mojtaba; Jafari, Mohieddin; Azimzadeh Jamalkandi, Sadegh; Davoodi, Seyed-Masoud

    2013-10-01

    Chronic sulfur mustard skin lesions (CSMSLs) are the most common complications of sulfur mustard exposure; however, its mechanism is not completely understood.According to clinical signs, there are similarities between CSMSL and atopic dermatitis (AD). In this study, proteomic results of AD were reviewed and the AD-associated protein-protein interaction network (PIN) was analyzed. According to centrality measurements, 16 proteins were designated as pivotal elements in AD mechanisms. Interestingly, most of these proteins had been reported in some sulfur mustard-related studies in late and acute phases separately. Based on the gene enrichment analysis, aging, cell response to stress, cancer, Toll- and NOD-like receptor and apoptosis signaling pathways have the greatest impact on the disease. By the analysis of directed protein interaction networks, it is concluded that TNF, IL-6, AKT1, NOS3 and CDKN1A are the most important proteins. It is possible that these proteins play role in the shared complications of AD and CSMSL including xerosis and itching. PMID:24117202

  11. Mustards and Vesicants

    SciTech Connect

    Young, Robert A; Bast, Cheryl B

    2009-01-01

    Vesicants (sulfur mustards, lewisite, and nitrogen mustards) are chemicals that cause blistering of the skin. Developed as chemical warfare agents, their biological activity is complex and not fully understood. These vesicants in liquid or vapor form are capable of causing injury to most any tissue. Contact with the skin results in erythema and blistering. Exposure to vapors produces ocular and respiratory effects which occur at exposures below those causing dermal effects. Systemic and long-lasting effects may occur, especially following acute exposures that result in severe injury. Multi-organ involvement and fluid loss shock resulting in death may follow severe exposures. As alkylating agents, all of the mustards are known or potential carcinogens. The carcinogenic potential of lewisite in humans is equivocal. Toxicity data in animals are available for the vesicants although data on sulfur mustard and lewisite are more extensive than for the nitrogen mustards. Data from tests with human volunteers and occupational exposure information are also available. These data collectively have provided a basis for the development of exposure standards, guidelines, and criteria for use in emergency planning and emergency response, and remediation efforts. The mode of action of the vesicants is complex, not fully understood, and represents an ongoing area of investigation especially with respect to treatment of vesicant-induced injury. Prevention of exposure and decontamination are critical initial steps in eliminating or minimizing injury. With the exception of arsenic chelating antidotes (e.g., British anti-lewisite; BAL) for lewisite, no antidotes exist for the vesicant agents. Medical management currently focuses on palliative treatment of signs and symptoms.

  12. The Mixture of Salvianolic Acids from Salvia miltiorrhiza and Total Flavonoids from Anemarrhena asphodeloides Attenuate Sulfur Mustard-Induced Injury.

    PubMed

    Li, Jianzhong; Chen, Linlin; Wu, Hongyuan; Lu, Yiming; Hu, Zhenlin; Lu, Bin; Zhang, Liming; Chai, Yifeng; Zhang, Junping

    2015-01-01

    Sulfur mustard (SM) is a vesicating chemical warfare agent used in numerous military conflicts and remains a potential chemical threat to the present day. Exposure to SM causes the depletion of cellular antioxidant thiols, mainly glutathione (GSH), which may lead to a series of SM-associated toxic responses. MSTF is the mixture of salvianolic acids (SA) of Salvia miltiorrhiza and total flavonoids (TFA) of Anemarrhena asphodeloides. SA is the main water-soluble phenolic compound in Salvia miltiorrhiza. TFA mainly includes mangiferin, isomangiferin and neomangiferin. SA and TFA possess diverse activities, including antioxidant and anti-inflammation activities. In this study, we mainly investigated the therapeutic effects of MSTF on SM toxicity in Sprague Dawley rats. Treatment with MSTF 1 h after subcutaneous injection with 3.5 mg/kg (equivalent to 0.7 LD50) SM significantly increased the survival levels of rats and attenuated the SM-induced morphological changes in the testis, small intestine and liver tissues. Treatment with MSTF at doses of 60 and 120 mg/kg caused a significant (p<0.05) reversal in SM-induced GSH depletion. Gene expression profiles revealed that treatment with MSTF had a dramatic effect on gene expression changes caused by SM. Treatment with MSTF prevented SM-induced differential expression of 93.8% (973 genes) of 1037 genes. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 36 pathways, such as the MAPK signaling pathway, pathways in cancer, antigen processing and presentation. These data suggest that MSTF attenuates SM-induced injury by increasing GSH and targeting multiple pathways, including the MAPK signaling pathway, as well as antigen processing and presentation. These results suggest that MSTF has the potential to be used as a potential therapeutic agent against SM injuries. PMID:26501264

  13. The Mixture of Salvianolic Acids from Salvia miltiorrhiza and Total Flavonoids from Anemarrhena asphodeloides Attenuate Sulfur Mustard-Induced Injury.

    PubMed

    Li, Jianzhong; Chen, Linlin; Wu, Hongyuan; Lu, Yiming; Hu, Zhenlin; Lu, Bin; Zhang, Liming; Chai, Yifeng; Zhang, Junping

    2015-01-01

    Sulfur mustard (SM) is a vesicating chemical warfare agent used in numerous military conflicts and remains a potential chemical threat to the present day. Exposure to SM causes the depletion of cellular antioxidant thiols, mainly glutathione (GSH), which may lead to a series of SM-associated toxic responses. MSTF is the mixture of salvianolic acids (SA) of Salvia miltiorrhiza and total flavonoids (TFA) of Anemarrhena asphodeloides. SA is the main water-soluble phenolic compound in Salvia miltiorrhiza. TFA mainly includes mangiferin, isomangiferin and neomangiferin. SA and TFA possess diverse activities, including antioxidant and anti-inflammation activities. In this study, we mainly investigated the therapeutic effects of MSTF on SM toxicity in Sprague Dawley rats. Treatment with MSTF 1 h after subcutaneous injection with 3.5 mg/kg (equivalent to 0.7 LD50) SM significantly increased the survival levels of rats and attenuated the SM-induced morphological changes in the testis, small intestine and liver tissues. Treatment with MSTF at doses of 60 and 120 mg/kg caused a significant (p<0.05) reversal in SM-induced GSH depletion. Gene expression profiles revealed that treatment with MSTF had a dramatic effect on gene expression changes caused by SM. Treatment with MSTF prevented SM-induced differential expression of 93.8% (973 genes) of 1037 genes. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 36 pathways, such as the MAPK signaling pathway, pathways in cancer, antigen processing and presentation. These data suggest that MSTF attenuates SM-induced injury by increasing GSH and targeting multiple pathways, including the MAPK signaling pathway, as well as antigen processing and presentation. These results suggest that MSTF has the potential to be used as a potential therapeutic agent against SM injuries.

  14. Progression of ocular sulfur mustard injury: development of a model system.

    PubMed

    Milhorn, Denise; Hamilton, Tracey; Nelson, Marian; McNutt, Patrick

    2010-04-01

    Exposure of tissues to sulfur mustard (SM) results in the formation of protein and nucleotide adducts that disrupt cellular metabolism and cause cell death. Subsequent pathologies involve a significant proinflammatory response, disrupted healing, and long-term defects in tissue architecture. Following ocular exposure, acute corneal sequelae include epithelial erosions, necrosis, and corneal inflammation. Longer term, a progressive injury becomes distributed throughout the anterior chamber, which ultimately causes a profound remodeling of corneal tissues. In many cases, debilitating and vision-threatening injuries reoccur months to years after the initial exposure. Preliminary data in humans suffering from chronic epithelial lesions suggest that thymosin beta4 (Tbeta4) may be a viable candidate to mitigate acute or long-term ocular SM injury. To evaluate therapeutic candidates, we have developed a rabbit ocular exposure model system. In this paper, we report molecular, histological, ultrastructural, and clinical consequences of rabbit ocular SM injury, which can be used to assess Tbeta4 efficacy, including timepoints at which Tbeta4 will be assessed for therapeutic utility.

  15. A simple degradation method for sulfur mustard at ambient conditions using nickelphthalocyanine incorporated polypyrrole modified electrode

    NASA Astrophysics Data System (ADS)

    Sharma, Pushpendra K.; Sikarwar, Bhavna; Gupta, Garima; Nigam, Anil K.; Tripathi, Brijesh K.; Pandey, Pratibha; Boopathi, Mannan; Ganesan, Kumaran; Singh, Beer

    2014-01-01

    Electrocatalytic degradation of sulfur mustard (SM) was studied using a gold electrode modified with nickelphthalocyanine and polypyrrole (NiPc/pPy/Au) in the presence of a cationic surfactant cetyltrimethyl ammonium bromide. Several techniques such as cyclic voltammetry, scanning electron microscopy, electrochemical impedance spectroscopy, energy dispersive X-ray spectroscopy and Raman spectroscopy have been employed for the characterization of modified electrodes. NiPc/pPy/Au modified electrode exhibited excellent electrochemical sensing and degradation ability towards SM. The present modification indicated two electron involvements in the electrocatalytic degradation of SM in addition to being an irreversible adsorption controlled process. Degraded products were identified by gas chromatography-mass spectrometry. Moreover, electrochemical parameters of oxidation of SM such as heterogeneous rate constant (0.436 s-1), transfer coefficient (0.47) and the number of electrons involved (2) were deduced from cyclic voltammetry results. The NiPc/pPy/Au modified electrode showed excellent electrocatalytic degradation towards SM when compared to bare gold, pPy/Au and NiPc/Au modified electrode at ambient conditions.

  16. Nitric Oxide Alleviates Salt Stress Inhibited Photosynthetic Performance by Interacting with Sulfur Assimilation in Mustard.

    PubMed

    Fatma, Mehar; Masood, Asim; Per, Tasir S; Khan, Nafees A

    2016-01-01

    The role of nitric oxide (NO) and sulfur (S) on stomatal responses and photosynthetic performance was studied in mustard (Brassica juncea L.) in presence or absence of salt stress. The combined application of 100 μM NO (as sodium nitroprusside) and 200 mg S kg(-1) soil (S) more prominently influenced stomatal behavior, photosynthetic and growth performance both in the absence and presence of salt stress. The chloroplasts from salt-stressed plants had disorganized chloroplast thylakoids, but combined application of NO and S resulted in well-developed chloroplast thylakoids and properly stacked grana. The leaves from plants receiving NO plus S exhibited lower superoxide ion accumulation under salt stress than the plants receiving NO or S. These plants also exhibited increased activity of ATP-sulfurylase (ATPS), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) and optimized NO generation that helped in minimizing oxidative stress. The enhanced S-assimilation of these plants receiving NO plus S resulted in increased production of cysteine (Cys) and reduced glutathione (GSH). These findings indicated that NO influenced photosynthesis under salt stress by regulating oxidative stress and its effects on S-assimilation, an antioxidant system and NO generation. The results suggest that NO improves photosynthetic performance of plants grown under salt stress more effectively when plants received S. PMID:27200007

  17. Nitric Oxide Alleviates Salt Stress Inhibited Photosynthetic Performance by Interacting with Sulfur Assimilation in Mustard

    PubMed Central

    Fatma, Mehar; Masood, Asim; Per, Tasir S.; Khan, Nafees A.

    2016-01-01

    The role of nitric oxide (NO) and sulfur (S) on stomatal responses and photosynthetic performance was studied in mustard (Brassica juncea L.) in presence or absence of salt stress. The combined application of 100 μM NO (as sodium nitroprusside) and 200 mg S kg−1 soil (S) more prominently influenced stomatal behavior, photosynthetic and growth performance both in the absence and presence of salt stress. The chloroplasts from salt-stressed plants had disorganized chloroplast thylakoids, but combined application of NO and S resulted in well-developed chloroplast thylakoids and properly stacked grana. The leaves from plants receiving NO plus S exhibited lower superoxide ion accumulation under salt stress than the plants receiving NO or S. These plants also exhibited increased activity of ATP-sulfurylase (ATPS), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) and optimized NO generation that helped in minimizing oxidative stress. The enhanced S-assimilation of these plants receiving NO plus S resulted in increased production of cysteine (Cys) and reduced glutathione (GSH). These findings indicated that NO influenced photosynthesis under salt stress by regulating oxidative stress and its effects on S-assimilation, an antioxidant system and NO generation. The results suggest that NO improves photosynthetic performance of plants grown under salt stress more effectively when plants received S. PMID:27200007

  18. Acute and chronic respiratory lesions induced by sulfur mustard in guinea pigs: Role of tachykinins

    SciTech Connect

    Calvet, J.H.; Trouiller, G.; Harf, A.

    1993-05-13

    We investigated in anesthetized guinea pigs the involvement of tachykinins in respiratory alterations after an airway intoxication by sulfur mustard (SM). Early lesions were evaluated after 5h. Respiratory system resistance (R) and compliance were measured by the occlusion method and airway microvascular permeability by measuring the Evans Blue dye concentration in the trachea and main bronchi. Two groups of animals were studied treated with capsaicin (which induces a tachykinin depletion) or by its vehicle. Capsaicin pretreatment had no effect on the measured parameters. We also measured 14 J after the intoxication tracheal epithelium neutral endopeptidase (NEP) (the main enzyme which degrades tachykinins). In addition bronchial responsiveness to exogenous substance P was studied in two groups of animals intoxicated with SM or not. Tracheal epithelium NEP activity was decreased from 0.448 + or 0.027 nmol.min- 1.mg protein- 1 in controls to 0. 182 + or 0.038 in intoxicated animals. Response to substance P was greater in intoxicated animals with R=2.98 + or - 1.57 cmH20.MI-1.s versus 0.35 + or 0.02 in controls, after 5.10-5 M aerosolized substance P These results suggest tachykinins are not preponderant in the early stage lesions but that bronchial hyperactivity is present at recovery, related to epithelium NEP depletion.

  19. Sulfur mustard-increased proteolysis following in vitro and in vivo exposures

    SciTech Connect

    Cowan, F.M.; Yourick, J.J.; Hurst, C.G.; Broomfield, C.A.; Smith, W.J.

    1993-05-13

    The pathologic mechanisms underlying sulfur mustard (HD)-induced skin vesication are as yet undefined. Papirmeister et al. (1) postulate enhanced proteolytic activity as a proximate cause of HD-induced cutaneous injury. Using a chromogenic peptide substrate assay, we previously reported that in vitro exposure of cell cultures to HD enhances proteolytic activity. We have continued our investigation of HD-increased proteolytic activity in vitro and have expanded our studies to include an in vivo animal model for HD exposure. In vitro exposure of human peripheral blood lymphocytes (PBL) to HD demonstrated that the increase in proteolytic activity is both time- and temperature-dependent. Using a panel of 10 protease substrates, we established that the HD-increased proteolysis was markedly different from that generated by plasminogen activator. The hairless guinea pig is an animal model used for the study of HD-induced dermal pathology. When control and HD-exposed human PBL and hairless guinea pig skin where examined, similarities in their protease substrate reactivities were observed. HD-exposed hairless guinea pig skin biopsies demonstrated increased proteolytic activity that was time-dependent. The HD-increased proteolytic response was similar in both in vitro and in vivo studies and may be useful for elucidating both the mechanism of HD-induced vesication and potential treatment compounds.

  20. Constitutive expression of high-affinity sulfate transporter (HAST) gene in Indian mustard showed enhanced sulfur uptake and assimilation.

    PubMed

    Abdin, M Z; Akmal, M; Ram, M; Nafis, T; Alam, P; Nadeem, M; Khan, M A; Ahmad, A

    2011-07-01

    Lycopersicon esculantum sulfate transporter gene (LeST 1.1) encodes a high-affinity sulfate transporter (HAST) located in root epidermis. In this study, the LeST 1.1 gene was constitutively expressed in Indian mustard (Brassica juncea cv. Pusa Jai Kisan). Transgenic as well as untransformed plants were grown in sulfur-insufficient (25 and 50 μM) and sulfur-sufficient (1,000 μM) conditions for 30 days. Two-fold increase was noticed in the sulfate uptake rate of transgenic plants grown in both sulfur-insufficient and -sufficient conditions as compared to untransformed plants. The transgenic B. juncea plants were able to accumulate higher biomass and showed improved sulfur status even in sulfur-insufficient conditions when compared with untransformed plants. Chlorophyll content, ATP sulfurylase activity and protein content were also higher in transgenic plants than untranformed plants under sulfur-insufficient conditions. Our results, thus, clearly indicate that constitutive expression of LeST 1.1 gene in B. juncea had led to enhanced capacity of sulfur uptake and assimilation even in sulfur-insufficient conditions. This approach can also be used in other crops to enhance their sulfate uptake and assimilation potential under S-insufficient conditions. PMID:20938698

  1. Procedures for Analysis of Dried Plasma Using Microsampling Devices to Detect Sulfur Mustard-Albumin Adducts for Verification of Poisoning.

    PubMed

    John, Harald; Willoh, Sophia; Hörmann, Philipp; Siegert, Markus; Vondran, Antje; Thiermann, Horst

    2016-09-01

    Incorporation of the chemical warfare agent sulfur mustard (SM) produces a covalent adduct with human serum albumin (HSA) representing an established plasma biomarker of poisoning. Bioanalytical verification requires both plasma generation from whole blood and shipping to specialized laboratories following strict guidelines for complex packaging. These needs often push the infrastructural boundary in crisis regions and war zones. Therefore, we herein originally introduce different reliable bioanalytical procedures using filter paper as well as novel volumetric microsampling tools (Mitra devices and Noviplex DUO cards) to generate dried plasma samples not liable to the shipping constraints. In addition, the Noviplex device enables in-transit separation of plasma from whole blood without the need of a centrifuge. Plasma-loaded and dried devices were subjected to pronase treatment yielding the alkylated dipeptide hydroxyethylthioethyl-CysPro (HETE-CP) derived from the HSA-SM adduct that was detected by microbore liquid chromatography-electrospray ionization tandem-mass spectrometry (μLC-ESI MS/MS). For all devices, samples exposed to SM yielded excellent linearity (0.025-50 μM SM) and good precision (≤13%) and fulfilled forensic quality criteria for ion ratios of qualifying and quantifying product ions. Stability of the HSA-SM adduct in dried and liquid plasma is shown under conditions of three climatic zones (temperate climate, hot and dry climate, and hot and humid climate) for at least 9 days simulating the period of delayed sample shipping. Our results originally document that dried plasma is appropriate for storage and shipping at ambient temperature and that novel microsampling tools are of essential benefit when targeting the HSA-SM adduct for verification analysis. PMID:27482832

  2. Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect

    SciTech Connect

    Gerecke, Donald R. Chen Minjun; Isukapalli, Sastry S.; Gordon, Marion K.; Chang, Y.-C.; Tong Weida; Androulakis, Ioannis P.; Georgopoulos, Panos G.

    2009-01-15

    Sulfur mustard (HD, SM), is a chemical warfare agent that within hours causes extensive blistering at the dermal-epidermal junction of skin. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the various groups. Pathway analysis employing the KEGG library and Ingenuity Pathway Analysis (IPA) indicated that cytokine-cytokine receptor interaction, cell adhesion molecules (CAMs), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Selected genes were chosen for RT-PCR verification and showed correlations in the general trends for the microarrays. Interleukin 1 beta was checked for biological analysis to confirm the presence of protein correlated to the corresponding microarray data. The impact of a matrix metalloproteinase inhibitor, MMP-2/MMP-9 inhibitor I, against SM exposure was assessed. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors.

  3. Structural changes in the skin of hairless mice following exposure to sulfur mustard correlate with inflammation and DNA damage.

    PubMed

    Joseph, Laurie B; Gerecke, Donald R; Heck, Diane E; Black, Adrienne T; Sinko, Patrick J; Cervelli, Jessica A; Casillas, Robert P; Babin, Michael C; Laskin, Debra L; Laskin, Jeffrey D

    2011-10-01

    Sulfur mustard (SM, bis(2-chloroethyl)sulfide) is a bifunctional alkylating agent that causes dermal inflammation, edema and blistering. To investigate the pathogenesis of SM-induced injury, we used a vapor cup model which provides an occlusive environment in which SM is in constant contact with the skin. The dorsal skin of SKH-1 hairless mice was exposed to saturated SM vapor or air control. Histopathological changes, inflammatory markers and DNA damage were analyzed 1-14 days later. After 1 day, SM caused epidermal thinning, stratum corneum shedding, basal cell karyolysis, hemorrhage and macrophage and neutrophil accumulation in the dermis. Cleaved caspase-3 and phosphorylated histone 2A.X (phospho-H2A.X), markers of apoptosis and DNA damage, respectively, were increased whereas proliferating cell nuclear antigen (PCNA) was down-regulated after SM exposure. By 3 days, epithelial cell hypertrophy, edema, parakeratosis and loss of epidermal structures were noted. Enzymes generating pro-inflammatory mediators including myeloperoxidase and cyclooxygenase-2 were upregulated. After 7 days, keratin-10, a differentiation marker, was evident in the stratum corneum. This was associated with an underlying eschar, as neoepidermis began to migrate at the wound edges. Trichrome staining revealed increased collagen deposition in the dermis. PCNA expression in the epidermis was correlated with hyperplasia, hyperkeratosis, and parakeratosis. By 14 days, there was epidermal regeneration with extensive hyperplasia, and reduced expression of cleaved caspase-3, cyclooxygenase-2 and phospho-H2A.X. These findings are consistent with the pathophysiology of SM-induced skin injury in humans suggesting that the hairless mouse can be used to investigate the dermatoxicity of vesicants and the potential efficacy of countermeasures.

  4. Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect

    PubMed Central

    Gerecke, Donald R.; Chen, Minjun; Isukapalli, Sastry S.; Gordon, Marion K.; Chang, Yoke-Chen; Tong, Weida; Androulakis, Ioannis P.; Georgopoulos, Panos G.

    2011-01-01

    Sulfur mustard (HD, SM), is a chemical warfare agent that within hours causes extensive blistering at the dermal–epidermal junction of skin. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the various groups. Pathway analysis employing the KEGG library and Ingenuity Pathway Analysis (IPA) indicated that cytokine–cytokine receptor interaction, cell adhesion molecules (CAMs), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Selected genes were chosen for RT-PCR verification and showed correlations in the general trends for the microarrays. Interleukin 1 beta was checked for biological analysis to confirm the presence of protein correlated to the corresponding microarray data. The impact of a matrix metalloproteinase inhibitor, MMP-2/MMP-9 inhibitor I, against SM exposure was assessed. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors. PMID:18955075

  5. Ocular injuries following sulfur mustard exposure--pathological mechanism and potential therapy.

    PubMed

    Kadar, Tamar; Dachir, Shlomit; Cohen, Liat; Sahar, Rita; Fishbine, Eliezer; Cohen, Maayan; Turetz, Joseph; Gutman, Hila; Buch, Hillel; Brandeis, Rachel; Horwitz, Vered; Solomon, Abraham; Amir, Adina

    2009-09-01

    Sulfur mustard (SM) is a potent vesicant, known for its ability to cause incapacitation and prolonged injuries to the eyes, skin and respiratory system. The toxic ocular events following sulfur mustard exposure are characterized by several stages: photophobia starting a few hours after exposure, an acute injury phase characterized by inflammation of the anterior segment and corneal erosions and a delayed phase appearing following a clinically silent period (years in human). The late injury appeared in part of the exposed eyes, expressed by epithelial defects and corneal neovascularization (NV), that lead to vision deficits and even blindness. During the last years we have characterized the temporal development of ocular lesions following SM vapor exposure in rabbits and have shown the existence of two sub-populations of corneas, those exhibiting delayed ocular lesions (clinically impaired) and those exhibiting only minor injuries if at all (clinically non-impaired). The aim of the present study was to investigate the pathological mechanism underlying the delayed injury by focusing on the unique characteristics of each sub-population and to test the efficacy of potential treatments. Clinically impaired corneas were characterized by chronic inflammation, increased matrix metalloproteinase (MMP) activity, poor innervation and limbal damage. Moreover, using impression cytology and histology, we identified the delayed lesions as typical for an ocular surface disorder under the category of limbal epithelial stem cell deficiency (LSCD). These results point to therapeutic directions, using anti-inflammatory drugs, MMPs inhibitors, neurotrophic factors and amniotic membrane transplantation. Topical anti-inflammatory drugs, either steroid (Dexamycin, DEX) or non-steroidal anti-infllammatory drug (NSAID, Voltaren Ophtha) were found to be beneficial in ameliorating the initial inflammatory response and in postponing the development of corneal NV, when given during the first

  6. Involvement of ethylene in reversal of salt-inhibited photosynthesis by sulfur in mustard.

    PubMed

    Nazar, Rahat; Khan, Md Iqbal R; Iqbal, Noushina; Masood, Asim; Khan, Nafees A

    2014-10-01

    Sulfur (S) assimilation results in the synthesis of cysteine (Cys), a common metabolite for the formation of both reduced glutathione (GSH) and ethylene. Thus, ethylene may have regulatory interaction with GSH in the alleviation of salt stress. The involvement of ethylene in the alleviation of salt stress by S application was studied in mustard (Brassica juncea cv. Pusa Jai Kisan). First, the effects of 0, 0.5, 1.0 and 2.0 mM SO4 (2) (-) were studied on photosynthetic and growth parameters to ascertain the S requirement as sufficient-S and excess-S for the plant. In further experiments, the effects of sufficient-S (1 mM SO4 (2) (-) ) and excess-S (2 mM SO4 (2) (-) ) were studied on the alleviation of salt stress-induced by 100 mM NaCl, and ethylene involvement in the alleviation of salt stress by S. Under non-saline condition, excess-S increased ethylene with less content of Cys and GSH and adversely affected photosynthesis and growth. In contrast, excess-S maximally alleviated salt stress due to high demand for S and optimal ethylene formation, which maximally increased GSH and promoted photosynthesis and growth. The involvement of ethylene in S-mediated alleviation of salt stress was further substantiated by the reversal of the effects of excess-S on photosynthesis by aminoethoxyvinylglycine (AVG), ethylene biosynthesis inhibitor. The studies suggest that plants respond differentially to the S availability under non-saline and salt stress and excess-S was more potential in the alleviation of salt stress. Further, ethylene regulates plants' response and excess S-induced alleviation of salt stress and promotion of photosynthesis.

  7. Sulfur mustard induces an endoplasmic reticulum stress response in the mouse ear vesicant model

    SciTech Connect

    Chang, Yoke-Chen; Wang, James D.; Svoboda, Kathy K.; Casillas, Robert P.; Laskin, Jeffrey D.; Gordon, Marion K.; Gerecke, Donald R.

    2013-04-15

    The endoplasmic reticulum (ER) stress response is a cell survival pathway upregulated when cells are under severe stress. Severely damaged mouse ear skin exposed to the vesicant, sulfur mustard (bis-2-chloroethyl sulfide, SM), resulted in increased expression of ER chaperone proteins that accompany misfolded and incorrectly made proteins targeted for degradation. Time course studies with SM using the mouse ear vesicant model (MEVM) showed progressive histopathologic changes including edema, separation of the epidermis from the dermis, persistent inflammation, upregulation of laminin γ2 (one of the chains of laminin-332, a heterotrimeric skin glycoprotein required for wound repair), and delayed wound healing from 24 h to 168 h post exposure. This was associated with time related increased expression of the cell survival ER stress marker, GRP78/BiP, and the ER stress apoptosis marker, GADD153/CHOP, suggesting simultaneous activation of both cell survival and non-mitochondrial apoptosis pathways. Dual immunofluorescence labeling of a keratinocyte migration promoting protein, laminin γ2 and GRP78/BIP, showed colocalization of the two molecules 72 h post exposure indicating that the laminin γ2 was misfolded after SM exposure and trapped within the ER. Taken together, these data show that ER stress is induced in mouse skin within 24 h of vesicant exposure in a defensive response to promote cell survival; however, it appears that this response is rapidly overwhelmed by the apoptotic pathway as a consequence of severe SM-induced injury. - Highlights: ► We demonstrated ER stress response in the mouse ear vesicant model. ► We described the asymmetrical nature of wound repair in the MEVM. ► We identified the distribution of various ER stress markers in the MEVM.

  8. Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation

    SciTech Connect

    Rancourt, Raymond C. Veress, Livia A. Ahmad, Aftab Hendry-Hofer, Tara B. Rioux, Jacqueline S. Garlick, Rhonda B. White, Carl W.

    2013-10-01

    Sulfur mustard (SM) inhalation causes airway injury, with enhanced vascular permeability, coagulation, and airway obstruction. The objective of this study was to determine whether recombinant tissue factor pathway inhibitor (TFPI) could inhibit this pathogenic sequence. Methods: Rats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5 mg/kg) in vehicle, or vehicle alone, was instilled into the trachea. Arterial O{sub 2} saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma were analyzed for prothrombin, thrombin–antithrombin complex (TAT), active plasminogen activator inhibitor-1 (PAI-1) levels, and fluid fibrinolytic capacity. Lung steady-state PAI-1 mRNA was measured by RT-PCR analysis. Airway-capillary leak was estimated by BALF protein and IgM, and by pleural fluid measurement. In additional animals, airway cast formation was assessed by microdissection and immunohistochemical detection of airway fibrin. Results: Airway obstruction in the form of fibrin-containing casts was evident in central conducting airways of rats receiving CEES. TFPI decreased cast formation, and limited severe hypoxemia. Findings of reduced prothrombin consumption, and lower TAT complexes in BALF, demonstrated that TFPI acted to limit thrombin activation in airways. TFPI, however, did not appreciably affect CEES-induced airway protein leak, PAI-1 mRNA induction, or inhibition of the fibrinolytic activity present in airway surface liquid. Conclusions: Intratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury. - Highlights: • TFPI administration to rats after mustard inhalation reduces airway cast formation. • Inhibition of thrombin activation is the likely mechanism for limiting casts. • Rats given TFPI

  9. Reduction of erythema in hairless guinea pigs after cutaneous sulfur mustard vapor exposure by pretreatment with niacinamide, promethazine and indomethacin

    SciTech Connect

    Yourick, J.J.; Dawson, J.S.; Mitcheltree, L.W.

    1995-12-31

    Erythema is the initial symptom that occurs after sulfur mustard (HD) cutaneous exposure. The time course of HD-induced erythema is similar to that observed after UV irradiation, which can be reduced by indomethacin. Sulfur mustard lethality is decreased by using promethazine, which is an antihistamine. Niacinamide can reduce microvesication after HD vapor exposure in hairless guinea pig (HGP) skin. The present study examines the effect of the combined administration of niacinamide, indomethacin and promethazine used alone or in all possible combinations on the degree of erythema and histopathologic skin damage after HD exposure in HGP. Niacinamide (750 mg kg%`, i.p.), promethazine (12.5 mg kg%1, i.m.) or indomethacin (4 mg kg%1, p.o.) used singly or in combination was given as a 30-min pretreatment before an 8-min HD vapor cup skin exposure. Using a combination pretreatment of niacinamide, promethazine and indomethacin, erythema was reduced at 4 (91%) and 6 (55%) h, but not 24 h after HD. The incidence of histopathological skin changes (microvesicles, follicular involvement, epidermal necrosis, intracellular edema and pustular epidermatitis) 24 h after HD was not reduced. This study indicates that HD (induced erythema) may result from several different mechanisms, including inflammation, histamine release and DNA damage. It is suggested that two phases of inflammation may occur: an early phase sensitive to antihistamines and non-steroidal antiinflammatory drugs and a late phase of extensive cell damage that was not sensitive to these drug pretreatments.

  10. Glutathione and malondialdehyde levels in late pulmonary complications of sulfur mustard intoxication.

    PubMed

    Shohrati, Majid; Ghanei, Mostafa; Shamspour, Navvab; Babaei, Fatemeh; Abadi, Majid Norozi; Jafari, Mahvash; Harandi, Ali Amini; Ali, Amini Harandi

    2010-01-01

    It has been hypothesized that antioxidant and oxidant capacities may be related to the severity of obstructive lung impairment in patients with sulfur mustard (SM)-induced lung injuries. Our study was designed to measure the level of glutathione (GSH) and malondialdehyde (MDA) activities in patients intoxicated with SM and to evaluate the relationship between their activity and the severity of pulmonary dysfunction. A total of 250 patients with a history of exposure to a single high dose of SM gas and also 60 healthy nonsmoking individuals with no history of exposure to SM were selected. All patients underwent spirometry; based on its indices they were divided into two groups: mild (n = 140) and moderate-to-severe (n = 110) pulmonary dysfunction. Also, serum GSH and MDA concentration measurements were performed for all patients and controls. The mean GSH level in controls was 29.85 +/- 3.26 micromol/ml, which was significantly higher than in patients with mild and moderate-to-severe pulmonary dysfunction (19.02 +/- 2.36 and 17.89 +/- 2.16 micromol/ml, respectively). Also, the mean MDA level in controls was 0.69 +/- 0.09 micromol/ml, which was significantly lower than in patients with mild and moderate-to-severe pulmonary dysfunction (0.74 +/- 0.05 and 0.75 +/- 0.05 micromol/ml, respectively). There was a weak linear correlation between GSH level and some of the pulmonary function indices. On the other hand, there was no significant relationship between the MDA level and pulmonary indices. Our study confirmed important alterations in the oxidative-antioxidative system in patients suffering from SM-induced lung injuries, as shown by a decreased serum level of GSH and an increased level of MDA. Individuals with moderate-to-severe SM-induced lung injuries show a greater tendency for a decreased level of GSH and an increased level of MDA than those with mild injuries; however, there is only minimal association between pulmonary function parameters and the serum level of

  11. Evaluation of protective ointments used against dermal effects of nitrogen mustard, a vesicant warfare agent.

    PubMed

    Kenar, Levent; Karayilanoğlu, Turan; Yuksel, Altan; Gunhan, Omer; Kose, Songul; Kurt, Bulent

    2005-01-01

    Mustard, a vesicant warfare agent, has cytotoxic, mutagenic, and cytostatic effects via alkylation of DNA and inhibition of DNA replication. Since symptoms appear following a latent period, it can cause some subacute and chronic effects to occur and delay in the treatment. Therefore, the main approach should be the use of protective preparation to reduce the skin toxicity. Thus, this study was conducted in guinea pigs (350-400 g) shaved in areas of 10 x 10 cm. Mechlorethamine HCl (100 mg), a nitrogen mustard derivative, in ethanol was applied by spraying on hairless regions where previously prepared pharmaceutical topical formulations were medicated before. The experimental regions of the animals were kept preserved from environmental factors. Forty-eight hours after the application of the protective ointments and mechlorethamine consecutively, skin-damaging effects were macroscopically evaluated in terms of erythema formation, ulceration, necrosis, and inflammation occurrences. Then, punch biopsy was performed from these damaged sites for histopathological evaluation. Although numerous topical formulations were prepared and tested for protection, according to microscopic examination of the pathologic sections, tissue specimen treated with the ointment containing the mixture of zinc oxide, zinc chloride, dimethylpolysiloxane in a base of petroleum jelly was determined as being the most effective protective against skin injury caused by the vesicant agent.

  12. Desorption of bis(2-chloroethyl) sulfide, mustard agent, from the surface of hardened cement paste (HCP) wafers.

    PubMed

    Tang, Hairong; Zhou, Xuezhi; Guan, Yingqiang; Zhou, Liming; Wang, Xinming; Yan, Huijuan

    2013-05-01

    The decontamination of surfaces exposed to chemical warfare agents is an interesting scientific topic. The desorption behavior of bis(2-chloroethyl) sulfide (sulfur mustard, HD) from the surface of the HD-contaminated hardened cement paste (HCP) was investigated under different weather conditions, which should provide scientific reference data for protection and decontamination projects involving HD-contaminated HCP in different conditions. The desorption of HD from the surface of HCP wafers was studied, and the effects of the purge air flow rate, water content, sorption temperature, and substrate age were investigated. HD desorption was detected from the surface of HD-contaminated HCP, but the desorption velocity was relatively slow. The desorption quantity remained within an order of magnitude throughout a time span of 36h (25°C at 200mL/min of purge air), and the amount of HD that was desorbed from each square meter of HCP surface was approximately 1.1g (25°C at 200mL/min of purge air), which was approximately 5.5 percent of the total HD that was initially applied. A higher flow rate of the purge air, increased water content, and longer substrate age of HCP all increased the HD desorption. In contrast, increased temperatures suppressed HD desorption. PMID:23395389

  13. Inhibition of NADPH cytochrome P450 reductase by the model sulfur mustard vesicant 2-chloroethyl ethyl sulfide is associated with increased production of reactive oxygen species.

    PubMed

    Gray, Joshua P; Mishin, Vladimir; Heck, Diane E; Laskin, Debra L; Laskin, Jeffrey D

    2010-09-01

    Inhalation of vesicants including sulfur mustard can cause significant damage to the upper airways. This is the result of vesicant-induced modifications of proteins important in maintaining the integrity of the lung. Cytochrome P450s are the major enzymes in the lung mediating detoxification of sulfur mustard and its metabolites. NADPH cytochrome P450 reductase is a flavin-containing electron donor for cytochrome P450. The present studies demonstrate that the sulfur mustard analog, 2-chloroethyl ethyl sulfide (CEES), is a potent inhibitor of human recombinant cytochrome P450 reductase, as well as native cytochrome P450 reductase from liver microsomes of saline and beta-naphthoflavone-treated rats, and cytochrome P450 reductase from type II lung epithelial cells. Using rat liver microsomes from beta-naphthoflavone-treated rats, CEES was found to inhibit CYP 1A1 activity. This inhibition was overcome by microsomal cytochrome P450 reductase from saline-treated rats, which lack CYP 1A1 activity, demonstrating that the CEES inhibitory activity was selective for cytochrome P450 reductase. Cytochrome P450 reductase also generates reactive oxygen species (ROS) via oxidation of NADPH. In contrast to its inhibitory effects on the reduction of cytochrome c and CYP1A1 activity, CEES was found to stimulate ROS formation. Taken together, these data demonstrate that sulfur mustard vesicants target cytochrome P450 reductase and that this effect may be an important mechanism mediating oxidative stress and lung injury.

  14. Inhibition of NADPH cytochrome P450 reductase by the model sulfur mustard vesicant 2-chloroethyl ethyl sulfide is associated with increased production of reactive oxygen species

    SciTech Connect

    Gray, Joshua P.; Mishin, Vladimir; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2010-09-01

    Inhalation of vesicants including sulfur mustard can cause significant damage to the upper airways. This is the result of vesicant-induced modifications of proteins important in maintaining the integrity of the lung. Cytochrome P450s are the major enzymes in the lung mediating detoxification of sulfur mustard and its metabolites. NADPH cytochrome P450 reductase is a flavin-containing electron donor for cytochrome P450. The present studies demonstrate that the sulfur mustard analog, 2-chloroethyl ethyl sulfide (CEES), is a potent inhibitor of human recombinant cytochrome P450 reductase, as well as native cytochrome P450 reductase from liver microsomes of saline and {beta}-naphthoflavone-treated rats, and cytochrome P450 reductase from type II lung epithelial cells. Using rat liver microsomes from {beta}-naphthoflavone-treated rats, CEES was found to inhibit CYP 1A1 activity. This inhibition was overcome by microsomal cytochrome P450 reductase from saline-treated rats, which lack CYP 1A1 activity, demonstrating that the CEES inhibitory activity was selective for cytochrome P450 reductase. Cytochrome P450 reductase also generates reactive oxygen species (ROS) via oxidation of NADPH. In contrast to its inhibitory effects on the reduction of cytochrome c and CYP1A1 activity, CEES was found to stimulate ROS formation. Taken together, these data demonstrate that sulfur mustard vesicants target cytochrome P450 reductase and that this effect may be an important mechanism mediating oxidative stress and lung injury.

  15. Inhibition of NADPH cytochrome P450 reductase by the model sulfur mustard vesicant 2-chloroethyl ethyl sulfide is associated with increased production of reactive oxygen species.

    PubMed

    Gray, Joshua P; Mishin, Vladimir; Heck, Diane E; Laskin, Debra L; Laskin, Jeffrey D

    2010-09-01

    Inhalation of vesicants including sulfur mustard can cause significant damage to the upper airways. This is the result of vesicant-induced modifications of proteins important in maintaining the integrity of the lung. Cytochrome P450s are the major enzymes in the lung mediating detoxification of sulfur mustard and its metabolites. NADPH cytochrome P450 reductase is a flavin-containing electron donor for cytochrome P450. The present studies demonstrate that the sulfur mustard analog, 2-chloroethyl ethyl sulfide (CEES), is a potent inhibitor of human recombinant cytochrome P450 reductase, as well as native cytochrome P450 reductase from liver microsomes of saline and beta-naphthoflavone-treated rats, and cytochrome P450 reductase from type II lung epithelial cells. Using rat liver microsomes from beta-naphthoflavone-treated rats, CEES was found to inhibit CYP 1A1 activity. This inhibition was overcome by microsomal cytochrome P450 reductase from saline-treated rats, which lack CYP 1A1 activity, demonstrating that the CEES inhibitory activity was selective for cytochrome P450 reductase. Cytochrome P450 reductase also generates reactive oxygen species (ROS) via oxidation of NADPH. In contrast to its inhibitory effects on the reduction of cytochrome c and CYP1A1 activity, CEES was found to stimulate ROS formation. Taken together, these data demonstrate that sulfur mustard vesicants target cytochrome P450 reductase and that this effect may be an important mechanism mediating oxidative stress and lung injury. PMID:20561902

  16. Veterans at risk: The health effects of mustard gas and lewisite

    SciTech Connect

    Pechura, C.M.; Rall, D.P.

    1993-01-01

    So vivid were the memories of the first use of mustard gas (sulfur mustard) by the Germans in World War I that the United States government began to prepare for chemical warfare even before the Japanese attacked Pearl Harbor in 1941. This work was also spurred by the fury of war in Europe and reports of Japanese use of sulfur mustard against the Chinese. The US preparations included the establishment of war-related research programs organized by President Roosevelt under the White House Office of Scientific Research and Development (OSRD). Two groups under the OSRD became involved in secret testing programs concerned with mustard agents (Sulfur and nitrogen mustard) and Lewisite: The Committee on Medical Research; This group studied protective ointments and other treatments through the National Research Council's Committee on Treatment of Gas Casualties, and The National Defense Research Committee; This group studied protective clothing and gas masks through military units such as the Chemical Warfare Service.

  17. Quantitation of the sulfur mustard metabolites 1,1'-sulfonylbis[2-(methylthio)ethane] and thiodiglycol in urine using isotope-dilution Gas chromatography-tandem mass spectrometry.

    PubMed

    Boyer, Anne E; Ash, Doris; Barr, Dana B; Young, Carrie L; Driskell, W J; Whitehead, Ralph D; Ospina, Maria; Preston, Kerry E; Woolfitt, Adrian R; Martinez, Rodolfo A; Silks, L A Pete; Barr, John R

    2004-01-01

    Sulfur mustard (HD), or bis(2-chloroethyl)sulfide, has several urinary metabolites that can be measured to assess human exposure. These metabolites include the simple hydrolysis product thiodiglycol (TDG) and its oxidative analogue, TDG-sulfoxide, as well as metabolites of the glutathione/b-lyase pathway 1,1'-sulfonylbis[2-(methyl-sulfinyl)ethane] (SBMSE) and 1-methyl-sulfinyl-2-[(methylthio)ethyl-sulfonyl]ethane (MSMTESE). Current methods focus on either the TDG or the b-lyase metabolites. We have developed a single method that measures products of both metabolic branches, with the reduced compound of SBMSE and MSMTESE, 1,1'-sulfonylbis [2(methylthio)ethane] (SBMTE), as the definitive analyte and TDG as a confirmation analyte. Sample preparation included b-glucuronidase hydrolysis for TDG-glucuronide conjugates, titanium trichloride reduction of sulfoxides to SBMTE and TDG, solid-phase extraction, and a chemical derivatization. We analyzed samples using gas chromatography-tandem mass spectrometry with quantitation using isotope-dilution calibration. The method limits of detection for TDG and SBMTE were 0.5 ng/mL and 0.25 ng/mL, respectively, with relative standard deviations of less than 10%. Urine samples from individuals with no known exposure to mustard agent HD had measurable concentrations of TDG, but no SBMTE was detected. The geometric mean concentration of TDG was 3.43 ng/mL, with concentrations ranging from < 0.5 ng/mL to 20 ng/mL. PMID:15239851

  18. Serum level of substance P in patients with lung injuries due to sulfur mustard

    PubMed Central

    Najafian, Bita; Shohrati, Majid; Harandi, Ali Amini; Mahyar, Shiva; Khaheshi, Isa; Ghanei, Mostafa

    2014-01-01

    Background: Chronic bronchiolitis is the most important problems of chemical victims of mustard gas. Diverse studies suggest that substance P (SP) as a member of tachykinin neuropeptides, has a significant role in the neurogenic inflammation processes of the airways and lungs. We aimed to determine the serum level of SP in chemical victims of mustard gas and compare it with normal subjects. Materials and Methods: The chemical victims were divided into the 2 groups of 30:A group with mild to moderate pulmonary symptoms and other group with moderate to severe symptoms and compared with 3rd group as healthy controls. After preparing our samples and using the SP kit, final analysis was performed with enzyme-linked immunosorbent assay reader. Results: The Concentration of circulatory SP levels in the chemical patients was 2.86 ± 1.47 ng/ml and had not a significant difference with the control group (3.15 ± 1.03 ng/ml) (P > 0.05). The circulatory SP levels were 2.48 ± 0.92 ng/ml and 3.28 ± 1.73 ng/ml in patients with moderate to severe symptoms and mild to moderates (P < 0.05) respectively. Conclusion: The SP may have a role in pulmonary complications of mustard gas. The lower level of SP in the moderate to severe patients may be due to corticosteroid consumption in such severe cases. However, further studies are needed to clarify the roles and mechanism of SP in this setting. PMID:25161984

  19. Involvement of ethylene in gibberellic acid-induced sulfur assimilation, photosynthetic responses, and alleviation of cadmium stress in mustard.

    PubMed

    Masood, Asim; Khan, M Iqbal R; Fatma, Mehar; Asgher, Mohd; Per, Tasir S; Khan, Nafees A

    2016-07-01

    The role of gibberellic acid (GA) or sulfur (S) in stimulation of photosynthesis is known. However, information on the involvement of ethylene in GA-induced photosynthetic responses and cadmium (Cd) tolerance is lacking. This work shows that ethylene is involved in S-assimilation, photosynthetic responses and alleviation of Cd stress by GA in mustard (Brassica juncea L.). Plants grown with 200 mg Cd kg(-1) soil were less responsive to ethylene despite high ethylene evolution and showed photosynthetic inhibition. Plants receiving 10 μM GA spraying plus 100 mg S kg(-1) soil supplementation exhibited increased S-assimilation and photosynthetic responses under Cd stress. Application of GA plus S decreased oxidative stress of plants grown with Cd and limited stress ethylene formation to the range suitable for promoting sulfur use efficiency (SUE), glutathione (GSH) production and photosynthesis. The role of ethylene in GA-induced S-assimilation and reversal of photosynthetic inhibition by Cd was substantiated by inhibiting ethylene biosynthesis with the use of aminoethoxyvinylglycine (AVG). The suppression of S-assimilation and photosynthetic responses by inhibiting ethylene in GA plus S treated plants under Cd stress indicated the involvement of ethylene in GA-induced S-assimilation and Cd stress alleviation. The outcome of the study is important to unravel the interaction between GA and ethylene and their role in Cd tolerance in plants. PMID:26998941

  20. Involvement of ethylene in gibberellic acid-induced sulfur assimilation, photosynthetic responses, and alleviation of cadmium stress in mustard.

    PubMed

    Masood, Asim; Khan, M Iqbal R; Fatma, Mehar; Asgher, Mohd; Per, Tasir S; Khan, Nafees A

    2016-07-01

    The role of gibberellic acid (GA) or sulfur (S) in stimulation of photosynthesis is known. However, information on the involvement of ethylene in GA-induced photosynthetic responses and cadmium (Cd) tolerance is lacking. This work shows that ethylene is involved in S-assimilation, photosynthetic responses and alleviation of Cd stress by GA in mustard (Brassica juncea L.). Plants grown with 200 mg Cd kg(-1) soil were less responsive to ethylene despite high ethylene evolution and showed photosynthetic inhibition. Plants receiving 10 μM GA spraying plus 100 mg S kg(-1) soil supplementation exhibited increased S-assimilation and photosynthetic responses under Cd stress. Application of GA plus S decreased oxidative stress of plants grown with Cd and limited stress ethylene formation to the range suitable for promoting sulfur use efficiency (SUE), glutathione (GSH) production and photosynthesis. The role of ethylene in GA-induced S-assimilation and reversal of photosynthetic inhibition by Cd was substantiated by inhibiting ethylene biosynthesis with the use of aminoethoxyvinylglycine (AVG). The suppression of S-assimilation and photosynthetic responses by inhibiting ethylene in GA plus S treated plants under Cd stress indicated the involvement of ethylene in GA-induced S-assimilation and Cd stress alleviation. The outcome of the study is important to unravel the interaction between GA and ethylene and their role in Cd tolerance in plants.

  1. Plastic antibody for the recognition of chemical warfare agent sulphur mustard.

    PubMed

    Boopathi, M; Suryanarayana, M V S; Nigam, Anil Kumar; Pandey, Pratibha; Ganesan, K; Singh, Beer; Sekhar, K

    2006-06-15

    Molecularly imprinted polymers (MIPs) known as plastic antibodies (PAs) represent a new class of materials possessing high selectivity and affinity for the target molecule. Since their discovery, PAs have attracted considerable interest from bio- and chemical laboratories to pharmaceutical institutes. PAs are becoming an important class of synthetic materials mimicking molecular recognition by natural receptors. In addition, they have been utilized as catalysts, sorbents for solid-phase extraction, stationary phase for liquid chromatography and mimics of enzymes. In this paper, first time we report the preparation and characterization of a PA for the recognition of blistering chemical warfare agent sulphur mustard (SM). The SM imprinted PA exhibited more surface area when compared to the control non-imprinted polymer (NIP). In addition, SEM image showed an ordered nano-pattern for the PA of SM that is entirely different from the image of NIP. The imprinting also enhanced SM rebinding ability to the PA when compared to the NIP with an imprinting efficiency (alpha) of 1.3.

  2. Protection against the acute and delayed toxicities of sulfur mustard. Final report, 4 December 1992-3 March 1996

    SciTech Connect

    Ludlum, D.B.

    1996-04-01

    Based on the chemotherapeutic literature and cell culture studies of sulfur mustard (SM) toxicity reported here, we believe that DNA repair mechanisms act as cellular defenses against SM toxicity. Cell culture studies show that survival is increased by the nucleotide excision repair mechanism while biochemical studies show that human as well as bacterial glycosylase enzymes can release two SM- induced DNA adducts: 7-hydroxyethylthioethyl guanine and 3-hydroxyethylthioethyl adenine. The growth of cultured human fibroblasts exposed to 10 uM SM appears to be enhanced in comparison with cells incubated continuously at 37 deg C by subjecting them to a period of hypothermia at 28 deg C before returning them to 37 deg C incubation. Cells held at 28 deg C undergo cell cycle arrest and we believe that this arrest may allow more time for DNA repair before the next round of cell division, thus enhancing survival. Concurrently, we have developed a 32P-postlabeling method that can detect one 7-hydroxy-ethylthioethyl guanine in 10(6) DNA nucleotides in DNA extracted from SM-exposed cells. This method should prove useful in both exposure and DNA repair studies.

  3. Hypochlorite solution as a decontaminant in sulfur mustard contaminated skin defects in the euthymic hairless guinea pig

    SciTech Connect

    Gold, M.B.; Bongiovanni, R.; Scharf, B.A.; Gresham, V.C.; Woodward, C.L.

    1994-12-31

    Hypochlorite solutions are thought to be efficacious when used to topically decontaminate intact skin. However, few studies have examined the efficacy of decontamination of chemically contaminated wounds. Therefore, we compared the decontamination efficacy of sodium hypochlorite (0.5% and 2.5% solutions), calcium hypochlorite (0.5% and 2.5% solutions) and sterile water to untreated controls in wounds exposed to sulfur mustard (HD). Anesthetized euthymic hairless guinea pigs (EHGP) (n=6) were exposed to 20 mg/kg (approximately 0.4 LD%) HD in a full-thickness 8 mm surgical biopsy skin defect (i.e., wound). Each animal was subsequently decontaminated, after a two-minute intra-wound exposure to liquid HD, with nothing or one of the decontamination solutions. Decontamination efficacy was determined by the visual grading of the HD-traumatized wound lesion and by comparison of the expected HD-induced leukocyte suppression. Leukocyte suppression was inconsistent in all animals; therefore, the visual grading was the only viable evaluation method. No significant differences were observed among wounds decontaminated with any of the solutions. However, the skin surrounding non-decontaminated (but exposed) control animals showed the least visual pathology. The lesions induced following decontamination are presumed to be due to the mechanical flushing of HD onto the peri-lesional skin, or by chemical damage induced by the solution, or ND-solution interaction. Further studies are required to best delineate the optimal decontamination process for HD contaminated wounds.

  4. Niacinamide pretreatment reduces microvesicle formation in hairless guinea pigs cutaneously exposed to sulfur mustard. (Reannouncement with new availability information)

    SciTech Connect

    Yourick, J.J.; Clark, C.R.; Mitcheltree, L.W.

    1991-12-31

    It has been proposed that sulfur mustard (HD) may indirectly activate poly(ADP-ribose) polymerase (PADPRP) by alkylating cellular DNA (Papirmeister et al., 1985). Activation of PADPRP results in the depletion of cellular NAD+ which initiates a series of biochemical processes that have been proposed to culminate in blister formation. Preventing PADPRP activation and NAD+ depletion should inhibit blister formation. Niacinamide is both an inhibitor of PADPRP and a precursor for NAD+ synthesis. The present study was undertaken to determine whether niacinamide can protect against HD-induced microvesication in cutaneously exposed hairless guinea pigs. Each site was exposed to HD for 8 min by means of a vapor cup. Niacinamide (750 mg/kg, ip) given as a 30-min pretreatment inhibited microvesicle formation by 50% after HD application. However, niacinamide given 2 hr after HD application did not reduce microvesicle formation. There was no benefit when niacinamide was given as both a pretreatment and treatment when compared to niacinamide given only as a pretreatment. The reduction in microvesication 24 hr after HD did not correlate with skin NAD+ content. Niacinamide did not reduce the degree of erythema or edema. Ballooning degeneration of basal epidermal cells was present in some niacinamide pretreated HD exposure sites.

  5. Role of Reactive Oxygen and Nitrogen Species in Olfactory Epithelial Injury by the Sulfur Mustard Analogue 2-Chloroethyl Ethyl Sulfide

    PubMed Central

    O'Neill, Heidi C.; Orlicky, David J.; Hendry-Hofer, Tara B.; Loader, Joan E.; Day, Brian J.; White, Carl W.

    2011-01-01

    The inhalation of sulfur mustard (SM) causes substantial deposition in the nasal region. However, specific injury has not been characterized. 2-chloroethyl ethyl sulfide (CEES) is an SM analogue used to model injury and screen potential therapeutics. After the inhalation of CEES, damage to the olfactory epithelium (OE) was extensive. Terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling-positive cells were present by 4 hours, and maximal at 18–72 hours. Cleaved caspase 3 immunohistochemistry (IHC) was maximal at 18 hours after the inhalation of 5% CEES. Olfactory marker protein (OMP)–positive olfactory neurons were markedly decreased at 18 hours. IHC-positive cells for 3-nitrotyrosine (3-NT) within epithelium were elevated by 8 hours, waning by 18 hours, and absent by 72 hours. AEOL 10150, a catalytic manganoporphyrin antioxidant, administered both subcutaneously (5 mg/kg) and intranasally (50 μM, “combined treatment”), decreased OE injury. CEES-induced increases in markers of cell death were decreased by combined treatment involving AEOL 10150. CEES-induced changes in OMP and 3-NT immunostaining were markedly improved by combined treatment involving AEOL 10150. The selective inducible nitric oxide synthase inhibitor 1400W (5 mg/kg, subcutaneous), administered 1 hour after inhalation and thereafter every 4 hours (five doses), also reduced OE damage with improved OMP and 3-NT staining. Taken together, these data indicate that reactive oxygen and nitrogen species are important mediators in CEES-induced nasal injury. PMID:21642592

  6. Proteomic assessment of sulfur mustard-induced protein adducts and other protein modifications in human epidermal keratinocytes

    SciTech Connect

    Mol, Marijke A.E. Berg, Roland M. van den; Benschop, Henk P.

    2008-07-01

    Although some toxicological mechanisms of sulfur mustard (HD) have been uncovered, new knowledge will allow for advanced insight in the pathways that lead towards epidermal-dermal separation in skin. In the present investigation, we aimed to survey events that occur at the protein level in human epidermal keratinocytes (HEK) during 24 h after exposure to HD. By using radiolabeled {sup 14}C-HD, it was found that proteins in cultured HEK are significant targets for alkylation by HD. HD-adducted proteins were visualized by two-dimensional gel electrophoresis and analyzed by mass spectrometry. Several type I and II cytokeratins, actin, stratifin (14-3-3{sigma}) and galectin-7 were identified. These proteins are involved in the maintenance of the cellular cytoskeleton. Their alkylation may cause changes in the cellular architecture and, in direct line with that, be determinative for the onset of vesication. Furthermore, differential proteomic analysis was applied to search for novel features of the cellular response to HD. Partial breakdown of type I cytokeratins K14, K16 and K17 as well as the emergence of new charge variants of the proteins heat shock protein 27 and ribosomal protein P0 were observed. Studies with caspase inhibitors showed that caspase-6 is probably responsible for the breakdown of type I cytokeratins in HEK. The significance of the results is discussed in terms of toxicological relevance and possible clues for therapeutic intervention.

  7. Helium:oxygen versus air:oxygen noninvasive positive-pressure ventilation in patients exposed to sulfur mustard.

    PubMed

    Ghanei, Mostafa; Rajaeinejad, Mohsen; Motiei-Langroudi, Rouzbeh; Alaeddini, Farshid; Aslani, Jafar

    2011-01-01

    Exposure to sulfur mustard (SM) causes a variety of respiratory symptoms, such as chronic bronchitis and constrictive bronchiolitis. This study assessed the effectiveness of noninvasive positive-pressure ventilation, adjunct with 79:21 helium:oxygen instead of 79:21 air:oxygen, in 24 patients with a previous exposure to SM presenting with acute respiratory failure. Both air:oxygen and helium:oxygen significantly decreased systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse rate, respiratory rate, dyspnea, and increased oxygen saturation (P values: .007, .029, .002, <.001, <.001, <.001, and .002 for air:oxygen, respectively, and <.001, .020, .001, <.001, <.001, <.001, and .002, for helium:oxygen, respectively). Moreover, helium:oxygen more potently improved systolic pressure, mean arterial pressure, pulse rate, respiratory rate, and dyspnea (P values: .012, .048, <.001, <.001, and .012, respectively). The results of our study support the benefit of using helium:oxygen adjunct with noninvasive positive-pressure ventilation in patients exposed to SM with acute respiratory decompensation.

  8. The Role of Serum Level of Interleukin-6 in Severity of Pulmonary Complications of Sulfur Mustard Injuries

    PubMed Central

    Shohrati, Majid; Amini-Harandi, Ali; Najafian, Bita; Saburi, Amin; Ghanei, Mostafa

    2014-01-01

    Diverse studies suggest that interleukin-6 (IL6), as a member of cytokines family, has a major role in inflammatory processes of airways and lungs. In this study, an attempt was made to determine the serum level of IL6 in sulfur mustard (SM) injured patients and its comparison with controls. The measured IL6 mean level in patients with chemical injuries (0.76±0.3 ng/ml) was significantly higher than the control group’s mean level (0.34±0.12 ng/ml). Furthermore, patients with moderate to severe symptoms had a serum level of (0.95±0.92 ng/ml) which was significantly higher than mild (0.47±0.54) and control (0.34±0.12) groups. The outcome of this research program demonstrates that an increase in serum level of IL6 can have a role in pulmonary complications of SM, similar to other well defined pulmonary diseases.  However, further studies are required to clarify the role and mechanism of IL6 in such patients. PMID:25031491

  9. Medical defense against blistering chemical warfare agents.

    PubMed

    Smith, W J; Dunn, M A

    1991-08-01

    First used in World War I, chemical blistering agents present a serious medical threat that has stimulated renewed interest in the light of extensive use in recent conflicts. Current medical management cannot yet prevent or minimize injury from the principal agent of concern--sulfur mustard. Research directed at this goal depends on defining effective intervention in the metabolic alterations induced by exposure to sulfur mustard.

  10. Sulfur Mustard Effects on Mental Health and Quality-of-Life: A Review

    PubMed Central

    Razavi, Seyed Mansour; Negahban, Zahra; Pirhosseinloo, Mohsen; Razavi, Mahdiyeh Sadat; Hadjati, Gholamreza; Salamati, Payman

    2014-01-01

    Objective: Mental disorders are more common among the chemically injured veterans rather the than the normal population. The main aim of this study was to evaluate the effects of mustard gas (MG) on mental health and quality-of-life (QOL) in the people exposed to it based on reviewing valid published articles. Methods: We searched English databases including Medline, ISI and Scopus as well as Farsi databases including Iranmedex and Irandoc and reviewed them. The used keywords were in two English and Farsi languages. Forty related full texts out of more than 300 articles were assessed and for their qualification, only the publications in accredited journals were considered sufficient. Results: The average mental health score of victims using the general health questionnaire (GHQ) was 48.92. The frequency of anxiety was (18-65%), insomnia (13.63%), social performance disturbances (10.73%), severe depression (6-46%), low concentration (54%), emotional problems (98%), behavioral abnormalities (80%), thought processing disturbances (14%), memory impairment (80%), personality disorders (31%), seizures (6%), psychosis (3%). Post-traumatic stress disorder (PTSD) is one of the most common and important disorders with lifetime PTSD (8-59%), current PTSD (2-33%) and the QOL in chemical warfare victims decreased. Conclusion: Exposure to chemical weapons may lead to physical, mental, social, and economic damages and consequently decrease the victims’ (QOL. Therefore, they should be taken into more care. PMID:25780370

  11. Expression of proliferative and inflammatory markers in a full-thickness human skin equivalent following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

    SciTech Connect

    Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.; Heck, Diane E.; Gerecke, Donald R.; Sinko, Patrick J.; Laskin, Debra L.; Laskin, Jeffrey D.

    2010-12-01

    Sulfur mustard is a potent vesicant that induces inflammation, edema and blistering following dermal exposure. To assess molecular mechanisms mediating these responses, we analyzed the effects of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide, on EpiDerm-FT{sup TM}, a commercially available full-thickness human skin equivalent. CEES (100-1000 {mu}M) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300-1000 {mu}M), CEES also disrupted keratin filament architecture in the stratum corneum. This was associated with time-dependent increases in expression of proliferating cell nuclear antigen, a marker of cell proliferation, and poly(ADP-ribose) polymerase (PARP) and phosphorylated histone H2AX, markers of DNA damage. Concentration- and time-dependent increases in mRNA and protein expression of eicosanoid biosynthetic enzymes including COX-2, 5-lipoxygenase, microsomal PGE{sub 2} synthases, leukotriene (LT) A{sub 4} hydrolase and LTC{sub 4} synthase were observed in CEES-treated skin equivalents, as well as in antioxidant enzymes, glutathione S-transferases A1-2 (GSTA1-2), GSTA3 and GSTA4. These data demonstrate that CEES induces rapid cellular damage, cytotoxicity and inflammation in full-thickness skin equivalents. These effects are similar to human responses to vesicants in vivo and suggest that the full thickness skin equivalent is a useful in vitro model to characterize the biological effects of mustards and to develop potential therapeutics.

  12. DNA-directed alkylating agents. 6. Synthesis and antitumor activity of DNA minor groove-targeted aniline mustard analogues of pibenzimol (Hoechst 33258)

    PubMed

    Gravatt, G L; Baguley, B C; Wilson, W R; Denny, W A

    1994-12-01

    A series of nitrogen mustard analogues of the DNA minor groove binding fluorophore pibenzimol (Hoechst 33258) have been synthesized and evaluated for antitumor activity. Conventional construction of the bisbenzimidazole ring system from the piperazinyl terminus, via two consecutive Pinner-type reactions, gave low yields of products contaminated with the 2-methyl analogue which proved difficult to separate. An alternative synthesis was developed, involving construction of the bisbenzimidazole from the mustard terminus, via Cu(2+)-promoted oxidative coupling of the mustard aldehydes with 3,4-diaminobenzonitrile to form the monobenzimidazoles, followed by a Pinner-type reaction and condensation with 4-(1-methyl-4-piperazinyl)-o-phenylenediamine. This process gives higher yields and pure products. The mustard analogues showed high hypersensitivity factors (IC50AA8/IC50 UV4), typical of DNA alkylating agents. There was a large increase in cytotoxicity (85-fold) across the homologous series which cannot be explained entirely by changes in mustard reactivity and may be related to altering orientation of the mustard with respect to the DNA resulting in different patterns of alkylation. Pibenzimol itself (which has been evaluated clinically as an anticancer drug) was inactive against P388 in vivo using a single-dose protocol, but the short-chain mustard homologues were highly effective, eliciting a proportion of long-term survivors.

  13. Aniline mustard analogues of the DNA-intercalating agent amsacrine: DNA interaction and biological activity.

    PubMed

    Fan, J Y; Valu, K K; Woodgate, P D; Baguley, B C; Denny, W A

    1997-04-01

    Two series of analogues of the clinical antileukemic drug and DNA-intercalating ligand amsacrine have been prepared, containing aniline mustard sidechains of varying reactivity, linked either at the 4-position of the intercalating acridine chromophore (type A) or at the 1'-position of the 9-anilino group (type B). DNase I footprinting assays showed that compounds of type B had stronger reversible binding to DNA than did compounds of type A. Compounds of each type showed similar patterns of alkylation-induced cleavage of DNA, and alkylate at the N7 of guanines in runs of guanines (similar to the pattern for untargeted mustards) as well as some adenines. Both classes of compounds crosslinked DNA, although those bearing relatively inactive mustards did so only at high drug/base pair ratios. However, while the patterns of DNA alkylation were broadly similar, the compounds were considerably more cytotoxic than analogous untargeted mustards. Comparison of their cytotoxicities in wild-type and DNA repair-deficient lines indicated this toxicity was due to DNA crosslinks (except for the least reactive SO2-linked mustards). The 4-linked analogues showed slightly higher in vivo antileukemic activity than the corresponding 1'-linked analogues.

  14. Inhalation of sulfur mustard causes long-term T cell-dependent inflammation: Possible role of Th17 cells in chronic lung pathology

    PubMed Central

    Mishra, Neerad C.; Rir-sima-ah, Jules; Grotendorst, Gary R.; Langley, Raymond J.; Singh, Shashi P.; Gundavarapu, Sravanthi; Weber, Waylon M.; Pena-Philippides, Juan C.; Duncan, Matthew R.; Sopori, Mohan L.

    2012-01-01

    Sulfur mustard (SM) is a highly toxic chemical warfare agent that remains a threat to human health. The immediate symptoms of pulmonary distress may develop into chronic lung injury characterized by progressive lung fibrosis, the major cause of morbidity among the surviving SM victims. Although SM has been intensely investigated, little is known about the mechanism(s) by which SM induces chronic lung pathology. Increasing evidence suggests that IL-17+ cells are critical in fibrosis, including lung fibrotic diseases. In this study we exposed F344 rats and cynomolgus monkeys to SM via inhalation and determined the molecular and cellular milieu in their lungs at various times after SM exposure. In rats, SM induced a burst of pro-inflammatory cytokines/chemokines within 72 h, including IL-1β, TNF-α, IL-2, IL-6, CCL2, CCL3, CCL11, and CXCL1 that was associated with neutrophilic infiltration into the lung. At 2 wk and beyond (chronic phase), lymphocytic infiltration and continued elevated expression of cytokines/chemokines were sustained. TGF-β, which was undetectable in the acute phase, was strongly upregulated in the chronic phase; these conditions persisted until the animals were sacrificed. The chronic phase was also associated with myofibroblast proliferation, collagen deposition, and presence of IL-17+ cells. At 30 days, SM inhalation promoted the accumulation of IL-17+ cells in the inflamed areas of monkey lungs. Thus, SM inhalation causes acute and chronic inflammatory responses; the latter is characterized by the presence of TGF-β, fibrosis, and IL-17+ cells in the lung. IL-17+ cells likely play an important role in the pathogenesis of SM-induced lung injury. PMID:22465472

  15. Identification of Reliable Reference Genes for Quantification of MicroRNAs in Serum Samples of Sulfur Mustard-Exposed Veterans

    PubMed Central

    Gharbi, Sedigheh; Shamsara, Mehdi; Khateri, Shahriar; Soroush, Mohammad Reza; Ghorbanmehr, Nassim; Tavallaei, Mahmood; Nourani, Mohammad Reza; Mowla, Seyed Javad

    2015-01-01

    Objective In spite of accumulating information about pathological aspects of sulfur mustard (SM), the precise mechanism responsible for its effects is not well understood. Circulating microRNAs (miRNAs) are promising biomarkers for disease diagnosis and prognosis. Accurate normalization using appropriate reference genes, is a critical step in miRNA expression studies. In this study, we aimed to identify appropriate reference gene for microRNA quantification in serum samples of SM victims. Materials and Methods In this case and control experimental study, using quantitative real-time polymerase chain reaction (qRT-PCR), we evaluated the suitability of a panel of small RNAs including SNORD38B, SNORD49A, U6, 5S rRNA, miR-423-3p, miR-191, miR-16 and miR-103 in sera of 28 SM-exposed veterans of Iran-Iraq war (1980-1988) and 15 matched control volunteers. Different statistical algorithms including geNorm, Normfinder, best-keeper and comparative delta-quantification cycle (Cq) method were employed to find the least variable reference gene. Results miR-423-3p was identified as the most stably expressed reference gene, and miR- 103 and miR-16 ranked after that. Conclusion We demonstrate that non-miRNA reference genes have the least stabil- ity in serum samples and that some house-keeping miRNAs may be used as more reliable reference genes for miRNAs in serum. In addition, using the geometric mean of two reference genes could increase the reliability of the normalizers. PMID:26464821

  16. Epidermal hydration and skin surface lipids in patients with long-term complications of sulfur mustard poisoning

    PubMed Central

    Layegh, Pouran; Maleki, Masoud; Mousavi, Seyed Reza; Yousefzadeh, Hadis; Momenzadeh, Akram; Golmohammadzadeh, Shiva; Balali-Mood, Mahdi

    2015-01-01

    Background: Despite almost the three decades passed since the chemical attacks of Iraqi's army against the Iranian troops, some veterans are still suffering from long-term complications of sulfur mustard (SM) poisoning, including certain skin complaints specially dryness, burning, and pruritus. We thus aimed to evaluate the skin's water and lipid content in patients with a disability of >25% due to complications of SM poisoning and compare them with a matched control group. Materials and Methods: Sixty-nine male participants were included in this study; 43 SM-exposed patients, and 26 normal controls from their close relatives. The water and lipid content was measured in four different locations: Extensor and flexor sides of forearms and lateral and medial sides of legs by the Corneometer CM 820/Sebumeter SM 810. Collected data was analyzed and P ≤ 0.05 was considered as statistically significant. Results: The mean age of the patients and controls was 49.53 ± 11.34 (ranges: 40-71) and 29.08 ± 8.836 (ranges: 15-49 years), respectively. In the veterans group, the main cutaneous complaint was itching and skin dryness. Cherry angioma, dry skin, and pruritus were significantly more common in the SM-exposed cases than in the controls. (P = 0.01, 0.05, and 0.04, respectively). The moisture and lipid content of all areas were lower in the SM-exposed group, but it was only significant in skin sebum of lateral sides of legs (P = 0.02). Conclusion: Exposure to SM could decrease the function of stratum corneum and lipid production as a barrier, even after several years of its exposure. PMID:26622252

  17. Sulfur mustard primes human neutrophils for increased degranulation and stimulates cytokine release via TRPM2/p38 MAPK signaling

    SciTech Connect

    Ham, Hwa-Yong; Hong, Chang-Won; Lee, Si-Nae; Kwon, Min-Soo; Kim, Yeon-Ja; Song, Dong-Keun

    2012-01-01

    Sulfur mustard (2,2′-bis-chloroethyl-sulfide; SM) has been a military threat since the World War I. The emerging threat of bioterrorism makes SM a major threat not only to military but also to civilian world. SM injury elicits an inflammatory response characterized by infiltration of neutrophils. Although SM was reported to prime neutrophils, the mechanism has not been identified yet. In the present study, we investigated the mechanism of SM-induced priming in human neutrophils. SM increased [Ca{sup 2+}]{sub i} in human neutrophils in a concentration-dependent fashion. Transient receptor potential melastatin (TRPM) 2 inhibitors (clotrimazole, econazole and flufenamic acid) and silencing of TRPM2 by shRNA attenuated SM-induced [Ca{sup 2+}]{sub i} increase. SM primed degranulation of azurophil and specific granules in response to activation by fMLP as previously reported. SB203580, an inhibitor of p38 MAPK, inhibited SM-induced priming. Neither PD98057, an ERK inhibitor, nor SP600215, a JNK inhibitor, inhibited SM-induced priming. In addition, SM enhanced phosphorylation of NF-kB p65 and release of TNF-α, interleukin (IL)-6 and IL-8. SB203580 inhibited SM-induced NF-kB phosphorylation and cytokine release. These results suggest the involvement of TRPM2/p38 MAPK pathway in SM-induced priming and cytokines release in neutrophils. -- Highlights: ► SM increased [Ca{sup 2+}]{sub i} in human neutrophils through TPRM2-mediated calcium influx. ► SM primed degranulation of azurophil and specific granules. ► SM enhanced p38 MAPK and NF-κB p65 phosphorylation in human neutrophils. ► SM enhanced release of TNF-α, interleukin (IL)-6 and IL-8 from human neutrophils. ► SB203580 inhibited SM-induced priming, NF-κB p65 phosphorylation and cytokine release.

  18. Inhalation exposure to sulfur mustard in the guinea pig model: Clinical, biochemical and histopathological characterization of respiratory injuries

    SciTech Connect

    Allon, Nahum; Amir, Adina; Manisterski, Eliau; Rabinovitz, Ishay; Dachir, Shlomit; Kadar, Tamar

    2009-12-01

    Guinea pigs (GP) were exposed (head only) in individual plethysmographs to various concentrations of sulfur mustard vapor, determined online, using FTIR attached to flow chamber. The LCt{sub 50} and the inhaled LD{sub 50} were calculated at different time points post exposure. Surviving animals were monitored for clinical symptoms, respiratory parameters and body weight changes for up to 30 days. Clinical symptoms were noted at 3 h post exposure, characterized by erythematic and swelling nose with extensive mucous secretion (with or without bleeding). At 6 h post exposure most of the guinea pigs had breathing difficulties, rhonchi and dyspnea and few deaths were noted. These symptoms peaked at 48 h and were noted up to 8 days, associated with few additional deaths. Thereafter, a spontaneous healing was noted, characterized by recovery of respiratory parameters and normal weight gain with almost complete apparent healing within 2 weeks. Histopathological evaluation of lungs and trachea in the surviving GPs at 4 weeks post exposure revealed a dose-dependent residual injury in both lung and trachea expressed by abnormal recovery of the tracheal epithelium concomitant with a dose-dependent increase in cellular volume in the lungs. These abnormal epithelial regeneration and lung remodeling were accompanied with significant changes in protein, LDH, differential cell count and glutathione levels in the bronchoalveolar lavage (BAL). It is suggested that the abnormal epithelial growth and cellular infiltration into the lung as well as the continuous lung inflammation could cause recurrent lung injury similar to that reported for HD exposed human casualties.

  19. DRDE-07 and its analogues as promising cytoprotectants to nitrogen mustard (HN-2)--an alkylating anticancer and chemical warfare agent.

    PubMed

    Sharma, Manoj; Vijayaraghavan, R; Gautam, Anshoo

    2009-08-10

    Nitrogen mustard (HN-2), also known as mechlorethamine, is an alkylating anticancer agent as well as blister inducing chemical warfare agent. We evaluated the cytoprotective efficacy of amifostine, DRDE-07 and their analogues, and other antidotes of mustard agents against HN-2. Administration of 1 LD(50) of HN-2 (20mg/kg) percutaneously, decreased WBC count from 24h onwards. Liver glutathione (GSH) level decreased prominently and the maximum depletion was observed on 7th day post-HN-2 administration. Oxidised glutathione (GSSG) level increased significantly at 24h post-administration and subsequently showed a progressive decrease. Hepatic malondialdehyde (MDA) level and percent DNA damage increased progressively following HN-2 administration. The spleen weight decreased progressively and reached a minimum on 3-4 days with subsequent increase. The antidotes were administered repeatedly for 4 and 8 days after percutaneous administration of single sublethal dose (0.5 and 0.25 LD(50)) of HN-2. Treatment with DRDE-07, DRDE-30 and DRDE-35 significantly protected the changes in spleen weight, WBC count, GSH, GSSG, MDA and DNA damage following HN-2 administration (0.5 and 0.25 LD(50)). There was no alteration in the transaminases (AST and ALT), and alkaline phosphatase (ALP) activities, neither with HN-2 nor with antidotes. The present study shows that HN-2 is highly toxic by percutaneous route and DRDE-07, DRDE-30 and DRDE-35 can partially protect it.

  20. Development of a dynamic headspace gas chromatography-mass spectrometry method for on-site analysis of sulfur mustard degradation products in sediments.

    PubMed

    Magnusson, R; Nordlander, T; Östin, A

    2016-01-15

    Sampling teams performing work at sea in areas where chemical munitions may have been dumped require rapid and reliable analytical methods for verifying sulfur mustard leakage from suspected objects. Here we present such an on-site analysis method based on dynamic headspace GC-MS for analysis of five cyclic sulfur mustard degradation products that have previously been detected in sediments from chemical weapon dumping sites: 1,4-oxathiane, 1,3-dithiolane, 1,4-dithiane, 1,4,5-oxadithiephane, and 1,2,5-trithiephane. An experimental design involving authentic Baltic Sea sediments spiked with the target analytes was used to develop an optimized protocol for sample preparation, headspace extraction and analysis that afforded recoveries of up to 60-90%. The optimized method needs no organic solvents, uses only two grams of sediment on a dry weight basis and involves a unique sample presentation whereby sediment is spread uniformly as a thin layer inside the walls of a glass headspace vial. The method showed good linearity for analyte concentrations of 5-200 ng/g dw, good repeatability, and acceptable carry-over. The method's limits of detection for spiked sediment samples ranged from 2.5 to 11 μg/kg dw, with matrix interference being the main limiting factor. The instrumental detection limits were one to two orders of magnitude lower. Full-scan GC-MS analysis enabled the use of automated mass spectral deconvolution for rapid identification of target analytes. Using this approach, analytes could be identified in spiked sediment samples at concentrations down to 13-65 μg/kg dw. On-site validation experiments conducted aboard the research vessel R/V Oceania demonstrated the method's practical applicability, enabling the successful identification of four cyclic sulfur mustard degradation products at concentrations of 15-308μg/kg in sediments immediately after being collected near a wreck at the Bornholm Deep dumpsite in the Baltic Sea.

  1. Melatonin alleviates lung damage induced by the chemical warfare agent nitrogen mustard.

    PubMed

    Ucar, Muharrem; Korkmaz, Ahmet; Reiter, Russel J; Yaren, Hakan; Oter, Sükrü; Kurt, Bülent; Topal, Turgut

    2007-09-10

    The cytotoxic mechanism of mustards has not been fully elucidated; recently, we reported that reactive oxygen species, nitric oxide [produced by inducible nitric oxide synthase (iNOS)] and peroxynitrite are involved in the pathogenesis and responsible for mustard-induced toxicity. Melatonin, a potent antioxidant molecule, acts as an iNOS inhibitor and a peroxynitrite scavenger. Using the prototypic nitrogen mustard (mechlorethamine/HN2) as a model and based on its known cytotoxic mechanisms, the present study was performed to test melatonin for its capability in protecting the lungs of injured male Wistar rats. Lung mustard toxicity was induced via an intratracheally injection of HN2 (0.5mg/kg) dissolved in saline (100microl). Control animals were injected the same amount of saline only. Melatonin was administered intraperitoneally with two different doses (20mg/kg or 40mg/kg) beginning 1h before HN2 application and continued every 12h for six replications. Forty-eight hours after the last melatonin injection, the animals were sacrificed and their lungs were taken for further assay, i.e., malondialdehyde (MDA) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPx) and iNOS activity. Additionally their urine was collected for nitrite-nitrate (NO(x)) analysis. HN2 injection caused increased iNOS activity and MDA levels in lung tissue and NO(x) values in urine; lung GPx activity was significantly depressed. Melatonin restored all of these oxidative and nitrosative stress markers in a dose-dependent manner. In conclusion, the results of study provide evidence that melatonin may have the ability to reduce mustard-induced toxicity in the lungs.

  2. Hydrogen Peroxide Alleviates Nickel-Inhibited Photosynthetic Responses through Increase in Use-Efficiency of Nitrogen and Sulfur, and Glutathione Production in Mustard.

    PubMed

    Khan, M I R; Khan, Nafees A; Masood, Asim; Per, Tasir S; Asgher, Mohd

    2016-01-01

    The response of two mustard (Brassica juncea L.) cultivars differing in photosynthetic capacity to different concentrations of hydrogen peroxide (H2O2) or nickel (Ni) was evaluated. Further, the effect of H2O2 on photosynthetic responses of the mustard cultivars grown with or without Ni stress was studied. Application of 50 μM H2O2 increased photosynthesis and growth more prominently in high photosynthetic capacity cultivar (Varuna) than low photosynthetic capacity cultivar (RH30) grown without Ni stress. The H2O2 application also resulted in alleviation of photosynthetic inhibition induced by 200 mg Ni kg(-1) soil through increased photosynthetic nitrogen-use efficiency (NUE), sulfur-use efficiency (SUE), and glutathione (GSH) reduced production together with decreased lipid peroxidation and electrolyte leakage in both the cultivars. However, the effect of H2O2 was more pronounced in Varuna than RH30. The greater increase in photosynthetic-NUE and SUE and GSH production with H2O2 in Varuna resulted from higher increase in activity of nitrogen (N) and sulfur (S) assimilation enzymes, nitrate reductase and ATP-sulfurylase, respectively resulting in enhanced N and S assimilation. The increased N and S content contributed to the higher activity of ribulose-1,5-bisphosphate carboxylase under Ni stress. Application of H2O2 also regulated PS II activity and stomatal movement under Ni stress for maintaining higher photosynthetic potential in Varuna. Thus, H2O2 may be considered as a potential signaling molecule for augmenting photosynthetic potential of mustard plants under optimal and Ni stress conditions. It alleviates Ni stress through the regulation of stomatal and non-stomotal limitations, and photosynthetic-NUE and -SUE and GSH production. PMID:26870064

  3. Hydrogen Peroxide Alleviates Nickel-Inhibited Photosynthetic Responses through Increase in Use-Efficiency of Nitrogen and Sulfur, and Glutathione Production in Mustard.

    PubMed

    Khan, M I R; Khan, Nafees A; Masood, Asim; Per, Tasir S; Asgher, Mohd

    2016-01-01

    The response of two mustard (Brassica juncea L.) cultivars differing in photosynthetic capacity to different concentrations of hydrogen peroxide (H2O2) or nickel (Ni) was evaluated. Further, the effect of H2O2 on photosynthetic responses of the mustard cultivars grown with or without Ni stress was studied. Application of 50 μM H2O2 increased photosynthesis and growth more prominently in high photosynthetic capacity cultivar (Varuna) than low photosynthetic capacity cultivar (RH30) grown without Ni stress. The H2O2 application also resulted in alleviation of photosynthetic inhibition induced by 200 mg Ni kg(-1) soil through increased photosynthetic nitrogen-use efficiency (NUE), sulfur-use efficiency (SUE), and glutathione (GSH) reduced production together with decreased lipid peroxidation and electrolyte leakage in both the cultivars. However, the effect of H2O2 was more pronounced in Varuna than RH30. The greater increase in photosynthetic-NUE and SUE and GSH production with H2O2 in Varuna resulted from higher increase in activity of nitrogen (N) and sulfur (S) assimilation enzymes, nitrate reductase and ATP-sulfurylase, respectively resulting in enhanced N and S assimilation. The increased N and S content contributed to the higher activity of ribulose-1,5-bisphosphate carboxylase under Ni stress. Application of H2O2 also regulated PS II activity and stomatal movement under Ni stress for maintaining higher photosynthetic potential in Varuna. Thus, H2O2 may be considered as a potential signaling molecule for augmenting photosynthetic potential of mustard plants under optimal and Ni stress conditions. It alleviates Ni stress through the regulation of stomatal and non-stomotal limitations, and photosynthetic-NUE and -SUE and GSH production.

  4. Hydrogen Peroxide Alleviates Nickel-Inhibited Photosynthetic Responses through Increase in Use-Efficiency of Nitrogen and Sulfur, and Glutathione Production in Mustard

    PubMed Central

    Khan, M. I. R.; Khan, Nafees A.; Masood, Asim; Per, Tasir S.; Asgher, Mohd

    2016-01-01

    The response of two mustard (Brassica juncea L.) cultivars differing in photosynthetic capacity to different concentrations of hydrogen peroxide (H2O2) or nickel (Ni) was evaluated. Further, the effect of H2O2 on photosynthetic responses of the mustard cultivars grown with or without Ni stress was studied. Application of 50 μM H2O2 increased photosynthesis and growth more prominently in high photosynthetic capacity cultivar (Varuna) than low photosynthetic capacity cultivar (RH30) grown without Ni stress. The H2O2 application also resulted in alleviation of photosynthetic inhibition induced by 200 mg Ni kg-1 soil through increased photosynthetic nitrogen-use efficiency (NUE), sulfur-use efficiency (SUE), and glutathione (GSH) reduced production together with decreased lipid peroxidation and electrolyte leakage in both the cultivars. However, the effect of H2O2 was more pronounced in Varuna than RH30. The greater increase in photosynthetic-NUE and SUE and GSH production with H2O2 in Varuna resulted from higher increase in activity of nitrogen (N) and sulfur (S) assimilation enzymes, nitrate reductase and ATP-sulfurylase, respectively resulting in enhanced N and S assimilation. The increased N and S content contributed to the higher activity of ribulose-1,5-bisphosphate carboxylase under Ni stress. Application of H2O2 also regulated PS II activity and stomatal movement under Ni stress for maintaining higher photosynthetic potential in Varuna. Thus, H2O2 may be considered as a potential signaling molecule for augmenting photosynthetic potential of mustard plants under optimal and Ni stress conditions. It alleviates Ni stress through the regulation of stomatal and non-stomotal limitations, and photosynthetic-NUE and -SUE and GSH production. PMID:26870064

  5. Characterization of acute and long-term pathologies of superficial and deep dermal sulfur mustard skin lesions in the hairless guinea pig model.

    PubMed

    Dachir, Shlomit; Cohen, Maayan; Kamus-Elimeleh, Dikla; Fishbine, Eliezer; Sahar, Rita; Gez, Rellie; Brandeis, Rachel; Horwitz, Vered; Kadar, Tamar

    2012-01-01

    Sulfur mustard induces severe acute and prolonged damage to the skin and only partially effective treatments are available. We have previously validated the use of hairless guinea pigs as an experimental model for skin lesions. The present study aimed to characterize a model of a deep dermal lesion and to compare it with the previously described superficial lesion. Clinical evaluation of the lesions was conducted using reflectance colorimetry, trans-epidermal water loss and wound area measurements. Prostaglandin E(2) content, matrix metalloproteinase-2 and 9 activity, and histopathology were conducted up to 4 weeks post-exposure. Sulfur mustard skin injury, including erythema and edema, impairment of skin barrier and wounds developed in a dose-dependent manner. Prostaglandin E(2) content and matrix metalloproteinase-2 and 9 activities were elevated during the wound development and the healing process. Histological evaluation revealed severe damage to the epidermis and deep dermis and vesications. At 4 weeks postexposure, healing was not completed: significantly impaired stratum corneum, absence of hair follicles, and epidermal hyperplasia were observed. These results confirm the use of the superficial and deep dermal skin injuries in the hairless guinea pigs as suitable models that can be utilized for the investigation of the pathological processes of acute as well as long-term injuries. These models will be further used to develop treatments to improve the healing process and prevent skin damage and long-term effects. PMID:23082902

  6. Selection of non-steroidal anti-inflammatory drug and treatment regimen for sulfur mustard-induced cutaneous lesions.

    PubMed

    Plahovinsak, Jennifer L; Buccellato, Matthew A; Reid, Frances M; Graham, John S

    2016-09-01

    The inflammatory process plays an important role in sulfur mustard (HD) injury and HD pathogenesis, suggesting that anti-inflammatory treatments applied as soon as possible following HD injury may reduce tissue damage and accelerate healing. This study used the HD dermal weanling swine model to investigate the efficacy of two non-steroidal anti-inflammatory drugs, capsaicin and diclofenac, when applied in combination with the steroid, clobetasol. The therapeutic regimen was also investigated with respect to initiation of treatment post-exposure, frequency and duration. Yorkshire-cross pigs were randomly assigned to experimental groups, corresponding to all combinations of treatment (capsaicin with clobetasol or diclofenac with clobetasol), onset time (1, 2 or 4 h post-exposure), treatment duration (1, 3 or 5 days) and frequency of applications (2, 3 or 4 per day). For each animal, two sites on the ventral abdomen were exposed to 400 μL of neat HD for 8 min to achieve superficial dermal (SD) lesions and two sites were exposed to 400 μL neat HD for 30 min to achieve deep dermal (DD) lesions. Each treatment regimen was tested against a SD and a DD injury. Untreated SD and DD lesion sites served as within-animal controls. Assessments, up to one week post-challenge, included digital photographs, clinical assessments (lesion size measurements and modified Draize scoring), transepidermal water loss (TEWL), reflectance colorimetry and histopathologic evaluations that included an estimate for depth of injury and wound healing parameters. Diclofenac plus clobetasol treatment resulted in significant reductions in lesion contracture and modified Draize scores, increased barrier function (decreased TEWL), and increased healing as determined by histopathology for both SD and DD injury when compared with untreated sites and sites treated with capsaicin plus clobetasol. An increased duration of treatment from 1 to 5 days was most commonly associated with decreased

  7. Efficacy of Tiotropium Bromide and Rehabilitation Treatment on Pulmonary Function of Patients With Sulfur Mustard Lung Injury

    PubMed Central

    Shohrati, Majid; Jalili, Maryam; Afshar, Homa; Najafian, Bita; Qazvini, Ali; Zaeri, Meysam; Amini Harandi, Ali; Ghanei, Mostafa

    2015-01-01

    Background: Chronic pulmonary complication is the most common delayed toxic effect of sulfur mustard (SM) and it has no treatment so far. Objectives: To evaluate short-term therapeutic effects of inhaled tiotropium bromide and pulmonary rehabilitation on pulmonary function of patients with SM induced lung injury. Patients and Methods: In a randomized clinical trial, using convenient sampling method, 54 patients with chronic lung disease due to SM exposure were recruited in Baqiyatallah General Hospital, Tehran, Iran for a period of 2-month study. They were randomly divided into 3 groups of 18 participants each. Group 1 received routine drugs (Serevent, Flixotide), pulmonary rehabilitation 30 minutes/2 times a week, and tiotropium bromide 18 µg/day. Group 2 was treated with routine drugs and pulmonary rehabilitation and group 3 was only on the routine drugs. cardiopulmonary exercise test (CPET), plethysmographic measurements, and respiratory symptoms evaluation were performed before and after medical intervention. Results: In group 1, compared to group 3, significant differences were found with regard to symptoms of cough ([difference between the first and last visit in group 1: Diff 1] = -1.6, Diff 3 = -0.3, P = 0.01) and nocturnal dyspnea (Diff 1 = -1.9, Diff 3 = 0.0, P = 0.01), likewise, compared to group 2, significant differences were found with regard to lung function parameters of forced vital capacity (Diff 1 = 3.0, Diff 2 = -3.5, P = 0.03), forced expiratory volume in one second (Diff 1 = 3.9, Diff 2 = -5.6, P = 0.009), maximal mid-expiratory flow rate 25% - 75% (Diff 1 = 1.5, Diff 2 = -3.2, P = 0.007) and peak expiratory flow (Diff 1 = -2.06, Diff 2 = -4.3, P = 0.04). Total lung capacity (Diff 2 = 9.28, Diff 3 = -12.07, P = 0.02) and residual volume (Diff2 = 32.1, Diff3 = -27.6, P = 0.04) were increased in group 2 compared to group 3. There were no significant differences with regard to CPET results among all groups (P > 0.05). Conclusions: Inhalation of

  8. Selection of non-steroidal anti-inflammatory drug and treatment regimen for sulfur mustard-induced cutaneous lesions.

    PubMed

    Plahovinsak, Jennifer L; Buccellato, Matthew A; Reid, Frances M; Graham, John S

    2016-09-01

    The inflammatory process plays an important role in sulfur mustard (HD) injury and HD pathogenesis, suggesting that anti-inflammatory treatments applied as soon as possible following HD injury may reduce tissue damage and accelerate healing. This study used the HD dermal weanling swine model to investigate the efficacy of two non-steroidal anti-inflammatory drugs, capsaicin and diclofenac, when applied in combination with the steroid, clobetasol. The therapeutic regimen was also investigated with respect to initiation of treatment post-exposure, frequency and duration. Yorkshire-cross pigs were randomly assigned to experimental groups, corresponding to all combinations of treatment (capsaicin with clobetasol or diclofenac with clobetasol), onset time (1, 2 or 4 h post-exposure), treatment duration (1, 3 or 5 days) and frequency of applications (2, 3 or 4 per day). For each animal, two sites on the ventral abdomen were exposed to 400 μL of neat HD for 8 min to achieve superficial dermal (SD) lesions and two sites were exposed to 400 μL neat HD for 30 min to achieve deep dermal (DD) lesions. Each treatment regimen was tested against a SD and a DD injury. Untreated SD and DD lesion sites served as within-animal controls. Assessments, up to one week post-challenge, included digital photographs, clinical assessments (lesion size measurements and modified Draize scoring), transepidermal water loss (TEWL), reflectance colorimetry and histopathologic evaluations that included an estimate for depth of injury and wound healing parameters. Diclofenac plus clobetasol treatment resulted in significant reductions in lesion contracture and modified Draize scores, increased barrier function (decreased TEWL), and increased healing as determined by histopathology for both SD and DD injury when compared with untreated sites and sites treated with capsaicin plus clobetasol. An increased duration of treatment from 1 to 5 days was most commonly associated with decreased

  9. Applying pattern recognition methods to analyze the molecular properties of a homologous series of nitrogen mustard agents.

    PubMed

    Bartzatt, Ronald; Donigan, Laura

    2006-01-01

    The purpose of this research was to analyze the pharmacological properties of a homologous series of nitrogen mustard (N-mustard) agents formed after inserting 1 to 9 methylene groups (-CH2-) between 2 -N(CH2CH2Cl)2 groups. These compounds were shown to have significant correlations and associations in their properties after analysis by pattern recognition methods including hierarchical classification, cluster analysis, nonmetric multi-dimensional scaling (MDS), detrended correspondence analysis, K-means cluster analysis, discriminant analysis, and self-organizing tree algorithm (SOTA) analysis. Detrended correspondence analysis showed a linear-like association of the 9 homologs, and hierarchical classification showed that each homolog had great similarity to at least one other member of the series-as did cluster analysis using paired-group distance measure. Nonmetric multi-dimensional scaling was able to discriminate homologs 2 and 3 (by number of methylene groups) from homologs 4, 5, and 6 as a group, and from homologs 7, 8, and 9 as a group. Discriminant analysis, K-means cluster analysis, and hierarchical classification distinguished the high molecular weight homologs from low molecular weight homologs. As the number of methylene groups increased the aqueous solubility decreased, dermal permeation coefficient increased, Log P increased, molar volume increased, parachor increased, and index of refraction decreased. Application of pattern recognition methods discerned useful interrelationships within the homologous series that will determine specific and beneficial clinical applications for each homolog and methods of administration. PMID:16796353

  10. Comparison of the Lonidamine Potentiated Effect of Nitrogen Mustard Alkylating Agents on the Systemic Treatment of DB-1 Human Melanoma Xenografts in Mice

    PubMed Central

    Nath, Kavindra; Nelson, David S.; Putt, Mary E.; Leeper, Dennis B.; Garman, Bradley; Nathanson, Katherine L.; Glickson, Jerry D.

    2016-01-01

    Previous NMR studies demonstrated that lonidamine (LND) selectively diminishes the intracellular pH (pHi) of DB-1 melanoma and mouse xenografts of a variety of other prevalent human cancers while decreasing their bioenergetic status (tumor βNTP/Pi ratio) and enhancing the activities of melphalan and doxorubicin in these cancer models. Since melphalan and doxorubicin are highly toxic agents, we have examined three other nitrogen (N)-mustards, chlorambucil, cyclophosphamide and bendamustine, to determine if they exhibit similar potentiation by LND. As single agents LND, melphalan and these N-mustards exhibited the following activities in DB-1 melanoma xenografts; LND: 100% tumor surviving fraction (SF); chlorambucil: 100% SF; cyclophosphamide: 100% SF; bendamustine: 79% SF; melphalan: 41% SF. When combined with LND administered 40 min prior to administration of the N-mustard (to maximize intracellular acidification) the following responses were obtained; chlorambucil: 62% SF; cyclophosphamide: 42% SF; bendamustine: 36% SF; melphalan: 10% SF. The effect of LND on the activities of these N-mustards is generally attributed to acid stabilization of the aziridinium active intermediate, acid inhibition of glutathione-S-transferase, which acts as a scavenger of aziridinium, and acid inhibition of DNA repair by O6-alkyltransferase. Depletion of ATP by LND may also decrease multidrug resistance and increase tumor response. At similar maximum tolerated doses, our data indicate that melphalan is the most effective N-mustard in combination with LND when treating DB-1 melanoma in mice, but the choice of N-mustard for coadministration with LND will also depend on the relative toxicities of these agents, and remains to be determined. PMID:27285585

  11. MUSTARD GAS EXPOSURE AND CARCINOGENESIS OF LUNG

    PubMed Central

    Hosseini-khalili, Alireza; Haines, David D; Modirian, Ehsan; Soroush, Mohammadreza; Khateri, Shahriar; Joshi, Rashmi; Zendehdel, Kazem; Ghanei, Mostafa; Giardina, Charles

    2009-01-01

    Sulfur mustard (SM), also known as mustard gas, is an alkylating compound used as a chemical weapon in World War I and by Iraqi forces against Iranians and indigenous Iraqi Kurds during the Iran-Iraq War of the 1980s. Although SM is a proven carcinogen there are conflicting views regarding the carcinogenicity of a single exposure. The present study characterizes lung cancers formed in mustard gas victims from the Iran-Iraq War. Methods and Materials Demographic information and tumor specimens were collected from 20 Iranian male lung cancer patients with single high-dose SM exposures during the Iran-Iraq war. Formalin fixed, paraffin-embedded lung cancers were analyzed by immunohistochemistry for p53 protein. In addition, DNA was extracted from the tissues, PCR amplified and sequenced to identify mutations in the p53 and KRAS genes associated with SM exposure. Results A relatively early age of lung cancer onset (ranging from 28 to 73 with a mean of 48) in mustard gas victims, particularly those in the non-smoking population (mean age of 40.7), may be an indication of a unique etiology for these cancers. Seven of the 20 patients developed lung cancer before the age of 40. Five of 16 cancers from which DNA sequence data was obtainable provided information on eight p53 mutations (within exons 5–8). These mutations were predominately G to A transitions; a mutation consistent with the DNA lesion caused by SM. Two of the lung cancers had multiple p53 point mutations, similar to results obtained from factory workers chronically exposed to mustard agent. No mutations were detected in the KRAS gene. Discussion The distinguishing characteristics of lung carcinogenesis in these mustard gas victims suggest that a single exposure may increase the risk of lung cancer development in some individuals. PMID:19559099

  12. Design and synthesis of novel hydroxyanthraquinone nitrogen mustard derivatives as potential anticancer agents via a bioisostere approach.

    PubMed

    Zhao, Li-Ming; Ma, Feng-Yan; Jin, Hai-Shan; Zheng, Shilong; Zhong, Qiu; Wang, Guangdi

    2015-09-18

    A series of hydroxyanthraquinones having an alkylating N-mustard pharmacophore at 1'-position were synthesized via a bioisostere approach to evaluate their cytotoxicity against four tumor cell lines (MDA-MB-231, HeLa, MCF-7 and A549). These compounds displayed significant in vitro cytotoxicity against MDA-MB-231 and MCF-7 cells, reflecting the excellent selectivity for the human breast cancer. Among them, compound 5k was the most cytotoxic with IC50 value of 0.263 nM and is more potent than DXR (IC50 = 0.294 nM) in inhibiting the growth of MCF-7 cells. The excellent cytotoxicity and good selectivity of compound 5k suggest that it could be a promising lead for further design and development of anticancer agents, especially for breast cancer.

  13. Development of a dynamic headspace gas chromatography-mass spectrometry method for on-site analysis of sulfur mustard degradation products in sediments.

    PubMed

    Magnusson, R; Nordlander, T; Östin, A

    2016-01-15

    Sampling teams performing work at sea in areas where chemical munitions may have been dumped require rapid and reliable analytical methods for verifying sulfur mustard leakage from suspected objects. Here we present such an on-site analysis method based on dynamic headspace GC-MS for analysis of five cyclic sulfur mustard degradation products that have previously been detected in sediments from chemical weapon dumping sites: 1,4-oxathiane, 1,3-dithiolane, 1,4-dithiane, 1,4,5-oxadithiephane, and 1,2,5-trithiephane. An experimental design involving authentic Baltic Sea sediments spiked with the target analytes was used to develop an optimized protocol for sample preparation, headspace extraction and analysis that afforded recoveries of up to 60-90%. The optimized method needs no organic solvents, uses only two grams of sediment on a dry weight basis and involves a unique sample presentation whereby sediment is spread uniformly as a thin layer inside the walls of a glass headspace vial. The method showed good linearity for analyte concentrations of 5-200 ng/g dw, good repeatability, and acceptable carry-over. The method's limits of detection for spiked sediment samples ranged from 2.5 to 11 μg/kg dw, with matrix interference being the main limiting factor. The instrumental detection limits were one to two orders of magnitude lower. Full-scan GC-MS analysis enabled the use of automated mass spectral deconvolution for rapid identification of target analytes. Using this approach, analytes could be identified in spiked sediment samples at concentrations down to 13-65 μg/kg dw. On-site validation experiments conducted aboard the research vessel R/V Oceania demonstrated the method's practical applicability, enabling the successful identification of four cyclic sulfur mustard degradation products at concentrations of 15-308μg/kg in sediments immediately after being collected near a wreck at the Bornholm Deep dumpsite in the Baltic Sea. PMID:26711154

  14. Design and synthesis of novel quinazoline nitrogen mustard derivatives as potential therapeutic agents for cancer.

    PubMed

    Li, Shilei; Wang, Xiao; He, Yong; Zhao, Mingxia; Chen, Yurong; Xu, Jingli; Feng, Man; Chang, Jin; Ning, Hongyu; Qi, Chuanmin

    2013-09-01

    Thirteen novel quinazoline nitrogen mustard derivatives were designed, synthesized and evaluated for their anticancer activities in vitro and in vivo. Cytotoxicity assays were carried out in five cancer cell lines (HepG2, SH-SY5Y, DU145, MCF-7 and A549) and one normal human cell line (GES-1), in which compound 22b showed very low IC50 to HepG2 (the IC50 value is 3.06 μM), which was lower than Sorafenib. Compound 22b could inhibit cell cycle at S and G2/M phase and induce cell apoptosis. In the HepG2 xenograft model, 22b exhibited significant cancer growth inhibition with low host toxicity in vivo.

  15. SYNTHESIS OF SULFUR-BASED WATER TREATMENT AGENT FROM SULFUR DIOXIDE WASTE STREAMS

    SciTech Connect

    Robert C. Brown; Maohong Fan

    2001-12-01

    We propose a process that uses sulfur dioxide from coal combustion as a raw material to synthesize polymeric ferric sulfate (PFS), a water treatment agent. The process uses sodium chlorate as an oxidant and ferrous sulfate as an absorbent. The major chemical mechanisms in this reaction system include oxidation, hydrolysis, and polymerization. Oxidation determines sulfur conversion efficiency while hydrolysis and polymerization control the quality of product. Many factors, including SO{sub 2} inlet concentration, flow rate of simulated flue gas, reaction temperature, addition rate of oxidant and stirring rate, may affect the efficiencies of SO{sub 2} removal. Currently, the effects of SO{sub 2} inlet concentration, the flow rate of simulated flue gas and addition rate of flue gas on removal efficiencies of SO{sub 2}, are being investigated. Experiments shown in this report have demonstrated that the conversion efficiencies of sulfur dioxide with ferrous sulfate as an absorbent are in the range of 60-80% under the adopted process conditions. However, the conversion efficiency of sulfur dioxide may be improved by optimizing reaction conditions to be investigated. Partial quality indices of the synthesized products, including Fe{sup 2+} concentration and total iron concentration, have been evaluated.

  16. Sulfur mustard-induced microvesication in hairless guinea pigs: Effect of short-term niacinamide administration. (Reannouncement with new availability information)

    SciTech Connect

    Yourick, J.J.; Dawson, J.S.; Mitcheltree, L.W.

    1992-12-31

    It has been postulated that sulfur mustard (HD) damage may activate poly(ADP-ribose) polymerase (PADPRP), resulting in depletion of cellular NAD+. This biochemical alteration is postulated to result in blister (vesicle) formation. It has been previously demonstrated that niacinamide (NAM), an inhibitor of PADPRP and a precursor for NAD+ synthesis, may be useful as a pretreatment compound to reduce HD-induced microvesication. The present study was undertaken to determine whether niacinamide`s protective action could be extended beyond 24 hr and if the degree of microvesication is related to changes in skin NAD+ content. HD exposures were made by vapor cup to hairless guinea pigs. Niacinamide (750 mg/kg, ip) given as a 30-min pretreatment did not reduce the degree of microvesication 72 hr after HD compared to saline controls. However, niacinamide given as a 30-min pretreatment and at 6-, 24-, and 48-hr after HD, exhibited a 28% reduction in microvesication 72 hr after HD. Skin NAD+ content at 72 hr after HD was depleted by approximately 53% in the saline and NAM-treated groups. Skin NAD+ content was depleted despite NAM administration. Niacinamide did not reduce the degree of erythema at 48 or 72 hr. These results suggest that niacinamide`s protective effect against HD-induced microvesication may be extended for at least 72 hr, but NAM levels must be sustained during the post-HD period. The link between maintenance of skin NAD+ and reductions in microvesication is still uncertain.... Pretreatment, Niacinamide, Hairless guinea pig, Sulfur mustard microvesication.

  17. Role of TNFR1 in lung injury and altered lung function induced by the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

    SciTech Connect

    Sunil, Vasanthi R.; Patel-Vayas, Kinal; Shen, Jianliang; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2011-02-01

    Lung toxicity induced by sulfur mustard is associated with inflammation and oxidative stress. To elucidate mechanisms mediating pulmonary damage, we used 2-chloroethyl ethyl sulfide (CEES), a model sulfur mustard vesicant. Male mice (B6129) were treated intratracheally with CEES (3 or 6 mg/kg) or control. Animals were sacrificed 3, 7 or 14 days later and bronchoalveolar lavage (BAL) fluid and lung tissue collected. Treatment of mice with CEES resulted in an increase in BAL protein, an indication of alveolar epithelial damage, within 3 days. Expression of Ym1, an oxidative stress marker also increased in the lung, along with inducible nitric oxide synthase, and at 14 days, cyclooxygenase-2 and monocyte chemotactic protein-1, inflammatory proteins implicated in tissue injury. These responses were attenuated in mice lacking the p55 receptor for TNF{alpha} (TNFR1-/-), demonstrating that signaling via TNFR1 is key to CEES-induced injury, oxidative stress, and inflammation. CEES-induced upregulation of CuZn-superoxide dismutase (SOD) and MnSOD was delayed or absent in TNFR1-/- mice, relative to WT mice, suggesting that TNF{alpha} mediates early antioxidant responses to lung toxicants. Treatment of WT mice with CEES also resulted in functional alterations in the lung including decreases in compliance and increases in elastance. Additionally, methacholine-induced alterations in total lung resistance and central airway resistance were dampened by CEES. Loss of TNFR1 resulted in blunted functional responses to CEES. These effects were most notable in the airways. These data suggest that targeting TNF{alpha} signaling may be useful in mitigating lung injury, inflammation and functional alterations induced by vesicants.

  18. Chemical Agents

    MedlinePlus

    ... glycol Hydrazine Hydrofluoric acid Hydrogen chloride Lewisite Melamine Mercury Methyl bromide Methyl isocyanate Nicotine Nitrogen mustard Opioids ... L-3) Long-acting anticoagulant (super warfarin) M Mercury Methyl bromide Methyl isocyanate Mustard gas (H) (sulfur ...

  19. Sulfur mustard disrupts human α3β1-integrin receptors in concert with α6β4-integrin receptors and collapse of the keratin K5/K14 cytoskeleton

    NASA Astrophysics Data System (ADS)

    Werrlein, Robert J.; Braue, Catherine R.

    2004-06-01

    Sulfur mustard (SM; bis(2-chloroethyl) sulfide) is a chemical warfare agent that produces persistent, incapacitating blisters of the skin. The lesions inducing vesication remain elusive, and there is no completely effective treatment. Using mulitphoton microscopy and immunofluorescent staining, we found that exposing human epidermal keratinocytes (HEK) and intact epidermis to SM (400 μm for 5 min) caused progressive collapse of the keratin (K5/K14) cytoskeleton and depletion of α6β integrins. We now report that SM causes concomitant disruption nad collapse of the basal cell's α3β1-integrin receptors. At 1 h postexposure, images of Alexa488-conjugated HEK/α3β1 integrins showed almost complete withdrawal and disappearance of retraction fibers and a progressive loss of polarized mobility. With stero imaging, in vitro expression of this SM effect was characterized by collapse and abutment of adjacent cell membranes. At 2 h postexposure, there was an average 13% dorso-ventral collapse of HEK membranes that paralleled progressive collapse of the K5/K14 cytoskeleton. α3β1 integrin, like α6β4 integrin, is a regulator of cytoskeletal assembly, a receptor for laminin 5 and a mediator of HEK attachment to the basement membrane. Our images indicate that SM disrupts these receptors. We suggest that the progressive disruption destabilizes and potentiates blistering of the epidermal-dermal junction.

  20. Optimized verification method for detection of an albumin-sulfur mustard adduct at Cys(34) using a hybrid quadrupole time-of-flight tandem mass spectrometer after direct plasma proteolysis.

    PubMed

    John, Harald; Siegert, Markus; Gandor, Felix; Gawlik, Michael; Kranawetvogl, Andreas; Karaghiosoff, Konstantin; Thiermann, Horst

    2016-02-26

    The vesicant sulfur mustard (SM) is a banned chemical warfare agent that is controlled by the Organisation for the Prohibition of Chemical Weapons (OPCW). Bioanalytical procedures are mandatory for proving an alleged use and incorporation of SM into the body. We herein present the development and application of a novel optimized procedure suitable for qualitative verification analysis of plasma targeting the SM-adduct of human serum albumin (HSA) alkylated at the cysteine(34) residue. Diluted human plasma is directly mixed with pronase in an ultrafiltration device (10kDa cut-off) for proteolysis (4h, 37°C). Following ultrafiltration the filtrate is diluted and analyzed by microbore liquid chromatography-electrospray ionization high resolution tandem-mass spectrometry (μLC-ESI HR MS/MS) targeting the alkylated dipeptide hydroxyethylthioethyl-CysPro (HETE-CP). A hybrid quadrupole time-of-flight mass spectrometer provided high mass spectrometric resolution in the MS/MS mode enabling highest selectivity and sensitivity (lower limit of detection corresponding to 9.8nM SM in plasma). Kinetics of HETE-CP formation from heparin-, citrate-, and EDTA-plasma as well as serum are presented and the influence of different EDTA and pronase concentrations was characterized. The novel procedure was applied to plasma samples provided by the OPCW as well as to patientś plasma derived from real cases of SM-poisoning.

  1. Optimized verification method for detection of an albumin-sulfur mustard adduct at Cys(34) using a hybrid quadrupole time-of-flight tandem mass spectrometer after direct plasma proteolysis.

    PubMed

    John, Harald; Siegert, Markus; Gandor, Felix; Gawlik, Michael; Kranawetvogl, Andreas; Karaghiosoff, Konstantin; Thiermann, Horst

    2016-02-26

    The vesicant sulfur mustard (SM) is a banned chemical warfare agent that is controlled by the Organisation for the Prohibition of Chemical Weapons (OPCW). Bioanalytical procedures are mandatory for proving an alleged use and incorporation of SM into the body. We herein present the development and application of a novel optimized procedure suitable for qualitative verification analysis of plasma targeting the SM-adduct of human serum albumin (HSA) alkylated at the cysteine(34) residue. Diluted human plasma is directly mixed with pronase in an ultrafiltration device (10kDa cut-off) for proteolysis (4h, 37°C). Following ultrafiltration the filtrate is diluted and analyzed by microbore liquid chromatography-electrospray ionization high resolution tandem-mass spectrometry (μLC-ESI HR MS/MS) targeting the alkylated dipeptide hydroxyethylthioethyl-CysPro (HETE-CP). A hybrid quadrupole time-of-flight mass spectrometer provided high mass spectrometric resolution in the MS/MS mode enabling highest selectivity and sensitivity (lower limit of detection corresponding to 9.8nM SM in plasma). Kinetics of HETE-CP formation from heparin-, citrate-, and EDTA-plasma as well as serum are presented and the influence of different EDTA and pronase concentrations was characterized. The novel procedure was applied to plasma samples provided by the OPCW as well as to patientś plasma derived from real cases of SM-poisoning. PMID:26449527

  2. Pseudo-epidermis: A model system for investigating molecular and cellular pathways of cutaneous epidermal toxicity from sulfur mustard

    SciTech Connect

    Bernstein, I.A.; Bernstam, L.I.; Yang, Y.H.; Lin, P.P.; Vaughan, F.L.

    1993-05-13

    Damage to DNA, Inhibition of DNA replication and mitosis, appearance of abnormal keratin peptide and large differentiated cells and, finally, death of cells occur dose- and time-responsively in submerged cultures of keratinocytes exposed to bis-(b-chloroethyl)sulfide (BCES). However, the relevance of these parameters to vesication in human skin exposed to mustard in vivo has yet to be established. The pseudo-epidermis cultured from human cutaneous keratinocytes offers a system in which the pathogenic importance of each of these parameters can be evaluated. To establish the validity of the system, it is necessary to show that the pseudo-epidermis undergoes similar dose- and time-dependent cytotoxicity from BCES as is observed in the human skin after topical exposure to the mustard. This report includes data which demonstrate a dose- and time-dependent destruction of the germinative layer in human pseudo-epidermis after topical application of BCES. In addition, data are included to show that DNA is a primary target for BCES in pseudo-epidermis as it is in vivo. Also included in this report is a proposed sequence of molecular and cellular events to account for cytotoxicity in the germinative population of the pseudo-epidermis after exposure to BCES.

  3. Mechanisms of cutaneous vesication: Detection of sulfur mustard bis(2-chloroethyl) sulfide and metabolites after topical application in the isolated perfused

    SciTech Connect

    Spoo, J.W.; Monteiro-Rivier, N.A.; Riviere, J.E.

    1995-10-01

    The purpose of this study was to develop an assay to study the flux of sulfur mustard (HD) through the skin and determine if metabolites are formed due to the epidermal metabolism of HD after topical exposure of the isolated perfused porcine skin flap (IPPSF) to 14C-HD. Four IPPSFs were topically dosed with 2.85 mg of 14C-HD in ethanol. Venous perfusate samples were collected and added to a 34% solution of NaCI and snap-frozen to inhibit the metabolism of RD until time for assay. Perfusate samples were extracted using a solid-phase extraction cartridge with ethyl acetate and then assayed using gas chromatography. Two of the 4 IPPSFs showed detectable levels of RD in the venous perfusate 15 min after dosing, with 1 of these 2 IPPSFs showing detectable levels of RD in the perfusate 2 hours after dosing. All 4 IPPSFs had no more than 3 metabolites of RD appearing in the perfusate throughout the 2 hr experiment, with one of those metabolites identified as thiodiglycol. These experiments showed that little, if any, RD appears in the venous perfusate intact after percutaneous absorption and that epidermal metabolism of RD does occur to a significant degree in the IPPSF.

  4. A novel approach for high sensitive determination of sulfur mustard by derivatization and isotope-dilution LC-MS/MS analysis.

    PubMed

    Xu, Bin; Zong, Cheng; Nie, Zhiyong; Guo, Lei; Xie, Jianwei

    2015-01-01

    A new isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of sulfur mustard (SM) has been developed using a direct chemical derivatization method by nucleophile potassium thioacetate (PTA) in aqueous solution. The reaction conditions for derivatization, such as reaction temperature, time, solvent and concentration of PTA, were optimized for high performance. Reversed phase liquid chromatography was suitable for analysis of such a PTA derivatized SM in complex environmental samples. Compared with other conventional gas chromatography or gas chromatography-mass spectrometry methods for direct detection on SM, better sensitivity and selectivity were achieved by this direct derivatization and LC-MS/MS method, where SM can be detected as low as 0.05 ng/mL in acetonitrile. The linear range was from 0.1 to 1000 ng/mL. The relative standard deviation (RSD) of the intra-day precision was less than 11.8%, and RSD of the inter-day precision was less than 12.3%. The whole procedure for both derivatization and analysis was quick and simple, and the total time was less than 1h. This established method has been successfully employed for determination of spiking samples both in water and soil. A detection limit of 0.1 ng/mL was achieved for river water, while the SM in soil sample could be detected at 0.1 ng/g. PMID:25476305

  5. Hair analysis as a useful procedure for detection of vapour exposure to chemical warfare agents: simulation of sulphur mustard with methyl salicylate.

    PubMed

    Spiandore, Marie; Piram, Anne; Lacoste, Alexandre; Josse, Denis; Doumenq, Pierre

    2014-06-01

    Chemical warfare agents (CWA) are highly toxic compounds which have been produced to kill or hurt people during conflicts or terrorist attacks. Despite the fact that their use is strictly prohibited according to international convention, populations' exposure still recently occurred. Development of markers of exposure to CWA is necessary to distinguish exposed victims from unexposed ones. We present the first study of hair usage as passive sampler to assess contamination by chemicals in vapour form. This work presents more particularly the hair adsorption capacity for methyl salicylate used as a surrogate of the vesicant sulphur mustard. Chemical vapours toxicity through the respiratory route has historically been defined through Haber's law's concentration-time (Ct) product, and vapour exposure of hair to methyl salicylate was conducted with various times or doses of exposure in the range of incapacitating and lethal Ct products corresponding to sulphur mustard. Following exposure, extraction of methyl salicylate from hair was conducted by simple soaking in dichloromethane. Methyl salicylate could be detected on hair for vapour concentration corresponding to about one fifth of the sulphur mustard concentration that would kill 50% of exposed individuals (LCt50). The amount of methyl salicylate recovered from hair increased with time or dose of exposure. It showed a good correlation with the concentration-time product, suggesting that hair could be used like a passive sampler to assess vapour exposure to chemical compounds. It introduces great perspectives concerning the use of hair as a marker of exposure to CWA.

  6. Synthesis and evaluation of DNA-targeted spatially separated bis(aniline mustards) as potential alkylating agents with enhanced DNA cross-linking capability.

    PubMed

    Gourdie, T A; Prakash, A S; Wakelin, L P; Woodgate, P D; Denny, W A

    1991-01-01

    DNA-targeted separated bis-mustards were synthesized by attaching aniline mono-mustards at the 4- and 9-positions of the DNA-intercalating ligand 9-aminoacridine-4-carboxamide, with the intention of improving the low cross-link to monoadduct ratio found with most alkylating agents. The geometry of these compounds requires that, when the acridine binds to DNA by intercalation, one alkylating moiety is delivered to each DNA groove. Gel electrophoretic studies show that only one arm of these compounds (probably that attached to the 9-position) alkylates DNA, such alkylation occurring specifically in the major groove at the N7 of guanines. Cell-line studies confirm that the mode of cytotoxicity of these compounds (unlike that of untargeted aniline bis-mustards of comparable reactivity) is due to bulky DNA monoadduct formation. It is concluded that more information is required about the exact orientation of the initial monoadducts before ligands with specific DNA cross-linking ability can be designed.

  7. The synthesis and biological evaluation of new DNA-directed alkylating agents, phenyl N-mustard-4-anilinoquinoline conjugates containing a urea linker.

    PubMed

    Marvania, Bhavin; Kakadiya, Rajesh; Christian, Wilson; Chen, Tai-Lin; Wu, Ming-Hsi; Suman, Sharda; Tala, Kiran; Lee, Te-Chang; Shah, Anamik; Su, Tsann-Long

    2014-08-18

    We synthesized a series of phenyl N-mustard-4-anilinoquinoline conjugates to study their antitumorigenic effects. These agents were prepared by the condensation of 4-[N,N-bis(2-chloroethyl)amino]phenyl isocyanate with 6-amino-4-methylamino or 4-anilinoquinolines. The structure-activity relationship (SAR) studies revealed that the C2-methylquinoline derivatives (18a-o) were generally more cytotoxic than the C2-phenylquinoline conjugates (23a-d) in inhibiting the cell growth of various human tumor cell lines in vitro. However, the methylamino or aniline substituents at C4 of quinoline did not influence the cytotoxic effects. The title conjugates were capable of inducing DNA cross-linking and promoting cell-cycle arrest at the G2/M phase. This study demonstrates that phenyl N-mustard-4-anilinoquinoline conjugates are generally more potent than phenyl N-mustard-4-anilinoquinazoline conjugates against the cell growth of various tumor cell-lines.

  8. Chemical genetics analysis of an aniline mustard anticancer agent reveals complex I of the electron transport chain as a target.

    PubMed

    Fedeles, Bogdan I; Zhu, Angela Y; Young, Kellie S; Hillier, Shawn M; Proffitt, Kyle D; Essigmann, John M; Croy, Robert G

    2011-09-30

    The antitumor agent 11β (CAS 865070-37-7), consisting of a DNA-damaging aniline mustard linked to an androgen receptor (AR) ligand, is known to form covalent DNA adducts and to induce apoptosis potently in AR-positive prostate cancer cells in vitro; it also strongly prevents growth of LNCaP xenografts in mice. The present study describes the unexpectedly strong activity of 11β against the AR-negative HeLa cells, both in cell culture and tumor xenografts, and uncovers a new mechanism of action that likely explains this activity. Cellular fractionation experiments indicated that mitochondria are the major intracellular sink for 11β; flow cytometry studies showed that 11β exposure rapidly induced oxidative stress, mitochondria being an important source of reactive oxygen species (ROS). Additionally, 11β inhibited oxygen consumption both in intact HeLa cells and in isolated mitochondria. Specifically, 11β blocked uncoupled oxygen consumption when mitochondria were incubated with complex I substrates, but it had no effect on oxygen consumption driven by substrates acting downstream of complex I in the mitochondrial electron transport chain. Moreover, 11β enhanced ROS generation in isolated mitochondria, suggesting that complex I inhibition is responsible for ROS production. At the cellular level, the presence of antioxidants (N-acetylcysteine or vitamin E) significantly reduced the toxicity of 11β, implicating ROS production as an important contributor to cytotoxicity. Collectively, our findings establish complex I inhibition and ROS generation as a new mechanism of action for 11β, which supplements conventional DNA adduct formation to promote cancer cell death.

  9. DNA-directed alkylating ligands as potential antitumor agents: sequence specificity of alkylation by intercalating aniline mustards.

    PubMed

    Prakash, A S; Denny, W A; Gourdie, T A; Valu, K K; Woodgate, P D; Wakelin, L P

    1990-10-23

    The sequence preferences for alkylation of a series of novel parasubstituted aniline mustards linked to the DNA-intercalating chromophore 9-aminoacridine by an alkyl chain of variable length were studied by using procedures analogous to Maxam-Gilbert reactions. The compounds alkylate DNA at both guanine and adenine sites. For mustards linked to the acridine by a short alkyl chain through a para O- or S-link group, 5'-GT sequences are the most preferred sites at which N7-guanine alkylation occurs. For analogues with longer chain lengths, the preference of 5'-GT sequences diminishes in favor of N7-adenine alkylation at the complementary 5'-AC sequence. Magnesium ions are shown to selectively inhibit alkylation at the N7 of adenine (in the major groove) by these compounds but not the alkylation at the N3 of adenine (in the minor groove) by the antitumor antibiotic CC-1065. Effects of chromophore variation were also studied by using aniline mustards linked to quinazoline and sterically hindered tert-butyl-9-aminoacridine chromophores. The results demonstrate that in this series of DNA-directed mustards the noncovalent interactions of the carrier chromophores with DNA significantly modify the sequence selectivity of alkylation by the mustard. Relationships between the DNA alkylation patterns of these compounds and their biological activities are discussed.

  10. Nitrogen Mustards

    MedlinePlus

    ... your clothing, rapidly wash your entire body with soap and water, and get medical care as quickly ... mustard from your skin with large amounts of soap and water. Washing with soap and water will ...

  11. Organic Chemical Attribution Signatures for the Sourcing of a Mustard Agent and Its Starting Materials.

    PubMed

    Fraga, Carlos G; Bronk, Krys; Dockendorff, Brian P; Heredia-Langner, Alejandro

    2016-05-17

    Chemical attribution signatures (CAS) are being investigated for the sourcing of chemical warfare (CW) agents and their starting materials that may be implicated in chemical attacks or CW proliferation. The work reported here demonstrates for the first time trace impurities from the synthesis of tris(2-chloroethyl)amine (HN3) that point to the reagent and the specific reagent stocks used in the synthesis of this CW agent. Thirty batches of HN3 were synthesized using different combinations of commercial stocks of triethanolamine (TEA), thionyl chloride, chloroform, and acetone. The HN3 batches and reagent stocks were then analyzed for impurities by gas chromatography/mass spectrometry. All the reagent stocks had impurity profiles that differentiated them from one another. This was demonstrated by building classification models with partial least-squares discriminant analysis (PLSDA) and obtaining average stock classification errors of 2.4, 2.8, 2.8, and 11% by cross-validation for chloroform (7 stocks), thionyl chloride (3 stocks), acetone (7 stocks), and TEA (3 stocks), respectively, and 0% for a validation set of chloroform samples. In addition, some reagent impurities indicative of reagent type were found in the HN3 batches that were originally present in the reagent stocks and presumably not altered during synthesis. More intriguing, impurities in HN3 batches that were apparently produced by side reactions of impurities unique to specific TEA and chloroform stocks, and thus indicative of their use, were observed. PMID:27116337

  12. Allyl isothiocyanate from mustard seed is effective in reducing the levels of volatile sulfur compounds responsible for intrinsic oral malodor.

    PubMed

    Tian, Minmin; Hanley, A Bryan; Dodds, Michael W J

    2013-06-01

    Oral malodor is a major social and psychological issue that affects general populations. Volatile sulfur compounds (VSCs), particularly hydrogen sulfide (H₂S) and methyl mercaptan (CH₃SH), are responsible for most oral malodor. The objectives for this study were to determine whether allyl isothiocyanate (AITC) at an organoleptically acceptable level can eliminate VSCs containing a free thiol moiety and further to elucidate the mechanism of action and reaction kinetics. The study revealed that gas chromatograph with a sulfur detector demonstrated a good linearity, high accuracy and sensitivity on analysis of VSCs. Zinc salts eliminate the headspace level of H₂S but not CH₃SH. AITC eliminates both H₂S and CH₃SH via a nucleophilic addition reaction. In addition, a chemical structure-activity relationship study revealed that the presence of unsaturated group on the side chain of the isothiocyanate accelerates the elimination of VSCs. PMID:23470258

  13. Airway tissue factor-dependent coagulation activity in response to sulfur mustard analog 2-chloroethyl ethyl sulfide

    PubMed Central

    Rancourt, Raymond C.; Veress, Livia A.; Guo, XiaoLing; Jones, Tara N.; Hendry-Hofer, Tara B.

    2012-01-01

    Acute lung injury is a principal cause of morbidity and mortality in response to mustard gas (SM) inhalation. Obstructive, fibrin-containing airway casts have recently been reported in a rat inhalation model employing the SM analog 2-chloroethyl ethyl sulfide (CEES). The present study was designed to identify the mechanism(s) causing activation of the coagulation cascade after CEES-induced airway injury. Here we report that CEES inhalation elevates tissue factor (TF) activity and numbers of detached epithelial cells present in lavage fluid (BALF) from rats after exposure (18 h). In vitro studies using 16HBE cells, or with rat BALF, indicated that detached epithelial cells could convert factor X (FX) to the active form FXa when incubated with factor VII and could elicit rapid clotting of plasma. In addition, immunocytochemical analysis demonstrated elevated cell surface (TF) expression on CEES-exposed 16HBE cells as a function of time. However, total cell TF expression did not increase. Since membrane surfaces bearing TF are important determinants of clot initiation, anticoagulants directed against these entities were tested for ability to limit plasma clotting or FX activation capacity of BALF or culture media. Addition of tifacogin, a TF pathway inhibitor, effectively blocked either activity, demonstrating that the procoagulant actions of CEES were TF pathway dependent. Lactadherin, a protein capable of competing with clotting factors for phospholipid-binding sites, was partially effective in limiting these procoagulant actions. These findings indicate that TF pathway inhibition could be an effective strategy to prevent airway obstruction after SM or CEES inhalation. PMID:21964405

  14. Detection and identification of hydrolysis products of sulfur mustards at trace levels in environmental samples using liquid chromatography solid phase extraction combined with off-line nuclear magnetic resonance analysis.

    PubMed

    Meier, Urs C

    2013-04-19

    An LC-UV-SPE NMR method for the analysis of polar hydrolysis products of the chemical warfare agents known as sulfur mustards at low ppm levels in environmental samples is developed. The hydrolysis products thiodiglycol (I), bis(2-hydroxyethylthio)methane (II), 1,2-bis(2-hydroxyethylthio)ethane (III), 1,3-bis(2-hydroxyethylthio)propane (IV), 1,4-bis(2-hydroxyethylthio)butane (V), 1,5-bis(2-hydroxyethylthio)pentane (VI), bis(2-hydroxymethylthioethyl)ether (VII) and bis(2-hydroxyethylthioethyl)ether (VIII) are baseline separated within 11 min by the LC gradient program and trapped post-column on SPE cartridges. After elution in 2mm o.d. NMR tubes (1)H NMR spectra were recorded. Recoveries vary from 43±5 for I to 102±5% for VI and are limited by volume breakthrough. The detection limits of the LC-SPE NMR method vary between 200 ng for V and 450 ng for I. Increasing the injection volume is shown to be more effective than multiple trapping for the analytes I-VIII to increase the amount of material trapped on the SPE cartridges. The applicability of the developed method to the analysis of environmental samples was tested by the analysis of sample 293 provided by the 29th Official OPCW (Organization for the Prohibition of Chemical Weapons) Proficiency Test. The chromatographic and (1)H NMR data obtained by the method are highly reproducible and provide acceptable data for the identification of chemicals related to CWC (Chemical Weapons Convention) in case an off-site analysis for the verification of the CWC or OPCW Proficiency Tests according to the OPCW criteria for the acceptance of chromatographic and (1)H NMR spectral data. PMID:23518263

  15. Ethylene production is associated with alleviation of cadmium-induced oxidative stress by sulfur in mustard types differing in ethylene sensitivity.

    PubMed

    Asgher, Mohd; Khan, Nafees A; Khan, M Iqbal R; Fatma, Mehar; Masood, Asim

    2014-08-01

    We studied the response of ethylene-sensitive (Pusa Jai Kisan) and ethylene-insensitive (SS2) mustard (Brassica juncea) cultivars to 0, 0.5, 1.0 and 2.0 mM SO₄(2-), and the effect of 1.0 mM SO₄(2-) was studied in the amelioration of 50 µM cadmium (Cd). The Cd-induced oxidative stress and Cd accumulation were greater in SS2 than Pusa Jai Kisan, but sulfur (S) application alleviated Cd-induced oxidative stress more prominently in Pusa Jai Kisan by increasing S-metabolism and synthesis of reduced glutathione (GSH) and ethylene production; and promoted photosynthesis and plant dry mass under Cd stress. The ethylene-sensitive cultivar responded more to S treatment under Cd stress and showed increased activity of antioxidant system resulting in increased photosynthesis and growth. Cadmium treatment resulted in rapid increase in ethylene formation which adversely influenced photosynthesis and plant dry mass. However, S and ethephon application to Cd-treated plants lowered ethylene formation to optimal range responsible for maximal GSH synthesis and protection against Cd-induced oxidative stress. The similarity of the effectiveness of 1.0 mM SO₄(2-) with 200 µL L(-1) ethylene source as ethephon in alleviation of 50 µM Cd further verifies that differential alleviation of Cd toxicity in the two cultivars by S was dependent on ethylene production. The results suggest that ethylene production determines Cd stress alleviation by S via regulatory interaction with antioxidant metabolism. Thus, ethylene production and sensitivity bear a prominent role in alleviation of Cd stress by S and can be used as a criterion for developing Cd tolerant genotypes.

  16. Upregulation of miR-203 and miR-210 affect growth and differentiation of keratinocytes after exposure to sulfur mustard in normoxia and hypoxia.

    PubMed

    Deppe, Janina; Steinritz, Dirk; Santovito, Donato; Egea, Virginia; Schmidt, Annette; Weber, Christian; Ries, Christian

    2016-02-26

    Exposure of the skin to sulfur mustard (SM) results in long-term complications such as impaired tissue regeneration. Previous own studies in normal human epidermal keratinocytes (NHEK) treated with SM demonstrated reduced proliferation, premature differentiation and a restricted functionality of hypoxia-mediated signaling in the cells. Here, we investigated the involvement of microRNAs, miR-203 and miR-210, in these mechanisms. SM significantly upregulated the expression of miR-203 in NHEK when cultivated under normoxic and hypoxic conditions. SM had no effect on miR-210 under normoxia. However, miR-210 levels were greatly increased in NHEK when grown in hypoxia and further elevated upon exposure of the cells to SM. In normoxia and hypoxia, inhibition of miR-203 by transfection of NHEK with complementary oligonucleotides, anti-miR-203, attenuated the SM-induced impairment of metabolic activity and proliferation, and counteracted SM-promoted keratin-1 expression in these cells. Consistent ameliorating effects on dysregulated metabolic activity, proliferation and keratin-1 expression in SM-treated NHEK were obtained upon inhibition of miR-210 in these cells grown in hypoxia. Our findings provide evidence that miR-203 and miR-210 are key regulators in normal and SM-impaired keratinocyte functionality, and suggest potential usefulness of inhibitors against miR-203 and miR-210 for target-directed therapeutical intervention to improve re-epithelialization of SM-injured skin.

  17. Short-term Curcuminoid Supplementation for Chronic Pulmonary Complications due to Sulfur Mustard Intoxication: Positive Results of a Randomized Double-blind Placebo-controlled Trial.

    PubMed

    Panahi, Y; Ghanei, M; Bashiri, S; Hajihashemi, A; Sahebkar, A

    2015-11-01

    Pulmonary problems are among the most frequent chronic complications of sulfur mustard (SM) intoxication and are often accompanied by deregulated production of pro-inflammatory cytokines. Curcuminoids, comprising curcumin, demethoxycurcumin and bisdemethoxycurcumin, are phytochemicals with remarkable anti-inflammatory properties that are derived from dried rhizomes of the plant Curcuma longa L. (turmeric). The present pilot study aimed to investigate the clinical effects of supplementation with curcuminoids on markers of pulmonary function and systemic inflammation in SM-intoxicated subjects. In a randomized double-blind placebo-controlled trial, 89 male subjects who were suffering from chronic SM-induced pulmonary complications were recruited and assigned to either curcuminoids (500 mg TID per oral; n=45) or placebo (n=44) for a period of 4 weeks. Efficacy measures were changes in the spirometric parameters (FVC, FEV1, FEV1/FVC) and serum levels of inflammatory mediators including interleukins 6 (IL-6) and 8 (IL-8), tumor necrosis factor-α (TNFα), transforming growth factor-β (TGFβ), high-sensitivity C-reactive protein (hs-CRP), calcitonin gene related peptide (CGRP), substance P and monocyte chemotactic protein-1 (MCP-1). 78 subjects completed the trial. Although FEV1 and FVC remained comparable between the groups, there was a greater effect of curcuminoids vs. placebo in improving FEV1/FVC (p=0.002). Curcuminoids were also significantly more efficacious compared to placebo in modulating all assessed inflammatory mediators: IL-6 (p<0.001), IL-8 (p=0.035), TNFα (p<0.001), TGFβ (p<0.001), substance P (p=0.016), hs-CRP (p<0.001), CGRP (p<0.001) and MCP-1 (p<0.001). Curcuminoids were safe and well-tolerated throughout the trial. Short-term adjunctive therapy with curcuminoids can suppress systemic inflammation in patients suffering from SM-induced chronic pulmonary complications. PMID:25268878

  18. Regulation of Hsp27 and Hsp70 expression in human and mouse skin construct models by caveolae following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

    SciTech Connect

    Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.; Heck, Diane E.; Gerecke, Donald R.; Sinko, Patrick J.; Laskin, Debra L.; Laskin, Jeffrey D.

    2011-06-01

    Dermal exposure to the vesicant sulfur mustard causes marked inflammation and tissue damage. Basal keratinocytes appear to be a major target of sulfur mustard. In the present studies, mechanisms mediating skin toxicity were examined using a mouse skin construct model and a full-thickness human skin equivalent (EpiDerm-FT{sup TM}). In both systems, administration of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide (CEES, 100-1000 {mu}M) at the air surface induced mRNA and protein expression of heat shock proteins 27 and 70 (Hsp27 and Hsp70). CEES treatment also resulted in increased expression of caveolin-1, the major structural component of caveolae. Immunohistochemistry revealed that Hsp27, Hsp70 and caveolin-1 were localized in basal and suprabasal layers of the epidermis. Caveolin-1 was also detected in fibroblasts in the dermal component of the full thickness human skin equivalent. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that Hsp27 and Hsp70 were localized in caveolae. Treatment of mouse keratinocytes with filipin III or methyl-{beta}-cyclodextrin, which disrupt caveolar structure, markedly suppressed CEES-induced Hsp27 and Hsp70 mRNA and protein expression. CEES treatment is known to activate JNK and p38 MAP kinases; in mouse keratinocytes, inhibition of these enzymes suppressed CEES-induced expression of Hsp27 and Hsp70. These data suggest that MAP kinases regulate Hsp 27 and Hsp70; moreover, caveolae-mediated regulation of heat shock protein expression may be important in the pathophysiology of vesicant-induced skin toxicity.

  19. An improved method for retrospective quantification of sulfur mustard exposure by detection of its albumin adduct using ultra-high pressure liquid chromatography-tandem mass spectrometry.

    PubMed

    Liu, ChangCai; Liang, LongHui; Xiang, Yu; Yu, HuiLan; Zhou, ShiKun; Xi, HaiLing; Liu, ShiLei; Liu, JingQuan

    2015-09-01

    Sulfur mustard (HD) adduct to human serum albumin (ALB) at Cys-34 residue has become an important and long-term retrospective biomarker of HD exposure. Here, a novel, sensitive, and convenient approach for retrospective quantification of HD concentration exposed to plasma was established by detection of the HD-ALB adduct using ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with a novel non-isotope internal standard (IS). The HD-ALB adduct was isolated from HD-exposed plasma with blue Sepharose. The adduct was digested with proteinase K to form sulfur-hydroxyethylthioethyl ([S-HETE])-Cys-Pro-Phe tripeptide biomarker. The tripeptide adduct could be directly analyzed by UHPLC-MS/MS without an additional solid phase extraction (SPE), which was considered as a critical procedure in previous methods. The easily available 2-chloroethyl ethylsulfide (2-CEES) as HD surrogate was first reported to be used as IS in place of traditional d8-HD for quantification of HD exposure. Furthermore, 2-CEES was also confirmed to be a good IS alternative for quantification of HD exposure by investigation of product ion spectra for their corresponding tripeptide adducts which exhibited identical MS/MS fragmentation behaviors. The method was found to be linear between 1.00 and 250 ng•mL(-1) HD exposure (R(2)>0.9989) with precision of <4.50% relative standard deviation (%RSD), accuracy range between 96.5% and 114%, and a calculated limit of detection (LOD) of 0.532 ng•mL(-1). The lowest reportable limit (LRL) is 1.00 ng•mL(-1), over seven times lower than that of the previous method. The entire method required only 0.1 mL of plasma sample and took under 7 h without special sample preparation equipment. It is proven to be a sensitive, simple, and rugged method, which is easily applied in international laboratories to improve the capabilities for the analysis of biomedical samples related to verification of the Chemical Weapon Convention (CWC).

  20. Molecular biology basis for the response of poly(ADP-rib) polymerase and NAD metabolism to dna damage caused by mustard alkylating agents. Final report, 30 April 1990-30 July 1994

    SciTech Connect

    Smulson, M.E.

    1994-08-30

    During the course of this contract, we have performed a variety of experiments whose intent has been to provide a strategy to modulate the nuclear enzyme poly(ADP-ribose) polymerase (PADPRP) in cultured keratinocytes. During this study, human keratinocyte lines were stably transfected with the cDNA for human PADPRP in the antisense orientation under an inducible promoter. Induction of this antisense RNA by dexamethasone in cultured cells selectively lowered levels of PADPRP in RNA, protein, and enzyme activity. Induction of antisense RNA led to a reduction in the levels of PADPRP in individual cell nuclei, as well as the loss of the ability of cells to synthesize and modify proteins by poly(ADP-ribose) polymer in response to an alkylating agent. When keratinocyte clones containing the antisense construct or empty vector alone were grafted onto nude mice they formed histologically normal human skin. The PADPRP antisense construct was also inducible in vivo by the topical application of dexamethasone to the reconstituted epidermis. In addition, poly(ADP-ribose) polymer could be induced and detected in vivo following the topical application of a sulfur mustard to the grafted transfected skin layers. Accordingly, a model system has been developed in which the levels of PADPRP can be selectively manipulated in human keratinocytes in cell culture, and potentially in reconstituted epidermis as well.

  1. Sulfur polymer cement, a solidification and stabilization agent for hazardous and radioactive wastes

    SciTech Connect

    Darnell, G.R.

    1992-01-01

    Hydraulic cements have been the primary radioactive waste stabilization agents in the United States for 50 years. Twelve years ago, Brookhaven National Laboratory was funded by the Department of Energy's Defense Low-Level Waste Management Program to test and develop sulfur polymer cement (SPC). It has stabilized routine wastes as well as some troublesome wastes with high waste-to-agent ratios. The Department of Energy's Hazardous Waste Remedial Action Program joined the effort by providing funding for testing and developing sulfur polymer cement as a hazardous-waste stabilization agent. Sulfur polymer cement has passed all the laboratory scale tests required by the US Environmental Protection Agency and US Nuclear Regulatory Commission. Two decades of tests by the US Bureau of Mines and private concrete contractors indicate this agent is likely to exceed other agents in longevity. This bulletin provides technical data from pertinent tests conducted by these various entities.

  2. Sulfur polymer cement, a solidification and stabilization agent for hazardous and radioactive wastes

    SciTech Connect

    Darnell, G.R.

    1992-09-01

    Hydraulic cements have been the primary radioactive waste stabilization agents in the United States for 50 years. Twelve years ago, Brookhaven National Laboratory was funded by the Department of Energy`s Defense Low-Level Waste Management Program to test and develop sulfur polymer cement (SPC). It has stabilized routine wastes as well as some troublesome wastes with high waste-to-agent ratios. The Department of Energy`s Hazardous Waste Remedial Action Program joined the effort by providing funding for testing and developing sulfur polymer cement as a hazardous-waste stabilization agent. Sulfur polymer cement has passed all the laboratory scale tests required by the US Environmental Protection Agency and US Nuclear Regulatory Commission. Two decades of tests by the US Bureau of Mines and private concrete contractors indicate this agent is likely to exceed other agents in longevity. This bulletin provides technical data from pertinent tests conducted by these various entities.

  3. Th17/Treg-related cytokine imbalance in sulfur mustard exposed and stable chronic obstructive pulmonary (COPD) patients: correlation with disease activity.

    PubMed

    Imani, Saber; Salimian, Jafar; Fu, Junjiang; Ghanei, Mostafa; Panahi, Yunes

    2016-08-01

    In this study, we investigated expression changes of Th17/Treg-related cytokine in transbronchial lung biopsy (TBLBs) of sulfur mustard (SM) exposure, stable chronic obstructive pulmonary disease (COPD) patients and also compared it with a healthy control (HC) group. Here, ROR-γt, FoxP3, and Treg/Th17-related cytokines (IL-10, IL-17A, IL-6, and TGF-β1) were assessed using a combination of RT-QPCR and ELISA in 11 SM-exposed cases, 9 patients with GOLD stage II COPD diagnosed, and 8 HC. Our results showed that the levels of Foxp3 expression were lower and ROR-γt expression was higher in SM and COPD patients when compared with HC (all p values were less than 0.001). The relative Foxp3 expressions and Foxp3/ROR-γt ratio were positively correlated with FEV1 (%) pred (R = 0.682 and R = 0.602, respectively; p ≤ 0.001). However, the relative ROR-γt expressions were inversely correlated with FEV1 (%) pred (R= -0.75, p = 0.003) and relative Foxp3 expression (R= -0.704, p = 0.003). The mRNA and protein expression of IL-10 were significantly decreased in SM and COPD patients compared with HC (p < 0.001). An increase of IL-17A (∼7.2 fold) and TGF-β1 (∼5.6 fold) are involved in the lung exacerbation of SM and COPD patients. The expression of IL-6 was variable between three groups (p ≥ 0.05). In addition, an inverse correlation were observed between FEV1 (%) pred and expressions of IL-17A (R= -0.741), IL-6 (R= -0.673) and TGF-β1 (R= -0.632) (p ≤ 0.001). Instead, positive correlation was found between IL-10 ratios and FEV1 (%) pred (R = 0.777, p = 0.001). These findings suggest that Treg/Th17-mediated distributions are involved in the progression of chronic lung injury of SM and COPD patients.

  4. Effects of poly (ADP-ribose) polymerase-1 (PARP-1) inhibition on sulfur mustard-induced cutaneous injuries in vitro and in vivo

    PubMed Central

    Liu, Feng; Jiang, Ning; Xiao, Zhi-yong; Cheng, Jun-ping; Mei, Yi-zhou; Zheng, Pan; Wang, Li; Zhang, Xiao-rui; Zhou, Xin-bo

    2016-01-01

    Early studies with first-generation poly (ADP-ribose) polymerase (PARP) inhibitors have already indicated some therapeutic potential for sulfur mustard (SM) injuries. The available novel and more potential PARP inhibitors, which are undergoing clinical trials as drugs for cancer treatment, bring it back to the centre of interest. However, the role of PARP-1 in SM-induced injury is not fully understood. In this study, we selected a high potent specific PARP inhibitor ABT-888 as an example to investigate the effect of PARP inhibitor in SM injury. The results showed that in both the mouse ear vesicant model (MEVM) and HaCaT cell model, PARP inhibitor ABT-888 can reduce cell damage induced by severe SM injury. ABT-888 significantly reduced SM induced edema and epidermal necrosis in MEVM. In the HaCaT cell model, ABT-888 can reduce SM-induced NAD+/ATP depletion and apoptosis/necrosis. Then, we studied the mechanism of PARP-1 in SM injury by knockdown of PARP-1 in HaCaT cells. Knockdown of PARP-1 protected cell viability and downregulated the apoptosis checkpoints, including p-JNK, p-p53, Caspase 9, Caspase 8, c-PARP and Caspase 3 following SM-induced injury. Furthermore, the activation of AKT can inhibit autophagy via the regulation of mTOR. Our results showed that SM exposure could significantly inhibit the activation of Akt/mTOR pathway. Knockdown of PARP-1 reversed the SM-induced suppression of the Akt/mTOR pathway. In summary, the results of our study indicated that the protective effects of downregulation of PARP-1 in SM injury may be due to the regulation of apoptosis, necrosis, energy crisis and autophagy. However, it should be noticed that PARP inhibitor ABT-888 further enhanced the phosphorylation of H2AX (S139) after SM exposure, which indicated that we should be very careful in the application of PARP inhibitors in SM injury treatment because of the enhancement of DNA damage. PMID:27077006

  5. Rubber vulcanizing agents comprising reaction products of sulfur and unsaturated hydrocarbons

    SciTech Connect

    Johansson, A.H.; Woodruff, D.; Flanders, S.K.; Swigert, J.L.

    1988-04-26

    A process for making an improved vulcanizing agent is described comprising the steps of: A. providing starting materials consisting essentially of sulfur and an unsaturated reactant selected from at least one of d-limonene, 5-ethylidene-2-norbornene, styrene, and dicyclopentadiene; B. reacting the starting materials at a first temperature greater than the melting point of the sulfur and less than the temperature at which the sulfur begins to be converted to insoluble sulfur until substantially all of the unsaturated reactant is consumed, forming an intermediate product; C. maintaining the intermediate product at a second temperature greater than the melting point of the sulfur and the same as or different from the first temperature for a sufficient time to form an end product which is dispersible in rubber and provides less sulfur bloom than insoluble sulfur when incorporated in a rubber composition; and D. terminating the maintaining step by reducing the temperature of the end product, thereby maintaining the dispersibility of the end product in rubber.

  6. Wipe selection for the analysis of surface materials containing chemical warfare agent nitrogen mustard degradation products by ultra-high pressure liquid chromatography-tandem mass spectrometry.

    PubMed

    Willison, Stuart A

    2012-12-28

    Degradation products arising from nitrogen mustard chemical warfare agent were deposited on common urban surfaces and determined via surface wiping, wipe extraction, and liquid chromatography–tandem mass spectrometry detection. Wipes investigated included cotton gauze, glass fiber filter, non-woven polyester fiber and filter paper, and surfaces included several porous (vinyl tile, painted drywall, wood) and mostly non-porous (laminate, galvanized steel, glass) surfaces. Wipe extracts were analyzed by ultra-high pressure liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) and compared with high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) results. An evaluation of both techniques suggests UPLC–MS/MS provides a quick and sensitive analysis of targeted degradation products in addition to being nearly four times faster than a single HPLC run, allowing for greater throughput during a wide-spread release concerning large-scale contamination and subsequent remediation events. Based on the overall performance of all tested wipes, filter paper wipes were selected over other wipes because they did not contain interferences or native species (TEA and DEA) associated with the target analytes, resulting in high percent recoveries and low background levels during sample analysis. Other wipes, including cotton gauze, would require a pre-cleaning step due to the presence of large quantities of native species or interferences of the targeted analytes. Percent recoveries obtained from a laminate surface were 47–99% for all nitrogen mustard degradation products. The resulting detection limits achieved from wipes were 0.2 ng/cm(2) for triethanolamine (TEA), 0.03 ng/cm(2) for N-ethyldiethanolamine (EDEA), 0.1 ng/cm(2) for N-methyldiethanolamine (MDEA), and 0.1 ng/cm(2) for diethanolamine (DEA).

  7. Mustard vesicant-induced lung injury: Advances in therapy.

    PubMed

    Weinberger, Barry; Malaviya, Rama; Sunil, Vasanthi R; Venosa, Alessandro; Heck, Diane E; Laskin, Jeffrey D; Laskin, Debra L

    2016-08-15

    Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment and necrosis in the pharynx, trachea and bronchioles, while long-term consequences include fibrosis and, in some instances, cancer. Current therapies to treat mustard poisoning are primarily palliative and do not target underlying pathophysiologic mechanisms. New knowledge about vesicant-induced pulmonary disease pathogenesis has led to the identification of potentially efficacious strategies to reduce injury by targeting inflammatory cells and mediators including reactive oxygen and nitrogen species, proteases and proinflammatory/cytotoxic cytokines. Therapeutics under investigation include corticosteroids, N-acetyl cysteine, which has both mucolytic and antioxidant properties, inducible nitric oxide synthase inhibitors, liposomes containing superoxide dismutase, catalase, and/or tocopherols, protease inhibitors, and cytokine antagonists such as anti-tumor necrosis factor (TNF)-α antibody and pentoxifylline. Antifibrotic and fibrinolytic treatments may also prove beneficial in ameliorating airway obstruction and lung remodeling. More speculative approaches include inhibitors of transient receptor potential channels, which regulate pulmonary epithelial cell membrane permeability, non-coding RNAs and mesenchymal stem cells. As mustards represent high priority chemical threat agents, identification of effective therapeutics for mitigating toxicity is highly significant. PMID:27212445

  8. Evaluation of neutralized chemical agent identification sets (CAIS) for skin injury with an overview of the vesicant potential of agent degradation products.

    PubMed

    Olajos, E J; Olson, C T; Salem, H; Singer, A W; Hayes, T L; Menton, R G; Miller, T L; Rosso, T; MacIver, B

    1998-01-01

    Vesication and skin irritation studies were conducted in hairless guinea-pigs to determine the vesicant and skin irritation potential of chemically-neutralized Chemical Agent Identification Sets (CAIS). The CAIS are training items that contain chemical warfare-related material--sulfur mustard (HD), nitrogen mustard (HN) or lewisite (L)--and were declared obsolete in 1971. Animals were dosed topically with 'test article'--neat HD, 10% agent/chloroform solutions or product solutions (waste-streams) from neutralized CAIS--and evaluated for skin-damaging effects (gross and microscopic). Product solutions from the chemical neutralization of neat sulfur mustard resulted in microvesicle formation. All agent-dosed (HD or agent/chloroform solutions) sites manifested microblisters as well as other histopathological lesions of the skin. Waste-streams from the neutralization of agent (agent/chloroform or agent/charcoal) were devoid of vesicant activity. Cutaneous effects (erythema and edema) were consistent with the skin-injurious activity associated with the neutralizing reagent 1,3-dichloro-5,5-dimethylhydantoin (DCDMH). Chemical neutralization of CAIS was effective in eliminating/reducing the vesicant property of CAIS containing agent in chloroform or agent on charcoal but was inefficient in reducing the vesicant potential of CAIS containing neat sulfur mustard.

  9. Sulfur

    USGS Publications Warehouse

    Apodaca, L.E.

    2012-01-01

    In 2011, elemental sulfur and the byproduct sulfuric acid were produced at 109 operations in 29 states and the U.S. Virgin Islands. Total shipments were valued at about $1.6 billion. Elemental sulfur production was 8.2 Mt (9 million st); Louisiana and Texas accounted for about 53 percent of domestic production.

  10. Inflammatory mechanisms of pulmonary injury induced by mustards.

    PubMed

    Malaviya, Rama; Sunil, Vasanthi R; Venosa, Alessandro; Vayas, Kinal N; Heck, Diane E; Laskin, Jeffrey D; Laskin, Debra L

    2016-02-26

    Exposure of humans and animals to vesicants, including sulfur mustard (SM) and nitrogen mustard (NM), causes severe and debilitating damage to the respiratory tract. Both acute and long term pathological consequences are observed in the lung following a single exposure to these vesicants. Evidence from our laboratories and others suggest that macrophages and the inflammatory mediators they release play an important role in mustard-induced lung injury. In this paper, the pathogenic effects of SM and NM on the lung are reviewed, along with the potential role of inflammatory macrophages and mediators they release in mustard-induced pulmonary toxicity. PMID:26478570

  11. SYNTHESIS OF SULFUR-BASED WATER TREATMENT AGENT FROM SULFUR DIOXIDE WASTE STREAMS

    SciTech Connect

    Robert C. Brown; Maohong Fan; Adrienne Cooper

    2004-11-01

    Absorption of sulfur dioxide from a simulated flue gas was investigated for the production of polymeric ferric sulfate (PFS), a highly effective coagulant useful in treatment of drinking water and wastewater. The reaction for PFS synthesis took place near atmospheric pressure and at temperatures of 30-80 C. SO{sub 2} removal efficiencies greater than 90% were achieved, with ferrous iron concentrations in the product less than 0.1%. A factorial analysis of the effect of temperature, oxidant dosage, SO{sub 2} concentration, and gas flow rate on SO{sub 2} removal efficiency was carried out, and statistical analyses are conducted. The solid PFS was also characterized with different methods. Characterization results have shown that PFS possesses both crystalline and non-crystalline structure. The kinetics of reactions among FeSO{sub 4} {center_dot} 7H{sub 2}O, NaHSO{sub 3} and NaClO{sub 3} was investigated. Characterizations of dry PFS synthesized from SO{sub 2} show the PFS possesses amorphous structure, which is desired for it to be a good coagulant in water and wastewater treatment. A series of lab-scale experiments were conducted to evaluate the performance of PFS synthesized from waste sulfur dioxide, ferrous sulfate and sodium chlorate. The performance assessments were based on the comparison of PFS and other conventional and new coagulants for the removal of turbidity and arsenic under different laboratory coagulant conditions. Pilot plant studies were conducted at Des Moines Water Works in Iowa and at the City of Savannah Industrial and Domestic (I&D) Water Treatment Plant in Port Wentworth, Georgia. PFS performances were compared with those of conventional coagulants. The tests in both water treatment plants have shown that PFS is, in general, comparable or better than other coagulants in removal of turbidity and organic substances. The corrosion behavior of polymeric ferric sulfate (PFS) prepared from SO{sub 2} and ferric chloride (FC) were compared. Results

  12. SYNTHESIS OF SULFUR-BASED WATER TREATMENT AGENT FROM SULFUR DIOXIDE WASTE STREAMS

    SciTech Connect

    Robert C. Brown; Maohong Fan; Adrienne Cooper

    2002-10-01

    Absorption of sulfur dioxide from a simulated flue gas was investigated for the production of polymeric ferric sulfate (PFS), a highly effective coagulant useful in treatment of drinking water and wastewater. The reaction for PFS synthesis took place near atmospheric pressure and at temperatures of 30-80 C. SO{sub 2} removal efficiencies greater than 90% were achieved, with ferrous iron concentrations in the product less than 0.1%. A factorial analysis of the effect of temperature, oxidant dosage, SO{sub 2} concentration, and gas flow rate on SO{sub 2} removal efficiency was carried out, and statistical analyses are conducted. The solid PFS was also characterized with different methods. Characterization results have shown that PFS possesses both crystalline and non-crystalline structure. The kinetics of reactions among FeSO{sub 4} {center_dot} 7H{sub 2}O, NaHSO{sub 3} and NaClO{sub 3} was investigated. The PFS product was used in pilot-scale tests at a municipal water treatment facility and gave good results in removal of turbidity and superior results in removal of disinfection byproduct precursors (TOC, DOC, UV-254) when compared with equal doses of ferric chloride.

  13. DNA-directed alkylating agents. 3. Structure-activity relationships for acridine-linked aniline mustards: consequences of varying the length of the linker chain.

    PubMed

    Valu, K K; Gourdie, T A; Boritzki, T J; Gravatt, G L; Baguley, B C; Wilson, W R; Wakelin, L P; Woodgate, P D; Denny, W A

    1990-11-01

    Four series of acridine-linked aniline mustards have been prepared and evaluated for in vitro cytotoxicity, in vivo antitumor activity, and DNA cross-linking ability. The anilines were attached to the DNA-intercalating acridine chromophores by link groups (-O-, -CH2-, -S-, and -SO2-) of widely varying electronic properties, providing four series of widely differing mustard reactivity where the alkyl chain linking the acridine and mustard moieties was varied from two to five carbons. Relationships were sought between chain length and biological properties. Within each series, increasing the chain length did not alter the reactivity of the alkylating moiety but did appear to position it differently on the DNA, since cross-linking ability (measured by agarose gel assay) altered with chain length, being maximal with the C4 analogue. The in vivo antitumor activities of the compounds depended to some extent on the reactivity of the mustard, with the least reactive SO2 compounds being inactive. However, DNA-targeting did appear to allow the use of less reactive mustards, since the S-linked acridine mustards showed significant activity whereas the parent S-mustard did not. Within each active series, the most active compound was the C4 homologue, suggesting some relationship between activity and extent of DNA alkylation.

  14. Sulfur compounds in therapy: Radiation-protective agents, amphetamines, and mucopolysaccharide sulfation

    SciTech Connect

    Foye, W.O. )

    1992-09-01

    Sulfur-containing compounds have been used in the search for whole-body radiation-protective compounds, in the design of amphetamine derivatives that retain appetite-suppressive effects but lack most behavioral effects characteristic of amphetamines, and in the search for the cause of kidney stone formation in recurrently stoneforming patients. Organic synthetic procedures were used to prepare radiation-protective compounds having a variety of sulfur-containing functional groups, and to prepare amphetamine derivatives having electron-attracting sulfur functions. In the case of the kidney stone causation research, isolation of urinary mucopolysaccharides (MPS) from recurrently stoneforming patients was carried out and the extent of sulfation of the MPS was determined by electrophoresis. Whole-body radiation-protective agents with a high degree of protection against lethal doses of gamma-radiation in mice were found in a series of quinolinium and pyridinium bis(methylthio) and methylthio amino derivatives. Mechanism studies showed that the copper complexes of these agents mimicked the beneficial action of superoxide dismutase. Electron-attracting sulfur-containing functions on amphetamine nitrogen, as well as 4'-amino nitrogen provided amphetamine derivatives with good appetite-suppressant effects and few or no adverse behavioral effects. Higher than normal levels of sulfation of the urinary MPS of stone formers suggested a cause for recurrent kidney stone formation. A sulfation inhibitor was found to prevent recurrence of stone formation and inhibit growth of existing stones. The inclusion of various sulfur-containing functions in organic molecules yielded compounds having whole-body radiation protection from lethal doses of gamma-radiation in animals. The presence of electron-attracting sulfur functions in amphetamine gave derivatives that retained appetite-suppressant effects and eliminated most adverse behavioral effects.

  15. Integrated application of some compatible biocontrol agents along with mustard oil seed cake and furadan on Meloidogyne incognita infecting tomato plants

    PubMed Central

    Goswami, Bijoy Kumar; Pandey, Rajesh Kumar; Rathour, Kabindra Singh; Bhattacharya, Chaitali; Singh, Lokendra

    2006-01-01

    Experiments were carried out to study the effect of two fungal bioagents along with mustard oil cake and furadan against root knot nematode Meloidogyne incognita infecting tomato under greenhouse condition. Bioagents viz., Paecilomyces lilacinus and Trichoderma viride alone or in combination with mustard cake and furadan promoted plant growth, reduced number of galls/plant, egg masses/root system and eggs/egg mass. The fungal bioagents along with mustard cake and nematicide showed least nematodes reproduction factor as compared to untreated infested soil. PMID:17048300

  16. Relationship between airway reactivity induced by methacholine or ultrasonically nebulized distilled cold water and BAL fluid cellular constituents in patients with sulfur mustard gas-induced asthma.

    PubMed

    Emad, Ali; Emad, Yasaman

    2007-01-01

    The objective of this article was to evaluate the relationship between the bronchial reactivity to methacholine and distilled cold water and inflammatory bronchial alveolar lavage (BAL) cells in mustard gas-induced asthma. This was a randomized, crossover clinical study set in a university hospital. The patients were 17 veterans with mustard gas-induced asthma and 17 normal veterans as a control group. Inhalation challenges with ultrasonically nebulized distilled water and methacholine and BAL via bronchoscopy and were performed in all patients and subjects. All patients did sustain a 20% fall in FEV(1) after methacholine, whereas two of them did not with distilled cold water. The patients were sensitive to distilled cold water with a median PD20 of 8.44 +/- 6.55 mL and sensitive to methacholine with the median PC20 of 4.88 +/- 4.22 mg/mL. Significant correlation was found between PC20 of methacholine and PD20 of distilled cold water (r = -0.74, p = 0.005). The proportion of BAL macrophages was significantly lower in patients with asthma than in the control group (p = 0.001). The proportions of lymphocytes and neutrophils were similar in the two groups. The percentage of eosinophils was higher in BAL fluid from the asthmatics compared with that in BAL fluid from the control group (p < 0.001). The percentage of the BAL eosinophils significantly correlated with both PC20 of methacholine (r = - 0.58, p = 0.01) and PD20 of distilled cold water (r = -0.81, p = 0.002). No relationship between PC20 of methacholine or PD20 of distilled cold water was found for other inflammatory BAL cells. This study showed that in patients with mustard gas-induced asthma, the degree of airway responsiveness to both methacholine and distilled water was associated with the percentage of BAL eosinophils.

  17. Relationship between airway reactivity induced by methacholine or ultrasonically nebulized distilled cold water and BAL fluid cellular constituents in patients with sulfur mustard gas-induced asthma.

    PubMed

    Emad, Ali; Emad, Yasaman

    2007-01-01

    The objective of this article was to evaluate the relationship between the bronchial reactivity to methacholine and distilled cold water and inflammatory bronchial alveolar lavage (BAL) cells in mustard gas-induced asthma. This was a randomized, crossover clinical study set in a university hospital. The patients were 17 veterans with mustard gas-induced asthma and 17 normal veterans as a control group. Inhalation challenges with ultrasonically nebulized distilled water and methacholine and BAL via bronchoscopy and were performed in all patients and subjects. All patients did sustain a 20% fall in FEV(1) after methacholine, whereas two of them did not with distilled cold water. The patients were sensitive to distilled cold water with a median PD20 of 8.44 +/- 6.55 mL and sensitive to methacholine with the median PC20 of 4.88 +/- 4.22 mg/mL. Significant correlation was found between PC20 of methacholine and PD20 of distilled cold water (r = -0.74, p = 0.005). The proportion of BAL macrophages was significantly lower in patients with asthma than in the control group (p = 0.001). The proportions of lymphocytes and neutrophils were similar in the two groups. The percentage of eosinophils was higher in BAL fluid from the asthmatics compared with that in BAL fluid from the control group (p < 0.001). The percentage of the BAL eosinophils significantly correlated with both PC20 of methacholine (r = - 0.58, p = 0.01) and PD20 of distilled cold water (r = -0.81, p = 0.002). No relationship between PC20 of methacholine or PD20 of distilled cold water was found for other inflammatory BAL cells. This study showed that in patients with mustard gas-induced asthma, the degree of airway responsiveness to both methacholine and distilled water was associated with the percentage of BAL eosinophils. PMID:17894540

  18. Sulforaphane induces phase II detoxication enzymes in mouse skin and prevents mutagenesis induced by a mustard gas analog

    SciTech Connect

    Abel, E.L.; Boulware, S.; Fields, T.; McIvor, E.; Powell, K.L.; DiGiovanni, J.; Vasquez, K.M.; MacLeod, M.C.

    2013-02-01

    Mustard gas, used in chemical warfare since 1917, is a mutagenic and carcinogenic agent that produces severe dermal lesions for which there are no effective therapeutics; it is currently seen as a potential terrorist threat to civilian populations. Sulforaphane, found in cruciferous vegetables, is known to induce enzymes that detoxify compounds such as the sulfur mustards that react through electrophilic intermediates. Here, we observe that a single topical treatment with sulforaphane induces mouse epidermal levels of the regulatory subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, and also increases epidermal levels of reduced glutathione. Furthermore, a glutathione S-transferase, GSTA4, is also induced in mouse skin by sulforaphane. In an in vivo model in which mice are given a single mutagenic application of the sulfur mustard analog 2-(chloroethyl) ethyl sulfide (CEES), we now show that therapeutic treatment with sulforaphane abolishes the CEES-induced increase in mutation frequency in the skin, measured four days after exposure. Sulforaphane, a natural product currently in clinical trials, shows promise as an effective therapeutic against mustard gas. -- Highlights: ► Sulforaphane induces increased levels of glutathione in mouse skin. ► Sulforaphane induces increased levels of GSTA4 in mouse skin. ► Sulforaphane, applied after CEES-treatment, completely abolishes CEES-mutagenesis. ► The therapeutic effect may suggest a long biological half-life for CEES in vivo.

  19. Optimization of alkylating agent prodrugs derived from phenol and aniline mustards: a new clinical candidate prodrug (ZD2767) for antibody-directed enzyme prodrug therapy (ADEPT).

    PubMed

    Springer, C J; Dowell, R; Burke, P J; Hadley, E; Davis, D H; Blakey, D C; Melton, R G; Niculescu-Duvaz, I

    1995-12-22

    Sixteen novel potential prodrugs derived from phenol or aniline mustards and their 16 corresponding drugs with ring substitution and/or different alkylating functionalities were designed. The [[[4-]bis(2-bromoethyl)-(1a), [[[4-[bis(2-iodoethyl)-(1b), and [[[4-[(2-chloroethyl)-[2-(mesyloxy)ethyl]amino]phenyl]oxy] carbonyl]-L-glutamic acids (1c), their [[[2- and 3-substituted-4-[bis(2-chloroethyl)amino]phenyl]oxy]carbonyl]-L- glutamic acids (1e-1), and the [[3-substituted-4-[bis(2-chloroethyl)amino]phenyl]carbamoyl]-L- glutamic acids (1o-r) were synthesized. They are bifunctional alkylating agents in which the activating effect of the phenolic hydroxyl or amino function is masked through an oxycarbonyl or a carbamoyl bond to a glutamic acid. These prodrugs were designed to be activated to their corresponding phenol and aniline nitrogen mustard drugs at a tumor site by prior administration of a monoclonal antibody conjugated to the bacterial enzyme carboxypeptidase G2 (CPG2) in antibody-directed enzyme prodrug therapy (ADEPT). The synthesis of the analogous novel parent drugs (2a-r) is also described. The viability of a colorectal cell line (LoVo) was monitored with the potential prodrugs and the parent drugs. The differential in the cytotoxicity between the potential prodrugs and their corresponding active drugs ranged between 12 and > 195 fold. Compounds 1b-d,f,o exhibited substantial prodrug activity, since a cytotoxicity differential of > 100 was achieved compared to 2b-d,f,o respectively. The ability of the potential prodrugs to act as substrates for CPG2 was determined (kinetic parameters KM and kcat), and the chemical stability was measured for all the compounds. The unsubstituted phenols with different alkylating functionalities (1a-c) proved to have the highest ratio of the substrates kcat:KM. From these studies [[[4-[bis(2-iodoethyl)amino]phenyl]oxy]carbonyl]-L-glutamic acid (1b) emerges as a new ADEPT clinical trial candidate due to its physicochemical and

  20. TOXICOLOGY STUDIES OF LEWISITE AND SULFUR MUSTARD AGENTS:GENETIC TOXICITY OF LEWISITE (L) IN CHINESE HAMSTER OVARY CELLS

    SciTech Connect

    Jostes,R.F. Jr.; Sasser, LB; Rausch, R.J.

    1989-05-31

    The cytotoxic clastogenic and mutagenic effects of the arsenic containing vesicant, Lewisite (L) [dichloro(2-chlorovinyl) arsine], have been investigated using Chinese hamster ovary cells. One hour exposures to Lewisite were cytotoxic in uM amounts. The cell survival response yields a D37 of 0.6 uM and an extrapolation number of 2.5. The mutagenic response at the hypoxantnine-guanine phosporibosyl transferase (HGPRT) locus was sporadic and not significantly greater than control values when cells were exposed over a range of 0.125 to2.0 uM. Sister chromatid exchange (SCE) induction, a measure of chromosomal rearrangement, was weakly positive over a range of 0.25 to 1.0 uM but the values were not significantly greater than the control response. Chromosomal aberrations were induced at 0.75 and 1.0 UMin one experiment and 0.5 and 0.75 uM in another experiment. The Induced values were significantly greater than the control values. Lewisite appears to be cytotoxic and clastogenic in our investigations but SCE and mutation at the HGPRT locus are not significantly greater than control values. Lewisita toxicity was in some ways similar to radiomimetic chemicals such as bleomycin.

  1. Teratology studies of lewisite and sulfur mustard agents: Effects of lewisite in rats and rabbits: Final report: Part 2, Appendices

    SciTech Connect

    Hackett, P.L.; Sasser, L.B.; Rommereim, R.L.; Cushing, J.A.; Buschbom, R.L.; Kalkwarf, D.R.

    1987-12-31

    Lewisite was administered to rats and rabbits by intragastric intubation. Maternal animals were weighed periodically, and, at necropsy (20 dg (days of gestation) in rats and 30 dg in rabbits), were examined for gross lesions of major organs and reproductive performances; live fetuses were weighed and examined for external, internal and skeletal defects. In rats, a dose level of 1.5 mg/kg did not induce toxic or teratogenic responses in maternal animals or their fetuses. At 2.0 mg/kg, 10% maternal mortality, trends in decreased maternal and fetal body weights and a significant reduction in the number of viable fetuses were evident. In rabbit studies, maternal mortality occured in all but one of the lewisite treatment groups and range from 13% to 100% at dose levels of 0.07 and 1.5 mg/kg, respectively. This mortality rate limited the sample size and impaired the detection of statistical significance among treatments. However, at the lowest dose level of the teratology study (0.07 mg/kg), maternal mortality was the only indicator of lewisite toxicity; at the highest dose (0.6 mg/kg), significant findings included 86% maternal mortality, a decrease in maternal body weight gains and an increase in the incidence of fetal stunting, although only a tendency in decreased fetal body weights was observed. These results suggest that maternal mortality was the most important factor in predicting the induction of maternal and fetal effects and, therefore, a ''no observable effect level'' in maternal animals and their fetuses would be between 1.5 and 2.0 mg/kg in rats and less than 0.07 mg/kg in rabbits. Part 2 contains 6 appendices.

  2. Teratology studies of lewisite and sulfur mustard agents: Effects of lewisite in rats and rabbits: Final report

    SciTech Connect

    Hackett, P L; Sasser, L B; Rommereim, R L; Cushing, J A; Buschbom, R L; Kalkwarf, D R

    1987-12-31

    Lewisite was administered to rats and rabbits by intragastric intubation. Maternal animals were weighed periodically, and, at necropsy (20 dg (days of gestation) in rats and 30 dg in rabbits), were examined for gross lesions of major organs and reproductive performances; live fetuses were weighed and examined for external, internal and skeletal defect. In rats, a dose level of 1.5 mg/kg did not induce toxic or teratogenic responses in maternal and fetal body weights and a significant reduction in the number if viable fetuses were evident. In rabbit studies maternal mortality occurred in all but one of the lewisite treatment groups and ranged from 13% to 100% at dose levels of 0.07 and 1.5 mg/kg, respectively. This mortality rate limited the sample size and impaired the detection of statistical significance among treatments. However, at the lowest dose level of the teratology study (0.07 mg/kg, maternal mortality was the only indicator of lewisite toxicity; at the highst dose (0.6 mg/kg), significant findings included 86% maternal mortality, a decrease in maternal body weight gains and an increase in the incidence of fetal stunting, although only a tendency in decreased fetal body weights was observed. These results suggest that maternal mortality was the most important factor in predicting the induction of maternal and fetal effects and, therfore, a ''no observable effect level'' in maternal animals and their fetuses would be between 1.5 and 2.0 mg/kg in rats and less than 0.07 mg/kg in rabbits. 50 refs., 6 figs., 29 tabs.

  3. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Mutagenicity of Lewisite in the Salmonella Histidine Reversion Assay Final Report

    SciTech Connect

    Stewart, D. L.; Sass, E. J.; Fritz, L. K.; Sasser, L. B.

    1989-07-31

    The mutagenic potential of lewisite was evaluated in the standard plate incorporation method and by the preincubation modification of the Ames Salmonella/microsomal assay with tester strains TA97, TA98, TAlOO and TA102. All strains were tested with activation (20 and 50 {micro}l/ plate) and without activation. The lewisite was screened initially for toxicity with TA98 over a range of concentrations from 0.01 to 250 {micro}g of material per plate. However, concentrations selected for mutagenicity testing were adjusted to a range of 0.001 to 5 {micro}g/plate because of the sensitivity of tester strain TA102, which exhibited cytotoxicity at 0.01 ug/plate. No mutagenic response was exhibited by any of the strains in either method used. All other tester strains showed evidence of cytoxicity (reduction in mutagen response or sparse background lawn) at 5.0 {micro}g/plate or lower.

  4. Evaluation of focal defects on technetium-99m sulfur colloid scans with new hepatobiliary agents

    SciTech Connect

    Rao, B.K.; Pastakia, B.; Lieberman, L.M.

    1980-08-01

    In 3600 patients evaluated with technetium-99m sulfur colloid for metastatic liver disease, 40 had equivocal scans due to a solitary defect in the inferior margin of the right lobe. In these patients, the authors differentiated the gallbladder fossa from a metastatic focus using one of two new hepatobiliary agents: technetium-99m labeled pyridoxylideneglutamate and paraisopropylacetanilido iminodiacetic acid. The need for laparoscopic biopsy was obviated in a majority (78%) of the patients by identifying the gallbladder fossa.

  5. The sources, fate, and toxicity of chemical warfare agent degradation products.

    PubMed Central

    Munro, N B; Talmage, S S; Griffin, G D; Waters, L C; Watson, A P; King, J F; Hauschild, V

    1999-01-01

    We include in this review an assessment of the formation, environmental fate, and mammalian and ecotoxicity of CW agent degradation products relevant to environmental and occupational health. These parent CW agents include several vesicants: sulfur mustards [undistilled sulfur mustard (H), sulfur mustard (HD), and an HD/agent T mixture (HT)]; nitrogen mustards [ethylbis(2-chloroethyl)amine (HN1), methylbis(2-chloroethyl)amine (HN2), tris(2-chloroethyl)amine (HN3)], and Lewisite; four nerve agents (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX), tabun (GA), sarin (GB), and soman (GD)); and the blood agent cyanogen chloride. The degradation processes considered here include hydrolysis, microbial degradation, oxidation, and photolysis. We also briefly address decontamination but not combustion processes. Because CW agents are generally not considered very persistent, certain degradation products of significant persistence, even those that are not particularly toxic, may indicate previous CW agent presence or that degradation has occurred. Of those products for which there are data on both environmental fate and toxicity, only a few are both environmentally persistent and highly toxic. Major degradation products estimated to be of significant persistence (weeks to years) include thiodiglycol for HD; Lewisite oxide for Lewisite; and ethyl methyl phosphonic acid, methyl phosphonic acid, and possibly S-(2-diisopropylaminoethyl) methylphosphonothioic acid (EA 2192) for VX. Methyl phosphonic acid is also the ultimate hydrolysis product of both GB and GD. The GB product, isopropyl methylphosphonic acid, and a closely related contaminant of GB, diisopropyl methylphosphonate, are also persistent. Of all of these compounds, only Lewisite oxide and EA 2192 possess high mammalian toxicity. Unlike other CW agents, sulfur mustard agents (e.g., HD) are somewhat persistent; therefore, sites or conditions involving potential HD contamination should include an

  6. Interactive effects of sulfur and nitrogen supply on the concentration of sinigrin and allyl isothiocyanate in Indian mustard (Brassica juncea L.).

    PubMed

    Gerendás, Jóska; Podestát, Jana; Stahl, Thorsten; Kübler, Kerstin; Brückner, Hans; Mersch-Sundermann, Volker; Mühling, Karl H

    2009-05-13

    Food derived from Brassica species is rich in glucosinolates. Hydrolysis of these compounds by myrosinase yields isothiocyanates and other breakdown products, which due to their pungency represent the primary purpose of Indian mustard cultivation. Strong interactive effects of S (0.0, 0.2, and 0.6 g pot(-1)) and N (1, 2, and 4 g pot(-1)) supply on growth, seed yield, and the concentrations of glucosinolates and isothiocyanates in seeds were observed in growth experiments, reflecting the involvement of S-containing amino acids in both protein and glucosinolate synthesis. At intermediate S supply, a strong N-induced S limitation was apparent, resulting in high concentrations of sinigrin (12 micromol g(-1) of DM) and allyl isothiocyanate (213 micromol kg(-1) of DM) at low N supply only. Myrosinase activity in seeds increased under low N and low S supply, but the results do not suggest that sinigrin functions as a transient reservoir for S. PMID:19309148

  7. Enhancement of radiosensitivity in human glioblastoma cells by the DNA N-mustard alkylating agent BO-1051 through augmented and sustained DNA damage response

    PubMed Central

    2011-01-01

    Background 1-{4-[Bis(2-chloroethyl)amino]phenyl}-3-[2-methyl-5-(4-methylacridin-9-ylamino)phenyl]urea (BO-1051) is an N-mustard DNA alkylating agent reported to exhibit antitumor activity. Here we further investigate the effects of this compound on radiation responses of human gliomas, which are notorious for the high resistance to radiotherapy. Methods The clonogenic assay was used to determine the IC50 and radiosensitivity of human glioma cell lines (U87MG, U251MG and GBM-3) following BO-1051. DNA histogram and propidium iodide-Annexin V staining were used to determine the cell cycle distribution and the apoptosis, respectively. DNA damage and repair state were determined by γ-H2AX foci, and mitotic catastrophe was measure using nuclear fragmentation. Xenograft tumors were measured with a caliper, and the survival rate was determined using Kaplan-Meier method. Results BO-1051 inhibited growth of human gliomas in a dose- and time-dependent manner. Using the dosage at IC50, BO-1051 significantly enhanced radiosensitivity to different extents [The sensitizer enhancement ratio was between 1.24 and 1.50 at 10% of survival fraction]. The radiosensitive G2/M population was raised by BO-1051, whereas apoptosis and mitotic catastrophe were not affected. γ-H2AX foci was greatly increased and sustained by combined BO-1051 and γ-rays, suggested that DNA damage or repair capacity was impaired during treatment. In vivo studies further demonstrated that BO-1051 enhanced the radiotherapeutic effects on GBM-3-beared xenograft tumors, by which the sensitizer enhancement ratio was 1.97. The survival rate of treated mice was also increased accordingly. Conclusions These results indicate that BO-1051 can effectively enhance glioma cell radiosensitivity in vitro and in vivo. It suggests that BO-1051 is a potent radiosensitizer for treating human glioma cells. PMID:21244709

  8. Evaluation of Molecular Markers and Analytical Methods Documenting the Occurrence of Mustard Gas and Arsenical Warfare Agents in Soil.

    PubMed

    Sassolini, Alessandro; Brinchi, Giampaolo; Di Gennaro, Antonio; Dionisi, Simone; Dominici, Carola; Fantozzi, Luca; Onofri, Giorgio; Piazza, Rosario; Guidotti, Maurizio

    2016-09-01

    The chemicals warfare agents (CWAs) are an extremely toxic class of molecules widely produced in many industrialized countries for decades, these compounds frequently contained arsenic. The plants where the CWAs have been produced or the plants where they have been demilitarized after the Second World War with unacceptable techniques can represent a serious environmental problem. CWAs standards are difficult to find on market so in present work an environmental assessment method based on markers has been proposed. Triphenylarsine, phenylarsine oxide and thiodiglycol have been selected as markers. Three reliable analytical methods based on gaschromatography and mass detection have been proposed and tested for quantitative analysis of markers. Methods performance have been evaluated testing uncertainty, linearity, recovery and detection limits and also comparing detection limits with exposure limits of reference CWAs. Proposed assessment methods have been applied to a case study of a former industrial plant sited in an area characterized by a high background of mineral arsenic.

  9. Evaluation of Molecular Markers and Analytical Methods Documenting the Occurrence of Mustard Gas and Arsenical Warfare Agents in Soil.

    PubMed

    Sassolini, Alessandro; Brinchi, Giampaolo; Di Gennaro, Antonio; Dionisi, Simone; Dominici, Carola; Fantozzi, Luca; Onofri, Giorgio; Piazza, Rosario; Guidotti, Maurizio

    2016-09-01

    The chemicals warfare agents (CWAs) are an extremely toxic class of molecules widely produced in many industrialized countries for decades, these compounds frequently contained arsenic. The plants where the CWAs have been produced or the plants where they have been demilitarized after the Second World War with unacceptable techniques can represent a serious environmental problem. CWAs standards are difficult to find on market so in present work an environmental assessment method based on markers has been proposed. Triphenylarsine, phenylarsine oxide and thiodiglycol have been selected as markers. Three reliable analytical methods based on gaschromatography and mass detection have been proposed and tested for quantitative analysis of markers. Methods performance have been evaluated testing uncertainty, linearity, recovery and detection limits and also comparing detection limits with exposure limits of reference CWAs. Proposed assessment methods have been applied to a case study of a former industrial plant sited in an area characterized by a high background of mineral arsenic. PMID:27385368

  10. Arsenic and Old Mustard: Chemical Problems of Old Arsenical and 'Mustard' Munitions (Joseph F. Bunnett and Marian Mikotajczyk, Eds.)

    NASA Astrophysics Data System (ADS)

    Garrett, Benjamin

    1999-10-01

    What do Knute Rockne, Notre Dame's famed football coach, and Lewisite, a chemical warfare agent dubbed "the dew of death", have in common? Both owe their discovery to Father Julius Arthur Nieuwland.1 Rockne's legacy lives on in the Fighting Irish and their tradition of excellence on the gridiron. Lewisite, together with other arsenical- and mustard-type chemical warfare agents, provide a legacy that lives on, too, but with less cheerful consequences. The book Arsenic and Old Mustard: Chemical Problems of Old Arsenical and 'Mustard' Munitions makes clear the challenges faced in dealing with those consequences. This book documents the proceedings of a workshop devoted to arsenical- and mustard-type chemical warfare agents and their associated munitions. The workshop, held in Poland in 1996, included nine lectures, eight posters, and three discussion groups; and the contents of all these are presented. Major support for the workshop came from the Scientific Affairs Division of NATO as part of on ongoing series of meetings, cooperative research projects, and related efforts dealing with problems leftover from the Cold War and, in the case of the arsenicals and mustards, from conflicts dating to World War I. These problems can be seen in contemporary accounts, including a January 1999 news report that the U.S. Department of Defense intends to survey Washington, DC, areas near both American University and the Catholic University of America (CUA), site of the original synthesis of Lewisite, for chemical warfare agents and other materials disposed at the end of World War I.2 The first nine chapters of the book present the workshop's lectures. Of these, readers interested in chemical weapon destruction might find especially useful the first chapter, in which Ron Mansley of the Organisation for the Prohibition of Chemical Weapons presents a scholarly overview covering historical aspects of the arsenicals and mustards; their production and use; prospective destruction

  11. Preventive measures against the mustard gas: a review

    PubMed Central

    Razavi, Seyed Mansour; Karbakhsh, Mojgan

    2013-01-01

    The main aim in this study was to collect the experiences of Iranian researchers about sulfur mustard (SM) and provide a guideline for the prevention of abuse for this dangerous agent. We searched valid national and international databases using related key words in the two languages. We found 193 articles which had been published in medical journals. Among them, 25 articles had some implications about prevention measures. In this study, we have mentioned 8 preventive points before the attacks, 10 points during and 2 points afterwards, we also found 12 points for the prevention of people who were exposed with SM and suffering from respiratory, ocular, dermatologic and psychological complications. In conclusion, most of the published studies on chemical war victims in Iran are focused on diagnosis and treatment of late SM-induced complications. Hence, a research should be conducted separately in relation to the prevention. PMID:23741170

  12. Estimated Chemical Warfare Agent Surface Clearance Goals for Remediation Pre-Planning

    SciTech Connect

    Dolislager, Frederick; Bansleben, Dr. Donald; Watson, Annetta Paule

    2010-01-01

    Health-based surface clearance goals, in units of mg/cm2, have been developed for the persistent chemical warfare agents sulfur mustard (HD) and nerve agent VX as well as their principal degradation products. Selection of model parameters and critical receptor (toddler child) allow calculation of surface residue estimates protective for the toddler child, the general population and adult employees of a facilty that has undergone chemical warfare agent attack.

  13. Topical nitrogen mustard exposure causes systemic toxic effects in mice

    PubMed Central

    Goswami, Dinesh G.; Kumar, Dileep; Tewari-Singh, Neera; Orlicky, David J.; Jain, Anil K.; Kant, Rama; Rancourt, Raymond C.; Dhar, Deepanshi; Inturi, Swetha; Agarwal, Chapla; White, Carl W.; Agarwal, Rajesh

    2014-01-01

    Vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) are reported to be easily absorbed by skin upon exposure causing severe cutaneous injury and blistering. Our studies show that topical exposure of NM (3.2 mg) onto SKH-1 hairless mouse skin, not only caused skin injury, but also led to significant body weight loss and 40–80 % mortality (120 h post-exposure), suggesting its systemic effects. Accordingly, further studies herein show that NM exposure initiated an increase in circulating white blood cells by 24 h (neutrophils, eosinophils and basophils) and thereafter a decrease (neutrophils, lymphocytes and monocytes). NM exposure also reduced both white and red pulp areas of the spleen. In the small intestine, NM exposure caused loss of membrane integrity of the surface epithelium, abnormal structure of glands and degeneration of villi. NM exposure also resulted in the dilation of glomerular capillaries of kidneys, and an increase in blood urea nitrogen/creatinine ratio. Our results here with NM are consistent with earlier reports that exposure to higher SM levels can cause damage to the hematopoietic system, and kidney, spleen and gastrointestinal tract toxicity. These outcomes will add to our understanding of the toxic effects of topical vesicant exposure, which might be helpful towards developing effective countermeasures against injuries from acute topical exposures. PMID:25481215

  14. Mustard gas toxicity: the acute and chronic pathological effects.

    PubMed

    Ghabili, Kamyar; Agutter, Paul S; Ghanei, Mostafa; Ansarin, Khalil; Shoja, Mohammadali M

    2010-10-01

    Ever since it was first used in armed conflict, mustard gas (sulfur mustard, MG) has been known to cause a wide range of acute and chronic injuries to exposure victims. The earliest descriptions of these injuries were published during and in the immediate aftermath of the First World War, and a further series of accounts followed the Second World War. More recently, MG has been deployed in warfare in the Middle East and this resulted in large numbers of victims, whose conditions have been studied in detail at hospitals in the region. In this review, we bring together the older and more recent clinical studies on MG toxicity and summarize what is now known about the acute and chronic effects of the agent on the eyes, skin, respiratory tract and other physiological systems. In the majority of patients, the most clinically serious long-term consequences of MG poisoning are on the respiratory system, but the effects on the skin and other systems also have a significant impact on quality of life. Aspects of the management of these patients are discussed.

  15. Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

    PubMed

    Watson, A P; Griffin, G D

    1992-11-01

    The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and small quantities of the organic arsenical Lewisite [dichloro(2-chlorovinyl) arsine; agent L]. These agents can be dispersed in liquid, aerosol, or vapor form and are capable of producing severe chemical burns upon direct contact with tissue. Moist tissues such as the eyes, respiratory tract, and axillary areas are particularly affected. Available data summarizing acute dose response in humans and laboratory animals are summarized. Vesicant agents are also capable of generating delayed effects such as chronic bronchitis, carcinogenesis, or keratitis/keratopathy of the eye under appropriate conditions of exposure and dose. These effects may not become manifest until years following exposure. Risk analysis derived from carcinogenesis data indicates that sulfur mustard possesses a carcinogenic potency similar to that of benzo[a]pyrene. Because mustard agents are alkylating compounds, they destroy individual cells by reaction with cellular proteins, enzymes, RNA, and DNA. Once begun, tissue reaction is irreversible. Mustard agents are mutagenic; data for cellular and laboratory animal assays are presented. Reproductive effects have not been demonstrated in the offspring of laboratory rats. Acute Lewisite exposure has been implicated in cases of Bowen's disease, an intraepidermal squamous cell carcinoma. Lewisite is not known to generate reproductive or teratogenic effects.

  16. Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

    PubMed Central

    Watson, A P; Griffin, G D

    1992-01-01

    The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and small quantities of the organic arsenical Lewisite [dichloro(2-chlorovinyl) arsine; agent L]. These agents can be dispersed in liquid, aerosol, or vapor form and are capable of producing severe chemical burns upon direct contact with tissue. Moist tissues such as the eyes, respiratory tract, and axillary areas are particularly affected. Available data summarizing acute dose response in humans and laboratory animals are summarized. Vesicant agents are also capable of generating delayed effects such as chronic bronchitis, carcinogenesis, or keratitis/keratopathy of the eye under appropriate conditions of exposure and dose. These effects may not become manifest until years following exposure. Risk analysis derived from carcinogenesis data indicates that sulfur mustard possesses a carcinogenic potency similar to that of benzo[a]pyrene. Because mustard agents are alkylating compounds, they destroy individual cells by reaction with cellular proteins, enzymes, RNA, and DNA. Once begun, tissue reaction is irreversible. Mustard agents are mutagenic; data for cellular and laboratory animal assays are presented. Reproductive effects have not been demonstrated in the offspring of laboratory rats. Acute Lewisite exposure has been implicated in cases of Bowen's disease, an intraepidermal squamous cell carcinoma. Lewisite is not known to generate reproductive or teratogenic effects. PMID:1486858

  17. Sulfur polymer cement, a new stabilization agent for mixed and low- level radioactive waste

    SciTech Connect

    Darnell, G.R.

    1991-12-31

    Solidification and stabilization agents for radioactive, hazardous, and mixed wastes are failing to pass governmental tests at alarming rates. The Department of Energy`s National Low-Level Waste Management Program funded testing of Sulfur Polymer Cement (SPC) by Brookhaven National Laboratory during the 1980s. Those tests and tests by the US Bureau of Mines (the original developer of SPC), universities, states, and the concrete industry have shown SPC to be superior to hydraulic cements in most cases. Superior in what wastes can be successfully combined and in the quantity of waste that can be combined and still pass the tests established by the US Environmental Protection Agency and the US Nuclear Regulatory Commission.

  18. Sulfur polymer cement, a new stabilization agent for mixed and low- level radioactive waste

    SciTech Connect

    Darnell, G.R.

    1991-01-01

    Solidification and stabilization agents for radioactive, hazardous, and mixed wastes are failing to pass governmental tests at alarming rates. The Department of Energy's National Low-Level Waste Management Program funded testing of Sulfur Polymer Cement (SPC) by Brookhaven National Laboratory during the 1980s. Those tests and tests by the US Bureau of Mines (the original developer of SPC), universities, states, and the concrete industry have shown SPC to be superior to hydraulic cements in most cases. Superior in what wastes can be successfully combined and in the quantity of waste that can be combined and still pass the tests established by the US Environmental Protection Agency and the US Nuclear Regulatory Commission.

  19. Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse (II): effects of some currently used skin decontaminants (RSDL and Fuller's earth) against liquid sulphur mustard and VX exposure.

    PubMed

    Taysse, L; Dorandeu, F; Daulon, S; Foquin, A; Perrier, N; Lallement, G; Breton, P

    2011-06-01

    Using the hairless mouse screening model presented in the companion paper(1) the aim of this study was to assess two skin decontaminating systems: Fuller's earth (FE) and Reactive Skin Decontamination Lotion (RSDL) against two extremely toxic chemical warfare agents that represent a special percutaneous hazard, sulphur mustard (SM) and O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX). Five minutes after being exposed on the back to either 2 µL of neat sulphur mustard or 50 µg.kg(-1) of diluted VX, mice were decontaminated. Both systems were able to reduce blisters 3 days after SM exposure. However, RSDL was found to be more efficient than FE in reducing the necrosis of the epidermis and erosion. In the case of VX exposure, RSDL, whatever the ratio of decontaminant to toxicant used (RSDL 10, 20, 50), was not able to sufficiently prevent the inhibition of plasma cholinesterases taken as a surrogate marker of exposure and toxicity. Only FE reduced significantly the ChE inhibition. Some of these observations are different from our previous results obtained in domestic swine and these changes are thus discussed in the perspective of using SKH-1 hairless mice for the initial in vivo screening of decontaminants. PMID:20534641

  20. Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse (II): effects of some currently used skin decontaminants (RSDL and Fuller's earth) against liquid sulphur mustard and VX exposure.

    PubMed

    Taysse, L; Dorandeu, F; Daulon, S; Foquin, A; Perrier, N; Lallement, G; Breton, P

    2011-06-01

    Using the hairless mouse screening model presented in the companion paper(1) the aim of this study was to assess two skin decontaminating systems: Fuller's earth (FE) and Reactive Skin Decontamination Lotion (RSDL) against two extremely toxic chemical warfare agents that represent a special percutaneous hazard, sulphur mustard (SM) and O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX). Five minutes after being exposed on the back to either 2 µL of neat sulphur mustard or 50 µg.kg(-1) of diluted VX, mice were decontaminated. Both systems were able to reduce blisters 3 days after SM exposure. However, RSDL was found to be more efficient than FE in reducing the necrosis of the epidermis and erosion. In the case of VX exposure, RSDL, whatever the ratio of decontaminant to toxicant used (RSDL 10, 20, 50), was not able to sufficiently prevent the inhibition of plasma cholinesterases taken as a surrogate marker of exposure and toxicity. Only FE reduced significantly the ChE inhibition. Some of these observations are different from our previous results obtained in domestic swine and these changes are thus discussed in the perspective of using SKH-1 hairless mice for the initial in vivo screening of decontaminants.

  1. The use of melatonin to combat mustard toxicity. REVIEW.

    PubMed

    Korkmaz, Ahmet; Kunak, Zeki I; Paredes, Sergio D; Yaren, Hakan; Tan, Duan-Xian; Reiter, Russel J

    2008-10-01

    Among the most readily available chemical warfare agents, sulfur mustard (SM) has been the most widely used chemical weapon. The toxicity of SM as an incapacitating agent is of much greater importance than its ability to cause lethality. Oxidative stress is the first and key event in the pathogenesis of SM toxicity. The involvement of inducible nitric oxide (iNOS) in SM toxicity, however, also leads to elevated nitrosative stress; thus, the damage caused by SM is nitro-oxidative stress because of peroxynitrite (ONOO-) production. Once ONOO- is formed, it activates nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) leading to pro-inflammatory gene expression thereby promoting inflammation; additionally, ONOO- directly exerts harmful effects by damaging all biomolecules including lipids, proteins and DNA within cells. DNA damage is sensed by an important DNA repair enzyme, poly (ADP-ribose) polymerase (PARP); this enzyme repairs molecular damage by using nicotinamide adenine dinucleotide (NAD+) as a substrate. Over-activation of PARP, due to severe DNA damage, consumes vast amounts of the respiratory coenzyme NAD+ leading to a cellular energy crisis. This pathophysiologic mechanism eventually results in cellular dysfunction, apoptosis or necrosis. Therefore, classic antioxidants may have limited beneficial effects on SM toxicity. Melatonin is a multifunctional indolamine which counteracts virtually all pathophysiologic steps and displays significant beneficial effects against ONOO--induced cellular toxicity. Melatonin has the capability of scavenging both oxygen and nitrogen-based reactants including ONOO- and blocking transcriptional factors which induce pro-inflammatory cytokines. The delayed toxicity of SM, however, currently has no mechanistic explanation. We propose that epigenetic aberrations may be responsible for delayed detrimental effects of mustard poisoning. Therefore, as a putative epigenetic modulator, melatonin may also be beneficial to

  2. Abundance of four sulfur mustard-DNA adducts ex vivo and in vivo revealed by simultaneous quantification in stable isotope dilution-ultrahigh performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Yue, Lijun; Wei, Yuxia; Chen, Jia; Shi, Huiqin; Liu, Qin; Zhang, Yajiao; He, Jun; Guo, Lei; Zhang, Tingfen; Xie, Jianwei; Peng, Shuangqing

    2014-04-21

    Sulfur mustard (SM) is a highly reactive alkylating vesicant and causes blisters upon contact with skin, eyes, and respiratory organs. It covalently links with DNAs by forming four mono- or cross-link adducts. In this article, the reference standards of SM-DNA adducts and deuterated analogues were first synthesized with simplified procedures containing only one or two steps and using less toxic chemical 2-(2-chloroethylthio)ethanol or nontoxic chemical thiodiglycol as starting materials. A sensitive and high-throughput simultaneous quantification method of N(7)-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (N(7)-HETEG), O(6)-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (O(6)-HETEG), N(3)-[2-[(2-hydroxyethyl)thio]-ethyl]adenine (N(3)-HETEA), and bis[2-(guanin-7-yl)ethyl]sulfide (Bis-G) in the Sprague-Dawley rat derma samples was developed by stable isotope dilution-ultrahigh performance liquid chromatography-tandem mass spectrometry (ID-UPLC-MS/MS) with the aim of revealing the real metabolic behaviors of four adducts. The method was validated, the limit of detection (S/N ratio greater than 10) was 0.01, 0.002, 0.04, and 0.11 fmol on column for N(7)-HETEG, O(6)-HETEG, Bis-G, and N(3)-HETEA, respectively, and the lower limit of quantification (S/N ratio greater than 20) was 0.04, 0.01, 0.12, and 0.33 fmol on column for N(7)-HETEG, O(6)-HETEG, Bis-G, and N(3)-HETEA, respectively. The accuracy of this method was determined to be 76% to 129% (n = 3), and both the interday (n = 6) and intraday (n = 7) precisions were less than 10%. The method was further applied for the quantifications of four adducts in the derma of adult male Sprague-Dawley rats exposed to SM ex vivo and in vivo, and all adducts had time- and dose-effect relationships. To the best of our knowledge, this is the first time that the real presented status of four DNA adducts was simultaneously revealed by the MS-based method, in which Bis-G showed much higher abundance than the result previously reported and N(3

  3. Sulfuric acid as an agent of carbonate weathering constrained by δ13C DIC: Examples from Southwest China

    NASA Astrophysics Data System (ADS)

    Li, Si-Liang; Calmels, Damien; Han, Guilin; Gaillardet, Jérôme; Liu, Cong-Qiang

    2008-06-01

    Rock weathering by carbonic acid is thought to play an important role in the global carbon cycle because it can geologically sequestrate atmospheric CO 2. Current model of carbon cycle evolution usually assumes that carbonic acid is the major weathering agent and that other acids are not important. Here, we use carbon isotopic evidence and water chemistry of springs and rivers from the Beipanjiang River basin (Guizhou Province, Southwest China) to demonstrate that sulfuric acid is also an important agent of rock weathering. The δ13C of dissolved inorganic carbon (DIC) in the water samples ranges from - 13.1‰ to - 2.4‰, and correlates negatively to [HCO 3-]/([Ca 2+] + [Mg 2+]) ratios and positively to [SO 42-]/([Ca 2+] + [Mg 2+]) ratios. These relationships are interpreted as mixing diagrams between two reactions of carbonate weathering, using carbonic acid and sulfuric acid as a proton donor, respectively. Mixing proportions show that around 42% of the divalent cations in the spring water from Guizhou are originated from the interaction between carbonate minerals and sulfuric acid. It is shown that 40% of this sulfuric acid is derived from the atmosphere and has an anthropogenic origin. The remaining 60% are derived from the oxidative weathering of sulfide minerals in sedimentary rocks. Our results show the positive action of sulfuric acid on the chemical weathering of carbonate. Particularly, we show that sulfuric acid generated by coal combustion has increased by almost 20% the weathering rates of carbonate in Southwest China. This is a clear evidence that human activities are changing the weathering rates of rocks and demonstrates a negative feedback on the acidification of the ocean by greenhouse gases. Because of the involvement of sulfuric acid in weathering reactions, 63% of the alkalinity exported by rivers is derived from carbonate, instead of 50% when atmospheric CO 2 is the only acid involved in chemical weathering of carbonate. In the Guizhou

  4. A chick model for the mechanisms of mustard gas neurobehavioral teratogenicity.

    PubMed

    Wormser, Uri; Izrael, Michal; Van der Zee, Eddy A; Brodsky, Berta; Yanai, Joseph

    2005-01-01

    The chemical warfare blistering agent, sulfur mustard (SM), is a powerful mutagen and carcinogen. Due to its similarity to the related chemotherapy agents nitrogen mustard (mechlorethamine), it is expected to act as a developmental neurotoxicant. The present study was designed to establish a chick model for the mechanisms of SM on neurobehavioral teratogenicity, free of confounds related to mammalian maternal effects. Chicken eggs were injected with SM at a dose range of 0.0017-17.0 microg/kg of egg, which is below the threshold for dysmorphology, on incubation days (ID) 2 and 7, and then tests were conducted posthatching. Exposure to SM elicited significant deficits in the intermedial part of the hyperstriatum ventrale (IMHV)-related imprinting behavior. Parallel decreases were found in the level of membrane PKCgamma in the IMHV, while eliciting no net change in cytosolic PKCgamma. The chick, thus, provides a suitable model for the rapid evaluation of SM behavioral teratogenicity and elucidation of the mechanisms underlying behavioral anomalies. The results obtained, using a model that controls for confounding maternal effects, may be replicated in the mammalian model and provide the groundwork for studies designed to offset or reverse the SM-induced neurobehavioral defects in both avian and mammals.

  5. Mustard gas exposure in Iran–Iraq war – A scientometric study

    PubMed Central

    Nokhodian, Zary; ZareFarashbandi, Firoozeh; Shoaei, Parisa

    2015-01-01

    Background: The Iranian victims of sulfur mustard attack are now more than 20 years post-exposure and form a valuable cohort for studying the chronic effects of an exposure to sulfur mustard. Articles on sulfur mustard exposure in Iran–Iraq war were reviewed using three known international databases such as Scopus, Medline, and ISI. The objectives of the study were measurement of the author-wise distribution, year-wise distribution, subject area wise, and assessment of highly cited articles. Materials and Methods: We searched three known international databases, Scopus, Medline, and the international statistical institute (ISI), for articles related to mustard gas exposure in Iran–Iraq war, published between 1988 and 2012. The results were analyzed using scientometric methods. Results: During the 24 years under examination, about 90 papers were published in the field of mustard gas in Iran–Iraq war. Original article was the most used document type forming 51.4% of all the publications. The number of articles devoted to mustard gas and Iran–Iraq war research increased more than 10-fold, from 1 in 1988 to 11 in 2011. Most of the published articles (45.7%) included clinical and paraclinical investigations of sulfur mustard in Iranian victims. The most highly productive author was Ghanei who occupied the first rank in the number of publications with 20 papers. The affiliation of most of the researchers was Baqiyatallah Medical Sciences University (research center of chemical injuries and dermatology department) in Iran. Conclusion: This article has highlighted the quantitative share of Iran in articles on sulfur mustard and lays the groundwork for further research on various aspects of related problems. PMID:26430683

  6. Molecular biological basis for the response of poly(ADP-rib) polymerase and NAD metabolism to DNA damage caused by mustard alkylating agents. Midterm report

    SciTech Connect

    Smulson, M.E.

    1996-07-01

    During the course of this contract, we have performed a variety of experiments to provide a strategy to modulate the nuclear enzyme poly(ADP-ribose) polymerase (PARP), in cultured keratinocytes. This enzyme modifies a variety of nuclear proteins utilizing NAD. DNA is required for the catalytic activity of the enzyme and the activity is dependent upon the presence of strand breaks in this DNA. It has been hypothesized that human skin exposed to mustards may develop blisters due to a generalized lowering of NAD in exposed skin cells. During the contract period, we have established a stably transfected human keratinocyte cell line which expresses antisense transcripts to PARP mRNA when these keratinocyte were grafted onto nude mice they formed histologically normal human skin. Accordingly, a model system has been developed in which the levels of PARP can be selectively manipulated in human keratinocytes in reconstituted epidermis as well. We also showed that PARP was proteolytically cleaved at the onset of spontaneous apoptosis following proteolytic conversion of CPP32b to its active form, termed `apopain`. Having characterized the events associated with apoptosis, we determined, during the last period, whether any or all of these features could be observed following exposure of keratinocytes to SM.

  7. Characterization of Lung Fibroblasts More than Two Decades after Mustard Gas Exposure

    PubMed Central

    Pirzad Jahromi, Gila; Ghanei, Mostafa; Hosseini, Seyed Kazem; Shamsaei, Alireza; Gholipourmalekabadi, Mazaher; Koochaki, Ameneh; Karkuki Osguei, Nushin; Samadikuchaksaraei, Ali

    2015-01-01

    Purpose In patients with short-term exposure to the sulfur mustard gas, the delayed cellular effects on lungs have not been well understood yet. The lung pathology shows a dominant feature consistent with obliterative bronchiolitis, in which fibroblasts play a central role. This study aims to characterize alterations to lung fibroblasts, at the cellular level, in patients with delayed respiratory complications after short-term exposure to the sulfur mustard gas. Methods Fibroblasts were isolated from the transbronchial biopsies of patients with documented history of exposure to single high-dose sulfur mustard during 1985–7 and compared with the fibroblasts of control subjects. Results Compared with controls, patients’ fibroblasts were thinner and shorter, and showed a higher population doubling level, migration capacity and number of filopodia. Sulfur mustard decreased the in vitro viability of fibroblasts and increased their sensitivity to induction of apoptosis, but did not change the rate of spontaneous apoptosis. In addition, higher expression of alpha smooth muscle actin showed that the lung's microenvironment in these patients is permissive for myofibroblastic differentiation. Conclusions These findings suggest that in patients under the study, the delayed pulmonary complications of sulfur mustard should be considered as a unique pathology, which might need a specific management by manipulation of cellular components. PMID:26679937

  8. Final report : multicomponent forensic signature development : interactions with common textiles; mustard precursors and simulants.

    SciTech Connect

    Van Benthem, Mark Hilary; Mowry, Curtis Dale; Kotula, Paul Gabriel; Borek, Theodore Thaddeus, III

    2010-02-01

    2-Chloroethyl phenyl sulfide (CEPS), a surrogate compound of the chemical warfare agent sulfur mustard, was examined using thermal desorption coupled gas chromatography-mass spectrometry (TD/GC-MS) and multivariate analysis. This work describes a novel method of producing multiway data using a stepped thermal desorption. Various multivariate analysis schemes were employed to analyze the data. These methods may be able to discern different sources of CEPS. In addition, CEPS was applied to cotton, nylon, polyester, and silk swatches. These swatches were placed in controlled humidity chambers maintained at 23%, 56%, and 85% relative humidity. At regular intervals, samples were removed from each test swatch, and the samples analyzed using TD/GC-MS. The results were compared across fabric substrate and humidity.

  9. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

    SciTech Connect

    Jain, Anil K.; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J.; Agarwal, Chapla; White, Carl W.; Agarwal, Rajesh

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2 mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. - Highlights: • Silibinin treatment attenuated nitrogen mustard (NM)-induced skin injury. • Silibinin affects pathways associated with DNA damage, inflammation and vesication. • The efficacy of silibinin could also be associated with oxidative stress. • These results support testing and optimization of

  10. Detection of Sulfur Reddening Agents in Irradiated Jupiter Trojans Ice Analogs

    NASA Astrophysics Data System (ADS)

    Mahjoub, Ahmed; Poston, Michael; Blacksberg, Jordana; Brown, Michael E.; Hand, Kevin P.; Eiler, John; Ehlmann, Bethany; Hodyss, Robert; Carlson, Robert W.; Choukroun, Mathieu; Wong, Ian

    2016-10-01

    Dynamical models, such as the Nice model, suggest that Trojan asteroids are formed out of the same body of material that produced the Kuiper Belt. In addition, telescopic observations show a color bimodality in VNIR spectral slopes of both Trojan asteroids and small KBOs. In one hypothesis, Wong & Brown (AJ, 2016, in revision) interpret the spectrally red and less red Trojans as descendant of sulfur-containing and sulfur-less primordial trans-Neptunian objects that experienced heating and irradiation during their migration inward. A sharp difference in the surface composition (i.e. presence or absence of sulfur) of the common progenitors of KBOs and Trojans would lead to different products of radiation chemistry, which in turn could lead to the observed color bimodality. In this paper, we address the issue of color bimodality through laboratory simulation. Electron irradiation products of ices containing CH3OH-NH3-H2O (without H2S) and H2S-CH3OH-NH3-H2O (with H2S) were examined. Temperature Programmed Desorption (TPD) of the post-irradiation mixtures shows mass spectra corresponding to small red sulfur allotropes (S2, S3, S4) desorbing while heating H2S-containing films. The production of these small allotropes likely contributes to the reddening slope observed in previously reported "with H2S" samples (Poston, M., et al. LPSC #2265, 2015) and adds significant soundness to the hypothesis connecting the color bimodality in Jupiter Trojans to sulfur chemistry. These small polymers are reactive and could further polymerize due to thermal processing, producing larger yellow sulfur polymers. We hypothesize that such polymerization would occur as a consequence of heating and increased irradiation experienced by an object as it migrated from the primordial trans-Neptunian disk to the current orbit of Trojans. This could explain the difference in the degree of spectral reddening observed between KBOs and Trojans.This work has been supported by the Keck Institute for Space

  11. Possible protein phosphatase inhibition by bis(hydroxyethyl) sulfide, a hydrolysis product of mustard gas

    SciTech Connect

    Brimfield, A.A.

    1995-12-31

    Recently, the natural vesicant cantharidin was shown to bind exclusively to and inhibit protein phosphatase 2A (PP2A) in mouse tissue extracts (Li and Casida (1992) Proc. Nati. Acad. Sci. USA 89, 11867-11870). To explore the generality of this effect in vesicant action, we measured the protein serinelthreonine phosphatase activity in mouse liver cytosol (in the form of the okadaic acid inhibitable increment of p-nitrophenyl phosphate (p-NPP) phosphatase activity) in the presence of aqueous sulfur mustard or its hydrolysis product, bis(hydroxyethyl)sulfide (TDG). Sulfur mustard inhibited p-NPP hydrolysis. However, inhibition correlated with the time elapsed between thawing and the addition of mustard to the enzyme preparation, not with concentration. TDG exhibited a direct, concentration-related inhibition of p-NPP hydrolysis between 30 and 300 1LM. We conclude that sulfur mustard also has an inhibitory effect on protein serinelthreonine phosphatases. However, the inhibition is an effect of its non-alkykating hydrolysis product TDG, not of sulfur mustard itself.

  12. Phytotoxicity of mustard seed meals alone and in combinations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mustard seed meal is produced when oil is extracted from brassicaceous seeds. The high glucosinolate content of these seed meals makes them of interest as management agents for weeds and soilborne pathogens. Previous studies indicated that seed meals from Brassica juncea and Sinapis alba are nemat...

  13. An examination of sulfur polymer cement as a waste encapsulation agent

    SciTech Connect

    McNew, E.B.

    1995-12-31

    Sulfur polymer cement (SPC) is a unique material having potential applications for hazardous and radioactive waste encapsulation. This material was originally developed by the US Bureau of Mines as an acid and chemical resistant construction cement and has since been applied in tie waste encapsulation field. The material is easily prepared from elemental sulfur and organic dienes. It is an easy to use low-viscosity thermoplastic, and has many favorable properties such as low porosity, high compressive strength, and resistance to chemical attack. The results of several invetigations on this material will be discussed, and include: (1) the chemical form and physical structure of the material, (2) the compressive strength of cylindrical test samples after gamma radiation testing, (3) the aqueous leaching behavior of lead, cerium, cesium, cobalt, and strontium from SPC-ash mixtures at room and elevated temperatures, (4) the casting compatibility of mixtures of SPC with different waste materials, (5) the ability of SPC to encapsulate elemental mercury contaminated soils, (6) laboratory and field studies of SPC biocorrosion by Thiobacillus bacteria, (7) small scale (10 kg) SPC-ash monolith casting studies, and (8) methods for the formulation of a grade of SPC more applicable to the encapsulation of aggregate waste materials.

  14. A new facile route for synthesizing of graphene oxide using mixture of sulfuric-nitric-phosphoric acids as intercalating agent

    NASA Astrophysics Data System (ADS)

    Panwar, Vinay; Chattree, Ananya; Pal, Kaushik

    2015-09-01

    In this work, graphene oxide (GO) has been prepared through three different processes namely, eco-friendly Hummers method, modification in improved Hummers method and a new approach. This new approach has been designed by changing some processing parameters and intercalating agent for significant reduction in processing time and to improve the quantity of GO in comparison to the other two methods. This has been achieved through better oxidization of graphite using nitric-sulfuric acid (HNO3-H2SO4) as intercalating agent. X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Energy-dispersive X-ray spectroscopy (EDX), Raman spectroscopy, Atomic Force Microscopy (AFM), X-ray photoelectron spectroscopy (XPS), UV-visible spectroscopy, and Thermogravimetric analysis (TGA) are used to characterize the GO prepared through different processes. These characterizations have confirmed an improved exfoliation of graphite, using addition of HNO3 in intercalating agent, in a short processing time and bring on higher yield of GO via this new process.

  15. Oxidation of aqueous sulfur dioxide. 3. The effects of chelating agents and phenolic antioxidants

    SciTech Connect

    Lim, P.K.; Huss, A. Jr.; Eckert, C.A.

    1982-10-14

    The inhibiting effects of chelating agents (1,10-phenanthroline and EDTA) and phenolic antioxidants (phenol, hydroquinone, resorcinol, pyrocatechol, phloroglucinol, and pyrogallol) on the catalyzed oxidations of low- and high-pH aqueous S(IV) solutions were investigated. Both the low-pH Mn(II)- and Fe(II)-catalyzed reactions were inhibited by phenolic antioxidants, with the effect on the Mn(II)-catalyzed reaction being much more pronounced. The chelating agents, on the other hand, had a far greater inhibiting influence on the Fe(II)-catalyzed reaction. The high-pH Cu(II)-catalyzed reaction was markedly inhibited by both chelating agents and antioxidants. The results support our previous conclusion that the previously accepted uncatalyzed oxidations of S(IV) were in fact primarily trace-metal catalyzed. 7 figures.

  16. Glutathione-garlic sulfur conjugates: slow hydrogen sulfide releasing agents for therapeutic applications.

    PubMed

    Bhuiyan, Ashif Iqbal; Papajani, Vilma Toska; Paci, Maurizio; Melino, Sonia

    2015-01-01

    Natural organosulfur compounds (OSCs) from Allium sativum L. display antioxidant and chemo-sensitization properties, including the in vitro inhibition of tumor cell proliferation through the induction of apoptosis. Garlic water- and oil-soluble allyl sulfur compounds show distinct properties and the capability to inhibit the proliferation of tumor cells. In the present study, we optimized a new protocol for the extraction of water-soluble compounds from garlic at low temperatures and the production of glutathionyl-OSC conjugates during the extraction. Spontaneously, Cys/GSH-mixed-disulfide conjugates are produced by in vivo metabolism of OSCs and represent active molecules able to affect cellular metabolism. Water-soluble extracts, with (GSGaWS) or without (GaWS) glutathione conjugates, were here produced and tested for their ability to release hydrogen sulfide (H2S), also in the presence of reductants and of thiosulfate:cyanide sulfurtransferase (TST) enzyme. Thus, the TST catalysis of the H2S-release from garlic OSCs and their conjugates has been investigated by molecular in vitro experiments. The antiproliferative properties of these extracts on the human T-cell lymphoma cell line, HuT 78, were observed and related to histone hyperacetylation and downregulation of GAPDH expression. Altogether, the results presented here pave the way for the production of a GSGaWS as new, slowly-releasing hydrogen sulfide extract for potential therapeutic applications. PMID:25608858

  17. Limitations and challenges in treatment of acute chemical warfare agent poisoning.

    PubMed

    Thiermann, Horst; Worek, Franz; Kehe, Kai

    2013-12-01

    Recent news from Syria on a possible use of chemical warfare agents made the headlines. Furthermore, the motivation of terrorists to cause maximal harm shifts these agents into the public focus. For incidents with mass casualties appropriate medical countermeasures must be available. At present, the most important threats arise from nerve agents and sulfur mustard. At first, self-protection and protection of medical units from contamination is of utmost importance. Volatile nerve agent exposure, e.g. sarin, results in fast development of cholinergic crisis. Immediate clinical diagnosis can be confirmed on-site by assessment of acetylcholinesterase activity. Treatment with autoinjectors that are filled with 2mg atropine and an oxime (at present obidoxime, pralidoxime, TMB-4 or HI-6) are not effective against all nerve agents. A more aggressive atropinisation has to be considered and more effective oximes (if possible with a broad spectrum or a combination of different oximes) as well as alternative strategies to cope with high acetylcholine levels at synaptic sites should be developed. A further gap exists for the treatment of patients with sustained cholinergic crisis that has to be expected after exposure to persistent nerve agents, e.g. VX. The requirement for long-lasting artificial ventilation can be reduced with an oxime therapy that is optimized by using the cholinesterase status for guidance or by measures (e.g. scavengers) that are able to reduce the poison load substantially in the patients. For sulfur mustard poisoning no specific antidote is available until now. Symptomatic measures as used for treatment of burns are recommended together with surgical or laser debridement. Thus, huge amounts of resources are expected to be consumed as wound healing is impaired. Possible depots of sulfur mustard in tissues may aggravate the situation. More basic knowledge is necessary to improve substantially therapeutic options. The use of stem cells may provide a new

  18. Limitations and challenges in treatment of acute chemical warfare agent poisoning.

    PubMed

    Thiermann, Horst; Worek, Franz; Kehe, Kai

    2013-12-01

    Recent news from Syria on a possible use of chemical warfare agents made the headlines. Furthermore, the motivation of terrorists to cause maximal harm shifts these agents into the public focus. For incidents with mass casualties appropriate medical countermeasures must be available. At present, the most important threats arise from nerve agents and sulfur mustard. At first, self-protection and protection of medical units from contamination is of utmost importance. Volatile nerve agent exposure, e.g. sarin, results in fast development of cholinergic crisis. Immediate clinical diagnosis can be confirmed on-site by assessment of acetylcholinesterase activity. Treatment with autoinjectors that are filled with 2mg atropine and an oxime (at present obidoxime, pralidoxime, TMB-4 or HI-6) are not effective against all nerve agents. A more aggressive atropinisation has to be considered and more effective oximes (if possible with a broad spectrum or a combination of different oximes) as well as alternative strategies to cope with high acetylcholine levels at synaptic sites should be developed. A further gap exists for the treatment of patients with sustained cholinergic crisis that has to be expected after exposure to persistent nerve agents, e.g. VX. The requirement for long-lasting artificial ventilation can be reduced with an oxime therapy that is optimized by using the cholinesterase status for guidance or by measures (e.g. scavengers) that are able to reduce the poison load substantially in the patients. For sulfur mustard poisoning no specific antidote is available until now. Symptomatic measures as used for treatment of burns are recommended together with surgical or laser debridement. Thus, huge amounts of resources are expected to be consumed as wound healing is impaired. Possible depots of sulfur mustard in tissues may aggravate the situation. More basic knowledge is necessary to improve substantially therapeutic options. The use of stem cells may provide a new

  19. Mustard Gas: Its Pre-World War I History

    NASA Astrophysics Data System (ADS)

    Duchovic, Ronald J.; Vilensky, Joel A.

    2007-06-01

    Mustard gas is perhaps the best-known chemical warfare agent and is commonly associated with World War I, both in its first use in warfare and its first synthesis. Although the former is correct, the latter is not. We review here the history of the repeated synthesis of mustard gas by 19th century European chemists. The techniques developed by these chemists were the ones relied upon by both the Central Powers and the Allies to manufacture this agent during World War I. Further, a historical review of mustard gas synthesis highlights the increasing sophistication of the chemical sciences. In particular, during the latter half of the 19th century, the concepts of atomic mass, chemical periodicity, and chemical structure underwent a rapid development that culminated in the application of quantum mechanics to chemistry in the 20th century. A comparison is made of the molecular formula for mustard gas from the 19th century with that of the 21st century, demonstrating that the concept of atomic mass has undergone significant refinement over this period of time.

  20. Poisoning of a silica supported cobalt catalyst due to the presence of sulfur impurities in syngas during Fischer-Tropsch synthesis: Effect of chelating agent

    SciTech Connect

    Bambal, A.S.; Gardner, T.H.; Kugler, E.L.; Dadyburjor, D.B.

    2012-01-01

    Sulfur compounds that are generally found in syngas derived from coal and biomass are a poison to Fischer-Tropsch (FT) catalysts. The presence of sulfur impurities in the ppm range can limit the life of a FT catalyst to a few hours or a few days. In this study, FT synthesis was carried out in a fixed-bed reactor at 230 °C, 20 bar, and 13,500 Ncm3/h/gcat for 72 h using syngas with H2/CO = 2.0. Cobalt-based catalysts were subjected to poisoning by 10 and 50 ppm sulfur in the syngas. The performance of FT catalyst was compared in context of syngas conversion, product selectivities and yields, during the poisoning as well as post-poisoning stages. At both the impurity concentrations, the sulfur was noted to cause permanent loss in the activity, possibly by adsorbing irreversibly on the surface. The sulfur poison affects the hydrogenation and the chain-propagation ability of the catalysts, and shifts the product selectivity towards short-chain hydrocarbons with higher percentages of olefins. Additional diffusion limitations caused due to sulfur poisoning are thought to alter the product selectivity. The shifts in product selectivities suggest that the sulfur decreases the ability of the catalyst to form C-C bonds to produce longer-chain hydrocarbons. The selective blocking of sulfur is thought to affect the hydrogenation ability on the catalyst, resulting in more olefins in the product after sulfur poisoning. The sulfur poisoning on the cobalt catalyst is expected to cause an increase in the number of sites responsible for WGS or to influence the Boudouard reaction, resulting in a higher CO2 selectivity. Both the sites responsible for CO adsorptions as well as the sites for chain growth are poisoned during the poisoning. Additionally, the performance of a base-case cobalt catalyst is compared with that of catalysts modified by chelating agents (CAs). The superior performance of CA-modified catalysts during sulfur poisoning is attributed to the presence of smaller

  1. Guidelines for chemical warfare agents in military field drinking water. Final report

    SciTech Connect

    1995-10-01

    CW agents are generally designed to be used on opposing military forces to produce death or incapacitation. When they are used in military attacks, they are potential contaminants of field drinking-water supplies. CW agents that could appear in military field water and that are of particular concern to the Army are 3-quinuclidinyl benzilate (BZ), organophosphorus nerve agents (GA, GB, GD, and VX), sulfur mustard agents (HD, THD, and HT), T-2 toxin (a fungal metabolite), lewisite (an arsenical vesicant), and cyanide. The Army requested that the National Research Council (NRC) review the toxicity of selected CW agents and assess the adequacy of its proposed field drinking-water standards. The report presents the subcommittee`s evaluations of the Army`s proposed standards. The report also presents the subcommittee`s recommendations for preventing adverse health effects in military personnel exposed to CW agents in field drinking water and for improving the toxicity data base for these CW agents.

  2. The fate of the chemical warfare agent during DNA extraction.

    PubMed

    Wilkinson, Della A; Hulst, Albert G; de Reuver, Leo P J; van Krimpen, Simon H; van Baar, Ben M L

    2007-11-01

    Forensic laboratories do not have the infrastructure to process or store contaminated DNA samples that have been recovered from a crime scene contaminated with chemical or biological warfare agents. Previous research has shown that DNA profiles can be recovered from blood exposed to several chemical warfare agents after the agent has been removed. The fate of four toxic agents, sulfur mustard, sodium 2-fluoroacetate, sarin, and diazinon, in a lysis buffer used in Promega DNA IQ extraction protocol was studied to determine if extraction would render the samples safe. Two independent analytical methods were used per agent, selected from GC-MS, 1H NMR, 19F NMR, (31)P NMR, or LC-ES MS. The methods were validated before use. Determinations were carried out in a semi-quantitative way, by direct comparison to standards. Agent levels in the elution buffer were found to be below the detectable limits for mustard, sarin, sodium 2-fluoroacetate or low (<0.02 mg/mL) for diazinon. Therefore, once extracted these DNA samples could be safely processed in a forensic laboratory. PMID:18093062

  3. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin.

    PubMed

    Jain, Anil K; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. PMID:25791923

  4. [Chemical treatment and decomposition technique of the chemical warfare agents containing arsenicals].

    PubMed

    Kaise, Toshikazu; Kinoshita, Kenji

    2009-01-01

    The old Japanese army developed several chemical warfare agents on Ohkuno Island in Seto inland sea, Hiroshima Japan, during the period between 1919 and 1944. These chemical agents including yperite (mustard; irritating agent), lewisite (irritating agent), diphenylchloroarsine (DA; vomiting agent), diphenylcyanoarsine (DC; vomiting agent) and other poisonous gases were manufactured to be used in China. After World War II, the old Japanese army abandoned or dumped these agents into seas inside or outside of Japan and interior of China. Rather than being used for terrorism, these chemical warfare agents containing arsenicals may cause injury to some workers at the digging site of abandoned chemical weapons. Moreover, the leakage of chemical agents or an explosion of the bomb may result in environmental pollution, as a result, it is highly possible to cause serious health damage to the residents. There are still many abandoned or dumped warfare agents in Japan and China, therefore chemical agents containing arsenic are needed to be treated with alkaline for decomposition or to decompose with oxidizing agent. Presently, a large quantity of chemical agents and the contaminated soil are processed by combustion, and industrial waste is treated with sulfur compounds as the insoluble sulfur arsenic complex. This report describes the methods for the disposal of these organic arsenic agents that have been implemented until present and examines the future prospects. PMID:19122436

  5. Protocol for determination of chemical warfare agent simulant movement through porous media

    SciTech Connect

    Jenkins, R.A.; Buchanan, M.V.; Merriweather, R.; Ilgner, R.H.; Gayle, T.M.; Moneyhun, J.H.; Watson, A.P.

    1992-07-01

    In the event of an unplanned release of chemical warfare agent during any phase of the Chemical Stockpile Disposal Program (CSDP), a (small) potential exists for contamination of buildings and materials used in their construction. Guidelines for unrestricted access to potentially agent-contaminated private and public property are presently undefined due to uncertainties regarding the adequacy of decontaminating porous surfaces such as wood, masonry and gypsum wall board. Persistent agents such as VX or mustard are particularly problematic. The report which follows documents a measurement protocol developed in a scoping investigation characterizing the permeation of chemical warfare agent simulants [diisopropylmethyl phosphonate (DIMP) for warfare agent GB, dimethylmethyl phosphonate (DMMP) for warfare agent VX and chlorethylethyl sulfide (CEES) for warfare agent sulfur mustard] through several, common porous, construction materials. The ``porous media`` selected for examination were wood, brick, cinder block, and gypsum wall board. Simulants were tested rather than actual warfare agents because of their low toxicity, commercial availability, and the lack of surety capability at Oak Ridge National Laboratory (ORNL). The present work is considered a protocol for confirmation testing with ``live`` agents.

  6. Protocol for determination of chemical warfare agent simulant movement through porous media

    SciTech Connect

    Jenkins, R.A.; Buchanan, M.V.; Merriweather, R.; Ilgner, R.H.; Gayle, T.M.; Moneyhun, J.H.; Watson, A.P.

    1992-07-01

    In the event of an unplanned release of chemical warfare agent during any phase of the Chemical Stockpile Disposal Program (CSDP), a (small) potential exists for contamination of buildings and materials used in their construction. Guidelines for unrestricted access to potentially agent-contaminated private and public property are presently undefined due to uncertainties regarding the adequacy of decontaminating porous surfaces such as wood, masonry and gypsum wall board. Persistent agents such as VX or mustard are particularly problematic. The report which follows documents a measurement protocol developed in a scoping investigation characterizing the permeation of chemical warfare agent simulants (diisopropylmethyl phosphonate (DIMP) for warfare agent GB, dimethylmethyl phosphonate (DMMP) for warfare agent VX and chlorethylethyl sulfide (CEES) for warfare agent sulfur mustard) through several, common porous, construction materials. The porous media'' selected for examination were wood, brick, cinder block, and gypsum wall board. Simulants were tested rather than actual warfare agents because of their low toxicity, commercial availability, and the lack of surety capability at Oak Ridge National Laboratory (ORNL). The present work is considered a protocol for confirmation testing with live'' agents.

  7. Evaluation of the vesicating properties of neutralized chemical agent identification sets. Final report, November 1995-August 1997

    SciTech Connect

    Olajos, E.J.; Salem, H.; Gieseking, J.K.

    1997-08-01

    Vesication and skin irritation studies were conducted in hairless guinea-pigs to determine the vesicant and skin irritation potential of Chemical Agent Identification Sets (CAIS). Guinea-pigs were topically dosed with `test article` NEAT HD, 10% agent/chloroform solutions, or product solutions (wastestreams) and evaluated for skin-damaging effects (gross and light microscopic). Product solutions from the chemical neutralization of neat sulfur mustard resulted in microvesicle formation (vesication). All agent-dosed (agent/chloroform solutions or HD) sites exhibited microblisters, as well as other histopathologic lesions of the skin. Wastestreams from the neutalization of agent (agent/chloroform; agent on charcoal) were devoid of microvesicant activity. Dermal irritant effects (erythema and edema) were consistent with the skin-injurious activity associated with the neutralizing reagent 1,3-dichloro-5,5-dimethylhydantoin (DCDMH).

  8. Down-regulation of TGF-b1, TGF-b receptor 2, and TGF-b-associated microRNAs, miR-20a and miR-21, in skin lesions of sulfur mustard-exposed Iranian war veterans.

    PubMed

    Valizadeh, Mohadeseh; Mirzaei, Behnaz; Tavallaei, Mahmood; Noorani, Mohammad Reza; Amiri, Mojtaba; Soroush, Mohammad Reza; Mowla, Seyed Javad

    2015-01-01

    Sulfur mustard (SM) affects divergent cellular pathways including cell cycle, apoptosis, necrosis, and inflammatory responses. SM-induced lesions in skin include late-onset hyper-pigmentation, xerosis, and atrophy. It seems that TGF-b signaling pathway is a major player for SM pathogenesis. Here, we have employed a real-time polymerase chain reaction (PCR) approach to evaluate the expression alterations of all TGF-b variants and their receptors in skin biopsies obtained from 10 Iran-Iraq war veterans. Using specific LNA primers, the expression alteration of a TGF-bR2 regulator, miR-20a, and TGF-b downstream target, miR-21, was also assessed in the same samples Our real-time PCR data revealed a significant down-regulation of TGF-b1 and TGF-bR2, the major mediators of TGF-b signaling pathway, in skin biopsies of SM-exposed patients (p = 0.0015 and p = 0.0115, respectively). Down-regulation of TGF-b signaling pathway seems to contribute in severe inflammation observed in SM-exposed patients' tissues. MiR-20a and miR-21, as two important TGF-b associated microRNAs (miRNAs), were also down-regulated in SM-exposed skin lesions, compared to those of control group (p = 0.0003). Based on our findings, these miRNAs could be directly or indirectly involve in the pathogenesis of SM. Altogether, our data suggest the suitability of TGF-b1, TGF-bR2, as well as miR-20a and miR-21 as potential biomarkers for diagnosis and treatment of SM-exposed patients. PMID:26498464

  9. Poisoning of a Silica-Supported Cobalt Catalyst due to Presence of Sulfur Impurities in Syngas during Fischer–Tropsch Synthesis: Effects of Chelating Agent

    SciTech Connect

    Bambal, Ashish S.; Guggilla, Vidya S.; Kugler, Edwin L.; Gardner, Todd H.; Dadyburjor, Dady B.

    2014-04-09

    The effects of sulfur impurities on the performance of cobalt-based Fischer–Tropsch catalysts are evaluated under industrially relevant operating conditions of temperature, pressure, and impurity levels. Chelating agents (CAs) were used to modify the SiO2 support, and the performances of the CA-modified catalysts are compared with conventional Co/SiO2 catalysts. For both the Co/SiO2 and CA-modified catalysts, the presence of sulfur in the inlet syngas results in a notable drop in the CO conversion, an undesired shift in the hydrocarbon selectivity toward short-chain hydrocarbons, more olefins in the products, and lower product yields. In the post-poisoning stage, i.e., after termination of sulfur introduction in the inlet syngas, the CA-modified catalysts recover activity and selectivity (to some extent at least), whereas such trends are not observed for the base-case, i.e., unmodified Co/SiO2 catalyst. Finally, the improved performance of the CA-modified catalysts in the presence of sulfur is attributed to higher densities of active sites.

  10. Sulphur mustard injuries of the skin. Pathophysiology and management.

    PubMed

    Rice, Paul

    2003-01-01

    Sulphur mustard is a vesicant (blistering agent), which produces chemical burns with widespread blistering. It was used extensively as a chemical warfare agent in the First World War, and has allegedly been employed in a number of conflicts since then, most recently by Iraq against Iran (1984-1987). The potential further use of mustard in military conflicts and by terrorists remains a significant threat that if realised in practice would result in a large number of casualties with severely incapacitating, partial thickness burns. Such injuries clearly present a huge potential wound care problem. The development and healing of mustard-induced cutaneous injuries has not only been observed in human casualties, but has been studied recently at the microscopic and ultrastructural levels in several animal models. Vesication generally begins on the second day after exposure, and may progress for up to 2 weeks. Wound healing is considerably slower than for a comparable thermal burn, and patients often require extended hospital treatment. The current management strategy is essentially symptomatic and supportive. Recently, two techniques for removing damaged tissue and improving wound healing have been investigated. Mechanical dermabrasion and laser debridement ('lasablation') both produced an increased rate of wound healing in animal models, and may be of benefit in a clinical context. PMID:15071821

  11. DESI-MS/MS of Chemical Warfare Agents and Related Compounds

    NASA Astrophysics Data System (ADS)

    D'Agostino, Paul A.

    Solid phase microextraction (SPME) fibers were used to headspace ­sample chemical warfare agents and their hydrolysis products from glass vials and glass vials containing spiked media, including Dacron swabs, office carpet, paper and fabric. The interface of the Z-spray source was modified to permit safe introduction of the SPME fibers for desorption electrospray ionization mass spectrometric (DESI-MS) analysis. A "dip and shoot" method was also developed for the rapid sampling and DESI-MS analysis of chemical warfare agents and their hydrolysis products in liquid samples. Sampling was performed by simply dipping fused silica, stainless steel or SPME tips into the organic or aqueous samples. Replicate analyses were completed within several minutes under ambient conditions with no sample pre-treatment, resulting in a significant increase in sample throughput. The developed sample handling and analysis method was applied to the determination of chemical warfare agent content in samples containing unknown chemical and/or biological warfare agents. Ottawa sand was spiked with sulfur mustard, extracted with water and autoclaved to ensure sterility. Sulfur mustard was completely hydrolysed during the extraction/autoclave step and thiodiglycol was identified by DESI-MS, with analyses generally being completed within 1 min using the "dip and shoot" method.

  12. Nrf2 Regulates the Sensitivity of Mouse Keratinocytes to Nitrogen Mustard via Multidrug Resistance-Associated Protein 1 (Mrp1).

    PubMed

    Udasin, Ronald G; Wen, Xia; Bircsak, Kristin M; Aleksunes, Lauren M; Shakarjian, Michael P; Kong, Ah-Ng Tony; Heck, Diane E; Laskin, Debra L; Laskin, Jeffrey D

    2016-01-01

    Sulfur mustard and nitrogen mustard (mechlorethamine, HN2) are potent vesicants developed as chemical warfare agents. These electrophilic, bifunctional alkylating agents cause skin injury, including inflammation, edema, and blistering. HN2 covalently modifies macromolecules such as DNA, RNA, and proteins or is scavenged by glutathione, forming adducts that can contribute to toxicity. Multidrug resistance-associated protein 1 (Mrp1/MRP1) is a transmembrane ATPase known to efflux glutathione-conjugated electrophiles. In the present studies, we examined the effects of modulating Mrp1-mediated transport activity on the sensitivity of primary and PAM212 mouse keratinocytes to HN2. Primary keratinocytes, and to a lesser extent, PAM212 cells, express Mrp1 mRNA and protein and possess Mrp1 functional activity, as measured by calcein efflux. Sulforaphane, an activator of Nrf2, increased Mrp1 mRNA, protein, and functional activity in primary keratinocytes and PAM212 cells and decreased their sensitivity to HN2-induced growth inhibition (IC(50) = 1.4 and 4.8 µM in primary keratinocytes and 1 and 13 µM in PAM212 cells, in the absence and presence of sulforaphane, respectively). The Mrp1 inhibitor, MK-571, reversed the effects of sulforaphane on HN2-induced growth inhibition in both primary keratinocytes and PAM212 cells. In primary keratinocytes from Nrf2(-/-) mice, sulforaphane had no impact on Mrp1 expression or activity, or on sensitivity to HN2, demonstrating that its effects depend on Nrf2. These data suggest that Mrp1-mediated efflux is important in regulating HN2-induced keratinocyte growth inhibition. Enhancing HN2 efflux from keratinocytes may represent a novel strategy for mitigating vesicant-induced cytotoxicity. PMID:26454883

  13. Serum Metabolomic Profiling of Sulphur Mustard-Exposed Individuals Using (1)H Nuclear Magnetic Resonance Spectroscopy.

    PubMed

    Zamani, Zahra; Ghanei, Mostafa; Panahi, Yunus; Arjmand, Mohammad; Sadeghi, Sedigheh; Mirkhani, Fatemeh; Parvin, Shahram; Salehi, Maryam; Sahebkar, Amirhossein; Vahabi, Farideh

    2016-01-01

    Sulphur mustard is an alkylating agent that reacts with different cellular components, causing acute and delayed complications that may remain for decades after exposure. This study aimed to identify differentially expressed metabolites between mustard-exposed individuals suffering from chronic complications compared with unexposed individuals as the control group. Serum samples were obtained from 15 mustard-exposed individuals and 15 apparently healthy unexposed individuals. Metabolomic profiling was performed using (1)H nuclear magnetic resonance spectroscopy, and analyses were carried out using Chenomex and MATLAB softwares. Metabolites were identified using Human Metabolome Database, and the main metabolic pathways were identified using MetaboAnalyst software. Chemometric analysis of serum samples identified 11 differentially expressed metabolites between mustard-exposed and unexposed groups. The main pathways that were influenced by sulphur mustard exposure were related to vitamin B6 (down-regulation), bile acid (up-regulation) and tryptophan (down-regulation) metabolism. Metabolism of vitamin B6, bile acids and tryptophan are the most severely impaired pathways in individuals suffering from chronic mustard-induced complications. These findings may find implications in the monitoring of exposed patients and identification of new therapeutic approaches.

  14. Inhibition of Listeria monocytogenes and Salmonella by combinations of oriental mustard, malic acid, and EDTA.

    PubMed

    Olaimat, Amin N; Holley, Richard A

    2014-04-01

    The antimicrobial activities of oriental mustard extract alone or combined with malic acid and EDTA were investigated against Salmonella spp. or Listeria monocytogenes at different temperatures. Five strain Salmonella or L. monocytogenes cocktails were separately inoculated in Brain Heart Infusion broth containing 0.5% (w/v) aqueous oriental mustard extract and incubated at 4 °C to 21 °C for 21 d. For inhibitor combination tests, Salmonella Typhimurium 02:8423 and L. monocytogenes 2-243 were individually inoculated in Mueller Hinton broth containing the mustard extract with either or both 0.2% (w/v) malic acid and 0.2% (w/v) EDTA and incubated at 10 °C or 21 °C for 10 to 14 d. Mustard extract inhibited growth of the L. monocytogenes cocktail at 4 °C up to 21 d (2.3 log10 CFU/mL inhibition) or at 10 °C for 7 d (2.4 log10 CFU/mL inhibition). Salmonella spp. viability was slightly, but significantly reduced by mustard extract at 4 °C by 21 d. Although hydrolysis of sinigrin in mustard extract by both pathogens was 2 to 6 times higher at 21 °C than at 4 °C to 10 °C, mustard was not inhibitory at 21 °C, perhaps because of the instability of its hydrolysis product (allyl isothiocyanate). At 21 °C, additive inhibitory effects of mustard extract with EDTA or malic acid led to undetectable levels of S. Typhimurium and L. monocytogenes by 7 d and 10 d, respectively. At 10 °C, S. Typhimurium was similarly susceptible, but combinations of antimicrobials were not more inhibitory to L. monocytogenes than the individual agents.

  15. Niobium(V) saponite clay for the catalytic oxidative abatement of chemical warfare agents.

    PubMed

    Carniato, Fabio; Bisio, Chiara; Psaro, Rinaldo; Marchese, Leonardo; Guidotti, Matteo

    2014-09-15

    A Nb(V)-containing saponite clay was designed to selectively transform toxic organosulfur chemical warfare agents (CWAs) under extremely mild conditions into nontoxic products with reduced environmental impact. Thanks to the insertion of Nb(V) sites within the saponite framework, a bifunctional catalyst with strong oxidizing and acid properties was obtained. Remarkable activity and high selectivity were observed for the oxidative abatement of (2-chloroethyl)ethyl sulfide (CEES), a simulant of sulfur mustard, at room temperature with aqueous hydrogen peroxide. This performance was significantly better compared to a conventional commercial decontamination powder.

  16. Corneal toxicity induced by vesicating agents and effective treatment options.

    PubMed

    Goswami, Dinesh G; Tewari-Singh, Neera; Agarwal, Rajesh

    2016-06-01

    The vesicating agents sulfur mustard (SM) and lewisite (LEW) are potent chemical warfare agents that primarily cause damage to the ocular, skin, and respiratory systems. However, ocular tissue is the most sensitive organ, and vesicant exposure results in a biphasic injury response, including photophobia, corneal lesions, corneal edema, ulceration, and neovascularization, and may cause loss of vision. There are several reports on ocular injury from exposure to SM, which has been frequently used in warfare. However, there are very few reports on ocular injury by LEW, which indicate that injury symptoms appear instantly after exposure and faster than SM. In spite of extensive research efforts, effective therapies for vesicant-induced ocular injuries, mainly to the most affected corneal tissue, are not available. Hence, we have established primary human corneal epithelial cells and rabbit corneal organ culture models with the SM analog nitrogen mustard, which have helped to test the efficacy of potential therapeutic agents. These agents will then be further evaluated against in vivo SM- and LEW-induced corneal injury models, which will assist in the development of potential broad-spectrum therapies against vesicant-induced ocular injuries. PMID:27327041

  17. 2,6-Dithiopurine, a nucleophilic scavenger, protects against mutagenesis in mouse skin treated in vivo with 2-(chloroethyl) ethyl sulfide, a mustard gas analog

    SciTech Connect

    Boulware, Stephen; Fields, Tammy; McIvor, Elizabeth; Powell, K. Leslie; Abel, Erika L.; Vasquez, Karen M.; MacLeod, Michael C.

    2012-09-01

    Sulfur mustard [bis(2-chloroethyl)sulfide, SM] is a well-known DNA-damaging agent that has been used in chemical warfare since World War I, and is a weapon that could potentially be used in a terrorist attack on a civilian population. Dermal exposure to high concentrations of SM produces severe, long-lasting burns. Topical exposure to high concentrations of 2-(chloroethyl) ethyl sulfide (CEES), a monofunctional analog of SM, also produces severe skin lesions in mice. Utilizing a genetically engineered mouse strain, Big Blue, that allows measurement of mutation frequencies in mouse tissues, we now show that topical treatment with much lower concentrations of CEES induces significant dose- and time-dependent increases in mutation frequency in mouse skin; the mutagenic exposures produce minimal toxicity as determined by standard histopathology and immunohistochemical analysis for cytokeratin 6 and the DNA-damage induced phosphorylation of histone H2AX (γ-H2AX). We attempted to develop a therapeutic that would inhibit the CEES-induced increase in mutation frequency in the skin. We observe that multi-dose, topical treatment with 2,6-dithiopurine (DTP), a known chemical scavenger of CEES, beginning 1 h post-exposure to CEES, completely abolishes the CEES-induced increase in mutation frequency. These findings suggest the possibility that DTP, previously shown to be non-toxic in mice, may be useful as a therapeutic agent in accidental or malicious human exposures to SM. -- Highlights: ► 200 mM 2-(chloroethyl) ethyl sulfide (CEES) induces mutations in mouse skin. ► This dose of CEES is not overtly toxic, as assayed by histopathology. ► 2,6-Dithiopurine (DTP), applied after CEES-treatment, abolishes CEES-mutagenesis. ► This supports the idea that sulfur mustards exhibit long biological half-lives.

  18. Clinically-Relevant Cutaneous Lesions by Nitrogen Mustard: Useful Biomarkers of Vesicants Skin Injury in SKH-1 Hairless and C57BL/6 Mice

    PubMed Central

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; White, Carl W.; Agarwal, Rajesh

    2013-01-01

    A paucity of clinically applicable biomarkers to screen therapies in laboratory is a limitation in the development of countermeasures against cutaneous injuries by chemical weapon, sulfur mustard (SM), and its analog nitrogen mustard (NM). Consequently, we assessed NM-caused progression of clinical cutaneous lesions; notably, skin injury with NM is comparable to SM. Exposure of SKH-1 hairless and C57BL/6 (haired) mice to NM (3.2 mg) for 12–120 h caused clinical sequelae of toxicity, including microblister formation, edema, erythema, altered pigmentation, wounding, xerosis and scaly dry skin. These toxic effects of NM were similar in both mouse strains, except that wounding and altered pigmentation at 12–24 h and appearance of dry skin at 24 and 72 h post-NM exposure were more pronounced in C57BL/6 compared to SKH-1 mice. Conversely, edema, erythema and microblister formation were more prominent in SKH-1 than C57BL/6 mice at 24–72 h after NM exposure. In addition, 40–60% mortality was observed following 120 h of NM exposure in the both mouse strains. Overall, these toxic effects of NM are comparable to those reported in humans and other animal species with SM, and thus represent clinically-relevant cutaneous injury endpoints in screening and optimization of therapies for skin injuries by vesicating agents. PMID:23826320

  19. Next Generation Non-particulate Dry Nonwoven Pad for Chemical Warfare Agent Decontamination

    SciTech Connect

    Ramkumar, S S; Love, A; Sata, U R; Koester, C J; Smith, W J; Keating, G A; Hobbs, L; Cox, S B; Lagna, W M; Kendall, R J

    2008-05-01

    New, non-particulate decontamination materials promise to reduce both military and civilian casualties by enabling individuals to decontaminate themselves and their equipment within minutes of exposure to chemical warfare agents or other toxic materials. One of the most promising new materials has been developed using a needlepunching nonwoven process to construct a novel and non-particulate composite fabric of multiple layers, including an inner layer of activated carbon fabric, which is well-suited for the decontamination of both personnel and equipment. This paper describes the development of a composite nonwoven pad and compares efficacy test results for this pad with results from testing other decontamination systems. The efficacy of the dry nonwoven fabric pad was demonstrated specifically for decontamination of the chemical warfare blister agent bis(2-chloroethyl)sulfide (H or sulfur mustard). GC/MS results indicate that the composite fabric was capable of significantly reducing the vapor hazard from mustard liquid absorbed into the nonwoven dry fabric pad. The mustard adsorption efficiency of the nonwoven pad was significantly higher than particulate activated carbon (p=0.041) and was similar to the currently fielded US military M291 kit (p=0.952). The nonwoven pad has several advantages over other materials, especially its non-particulate, yet flexible, construction. This composite fabric was also shown to be chemically compatible with potential toxic and hazardous liquids, which span a range of hydrophilic and hydrophobic chemicals, including a concentrated acid, an organic solvent and a mild oxidant, bleach.

  20. Histiocytosis X: treatment with topical nitrogen mustard.

    PubMed

    Berman, B; Chang, D L; Shupack, J L

    1980-07-01

    The case histories of two elderly patients with cutaneous histiocytosis X treated topically with nitrogen mustard are presented. The cutaneous lesions cleared within 2 to 3 weeks, and remission was maintained with daily topical administration of nitrogen mustard. The clinical impression of improvement was substantiated by light and electron microscopic studies prior to and after therapy.

  1. Cutaneous Injury-Related Structural Changes and Their Progression following Topical Nitrogen Mustard Exposure in Hairless and Haired Mice

    PubMed Central

    Orlicky, David J.; White, Carl W.; Agarwal, Rajesh

    2014-01-01

    To identify effective therapies against sulfur mustard (SM)-induced skin injuries, various animals have been used to assess the cutaneous pathology and related histopathological changes of SM injuries. However, these efforts to establish relevant skin injury endpoints for efficacy studies have been limited mainly due to the restricted assess of SM. Therefore, we employed the SM analog nitrogen mustard (NM), a primary vesicating and bifunctional alkylating agent, to establish relevant endpoints for efficient efficacy studies. Our published studies show that NM (3.2 mg) exposure for 12–120 h in both the hairless SKH-1 and haired C57BL/6 mice caused clinical sequelae of toxicity similar to SM exposure in humans. The NM-induced cutaneous pathology-related structural changes were further analyzed in this study and quantified morphometrically (as percent length or area of epidermis or dermis) of skin sections in mice showing these lesions. H&E stained skin sections of both hairless and haired mice showed that NM (12–120 h) exposure caused epidermal histopathological effects such as increased epidermal thickness, epidermal-dermal separation, necrotic/dead epidermis, epidermal denuding, scab formation, parakeratosis (24–120 h), hyperkeratosis (12–120 h), and acanthosis with hyperplasia (72–120 h). Similar NM exposure in both mice caused dermal changes including necrosis, edema, increase in inflammatory cells, and red blood cell extravasation. These NM-induced cutaneous histopathological features are comparable to the reported lesions from SM exposure in humans and animal models. This study advocates the usefulness of these histopathological parameters observed due to NM exposure in screening and optimization of rescue therapies against NM and SM skin injuries. PMID:24416404

  2. Disarming the mustard oil bomb.

    PubMed

    Ratzka, Andreas; Vogel, Heiko; Kliebenstein, Daniel J; Mitchell-Olds, Thomas; Kroymann, Juergen

    2002-08-20

    Plants are attacked by a broad array of herbivores and pathogens. In response, plants deploy an arsenal of defensive traits. In Brassicaceae, the glucosinolate-myrosinase complex is a sophisticated two-component system to ward off opponents. However, this so-called "mustard oil bomb" is disarmed by a glucosinolate sulfatase of a crucifer specialist insect, diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae). Sulfatase activity of this enzyme largely prevents the formation of toxic hydrolysis products arising from this plant defense system. Importantly, the enzyme acts on all major classes of glucosinolates, thus enabling diamondback moths to use a broad range of cruciferous host plants. PMID:12161563

  3. Sequence selectivity, cross-linking efficiency and cytotoxicity of DNA-targeted 4-anilinoquinoline aniline mustards.

    PubMed

    McClean, S; Costelloe, C; Denny, W A; Searcey, M; Wakelin, L P

    1999-06-01

    We have investigated the sequence selectivity, DNA binding site characteristics, interstrand cross-linking ability and cytotoxicity of four 4-anilinoquinoline aniline mustards related to the AT-selective minor groove-binding bisquaternary ammonium heterocycles. The compounds studied include two full mustards that differ in alkylating power, a half mustard and a quaternary anilinoquinolinium bismustard. We have also compared their cytotoxicity with their precursor diols and their toxicity and cross-linking ability with the classical alkylating agents melphalan and chlorambucil. We find that the anilinoquinoline aniline mustards weakly and non-specifically alkylate guanines in the major groove and that they bind strongly to AT-rich sequences in the minor groove, where they alkylate both adenines and guanines at the N3 position. The most preferred sites are classical minor groove binder AT-tracts to which all four ligands bind equally well. The remaining sites are AT-rich, but include GC base pairs, to which the ligands bind with preferences depending on their structure. The full mustards alkylate at the 3' ends of the binding site in an orientation that depends on the spatial disposition of the purines within the two strands. Generally speaking guanines are found to be much less reactive than adenines. The anilinoquinoline aniline mustards are interstrand cross-linking agents that are 60- to 100-fold more effective than melphalan, with the quaternary compound being the most efficacious. However, the type of binding site at which the cross-links occur is not clear, since distamycin challenge fails to antagonize them fully. The full mustards are 20- to 50-fold more cytotoxic than their diol precursors, are more cytotoxic than the half mustard and are 20- to 30-fold more active than melphalan and chlorambucil. The quaternary ligand is the most potent. Given the evidence to hand, it appears that antitumour activity correlates with capacity to cause interstrand cross

  4. Fly ash sulfur concrete

    SciTech Connect

    Head, W.J.; Liao, M.

    1981-05-01

    Two waste products, flyash and elemental sulfur, can be combined with a modifying agent to produce a potentially useful construction material, flyash sulfur concrete. Manufacturing processes and characteristics of this concrete are described. Compared with a conventional crushed stone aggregate, flyash sulfur concrete is a viable highway pavement base course material. The material's strength characteristics are analyzed. (1 diagram, 4 graphs, 2 photos, 9 references, 5 tables)

  5. Natural occurrence of bisphenol F in mustard.

    PubMed

    Zoller, Otmar; Brüschweiler, Beat J; Magnin, Roxane; Reinhard, Hans; Rhyn, Peter; Rupp, Heinz; Zeltner, Silvia; Felleisen, Richard

    2016-01-01

    Bisphenol F (BPF) was found in mustard up to a concentration of around 8 mg kg(-1). Contamination of the raw products or caused by the packaging could be ruled out. Also, the fact that only the 4,4'-isomer of BPF was detected spoke against contamination from epoxy resin or other sources where technical BPF is used. Only mild mustard made of the seeds of Sinapis alba contained BPF. In all probability BPF is a reaction product from the breakdown of the glucosinolate glucosinalbin with 4-hydroxybenzyl alcohol as an important intermediate. Hot mustard made only from brown mustard seeds (Brassica juncea) or black mustard seeds (Brassica nigra) contained no BPF. BPF is structurally very similar to bisphenol A and has a similar weak estrogenic activity. The consumption of a portion of 20 g of mustard can lead to an intake of 100-200 µg of BPF. According to a preliminary risk assessment, the risk of BPF in mustard for the health of consumers is considered to be low, but available toxicological data are insufficient for a conclusive evaluation. It is a new and surprising finding that BPF is a natural food ingredient and that this is the main uptake route. This insight sheds new light on the risk linked to the family of bisphenols. PMID:26555822

  6. Natural occurrence of bisphenol F in mustard

    PubMed Central

    Zoller, Otmar; Brüschweiler, Beat J.; Magnin, Roxane; Reinhard, Hans; Rhyn, Peter; Rupp, Heinz; Zeltner, Silvia; Felleisen, Richard

    2016-01-01

    ABSTRACT Bisphenol F (BPF) was found in mustard up to a concentration of around 8 mg kg−1. Contamination of the raw products or caused by the packaging could be ruled out. Also, the fact that only the 4,4ʹ-isomer of BPF was detected spoke against contamination from epoxy resin or other sources where technical BPF is used. Only mild mustard made of the seeds of Sinapis alba contained BPF. In all probability BPF is a reaction product from the breakdown of the glucosinolate glucosinalbin with 4-hydroxybenzyl alcohol as an important intermediate. Hot mustard made only from brown mustard seeds (Brassica juncea) or black mustard seeds (Brassica nigra) contained no BPF. BPF is structurally very similar to bisphenol A and has a similar weak estrogenic activity. The consumption of a portion of 20 g of mustard can lead to an intake of 100–200 µg of BPF. According to a preliminary risk assessment, the risk of BPF in mustard for the health of consumers is considered to be low, but available toxicological data are insufficient for a conclusive evaluation. It is a new and surprising finding that BPF is a natural food ingredient and that this is the main uptake route. This insight sheds new light on the risk linked to the family of bisphenols. PMID:26555822

  7. Differences in sequence selectivity of DNA alkylation by isomeric intercalating aniline mustards.

    PubMed

    Prakash, A S; Denny, W A; Wakelin, L P

    1990-01-01

    Two DNA-targeted mustard derivatives, N,N-bis(2-chloroethyl)-4-(5-[9-acridinylamino]-pentamido)aniline and 4-(9-[acridinylamino]butyl 4-(N,N-bis[2-chloroethyl]-aminobenzamide, which are isomeric compounds where the mustard is linked to the DNA-binding 9-aminoacridine moiety by either a -CONH- or a -NHCO- group, show significant differences in the sequence selectivity of their alkylation of DNA. The CONH isomer is a more efficient alxylating agent than the NHCO compound by an order of magnitude, consistent with the larger electron release of the CONH group to the aniline ring. However, the pattern of alkylation by the two compounds is also very different, with the CONH isomer preferring alkylation of guanines adjacent to 3'- or 5'-adenines and cytosines (for example those in sequences 5'-CGC, 5'-AGC, 5'-CGG and 5'-AGA) while the isomeric NHCO compound shows preference for guanines in runs of Gs. In addition, both isomers alkylate 3'-adenines in runs of adenines. Both compounds also show completely different patterns of alkylation to their untargeted mustard counterparts, since 4-MeCONH-aniline mustard alkylates all guanines and adenines in runs of adenines, while 4-Me2NCO-aniline mustard fails to alkylate DNA at all. These differences in alkylation patterns between the CONH- and its isomeric NHCO- compounds and their relationships between the alkylation patterns of the isomers and their biological activities are discussed.

  8. Suppression of Hyperactive Immune Responses Protects against Nitrogen Mustard Injury

    PubMed Central

    Au, Liemin; Meisch, Jeffrey P; Das, Lopa M; Binko, Amy M; Boxer, Rebecca S; Wen, Amy M; Steinmetz, Nicole F; Lu, Kurt Q

    2015-01-01

    DNA alkylating agents like nitrogen mustard (NM) are easily absorbed through the skin and exposure to such agents manifest not only in direct cellular death but also in triggering inflammation. We show that toxicity resulting from topical mustard exposure is mediated in part by initiating exaggerated host innate immune responses. Using an experimental model of skin exposure to NM we observe activation of inflammatory dermal macrophages that exacerbate local tissue damage in an inducible nitric oxide synthase (iNOS)-dependent manner. Subsequently these activated dermal macrophages reappear in the bone marrow to aid in disruption of hematopoiesis and contribute ultimately to mortality in an experimental mouse model of topical NM exposure. Intervention with a single dose of 25-hydroxyvitamin D3 (25(OH)D) is capable of suppressing macrophage-mediated iNOS production resulting in mitigation of local skin destruction, enhanced tissue repair, protection from marrow depletion, and rescue from severe precipitous wasting. These protective effects are recapitulated experimentally using pharmacological inhibitors of iNOS or by compounds that locally deplete skin macrophages. Taken together, these data highlight a critical unappreciated role of the host innate immune system in exacerbating injury following exposure to NM and support the translation of 25(OH)D in the therapeutic use against these chemical agents. PMID:26288355

  9. Free radical production from the interaction of 2-chloroethyl vesicants (mustard gas) with pyridine nucleotide-driven flavoprotein electron transport systems

    SciTech Connect

    Brimfield, A.A. Mancebo, A.M.; Mason, R.P.; Jiang, J.J.; Siraki, A.G.; Novak, M.J.

    2009-01-01

    The biochemical sequelae to chloroethyl mustard exposure correspond very well to toxic processes initiated by free radicals. Additionally, mustard solutions contain spontaneously formed cyclic onium ions which produce carbon free radicals when reduced electrochemically. Therefore, we hypothesized that the onium ions of sulfur or nitrogen mustards might produce carbon free radicals upon being reduced enzymatically, and that these radicals might constitute a metabolic activation. We set out to document radical production using an in vitro metabolic system and electron paramagnetic resonance (EPR). Our system consisted of NADPH, one of several pyridine nucleotide-driven flavoprotein reductases, cytochrome c as a terminal electron acceptor, various sulfur or nitrogen mustards and the spin trap {alpha}-[4-pyridyl-1-oxide]-N-tert-butylnitrone in buffer. Reactions were started by adding the reductase to the other materials, vortexing and immediately transferring the mixture to a 10 mm EPR flat cell. Repeated scans on a Bruker ESP 300E EPR spectrometer produced a triplet of doublets with hyperfine splitting constants of a{sub N} = 15.483 G and a{sub H} = 2.512 G. The outcome supported our hypothesis that carbon-centered free radicals are produced when mustard-related onium ions are enzymatically reduced. The EPR results varied little with the chloroethyl compound used or with porcine or human cytochrome P450 reductase, the reductase domain of rat brain neuronal nitric oxide synthase or rat liver thioredoxin reductase. Our results offer new insight into the basis for mustard-induced vesication and the outcome of exposure to different mustards. The free radical model provides an explanation for similarities in the lesions arising from mustard exposure and energy-based lesions such as those from heat, ultraviolet and nuclear radiation as well as damage across tissue types such as skin, eyes or airway epithelium.

  10. Ultrastructural pathology and immunohistochemistry of mustard gas lesion

    SciTech Connect

    Petrali, J.P.; Oglesby, S.B.; Hamilton, T.A.; Mills, K.R.

    1993-05-13

    The ultrastructural pathology of sulfur mustard gas (HD) skin toxicity has been characterized for several in vivo and in vitro model systems. In animal models, the pathology involves the latent lethal targeting of skin basal cells, a disabling of hemidesmosomes and a progressive edema of the lamina lucida, all of which contribute to the formation of characteristic microblisters at the dermal-epidermal junction. However, the effects of HD toxicity on structural proteins of extracellular domains of the dermal-epidermal junction have not been elucidated. We are beginning an immunohistochemical study of these domains in the hairless guinea pig and summarize here the time course effects of HD of three structural proteins: bullous pemphigoid antigen, laminin and Type IV collagen. The results of this combined ultrastructural and immunohistochemical study indicate that proteins of extracellular matrices of the basement membrane are antigenically altered during the development of HD-induced skin pathology and may contribute to the formation of microblisters.

  11. Review of the U.S. Army's health risk assessments for oral exposure to six chemical-warfare agents. Introduction.

    PubMed

    2000-03-01

    The U.S. Army is under a congressional mandate and the Chemical Weapons Convention of January 1993 to destroy its entire stockpile of chemical munitions. In addition to stockpiled munitions, nonstockpile chemical materiel (NSCM) has been identified for destruction. NSCM includes a host of lethal wastes from past disposal efforts, unserviceable munitions, chemically contaminated containers, chemical-production facilities, newly located chemical munitions, known sites containing substantial quantities of buried chemical weapons and wastes, and binary weapons and components. There are eight stockpile sites located in the continental United States and one on an island in the Pacific Ocean, and 82 NSCM locations have been identified. There are concerns, based on storage and past disposal practices, about soil and groundwater contamination at those sites. Six of the most commonly found chemical-warfare agents at stockpile and NSCM sites are the nerve agents GA, GB, GD, and VX and the vesicating (blistering) agents sulfur mustard and lewisite. To ensure that chemical contamination is reduced to safe concentrations at stockpile and NSCM sites before they are used for residential, occupational, or wildlife purposes, the U.S. Army requested that health-based exposure limits for GA, GB, GD, VX, sulfur mustard, and lewisite be developed to protect the public and the environment. Oak Ridge National Laboratory (ORNL) was asked to conduct the health risk assessments and propose chronic oral reference doses (RfDs) and, where appropriate, oral slope factors (SFs) for the six agents. RfDs are toxicological values developed for noncancer effects and used as reference points to limit human oral exposure to potentially hazardous concentrations of chemicals thought to have thresholds for their effects. RfDs are estimates (with uncertainty spanning an order of magnitude or greater) of daily oral chemical exposures that are unlikely to have deleterious effects during a human lifetime. For

  12. Histopathological and immunohistochemical evaluation of nitrogen mustard-induced cutaneous effects in SKH-1 hairless and C57BL/6 mice.

    PubMed

    Jain, Anil K; Tewari-Singh, Neera; Inturi, Swetha; Orlicky, David J; White, Carl W; Agarwal, Rajesh

    2014-03-01

    Sulfur mustard (SM) is a vesicant warfare agent which causes severe skin injuries. Currently, we lack effective antidotes against SM-induced skin injuries, in part due to lack of appropriate animal model(s) that can be used for efficacy studies in laboratory settings to identify effective therapies. Therefore, to develop a relevant mouse skin injury model, we examined the effects of nitrogen mustard (NM), a primary vesicant and a bifunctional alkylating agent that induces toxic effects comparable to SM. Specifically, we conducted histopathological and immunohistochemical evaluation of several applicable cutaneous pathological lesions following skin NM (3.2mg) exposure for 12-120h in SKH-1 and C57BL/6 mice. NM caused a significant increase in epidermal thickness, incidence of microvesication, cell proliferation, apoptotic cell death, inflammatory cells (neutrophils, macrophages and mast cells) and myleoperoxidase activity in the skin of both mouse strains. However, there was a more prominent NM-induced increase in epidermal thickness, and macrophages and mast cell infiltration, in SKH-1 mice relative to what was seen in C57BL/6 mice. NM also caused collagen degradation and edema at early time points (12-24h); however, at later time points (72 and 120h), dense collagen staining was observed, indicating either water loss or start of integument repair in both the mouse strains. This study provides quantitative measurement of NM-induced histopathological and immunohistochemical cutaneous lesions in both hairless and haired mouse strains that could serve as useful tools for screening and identification of effective therapies for treatment of skin injuries due to NM and SM. PMID:24373750

  13. Storage studies on mustard oil blends.

    PubMed

    Chugh, Bhawna; Dhawan, Kamal

    2014-04-01

    Mustard oil blends were investigated for fatty acid composition and oxidative stability during storage for 3 months at room temperature (15 °C to 35 °C). The blends were prepared using raw mustard oil with selected refined vegetable oils namely; palm, safflower, soybean, rice bran, sunflower and sesame oil (raw). The fatty acid compositions of all these blends were studied using GLC. The developed blends were found to obey the ideal fatty acid ratio as laid down by health agencies i.e. 1:2:1:: SFA:MUFA:PUFA. The oxidative stability of blends was studied by measuring peroxide value (PV), Kries and Thiobarbituric acid (TBA) test. Blends MPSu (mustard oil, palm oil and sunflower oil), MPT (mustard oil, palm oil and sesame oil) and MPGr (mustard oil, palm oil and groundnut oil) were more stable than other blends during storage. The presence of mustard oil in all blends might make them a healthier option for many consumers as it is a rich source of ω-3 fatty acids and has anti-carcinogenic properties.

  14. Sulphur mustard degradation on zirconium doped Ti-Fe oxides.

    PubMed

    Štengla, Václav; Grygar, Tomáš Matys; Opluštil, František; Němec, Tomáš

    2011-09-15

    Zirconium doped mixed nanodispersive oxides of Ti and Fe were prepared by homogeneous hydrolysis of sulphate salts with urea in aqueous solutions. Synthesized nanodispersive metal oxide hydroxides were characterised as the Brunauer-Emmett-Teller (BET) surface area and Barrett-Joiner-Halenda porosity (BJH), X-ray diffraction (XRD), infrared (IR) spectroscopy, scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) microanalysis, and acid-base titration. These oxides were taken for an experimental evaluation of their reactivity with sulphur mustard (chemical warfare agent HD or bis(2-chloroethyl)sulphide). The presence of Zr(4+) dopant tends to increase both the surface area and the surface hydroxylation of the resulting doped oxides in such a manner that it can contribute to enabling the substrate adsorption at the oxide surface and thus accelerate the rate of degradation of warfare agents. The addition of Zr(4+) to the hydrolysis of ferric sulphate with urea shifts the reaction route and promotes formation of goethite at the expense of ferrihydrite. We discovered that Zr(4+) doped oxo-hydroxides of Ti and Fe exhibit a higher degradation activity towards sulphur mustard than any other yet reported reactive sorbents. The reaction rate constant of the slower parallel reaction of the most efficient reactive sorbents is increased with the increasing amount of surface base sites.

  15. Chemical Warfare Agent Degradation and Decontamination

    SciTech Connect

    Talmage, Sylvia Smith; Watson, Annetta Paule; Hauschild, Veronique; Munro, Nancy B; King, J.

    2007-02-01

    The decontamination of chemical warfare agents (CWA) from structures, environmental media, and even personnel has become an area of particular interest in recent years due to increased homeland security concerns. In addition to terrorist attacks, scenarios such as accidental releases of CWA from U.S. stockpile sites or from historic, buried munitions are also subjects for response planning. To facilitate rapid identification of practical and effective decontamination approaches, this paper reviews pathways of CWA degradation by natural means as well as those resulting from deliberately applied solutions and technologies; these pathways and technologies are compared and contrasted. We then review various technologies, both traditional and recent, with some emphasis on decontamination materials used for surfaces that are difficult to clean. Discussion is limited to the major threat CWA, namely sulfur mustard (HD, bis(2-chloroethyl)sulfide), VX (O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate), and the G-series nerve agents. The principal G-agents are GA (tabun, ethyl N,N-dimethylphosphoramidocyanidate), GB (sarin, isopropyl methylphosphonofluoridate), and GD (soman, pinacolyl methylphosphonofluoridate). The chemical decontamination pathways of each agent are outlined, with some discussion of intermediate and final degradation product toxicity. In all cases, and regardless of the CWA degradation pathway chosen for decontamination, it will be necessary to collect and analyze pertinent environmental samples during the treatment phase to confirm attainment of clearance levels.

  16. Mustard Gas: Its Pre-World War I History

    ERIC Educational Resources Information Center

    Duchovic, Ronald J.; Vilensky, Joel A.

    2007-01-01

    The Meyer-Clarke synthetic method was used in the German process for large scale production of mustard gas during World War I, which clearly shows the historical connection of synthesis of mustard gas.

  17. A critical evaluation of the implications for risk based land management of the environmental chemistry of Sulphur Mustard.

    PubMed

    Ashmore, Matthew Howard; Nathanail, C Paul

    2008-11-01

    Sulphur Mustard, or "Mustard Gas" is in fact an oily liquid which was used as a chemical weapon primarily for its vesicant action which necessitates whole body protection. It is also now recognised as a carcinogenic agent upon chronic exposure. Soil contaminated with Sulphur Mustard continues to present both acute and chronic human health risks and risks to groundwater, surface water and the wider ecology at a number of sites globally and, in some cases, has done for many decades. This is at odds with the simple aqueous chemistry of the compound which would suggest that it should be short lived in the environment, especially in the presence of water. A number of studies have examined the possible factors for this longevity and, though the causes are generally assumed to be understood, the precise reasons have not yet been definitively determined and the evidence in support of the existing theories is at best circumstantial. At present, the prevailing view is that Sulphur Mustard is somehow protected by oligomeric or polymeric sulphonium species produced during incomplete hydrolysis reactions. The following review discusses the pertinent degradation mechanisms in the environment; hydrolysis and thermal degradation and the reasons put forward for the longevity of Sulphur Mustard in the literature. Other factors, such as the role of polymeric species in Sulphur Mustard droplets in modifying the mobility of the agent are also examined. Ultimately, without a thorough understanding of the abiotic fate of the Sulphur Mustard, uncertainties will remain in the application of risk assessment and remediation strategies to such sites, potentially compromising the validity or effectiveness of such actions.

  18. Development of an enzyme-linked immunosorbent assay method to detect mustard protein in mustard seed oil.

    PubMed

    Koppelman, Stef J; Vlooswijk, Riek; Bottger, Gina; Van Duijn, Gert; Van der Schaft, Peter; Dekker, Jacco; Van Bergen, Hans

    2007-01-01

    An enzyme-linked immunosorbent assay for the detection of mustard protein was developed. The assay is based on a polyclonal antiserum directed against a mixture of mustard proteins raised in rabbits. The assay has a detection limit of 1.5 ppm (milligrams per kilogram) and is suitable for the detection of traces of mustard protein in mustard seed-derived flavoring ingredients. Limited cross-reactivity testing showed that no other plant proteins reacted significantly. From the animal proteins tested, only milk showed some cross-reactivity. With this sensitive assay, it was shown that refined mustard seed oil produced by steam distillation does not contain detectable amounts of mustard protein. Mustard seed oil is used as a flavoring in very low quantities, typically between 40 and 200 mg/kg. Thus, 100 g of a food product flavored with 200 mg of mustard seed oil per kg containing < 1.5 mg of protein per kg would represent an amount of mustard seed protein of <30 ng. Taking into account the published literature on allergic reactions to the unintended ingestion of mustard, this conservatively low calculated level indicates that it is unlikely that food products containing mustard seed oil as a flavoring ingredient will elicit an allergic reaction in mustard-allergic individuals. PMID:17265878

  19. Retinoic acid conjugates as potential antitumor agents: synthesis and biological activity of conjugates with Ara-A, Ara-C, 3(2H)-furanone, and aniline mustard moieties.

    PubMed

    Manfredini, S; Simoni, D; Ferroni, R; Bazzanini, R; Vertuani, S; Hatse, S; Balzarini, J; De Clercq, E

    1997-11-01

    In a dual targeting approach, to explore the ability of tretinoin (all-trans-retinoic acid) to behave as a covalent carrier for cytotoxic entities, conjugates of retinoic acid with a few representative molecules, being important examples of antitumor pharmacophores (i.e., nucleoside analogues and alkylating agents), have been synthesized and tested for their cytostatic and differentiating activity. All compounds were stable to in vitro hydrolysis in human plasma and more lipophilic than the parent compounds, thus consenting enhanced uptake into the cells. Among the nucleoside analogues the Ara-C derivatives 3 and 6 and the Ara-A derivative 7 proved the most cytostatic (IC50 < 0.32 microgram/mL) resulting from 25- to > 144-fold more active (Ara-A derivatives) or at least as equally active (Ara-C derivatives) as compared to the parent nucleosides. Compound 3, endowed with a highly lipophilic silyl moiety at the 3' and 5' positions, showed the highest differentiating activity (54% and 44% differentiated HL-60 cells at 0.2 and 0.05 microgram/mL respectively). With regard to the retinoic acid conjugates of alkylating agents, compound 10 was the most cytostatic agent (IC50 < 0.32 microgram/mL) and the most potent differentiating agent (33-34% at 0.32 and 0.08 microgram/mL). These structures may also be regarded as analogs of either retinoic acid or the cytotoxic compound.

  20. Mesoporous titanium-manganese dioxide for sulphur mustard and soman decontamination

    SciTech Connect

    Stengl, Vaclav; Bludska, Jana; Oplustil, Frantisek; Nemec, Tomas

    2011-11-15

    Highlights: {yields} New nano-dispersive materials for warfare agents decontamination. {yields} 95% decontamination activities for sulphur mustard. {yields} New materials base on titanium and manganese oxides. -- Abstract: Titanium(IV)-manganese(IV) nano-dispersed oxides were prepared by a homogeneous hydrolysis of potassium permanganate and titanium(IV) oxo-sulphate with 2-chloroacetamide. Synthesised samples were characterised using Brunauer-Emmett-Teller (BET) surface area and Barrett-Joiner-Halenda porosity (BJH), X-ray diffraction (XRD), infrared spectroscopy (IR), and scanning electron microscopy (SEM). These oxides were taken for an experimental evaluation of their reactivity with sulphur mustard (HD or bis(2-chloroethyl)sulphide) and soman (GD or (3,3'-dimethylbutan-2-yl)-methylphosphonofluoridate). Mn{sup 4+} content affects the decontamination activity; with increasing Mn{sup 4+} content the activity increases for sulphur mustard and decreases for soman. The best decontamination activities for sulphur mustard and soman were observed for samples TiMn{sub 3}7 with 18.6 wt.% Mn and TiMn{sub 5} with 2.1 wt.% Mn, respectively.

  1. Biodegradation of mustard. Final report, April-October 1993

    SciTech Connect

    Young, R.J.

    1994-07-01

    A literature search to identify microorganisms of potential value for the degradation of mustard was carried out. Selection of microorganisms was based on tolerance to low pH and chloride ions, conditions that retard mustard hydrolysis. Several bacteria able to degrade organic sulfides and/or sulfonium compounds under these conditions were identified. Fungi and yeasts are also of potential use, as are enzymes from halo- and thermophilic organisms. The major difficulty in the use of microorganisms and enzymes for mustard degradation is the low solubility of mustard in water. Fungi, Sulfide, Halophilic, Microorganism, Yeast, Mustard, Bacteria, Degradation, Sulfonium, Acidophilic.

  2. Response of a high-glucuronidase human tumour xenograft to aniline mustard.

    PubMed

    Warenius, H M; Workman, P; Bleehen, N M

    1982-01-01

    The HT29R colonic adenocarcinoma xenograft has been shown to be rich in the enzyme beta-glucuronidase. Experiments in rodent systems have demonstrated a marked anti-tumour effect of the drug aniline mustard (AM) on tumours with high levels of this enzyme (e.g. the plasmacytomas PC5 and PC6). We have found that AM is no more effective than its analogue paramethyl aniline mustard (PMAM) or other alkylating agents against the HT29R xenograft. Amongst the possible explanations for this may be: (1) The wide shoulder on the cell-survival curve shown for exposure to alkylating agents of HT29R in vivo. (2) Lack of correlation between physiological availability of beta-glucuronidase and the high levels measured by the standard assay. (3) Increased beta-glucuronidase levels in host mouse marrow, making the latter potentially more susceptible to AM damage.

  3. Decontamination of adsorbed chemical warfare agents on activated carbon using hydrogen peroxide solutions.

    PubMed

    Osovsky, Ruth; Kaplan, Doron; Nir, Ido; Rotter, Hadar; Elisha, Shmuel; Columbus, Ishay

    2014-09-16

    Mild treatment with hydrogen peroxide solutions (3-30%) efficiently decomposes adsorbed chemical warfare agents (CWAs) on microporous activated carbons used in protective garments and air filters. Better than 95% decomposition of adsorbed sulfur mustard (HD), sarin, and VX was achieved at ambient temperatures within 1-24 h, depending on the H2O2 concentration. HD was oxidized to the nontoxic HD-sulfoxide. The nerve agents were perhydrolyzed to the respective nontoxic methylphosphonic acids. The relative rapidity of the oxidation and perhydrolysis under these conditions is attributed to the microenvironment of the micropores. Apparently, the reactions are favored due to basic sites on the carbon surface. Our findings suggest a potential environmentally friendly route for decontamination of adsorbed CWAs, using H2O2 without the need of cosolvents or activators.

  4. Decontamination of adsorbed chemical warfare agents on activated carbon using hydrogen peroxide solutions.

    PubMed

    Osovsky, Ruth; Kaplan, Doron; Nir, Ido; Rotter, Hadar; Elisha, Shmuel; Columbus, Ishay

    2014-09-16

    Mild treatment with hydrogen peroxide solutions (3-30%) efficiently decomposes adsorbed chemical warfare agents (CWAs) on microporous activated carbons used in protective garments and air filters. Better than 95% decomposition of adsorbed sulfur mustard (HD), sarin, and VX was achieved at ambient temperatures within 1-24 h, depending on the H2O2 concentration. HD was oxidized to the nontoxic HD-sulfoxide. The nerve agents were perhydrolyzed to the respective nontoxic methylphosphonic acids. The relative rapidity of the oxidation and perhydrolysis under these conditions is attributed to the microenvironment of the micropores. Apparently, the reactions are favored due to basic sites on the carbon surface. Our findings suggest a potential environmentally friendly route for decontamination of adsorbed CWAs, using H2O2 without the need of cosolvents or activators. PMID:25133545

  5. Discrimination between ricin and sulphur mustard toxicity in vitro using Raman spectroscopy.

    PubMed Central

    Notingher, I.; Green, C.; Dyer, C.; Perkins, E.; Hopkins, N.; Lindsay, C.; Hench, L. L.

    2004-01-01

    A Raman spectroscopy cell-based biosensor has been proposed for rapid detection of toxic agents, identification of the type of toxin and prediction of the concentration used. This technology allows the monitoring of the biochemical properties of living cells over long periods of time by measuring the Raman spectra of the cells non-invasively, rapidly and without use of labels (Notingher et al. 2004 doi:10.1016/j.bios.2004.04.008). Here we show that this technology can be used to distinguish between changes induced in A549 lung cells by the toxin ricin and the chemical warfare agent sulphur mustard. A multivariate model based on principal component analysis (PCA) and linear discriminant analysis (LDA) was used for the analysis of the Raman spectra of the cells. The leave-one-out cross-validation of the PCA-LDA model showed that the damaged cells can be detected with high sensitivity (98.9%) and high specificity (87.7%). High accuracy in identifying the toxic agent was also found: 88.6% for sulphur mustard and 71.4% for ricin. The prediction errors were observed mostly for the ricin treated cells and the cells exposed to the lower concentration of sulphur mustard, as they induced similar biochemical changes, as indicated by cytotoxicity assays. The concentrations of sulphur mustard used were also identified with high accuracy: 93% for 200 microM and 500 microM, and 100% for 1,000 microM. Thus, biological Raman microspectroscopy and PCA-LDA analysis not only distinguishes between viable and damaged cells, but can also discriminate between toxic challenges based on the cellular biochemical and structural changes induced by these agents and the eventual mode of cell death. PMID:16849154

  6. Enhanced cytostatic effectiveness of aniline mustard against 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors during regression in response to ovariectomy.

    PubMed

    Benckhuysen, C; Ter Hart, H G; Van Dijk, P J

    1981-01-01

    Sprague-Dawley rats bearing 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors were treated with either of two aromatic alkylating agents, aniline mustard or melphalan, alone or combined with ovariectomy. Both drugs were applied once a week for 8 weeks. Eight-four percent of the tumors responded to ovariectomy, 38% regressing completely and 46% regressing partially. Aniline mustard, though virtually ineffective as a single agent, appeared synergistic with ovariectomy: a 100% regression rate (72% complete, 28% partial) was observed for this combination. Treatment with melphalan was as effective as ovariectomy, but the combination of melphalan with ovariectomy was no more effective than either treatment alone. The end product of aniline mustard metabolism, p-hydroxyaniline mustard O-glucuronide, may be more extensively activated by beta-glucuronidase in hormonally regressing than in growing or stationary tumors. Intratumoral levels of beta-glucoronidase occurring in DMBA-induced tumors 4 days after ovariectomy were found to be similar to those in the aniline mustard-sensitive mouse plasma cell tumor ADJ/PC6. It remains to be more extensively studied whether an effect of endocrine treatment on tumor beta-glucuronidase levels, and possibly on intracellular distribution of enzyme, could be used therapeutically. An effectively scheduled cytostatic treatment (with a drug conjugate such as that formed metabolically from aniline mustard) in conjunction with ovariectomy might be effective in the treatment of hormone-responsive breast cancer.

  7. Mustard (Sinapis alba) Seed Meal Suppresses Weeds in Container Grown Ornamentals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mustard seed meal is a byproduct of mustard (Sinapis alba L.) grown and oil production. Developing new uses for mustard seed meal could increase the profitability of growing mustard. Seed meal of mustard, var. ‘IdaGold’ was applied to the soil surface to evaluate its effect on several common weeds...

  8. 'Dilute-and-shoot' RSLC-MS-MS method for fast detection of nerve and vesicant chemical warfare agent metabolites in urine.

    PubMed

    Rodin, Igor; Braun, Arcady; Stavrianidi, Andrey; Baygildiev, Timur; Shpigun, Oleg; Oreshkin, Dmitry; Rybalchenko, Igor

    2015-01-01

    A sensitive screening method based on fast liquid chromatography tandem mass-spectrometry (RSLC-MS-MS) has shown the feasibility of separation and detection of low concentration β-lyase metabolites of sulfur mustard and of nerve agent phosphonic acids in urine. The analysis of these compounds is of interest because they are specific metabolites of the chemical warfare agents (CWAs), sulfur mustard (HD), sarin (GB), soman (GD), VX and Russian VX (RVX). The 'dilute-and-shoot' RSLC-MS-MS method provides a sensitive and direct approach for determining CWA exposure in non-extracted non-derivatized samples from urine. Chromatographic separation of the metabolites was achieved using a reverse phase column with gradient mobile phases consisting of 0.5% formic acid in water and acetonitrile. Identification and quantification of species were achieved using electrospray ionization-tandem mass-spectrometry monitoring two precursor-to-product ion transitions for each compound. The method demonstrates linearity over at least two orders of magnitude and had detection limits of 0.5 ng/mL in urine.

  9. 'Dilute-and-shoot' RSLC-MS-MS method for fast detection of nerve and vesicant chemical warfare agent metabolites in urine.

    PubMed

    Rodin, Igor; Braun, Arcady; Stavrianidi, Andrey; Baygildiev, Timur; Shpigun, Oleg; Oreshkin, Dmitry; Rybalchenko, Igor

    2015-01-01

    A sensitive screening method based on fast liquid chromatography tandem mass-spectrometry (RSLC-MS-MS) has shown the feasibility of separation and detection of low concentration β-lyase metabolites of sulfur mustard and of nerve agent phosphonic acids in urine. The analysis of these compounds is of interest because they are specific metabolites of the chemical warfare agents (CWAs), sulfur mustard (HD), sarin (GB), soman (GD), VX and Russian VX (RVX). The 'dilute-and-shoot' RSLC-MS-MS method provides a sensitive and direct approach for determining CWA exposure in non-extracted non-derivatized samples from urine. Chromatographic separation of the metabolites was achieved using a reverse phase column with gradient mobile phases consisting of 0.5% formic acid in water and acetonitrile. Identification and quantification of species were achieved using electrospray ionization-tandem mass-spectrometry monitoring two precursor-to-product ion transitions for each compound. The method demonstrates linearity over at least two orders of magnitude and had detection limits of 0.5 ng/mL in urine. PMID:25326204

  10. Use of acid whey and mustard seed to replace nitrites during cooked sausage production.

    PubMed

    Wójciak, Karolina M; Karwowska, Małgorzata; Dolatowski, Zbigniew J

    2014-02-01

    The aim was to determine the effects of sea salt, acid whey, native and autoclaved mustard seed on the physico-chemical properties, especially colour formation, microbial stability and sensory evaluation of non-nitrite cooked sausage during chilling storage. The cooked pork sausages were divided into 4 groups (group I--control sausages with curing salt (2.8%) and water (5%) added; group II--sausages with sea salt (2.8%) and acid whey (5%) added; group III--sausages with sea salt (2.8%), acid whey (5%) and mustard seed (1%) added; group IV--sausages with sea salt (2.8%), acid whey (5%) and autoclaved mustard seed (1%) added). Instrumental colour (L*, a*, b*), oxygenation index (ΔR), 650/570 nm ratio, heme iron, pH value and water activity (aw) were determined 1 day after production and after 10, 20 and 30 days of refrigerated storage (4 °C). Sensory analysis was conducted immediately after production (day 1). Microbial analysis (lactic acid bacteria, total viable count, Clostridium spp.) was determinated at the end of storage (30 days). The autoclaved mustard with acid whey can be used at 1.0% (w/w) of model cooked sausages with beneficial effect on physico-chemical and sensory qualities of no-nitrite sausage. This product can be stored at refrigeration temperature for up to 30 days, in vacuum, with good acceptability. The colour, visual appearance and overall quality of samples with autoclaved mustard seed and acid whey were similar to the control with curing agent. PMID:24200566

  11. Use of acid whey and mustard seed to replace nitrites during cooked sausage production.

    PubMed

    Wójciak, Karolina M; Karwowska, Małgorzata; Dolatowski, Zbigniew J

    2014-02-01

    The aim was to determine the effects of sea salt, acid whey, native and autoclaved mustard seed on the physico-chemical properties, especially colour formation, microbial stability and sensory evaluation of non-nitrite cooked sausage during chilling storage. The cooked pork sausages were divided into 4 groups (group I--control sausages with curing salt (2.8%) and water (5%) added; group II--sausages with sea salt (2.8%) and acid whey (5%) added; group III--sausages with sea salt (2.8%), acid whey (5%) and mustard seed (1%) added; group IV--sausages with sea salt (2.8%), acid whey (5%) and autoclaved mustard seed (1%) added). Instrumental colour (L*, a*, b*), oxygenation index (ΔR), 650/570 nm ratio, heme iron, pH value and water activity (aw) were determined 1 day after production and after 10, 20 and 30 days of refrigerated storage (4 °C). Sensory analysis was conducted immediately after production (day 1). Microbial analysis (lactic acid bacteria, total viable count, Clostridium spp.) was determinated at the end of storage (30 days). The autoclaved mustard with acid whey can be used at 1.0% (w/w) of model cooked sausages with beneficial effect on physico-chemical and sensory qualities of no-nitrite sausage. This product can be stored at refrigeration temperature for up to 30 days, in vacuum, with good acceptability. The colour, visual appearance and overall quality of samples with autoclaved mustard seed and acid whey were similar to the control with curing agent.

  12. Proteomic analysis of DNA-protein cross-linking by antitumor nitrogen mustards.

    PubMed

    Loeber, Rachel L; Michaelson-Richie, Erin D; Codreanu, Simona G; Liebler, Daniel C; Campbell, Colin R; Tretyakova, Natalia Y

    2009-06-01

    Nitrogen mustards are antitumor agents used clinically for the treatment of a variety of neoplastic conditions. The biological activity of these compounds is typically attributed to their ability to induce DNA-DNA cross-links. However, nitrogen mustards are able to produce a variety of other lesions, including DNA-protein cross-links (DPCs). DPCs induced by nitrogen mustards are not well-characterized because of their structural complexity and the insufficient specificity and sensitivity of previously available experimental methodologies. In the present work, affinity capture methodology in combination with mass spectrometry-based proteomics was employed to identify mammalian proteins that form covalent cross-links to DNA in the presence of a simple nitrogen mustard, mechlorethamine. Following incubation of 5'-biotinylated DNA duplexes with nuclear protein extracts, DPCs were isolated by affinity capture on streptavidin beads, and the cross-linked proteins were identified by high-performance liquid chromatography-electrospray tandem mass spectrometry of tryptic peptides. Mechlorethamine treatment resulted in the formation of DPCs with nuclear proteins involved in chromatin regulation, DNA replication and repair, cell cycle control, transcriptional regulation, and cell architecture. Western blot analysis was employed to confirm protein identification and to quantify the extent of drug-mediated cross-linking. Mass spectrometry of amino acid-nucleobase conjugates found in total proteolytic digests revealed that mechlorethamine-induced DPCs are formed via alkylation of the N7 position of guanine in duplex DNA and cysteine thiols within the proteins to give N-[2-[S-cysteinyl]ethyl]-N-[2-(guan-7-yl)ethyl]methylamine lesions. The results described herein suggest that cellular exposure to nitrogen mustards leads to cross-linking of a large spectrum of nuclear proteins to chromosomal DNA, potentially contributing to the cytotoxic and mutagenic effects of these drugs.

  13. The chemical agent experience at Rocky Mountain Arsenal

    SciTech Connect

    Mohrman, G.

    1995-06-01

    Rocky Mountain Arsenal (RMA) was constructed and commissioned in 1942 for the production of sulfur mustard and other chemical munitions for possible use in World War II. RMA also became a production site for Lewisite and Sarin, including synthesis and munition filling. Other chemical agents such as Phosgene were routinely handled, filled into munitions and demilitarized. During the 1970`s and the early 1980`s, RMA served as a primary demilitarization facility for the destruction of chemical agents. Throughout its chemical weapons history, RMA generated waste materials from production, neutralization, decontamination and testing. These operations led to the possibility of chemical agent contamination in soils, process equipment and structures that have required special attention as part of the overall Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) environmental cleanup operations being conducted by the Program Manager Rocky Mountain Arsenal (PMRMA). Adjusting normal sampling operations associated with CERCLA-type activities for the special Army regulations covering chemical agents has been a difficult task. This presentation will describe the evolution of chemical agent related efforts and operations as they pertain to RMA environmental cleanup activities, to include field sampling requirements, analytical methods, commercial laboratory use and the role of the on-site PMRMA laboratory.

  14. Soil biotransformation of thiodiglycol, the hydrolysis product of mustard gas: understanding the factors governing remediation of mustard gas contaminated soil.

    PubMed

    Li, Hong; Muir, Robert; McFarlane, Neil R; Soilleux, Richard J; Yu, Xiaohong; Thompson, Ian P; Jackman, Simon A

    2013-02-01

    Thiodiglycol (TDG) is both the precursor for chemical synthesis of mustard gas and the product of mustard gas hydrolysis. TDG can also react with intermediates of mustard gas degradation to form more toxic and/or persistent aggregates, or reverse the pathway of mustard gas degradation. The persistence of TDG have been observed in soils and in the groundwater at sites contaminated by mustard gas 60 years ago. The biotransformation of TDG has been demonstrated in three soils not previously exposed to the chemical. TDG biotransformation occurred via the oxidative pathway with an optimum rate at pH 8.25. In contrast with bacteria isolated from historically contaminated soil, which could degrade TDG individually, a consortium of three bacterial strains isolated from the soil never contaminated by mustard gas was able to grow on TDG in minimal medium and in hydrolysate derived from an historical mustard gas bomb. Exposure to TDG had little impacts on the soil microbial physiology or on community structure. Therefore, the persistency of TDG in soils historically contaminated by mustard gas might be attributed to the toxicity of mustard gas to microorganisms and the impact to soil chemistry during the hydrolysis. TDG biodegradation may form part of a remediation strategy for mustard gas contaminated sites, and may be enhanced by pH adjustment and aeration. PMID:22752796

  15. Soil biotransformation of thiodiglycol, the hydrolysis product of mustard gas: understanding the factors governing remediation of mustard gas contaminated soil.

    PubMed

    Li, Hong; Muir, Robert; McFarlane, Neil R; Soilleux, Richard J; Yu, Xiaohong; Thompson, Ian P; Jackman, Simon A

    2013-02-01

    Thiodiglycol (TDG) is both the precursor for chemical synthesis of mustard gas and the product of mustard gas hydrolysis. TDG can also react with intermediates of mustard gas degradation to form more toxic and/or persistent aggregates, or reverse the pathway of mustard gas degradation. The persistence of TDG have been observed in soils and in the groundwater at sites contaminated by mustard gas 60 years ago. The biotransformation of TDG has been demonstrated in three soils not previously exposed to the chemical. TDG biotransformation occurred via the oxidative pathway with an optimum rate at pH 8.25. In contrast with bacteria isolated from historically contaminated soil, which could degrade TDG individually, a consortium of three bacterial strains isolated from the soil never contaminated by mustard gas was able to grow on TDG in minimal medium and in hydrolysate derived from an historical mustard gas bomb. Exposure to TDG had little impacts on the soil microbial physiology or on community structure. Therefore, the persistency of TDG in soils historically contaminated by mustard gas might be attributed to the toxicity of mustard gas to microorganisms and the impact to soil chemistry during the hydrolysis. TDG biodegradation may form part of a remediation strategy for mustard gas contaminated sites, and may be enhanced by pH adjustment and aeration.

  16. Novel hybrids of natural oridonin-bearing nitrogen mustards as potential anticancer drug candidates.

    PubMed

    Xu, Shengtao; Pei, Lingling; Wang, Chengqian; Zhang, Yun-Kai; Li, Dahong; Yao, Hequan; Wu, Xiaoming; Chen, Zhe-Sheng; Sun, Yijun; Xu, Jinyi

    2014-07-10

    A series of novel hybrids from natural product oridonin and nitrogen mustards were designed and synthesized to obtain more efficacious and less toxic antitumor agents. The antiproliferative evaluation showed that most conjugates were more potent than their parent compounds oridonin and clinically used nitrogen mustards against four human cancer cell lines (K562, MCF-7, Bel-7402, and MGC-803). Furthermore, the representative compounds 16a-c exhibited antiproliferative activities against the multidrug resistant cell lines (SW620/AD300 and NCI-H460/MX20). It was shown that the most effective compound 16b possesses a strong inhibitory activity with an IC50 value 21-fold lower than that of oridonin in MCF-7 cells and also exhibits selective cytotoxicity toward the cancer cells. Intriguingly, compound 16b has been demonstrated to significantly induce apoptosis and affect cell cycle progression in human hepatoma Bel-7402 cells. PMID:25050168

  17. Novel hybrids of natural oridonin-bearing nitrogen mustards as potential anticancer drug candidates.

    PubMed

    Xu, Shengtao; Pei, Lingling; Wang, Chengqian; Zhang, Yun-Kai; Li, Dahong; Yao, Hequan; Wu, Xiaoming; Chen, Zhe-Sheng; Sun, Yijun; Xu, Jinyi

    2014-07-10

    A series of novel hybrids from natural product oridonin and nitrogen mustards were designed and synthesized to obtain more efficacious and less toxic antitumor agents. The antiproliferative evaluation showed that most conjugates were more potent than their parent compounds oridonin and clinically used nitrogen mustards against four human cancer cell lines (K562, MCF-7, Bel-7402, and MGC-803). Furthermore, the representative compounds 16a-c exhibited antiproliferative activities against the multidrug resistant cell lines (SW620/AD300 and NCI-H460/MX20). It was shown that the most effective compound 16b possesses a strong inhibitory activity with an IC50 value 21-fold lower than that of oridonin in MCF-7 cells and also exhibits selective cytotoxicity toward the cancer cells. Intriguingly, compound 16b has been demonstrated to significantly induce apoptosis and affect cell cycle progression in human hepatoma Bel-7402 cells.

  18. 7 CFR 201.56-3 - Mustard family, Brassicaceae (Cruciferae).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., Chinese cabbage, cauliflower, collards, garden cress, upland cress, water cress, kale, Chinese kale, Siberian kale, kohlrabi, mustard, pakchoi, radish, rape, rutabaga, and turnip. (a) General description....

  19. 7 CFR 201.56-3 - Mustard family, Brassicaceae (Cruciferae).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., Chinese cabbage, cauliflower, collards, garden cress, upland cress, water cress, kale, Chinese kale, Siberian kale, kohlrabi, mustard, pakchoi, radish, rape, rutabaga, and turnip. (a) General description....

  20. 7 CFR 201.56-3 - Mustard family, Brassicaceae (Cruciferae).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., Chinese cabbage, cauliflower, collards, garden cress, upland cress, water cress, kale, Chinese kale, Siberian kale, kohlrabi, mustard, pakchoi, radish, rape, rutabaga, and turnip. (a) General description....

  1. 7 CFR 201.56-3 - Mustard family, Brassicaceae (Cruciferae).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., Chinese cabbage, cauliflower, collards, garden cress, upland cress, water cress, kale, Chinese kale, Siberian kale, kohlrabi, mustard, pakchoi, radish, rape, rutabaga, and turnip. (a) General description....

  2. 7 CFR 201.56-3 - Mustard family, Brassicaceae (Cruciferae).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., Chinese cabbage, cauliflower, collards, garden cress, upland cress, water cress, kale, Chinese kale, Siberian kale, kohlrabi, mustard, pakchoi, radish, rape, rutabaga, and turnip. (a) General description....

  3. O-alkyl S-3,3-dimethyl-2-oxobutyl dithiocarbonates as versatile sulfur-transfer agents in radical C(sp3)-H functionalization.

    PubMed

    Sato, Akinori; Yorimitsu, Hideki; Oshima, Koichiro

    2007-12-01

    Boiling of the title compounds in ethereal solvents or cycloalkanes in the presence of a radical initiator leads to radical C(sp3)-H functionalization, by which a sulfur atom is introduced into the ethereal solvents at the oxygenated carbon atom or into the cycloalkanes. Both acyclic and cyclic ethers, such as [18]crown-6 and [D8]THF, undergo the sulfur transfer. The reaction is useful for the synthesis of monothioacetals, thiols, and sulfides from simple starting materials.

  4. Putting Some Mustard into Economic Growth

    PubMed Central

    Evans, Robert G.

    2012-01-01

    On September 27, 2012, the University of Toronto launched the Fraser Mustard Institute for Human Development – an appropriate recognition of an extraordinary individual. Fraser was a keen student of the science of human development and, most particularly, of early child development (ECD). He was also a powerful and tireless advocate for translating science into action. His institute must do both. Action is needed also because 25% of Canadians lack the competencies to function effectively in a modern economy. Other countries do much better. Facing a low-growth future, we cannot afford to waste this untapped potential. Although Prime Minister Harper's personal ideology has no place for ECD, the Mustard Institute can help keep the flame alive. PMID:23968611

  5. Mustard bran in lactating dairy cow diets.

    PubMed

    Maiga, H A; Bauer, M L; Dahlen, C R; Badaruddin, M; Scholljegerdes, E J

    2011-06-01

    Two trials using lactating Holstein cows were conducted to evaluate effects of a diet containing oriental mustard bran on dry matter intake (DMI), milk production, milk components, and organoleptic properties. In experiment 1, 34 lactating cows (24 multiparous and 10 primiparous; days in milk ≥ 50 d) were used in a switchback design to determine the lactational response and organoleptic quality of milk when the diet contained 8% oriental mustard bran (MB) versus a control diet (CON). Mustard bran replaced a portion of soybean meal and all the beet pulp in the CON diet. Milk yields were greater for cows fed the MB diet; however, no differences were found in DMI, 3.5% fat- (FCM) or solids-corrected milk. Milk components and components production were not affected by treatment. Milk organoleptic qualities were not affected by diet. In experiment 2, 22 lactating cows (16 multiparous and 6 primiparous; days in milk ≥ 21 d) were assigned randomly within parity to receive MB or CON from wk 4 to 19 postpartum in a randomized complete block design. Cows were fed CON wk 1 to 3 postpartum. The MB diet contained the same ingredients as the CON, except sunflower seed and a portion of soybean meal were replaced with mustard bran. Milk and components data were collected during wk 3 postpartum and used as covariates to adjust treatment means. Intake was greater for cows fed the MB diet; however, daily milk, 3.5% FCM, and solids-corrected milk yields were not different between diets. Milk components and component yields were not affected by treatment. Milk urea concentration was less for cows fed the MB diet. Although cows fed the MB diet had greater DMI, this was not translated into a higher milk 3.5% FCM/DMI production efficiency ratio. During experiment 2, many cows fed MB experienced minor to severe hemolysis with bloody urine. This hemolysis believed to be caused by the S-methyl-cysteine sulfoxide contained in mustard bran could have affected milk production efficiency

  6. Effect of Greens and Soil Type, Sulfur Addition and Lithium Level on Leaf Constituents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A greenhouse experiment was conducted near Weslaco, Texas (Lat. 26o 8' N, Long. 97o 57' W) between Dec. 2006 and Feb 2007 to evaluate the effect of soil type, added sulfur and lithium level on the growth and leaf nutrients, particularly biofortified levels of Li and S, in spinach and mustard gree...

  7. Iron oxide functionalized graphene nano-composite for dispersive solid phase extraction of chemical warfare agents from aqueous samples.

    PubMed

    Chinthakindi, Sridhar; Purohit, Ajay; Singh, Varoon; Tak, Vijay; Goud, D Raghavender; Dubey, D K; Pardasani, Deepak

    2015-05-15

    Present study deals with the preparation and evaluation of graphene based magnetic nano-composite for dispersive solid phase extraction of Chemical Weapons Convention (CWC) relevant chemicals from aqueous samples. Nano-composite, Fe3O4@SiO2-G was synthesized by covalently bonding silica coated Fe3O4 onto the graphene sheets. Nerve agents (NA), Sulfur mustard (SM) and their non-toxic environmental markers were the target analytes. Extraction parameters like amount of sorbent, extraction time and desorption conditions were optimized. Dispersion of 20 milligram of sorbent in 200mL of water sample for 20min. followed by methanol/chloroform extraction produced average to good recoveries (27-94%) of targeted analytes. Recoveries of real agents exhibited great dependency upon sample pH and ionic strength. Sarin produced maximum recovery under mild acidic conditions (56% at pH 5) while VX demanded alkaline media (83% at pH 9). Salts presence in the aqueous samples was found to be advantageous, raising the recoveries to as high as 94% for SM. Excellent limits of detection (LOD) for sulphur mustard and VX (0.11ngmL(-1) and 0.19ngmL(-1) respectively) proved the utility of the developed method for the off-site analysis of CWC relevant chemicals.

  8. Iron oxide functionalized graphene nano-composite for dispersive solid phase extraction of chemical warfare agents from aqueous samples.

    PubMed

    Chinthakindi, Sridhar; Purohit, Ajay; Singh, Varoon; Tak, Vijay; Goud, D Raghavender; Dubey, D K; Pardasani, Deepak

    2015-05-15

    Present study deals with the preparation and evaluation of graphene based magnetic nano-composite for dispersive solid phase extraction of Chemical Weapons Convention (CWC) relevant chemicals from aqueous samples. Nano-composite, Fe3O4@SiO2-G was synthesized by covalently bonding silica coated Fe3O4 onto the graphene sheets. Nerve agents (NA), Sulfur mustard (SM) and their non-toxic environmental markers were the target analytes. Extraction parameters like amount of sorbent, extraction time and desorption conditions were optimized. Dispersion of 20 milligram of sorbent in 200mL of water sample for 20min. followed by methanol/chloroform extraction produced average to good recoveries (27-94%) of targeted analytes. Recoveries of real agents exhibited great dependency upon sample pH and ionic strength. Sarin produced maximum recovery under mild acidic conditions (56% at pH 5) while VX demanded alkaline media (83% at pH 9). Salts presence in the aqueous samples was found to be advantageous, raising the recoveries to as high as 94% for SM. Excellent limits of detection (LOD) for sulphur mustard and VX (0.11ngmL(-1) and 0.19ngmL(-1) respectively) proved the utility of the developed method for the off-site analysis of CWC relevant chemicals. PMID:25828545

  9. Detection and monitoring of early airway injury effects of half-mustard (2-chloroethylethylsulfide) exposure using high-resolution optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Kreuter, Kelly A.; Mahon, Sari B.; Mukai, David S.; Su, Jianping; Jung, Woong-Gyu; Narula, Navneet; Guo, Shuguang; Wakida, Nicole; Raub, Chris; Berns, Michael W.; George, Steven C.; Chen, Zhongping; Brenner, Matthew

    2009-07-01

    Optical coherence tomography (OCT) is a noninvasive, high-resolution imaging technology capable of delivering real-time, near-histologic images of tissues. Mustard gas is a vesicant-blistering agent that can cause severe and lethal damage to airway and lungs. The ability to detect and assess airway injury in the clinical setting of mustard exposure is currently limited. The purpose of this study is to assess the ability to detect and monitor progression of half-mustard [2-chloroethylethylsulfide (CEES)] airway injuries with OCT techniques. A ventilated rabbit mustard exposure airway injury model is developed. A flexible fiber optic OCT probe is introduced into the distal trachea to image airway epithelium and mucosa in vivo. Progression of airway injury is observed over eight hours with OCT using a prototype time-domain superluminescent diode OCT system. OCT tracheal images from CEES exposed animals are compared to control rabbits for airway mucosal thickening and other changes. OCT detects the early occurrence and progression of dramatic changes in the experimental group after exposure to CEES. Histology and immunofluorescence staining confirms this finding. OCT has the potential to be a high resolution imaging modality capable of detecting, assessing, and monitoring treatment for airway injury following mustard vesicant agent exposures.

  10. Detection and monitoring of early airway injury effects of half-mustard (2-chloroethylethylsulfide) exposure using high-resolution optical coherence tomography.

    PubMed

    Kreuter, Kelly A; Mahon, Sari B; Mukai, David S; Su, Jianping; Jung, Woong-Gyu; Narula, Navneet; Guo, Shuguang; Wakida, Nicole; Raub, Chris; Berns, Michael W; George, Steven C; Chen, Zhongping; Brenner, Matthew

    2009-01-01

    Optical coherence tomography (OCT) is a noninvasive, high-resolution imaging technology capable of delivering real-time, near-histologic images of tissues. Mustard gas is a vesicant-blistering agent that can cause severe and lethal damage to airway and lungs. The ability to detect and assess airway injury in the clinical setting of mustard exposure is currently limited. The purpose of this study is to assess the ability to detect and monitor progression of half-mustard [2-chloroethylethylsulfide (CEES)] airway injuries with OCT techniques. A ventilated rabbit mustard exposure airway injury model is developed. A flexible fiber optic OCT probe is introduced into the distal trachea to image airway epithelium and mucosa in vivo. Progression of airway injury is observed over eight hours with OCT using a prototype time-domain superluminescent diode OCT system. OCT tracheal images from CEES exposed animals are compared to control rabbits for airway mucosal thickening and other changes. OCT detects the early occurrence and progression of dramatic changes in the experimental group after exposure to CEES. Histology and immunofluorescence staining confirms this finding. OCT has the potential to be a high resolution imaging modality capable of detecting, assessing, and monitoring treatment for airway injury following mustard vesicant agent exposures. PMID:19725748

  11. Detection and monitoring of early airway injury effects of half-mustard (2-chloroethylethylsulfide) exposure using high-resolution optical coherence tomography

    PubMed Central

    Kreuter, Kelly A.; Mahon, Sari B.; Mukai, David S.; Su, Jianping; Jung, Woong-Gyu; Narula, Navneet; Guo, Shuguang; Wakida, Nicole; Raub, Chris; Berns, Michael W.; George, Steven C.; Chen, Zhongping; Brenner, Matthew

    2009-01-01

    Optical coherence tomography (OCT) is a non-invasive, high-resolution imaging technology capable of delivering real-time, near-histologic images of tissues. Mustard gas is a vesicant-blistering agent that can cause severe and lethal damage to airway and lungs. The ability to detect and assess airway injury in the clinical setting of mustard exposure is currently limited. The purpose of this study is to assess the ability to detect and monitor progression of half-mustard [2-chloroethylethylsulfide (CEES)] airway injuries with OCT techniques. A ventilated rabbit mustard exposure airway injury model is developed. A flexible fiber optic OCT probe is introduced into the distal trachea to image airway epithelium and mucosa in vivo. Progression of airway injury is observed over eight hours with OCT using a prototype time-domain superluminescent diode OCT system. OCT tracheal images from CEES exposed animals are compared to control rabbits for airway mucosal thickening and other changes. OCT detects the early occurrence and progression of dramatic changes in the experimental group after exposure to CEES. Histology and immunofluorescence staining confirms this finding. OCT has the potential to be a high resolution imaging modality capable of detecting, assessing, and monitoring treatment for airway injury following mustard vesicant agent exposures. PMID:19725748

  12. Sulfur Cycle

    NASA Technical Reports Server (NTRS)

    Hariss, R.; Niki, H.

    1985-01-01

    Among the general categories of tropospheric sulfur sources, anthropogenic sources have been quantified the most accurately. Research on fluxes of sulfur compounds from volcanic sources is now in progress. Natural sources of reduced sulfur compounds are highly variable in both space and time. Variables, such as soil temperature, hydrology (tidal and water table), and organic flux into the soil, all interact to determine microbial production and subsequent emissions of reduced sulfur compounds from anaerobic soils and sediments. Available information on sources of COS, CS2, DMS, and H2S to the troposphere in the following paragraphs are summarized; these are the major biogenic sulfur species with a clearly identified role in tropospheric chemistry. The oxidation of SO2 to H2SO4 can often have a significant impact on the acidity of precipitation. A schematic representation of some important transformations and sinks for selected sulfur species is illustrated.

  13. Technical support for recovery phase decision-making in the event of a chemical warfare agent release

    SciTech Connect

    Watson, A.; Shugart, L.; Buchanan, M.; Jenkins, R.; Kistner, S.; Halbrook, R.

    1995-12-31

    Persistent chemical warfare agents such as the nerve agent VX and sulfur mustard were originally designed as terrain denial materials on the chemical battlefield. As a consequence, they do not rapidly degrade. In the course of preparedness planning for disposal of the US unitary stockpile of chemical warfare agents, communities have raised the issue of determining environmental concentrations and the potential health consequences of persistent agents following any agent event. This issue is common to several chemical warfare munition and materiel disposal activities in the United States, as well as for developing verification and compliance monitoring programs integral to the international Chemical Weapons Convention. Experimental research supporting the development of environmental monitoring protocols are summarized. They include the development of blood cholinesterase activity as a biomonitor of nerve agent exposure in domestic beef and dairy cattle, horses and sheep; measuring the permeation rates of construction materials such as unpainted wood and gypsum wall board to agent simulants; and developing an experimental monitoring protocol for agents in meat and grain.

  14. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Mustard crop insurance provisions. 457.168 Section 457.168 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.168 Mustard crop...

  15. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Mustard crop insurance provisions. 457.168 Section 457.168 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.168 Mustard crop...

  16. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Mustard crop insurance provisions. 457.168 Section 457.168 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.168 Mustard crop...

  17. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Mustard crop insurance provisions. 457.168 Section 457.168 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.168 Mustard crop...

  18. Molecular orbital calculations on tumour-inhibitory aniline mustards: QSARs.

    PubMed

    Lewis, D F

    1989-02-01

    1. Molecular orbital calculations by the MINDO/3 method are reported for a series of 23 para-substituted aniline mustards. 2. Quantitative structure-activity relationships are presented which show that electronic structural parameters can be related to a number of features of aniline mustard reactivity.

  19. Mesoporous iron–manganese oxides for sulphur mustard and soman degradation

    SciTech Connect

    Štengl, Václav; Grygar, Tomáš Matys; Bludská, Jana; Opluštil, František; Němec, Tomáš

    2012-12-15

    Graphical abstract: Display Omitted Highlights: ► New nanodispersive materials based on Fe and Mn oxides for degradations of warfare agents. ► The best activities for the degradation of sulphur mustard (97.9% in 64 min) and soman (97.9% in 64 min). ► One pot synthesis with friendly transformed to industrial conditions. -- Abstract: Substituted iron(III)–manganese(III, IV) oxides, ammonio-jarosite and birnessite, were prepared by a homogeneous hydrolysis of potassium permanganate and iron(III) sulphate with 2-chloroacetamide and urea, respectively. Synthesised oxides were characterised using Brunauer–Emmett–Teller (BET) surface area and Barrett–Joiner–Halenda porosity (BJH), X-ray diffraction (XRD), infrared spectroscopy (IR), Raman spectroscopy and scanning electron microscopy (SEM). The oxides were taken for an experimental evaluation of their reactivity against sulphur mustard (HD) and soman (GD). When ammonio-jarosite formation is suppressed by adding urea to the reaction mixture, the reaction products are mixtures of goethite, schwertmannite and ferrihydrite, and their degradation activity against soman considerably increases. The best activities for the degradation of sulphur mustard (97.9% in 64 min) and soman (97.9% in 64 min) were observed for FeMn{sub 7}5 with 32.6 wt.% Fe (36.8 wt.% Mn) and FeMn{sub 3}7U with 60.8 wt.% Fe (10.1 wt.% Mn) samples, respectively.

  20. The treatment of sulphur mustard burns with laser debridement.

    PubMed

    Evison, D; Brown, R F R; Rice, P

    2006-01-01

    The chemical warfare agent, sulphur mustard (SM), is a potent blistering agent in man. Skin exposure can produce partial-thickness burns which take up to three months to heal. The aim of this study was to investigate the use of early laser ablation as a means of accelerating this exceptionally slow rate of healing. Four circular partial-thickness SM burns were induced on the dorsum of nine large white pigs (under general anaesthesia). At 72 h post-exposure, three burns per animal were ablated with a single pass of an UltraPulse 5000C CO(2) laser, at a fluence of 5-6 J cm(-2). All the burns were dressed with silver sulphadiazine and a semi-occlusive dressing. At one, two and three weeks post-surgery three animals were culled and all lesions excised for histological analysis. Burn depth was confirmed and measurements of the radii of regenerative epithelium were performed allowing the area of the zone of re-epithelialisation in each lesion to be calculated. Laser-treated lesions showed a significant increase (350%) in healing rates compared to controls (p<0.005). At two weeks, the laser-treated sites were 95% healed in comparison with control sites (28% healed). These data suggest that laser ablation may be effective in the treatment of partial-thickness SM-induced skin injury. PMID:16996434

  1. The treatment of sulphur mustard burns with laser debridement.

    PubMed

    Evison, D; Brown, R F R; Rice, P

    2006-01-01

    The chemical warfare agent, sulphur mustard (SM), is a potent blistering agent in man. Skin exposure can produce partial-thickness burns which take up to three months to heal. The aim of this study was to investigate the use of early laser ablation as a means of accelerating this exceptionally slow rate of healing. Four circular partial-thickness SM burns were induced on the dorsum of nine large white pigs (under general anaesthesia). At 72 h post-exposure, three burns per animal were ablated with a single pass of an UltraPulse 5000C CO(2) laser, at a fluence of 5-6 J cm(-2). All the burns were dressed with silver sulphadiazine and a semi-occlusive dressing. At one, two and three weeks post-surgery three animals were culled and all lesions excised for histological analysis. Burn depth was confirmed and measurements of the radii of regenerative epithelium were performed allowing the area of the zone of re-epithelialisation in each lesion to be calculated. Laser-treated lesions showed a significant increase (350%) in healing rates compared to controls (p<0.005). At two weeks, the laser-treated sites were 95% healed in comparison with control sites (28% healed). These data suggest that laser ablation may be effective in the treatment of partial-thickness SM-induced skin injury.

  2. Fate of chemical warfare agents and toxic industrial chemicals in landfills.

    PubMed

    Bartelt-Hunt, Shannon L; Barlaz, Morton A; Knappe, Detlef R U; Kjeldsen, Peter

    2006-07-01

    One component of preparedness for a chemical attack is planning for the disposal of contaminated debris. To assess the feasibility of contaminated debris disposal in municipal solid waste (MSW) landfills, the fate of selected chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) in MSW landfills was predicted with a mathematical model. Five blister agents [sulfur mustard (HD), nitrogen mustard (HN-2), lewisite (L), ethyldichloroarsine (ED), and phosgene oxime (CX)], eight nerve agents [tabun (GA), sarin (GB), soman (GD), GE, GF, VX, VG, and VM], one riot-control agent [CS], and two TICs [furan and carbon disulfide] were studied. The effects of both infiltration (climate) and contaminant biodegradability on fate predictions were assessed. Model results showed that hydrolysis and gas-phase advection were the principal fate pathways for CWAs and TICs, respectively. Apart from CX and the TICs, none of the investigated compounds was predicted to persist in a landfill for more than 5 years. Climate had little impact on CWA/TIC fate, and biodegradability was only important for compounds with long hydrolysis half-lives. Monte Carlo simulations were performed to assess the influence of uncertainty in model input parameters on CWA/TIC fate predictions. Correlation analyses showed that uncertainty in hydrolysis rate constants was the primary contributor to variance of CWA fate predictions, while uncertainty in the Henry's Law constant and landfill gas-production rate accounted for most of the variance of TIC fate predictions. CWA hydrolysates were more persistent than the parent CWAs, but limited information is available on abiotic or biotic transformation rates for these chemicals. PMID:16856738

  3. Identification of the major lesion from the reaction of an acridine-targeted aniline mustard with DNA as an adenine N1 adduct.

    PubMed

    Boritzki, T J; Palmer, B D; Coddington, J M; Denny, W A

    1994-01-01

    DNA adducts of two acridine-linked aniline half-mustards have been isolated and identified. The compound where the half-mustard is attached to the DNA-targeting acridine moiety by a short linker chain alkylates both double- and single-stranded DNA exclusively at guanine N7, as do the majority of known aromatic and aliphatic nitrogen mustards. The longer-chain analogue, also containing a more reactive half-mustard, shows a strikingly different pattern, alkylating double-stranded DNA to yield primarily (> 90%) the adenine N1 adduct, together with < 10% of the adenine N3 adduct and only trace amounts of the guanine N7 adduct. In the presence of MgCl2 (which is known not to inhibit the interaction of drugs at minor groove sites), the adenine N3 adduct is the major product. The latter compound is the first known aniline mustard (and apparently the first known alkylating agent of any type) to preferentially alkylate adenine at the N1 position in duplex DNA. These results are consistent with previous work [Prakash et al. (1990) Biochemistry 29, 9799-9807], which showed that the preferred site of DNA alkylation by the corresponding long-chain acridine-linked aniline bis-mustards in general was at major groove sites of adenines and identifies the major site of alkylation as adenine N1 and not N7. This selectivity for adenine N1 alkylation is suggested to result from a preference for the acridine mustard side chain of these compounds to project into the major groove following intercalation of the acridine, coupled with structural distortion of the DNA helix to make the N1 positions of adenines adjacent to the intercalation sites more accessible.

  4. Technical support for recovery phase decision-making in the event of a chemical warfare agent release

    SciTech Connect

    Watson, A.; Kistner, S.; Halbrook, R.

    1995-12-31

    In late 1985, Congress mandated that the U.S. stockpile of lethal unitary chemical agents and munitions be destroyed by the Department of the Army in a manner that provides maximum protection to the environment, the general public and personnel involved in the disposal program (Public Law 99-1, Section 1412, Title 14, Part b). These unitary munitions were last manufactured in the late 1960`s. The stockpiled inventory is estimated to approximate 25,000-30,000 tons, an includes organophosphate ({open_quotes}nerves{close_quotes}) agents such as VX [O-ethylester of S-(diisopropyl aminoethyl) methyl phosphonothiolate, C{sub 11}H{sub 26}NO{sub 2}PS] and vesicant ({open_quotes}blister{close_quotes}) agents such as Hd [sulfur mustard; bis (2-chloroethyl sulfide), C{sub 4}H{sub 8}Cl{sub 2}S]. The method of agent destruction selected by the Department of the Army is combined high-temperature and high-residence time incineration at secured military installations where munitions are currently stockpiled. This program supports the research program to address: the biomonitoring of nerve agent exposure; agent detection limits in foods and milk; and permeation of agents through porous construction materials.

  5. Evaluation of Chemical Warfare Agent Percutaneous Vapor Toxicity: Derivation of Toxicity Guidelines for Assessing Chemical Protective Ensembles.

    SciTech Connect

    Watson, A.P.

    2003-07-24

    Percutaneous vapor toxicity guidelines are provided for assessment and selection of chemical protective ensembles (CPEs) to be used by civilian and military first responders operating in a chemical warfare agent vapor environment. The agents evaluated include the G-series and VX nerve agents, the vesicant sulfur mustard (agent HD) and, to a lesser extent, the vesicant Lewisite (agent L). The focus of this evaluation is percutaneous vapor permeation of CPEs and the resulting skin absorption, as inhalation and ocular exposures are assumed to be largely eliminated through use of SCBA and full-face protective masks. Selection of appropriately protective CPE designs and materials incorporates a variety of test parameters to ensure operability, practicality, and adequacy. One aspect of adequacy assessment should be based on systems tests, which focus on effective protection of the most vulnerable body regions (e.g., the groin area), as identified in this analysis. The toxicity range of agent-specific cumulative exposures (Cts) derived in this analysis can be used as decision guidelines for CPE acceptance, in conjunction with weighting consideration towards more susceptible body regions. This toxicity range is bounded by the percutaneous vapor estimated minimal effect (EME{sub pv}) Ct (as the lower end) and the 1% population threshold effect (ECt{sub 01}) estimate. Assumptions of exposure duration used in CPE certification should consider that each agent-specific percutaneous vapor cumulative exposure Ct for a given endpoint is a constant for exposure durations between 30 min and 2 hours.

  6. ADAM17 Inhibitors Attenuate Corneal Epithelial Detachment Induced by Mustard Exposure

    PubMed Central

    DeSantis-Rodrigues, Andrea; Chang, Yoke-Chen; A. Hahn, Rita; P. Po, Iris; Zhou, Peihong; Lacey, C. Jeffrey; Pillai, Abhilash; C. Young, Sherri; A. Flowers II, Robert; A. Gallo, Michael; D. Laskin, Jeffrey; R. Gerecke, Donald; K. H. Svoboda, Kathy; D. Heindel, Ned; Gordon, Marion K.

    2016-01-01

    Purpose Sulfur mustard, nitrogen mustard (NM), and 2-chloroethyl ethyl sulfide all cause corneal injury with epithelial–stromal separation, differing only by degree. Injury can resolve in a few weeks or develop into chronic corneal problems. These vesicants induce microbullae at the epithelial–stromal junction, which is partially caused by cleavage of transmembranous hemidesmosomal collagen XVII, a component anchoring the epithelium to the stroma. ADAM17 is an enzyme involved in wound healing and is able to cleave collagen XVII. The activity of ADAM17 was inhibited in vesicant-exposed corneas by four different hydroxamates, to evaluate their therapeutic potential when applied 2 hours after exposure, thereby allowing ADAM17 to perform its early steps in wound healing. Methods Rabbit corneal organ cultures exposed to NM for 2 hours were washed, then incubated at 37°C for 22 hours, with or without one of the four hydroxamates (dose range, 0.3–100 nmol in 20 μL, applied four times). Corneas were analyzed by light and immunofluorescence microscopy, and ADAM17 activity assays. Results Nitrogen mustard–induced corneal injury showed significant activation of ADAM17 levels accompanying epithelial–stromal detachment. Corneas treated with hydroxamates starting 2 hours post exposure showed a dose-dependent ADAM17 activity inhibition up to concentrations of 3 nmol. Of the four hydroxamates, NDH4417 (N-octyl-N-hydroxy-2-[4-hydroxy-3-methoxyphenyl] acetamide) was most effective for inhibiting ADAM17 and retaining epithelial–stromal attachment. Conclusions Mustard exposure leads to corneal epithelial sloughing caused, in part, by the activation of ADAM17 at the epithelial–stromal junction. Select hydroxamate compounds applied 2 hours after NM exposure mitigated epithelial–stromal separation. PMID:27058125

  7. Pirfenidone; can it be a new horizon for the treatment of pulmonary fibrosis in mustard gas-intoxicated patients?

    PubMed Central

    2013-01-01

    Sulfur mustard is an alkylating substance still regarded as a threat in chemical warfare and terrorism. Lung parenchymal damage occurs in the most severe inhalational exposures. It accompanies an increased risk of respiratory tract carcinomas and chronic respiratory sequelae including chronic bronchitis, bronchiectasis, pulmonary fibrosis, interstitial lung disease, emphysema, and bronchiolitis obliterans. Pirfenidone is an antifibrotic with anti-inflammatory and anti hydroxyl radical activities which stabilizes pulmonary function in idiopathic pulmonary fibrosis patients. It can be suggested in chronically exposed soldiers or workers with signs and symptoms of pulmonary fibrosis to improve their quality of life and even prognosis. PMID:23418997

  8. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    SciTech Connect

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Ammar, David A.; Agarwal, Chapla; Tyagi, Puneet; Kompella, Uday B.; Enzenauer, Robert W.; Petrash, J. Mark; Agarwal, Rajesh

    2012-10-01

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

  9. Lunar sulfur

    NASA Technical Reports Server (NTRS)

    Kuck, David L.

    1991-01-01

    Ideas introduced by Vaniman, Pettit and Heiken in their 1988 Uses of Lunar Sulfur are expanded. Particular attention is given to uses of SO2 as a mineral-dressing fluid. Also introduced is the concept of using sulfide-based concrete as an alternative to the sulfur-based concretes proposed by Leonard and Johnson. Sulfur is abundant in high-Ti mare basalts, which range from 0.16 to 0.27 pct. by weight. Terrestrial basalts with 0.15 pct. S are rare. For oxygen recovery, sulfur must be driven off with other volatiles from ilmenite concentrates, before reduction. Troilite (FeS) may be oxidized to magnetite (Fe3O4) and SO2 gas, by burning concentrates in oxygen within a magnetic field, to further oxidize ilmenite before regrinding the magnetic reconcentration. SO2 is liquid at -20 C, the mean temperature underground on the Moon, at a minimum of 0.6 atm pressure. By using liquid SO2 as a mineral dressing fluid, all the techniques of terrestrial mineral separation become available for lunar ores and concentrates. Combination of sulfur and iron in an exothermic reaction, to form iron sulfides, may be used to cement grains of other minerals into an anhydrous iron-sulfide concrete. A sulfur-iron-aggregate mixture may be heated to the ignition temperature of iron with sulfur to make a concrete shape. The best iron, sulfur, and aggregate ratios need to be experimentally established. The iron and sulfur will be by-products of oxygen production from lunar minerals.

  10. Lunar sulfur

    NASA Astrophysics Data System (ADS)

    Kuck, David L.

    Ideas introduced by Vaniman, Pettit and Heiken in their 1988 Uses of Lunar Sulfur are expanded. Particular attention is given to uses of SO2 as a mineral-dressing fluid. Also introduced is the concept of using sulfide-based concrete as an alternative to the sulfur-based concretes proposed by Leonard and Johnson. Sulfur is abundant in high-Ti mare basalts, which range from 0.16 to 0.27 pct. by weight. Terrestrial basalts with 0.15 pct. S are rare. For oxygen recovery, sulfur must be driven off with other volatiles from ilmenite concentrates, before reduction. Troilite (FeS) may be oxidized to magnetite (Fe3O4) and SO2 gas, by burning concentrates in oxygen within a magnetic field, to further oxidize ilmenite before regrinding the magnetic reconcentration. SO2 is liquid at -20 C, the mean temperature underground on the Moon, at a minimum of 0.6 atm pressure. By using liquid SO2 as a mineral dressing fluid, all the techniques of terrestrial mineral separation become available for lunar ores and concentrates. Combination of sulfur and iron in an exothermic reaction, to form iron sulfides, may be used to cement grains of other minerals into an anhydrous iron-sulfide concrete. A sulfur-iron-aggregate mixture may be heated to the ignition temperature of iron with sulfur to make a concrete shape. The best iron, sulfur, and aggregate ratios need to be experimentally established. The iron and sulfur will be by-products of oxygen production from lunar minerals.

  11. Models of invasion and establishment of African Mustard (Brassica tournefortii)

    USGS Publications Warehouse

    Berry, Kristin H.; Gowan, Timothy A.; Miller, David M.; Brooks, Matthew L.

    2015-01-01

    Introduced exotic plants can drive ecosystem change. We studied invasion and establishment ofBrassica tournefortii (African mustard), a noxious weed, in the Chemehuevi Valley, western Sonoran Desert, California. We used long-term data sets of photographs, transects for biomass of annual plants, and densities of African mustard collected at irregular intervals between 1979 and 2009. We suggest that African mustard may have been present in low numbers along the main route of travel, a highway, in the late 1970s; invaded the valley along a major axial valley ephemeral stream channel and the highway; and by 2009, colonized 22 km into the eastern part of the valley. We developed predictive models for invasibility and establishment of African mustard. Both during the initial invasion and after establishment, significant predictor variables of African mustard densities were surficial geology, proximity to the highway and axial valley ephemeral stream channel, and number of small ephemeral stream channels. The axial valley ephemeral stream channel was the most vulnerable of the variables to invasions. Overall, African mustard rapidly colonized and quickly became established in naturally disturbed areas, such as stream channels, where geological surfaces were young and soils were weakly developed. Older geological surfaces (e.g., desert pavements with soils 140,000 to 300,000 years old) were less vulnerable. Microhabitats also influenced densities of African mustard, with densities higher under shrubs than in the interspaces. As African mustard became established, the proportional biomass of native winter annual plants declined. Early control is important because African mustard can colonize and become well established across a valley in 20 yr.

  12. Pityriasis rosea-like eruptions due to mustard oil application.

    PubMed

    Zawar, Vijay

    2005-01-01

    A young man employed in a construction company, presented with cutaneous lesions clinically simulating pityriasis rosea. Satisfactory and complete response to corticosteroids and antihistamines was followed by recurrence. Multiple recurrences within a short span of time arose a suspicion of alternative diagnosis. Site visit helped us to rule out occupational contact dermatitis. Further history taking revealed that he was recently using mustard oil for body massage. Subsequent patch testing confirmed contact hypersensitivity to mustard oil. Avoidance of the contact with mustard oil arrested appearance of further skin lesions. We stress the importance of taking a good history in clinical practice in disclosing a possible contactant. PMID:16394442

  13. Synergistic action of tropospheric ozone and carbon dioxide on yield and nutritional quality of Indian mustard (Brassica juncea (L.) Czern.).

    PubMed

    Singh, Satyavan; Bhatia, Arti; Tomer, Ritu; Kumar, Vinod; Singh, B; Singh, S D

    2013-08-01

    Field experiments were conducted in open top chamber during rabi seasons of 2009-10 and 2010-11 at the research farm of the Indian Agricultural Research Institute, New Delhi to study the effect of tropospheric ozone (O3) and carbon dioxide (CO2) interaction on yield and nutritional quality of Indian mustard (Brassica juncea (L.) Czern.). Mustard plants were grown from emergence to maturity under different treatments: charcoal-filtered air (CF, 80-85 % less O3 than ambient O3 and ambient CO2), nonfiltered air (NF, 5-10 % less O3 than ambient O3 and ambient CO2 ), nonfiltered air with elevated carbon dioxide (NF + CO2, NF air and 550 ± 50 ppm CO2), elevated ozone (EO, NF air and 25-35 ppb elevated O3), elevated ozone along with elevated carbon dioxide (EO + CO2, NF air, 25-35 ppb O3 and 550 ± 50 ppm CO2), and ambient chamber less control (AC, ambient O3 and CO2). Elevated O3 exposure led to reduced photosynthesis and leaf area index resulting in decreased seed yield of mustard. Elevated ozone significantly decreased the oil and micronutrient content in mustard. Thirteen to 17 ppm hour O3 exposure (accumulated over threshold of 40 ppm, AOT 40) reduced the oil content by 18-20 %. Elevated CO2 (500 ± 50 ppm) along with EO was able to counter the decline in oil content in the seed, and it increased by 11 to 13 % over EO alone. Elevated CO2, however, decreased protein, calcium, zinc, iron, magnesium, and sulfur content in seed as compared to the nonfiltered control, whereas removal of O3 from air in the charcoal-filtered treatment resulted in a significant increase in the same.

  14. DNA damage in internal organs after cutaneous exposure to sulphur mustard

    SciTech Connect

    Batal, Mohamed; Boudry, Isabelle; Mouret, Stéphane; Cléry-Barraud, Cécile; Wartelle, Julien; Bérard, Izabel

    2014-07-01

    Sulphur mustard (SM) is a chemical warfare agent that attacks mainly skin, eye and lungs. Due to its lipophilic properties, SM is also able to diffuse through the skin and reach internal organs. DNA represents one of the most critical molecular targets of this powerful alkylating agent which modifies DNA structure by forming monoadducts and biadducts. These DNA lesions are involved in the acute toxicity of SM as well as its long-term carcinogenicity. In the present work we studied the formation and persistence of guanine and adenine monoadducts and guanine biadducts in the DNA of brain, lungs, kidneys, spleen, and liver of SKH-1 mice cutaneously exposed to 2, 6 and 60 mg/kg of SM. SM-DNA adducts were detected in all studied organs, except in liver at the two lowest doses. Brain and lungs were the organs with the highest level of SM-DNA adducts, followed by kidney, spleen and liver. Monitoring the level of adducts for three weeks after cutaneous exposure showed that the lifetime of adducts were not the same in all organs, lungs being the organ with the longest persistence. Diffusion from skin to internal organs was much more efficient at the highest compared to the lowest dose investigated as the result of the loss of the skin barrier function. These data provide novel information on the distribution of SM in tissues following cutaneous exposures and indicate that brain is an important target. - Highlights: • Sulphur mustard reaches internal organs after skin exposure • Adducts are detected in the DNA of internal organs • Brain is the organ with the highest level of DNA damage • The barrier function of skin is lost at high dose of sulphur mustard • DNA adducts persist in organs for 2 or 3 weeks.

  15. Pathways of the eye's response to topical nitrogen mustard.

    PubMed

    Jampol, L M; Axelrod, A; Tessler, H

    1976-06-01

    We studied the effect of prior corneal herpes simplex infection with its resultant corneal hypesthesia on the irritative response of the rabbit eye to topical nitrogen mustard. Both the miosis and the breakdown of the blood-aqueous barrier that follow the application of topical nitrogen mustard were diminished in eyes infected three weeks previously with herpes simplex virus. Nonspecific corneal scarring did not affect the response. This suggests again that an axon reflex requiring intact sensory innervation mediates the response to nitrogen mustard. Pretreatment of normal (noninfected) rabbits with systemic H1 and H2 antihistamines, topical scopolamine hydrobromide, or topical and systemic corticosteroids was ineffective in blocking the miosis or increased protein in the aqueous humor following topical nitrogen mustard. PMID:6401

  16. Ionic dependence of sulphur mustard cytotoxicity

    SciTech Connect

    Sawyer, Thomas W. Nelson, Peggy; Bjarnason, Stephen; Vair, Cory; Shei Yimin; Tenn, Catherine; Lecavalier, Pierre; Burczyk, Andrew

    2010-09-15

    The effect of ionic environment on sulphur mustard (bis 2-chloroethyl sulphide; HD) toxicity was examined in CHO-K1 cells. Cultures were treated with HD in different ionic environments at constant osmolar conditions (320 mOsM, pH 7.4). The cultures were refed with fresh culture medium 1 h after HD exposure, and viability was assessed. Little toxicity was apparent when HD exposures were carried out in ion-free sucrose buffer compared to LC{sub 50} values of {approx} 100-150 {mu}M when the cultures were treated with HD in culture medium. Addition of NaCl to the buffer increased HD toxicity in a salt concentration-dependent manner to values similar to those obtained in culture medium. HD toxicity was dependent on both cationic and anionic species with anionic environment playing a much larger role in determining toxicity. Substitution of NaI for NaCl in the treatment buffers increased HD toxicity by over 1000%. The activity of the sodium hydrogen exchanger (NHE) in recovering from cytosolic acidification in salt-free and in different chloride salts did not correlate with the HD-induced toxicity in these buffers. However, the inhibition by HD of intracellular pH regulation correlated with its toxicity in NaCl, NaI and sucrose buffers. Analytical chemical studies and the toxicity of the iodine mustard derivative ruled out the role of chemical reactions yielding differentially toxic species as being responsible for the differences in HD toxicity observed. This work demonstrates that the early events that HD sets into motion to cause toxicity are dependent on ionic environment, possibly due to intracellular pH deregulation.

  17. Urinary and cutaneous complications of sulphur mustard poisoning preceding pulmonary and ocular involvement: an unusual sequence of symptoms.

    PubMed

    Emadi, S N; Moeineddin, F; Sorush, M R

    2009-07-01

    Sulphur mustard was used as a disabling chemical warfare agent during World War I, and, in more recent times, the Iran-Iraq conflict. Various chronic and acute complications have been documented in almost 100,000 Iranian victims to date. Several individual and environmental factors affect the severity and persistency of the complications. The most common adverse effects occur in the respiratory system, skin and eyes, with ocular and respiratory features usually preceding cutaneous lesions. In this paper, we present the unusual case of a chemical victim presenting with characteristic mustard scar leading to stenosis of the external meatus. In this case, initial cutaneous involvement of the injured external genitalia and thighs preceded the ocular and respiratory symptoms. We discuss the possible aetiologies.

  18. Ring fusion strategy for synthesis and lead optimization of sulfur-substituted anthra[1,2-c][1,2,5]thiadiazole-6,11-dione derivatives as promising scaffold of antitumor agents.

    PubMed

    Lee, Yu-Ru; Chen, Tsung-Chih; Lee, Chia-Chung; Chen, Chun-Liang; Ahmed Ali, Ahmed Atef; Tikhomirov, Alexander; Guh, Jih-Hwa; Yu, Dah-Shyong; Huang, Hsu-Shan

    2015-09-18

    A series of sulfur-substituted anthra[1,2-c][1,2,5]thiadiazole-6,11-diones were synthesized and evaluated using the cell proliferations, apoptosis and NCI-60 cell panel assays. Also, the signaling pathways that account for their activities were investigated. Compounds 2, 3, 4a, 4d, 4f, 4i, 4k, 5b, 5c, 5d, 5f, 5g, 6b, 6c, 6d, 6e, 6g, 7a and 7g were selected by NCI. Among the tested compounds, 6g appeared to be the most active compound of this series that not only induced apoptosis in DU-145 cancer cells but also attenuated the ERK1/2 and p38 signaling pathways. All test compounds exhibited diverse cytostatic and cytotoxic activities that warrant further development as potential anticancer agents.

  19. Zirconium doped nano-dispersed oxides of Fe, Al and Zn for destruction of warfare agents

    SciTech Connect

    Stengl, Vaclav; Houskova, Vendula; Bakardjieva, Snejana; Murafa, Nataliya; Marikova, Monika; Oplustil, Frantisek; Nemec, Tomas

    2010-11-15

    Zirconium doped nano dispersive oxides of Fe, Al and Zn were prepared by a homogeneous hydrolysis of the respective sulfate salts with urea in aqueous solutions. Synthesized metal oxide hydroxides were characterized using Brunauer-Emmett-Teller (BET) surface area and Barrett-Joiner-Halenda porosity (BJH), X-ray diffraction (XRD), infrared spectroscopy (IR), scanning electron microscopy (SEM) and energy-dispersive X-ray microanalysis (EDX). These oxides were taken for an experimental evaluation of their reactivity with sulfur mustard (HD or bis(2-chloroethyl)sulfide), soman (GD or (3,3'-Dimethylbutan-2-yl)-methylphosphonofluoridate) and VX agent (S-[2-(diisopropylamino)ethyl]-O-ethyl-methylphosphonothionate). The presence of Zr{sup 4+} dopant can increase both the surface area and the surface hydroxylation of the resulting doped oxides, decreases their crystallites' sizes thereby it may contribute in enabling the substrate adsorption at the oxide surface thus it can accelerate the rate of degradation of warfare agents. Addition of Zr{sup 4+} converts the product of the reaction of ferric sulphate with urea from ferrihydrite to goethite. We found out that doped oxo-hydroxides Zr-FeO(OH) - being prepared by a homogeneous hydrolysis of ferric and zirconium oxo-sulfates mixture in aqueous solutions - exhibit a comparatively higher degradation activity towards chemical warfare agents (CWAs). Degradation of soman or VX agent on Zr-doped FeO(OH) containing ca. 8.3 wt.% of zirconium proceeded to completion within 30 min.

  20. Survey: Destruction of chemical agent simulants in supercritical water oxidation. Master's thesis

    SciTech Connect

    Blank, M.R.

    1992-07-01

    The supercritical water oxidation (SCWO) process exhibits distinct advantages for destruction of toxic wastes. Examples of these wastes are two chemical agent simulants, dimethyl methylphosphonate (DMMP) and thiodiglycol (2,2'-thiodiethanol). DMMP is similar to the nerve agent GB Sarin in structure, and thiodiglycol is a hydrolysis product of the blister agent HD Sulfur Mustard. Both simulants are miscible in water and relatively non-toxic in comparison to the actual chemical agents. Using a Laboratory-scale, batch three temperatures were investigated: 425 deg C, 450 deg C, and 500 deg C with an initial concentration of one percent by volume, 11,450 mg/L for DMMP and 12,220 mg/L for thiodiglycol. Residence times investigated were: 1, 2, 3, 6, and 8 minutes. Reactor beat-up (H.U.) was determined to be one minute. Both pyrolysis and oxidation tests were conducted. Oxygen levels were uniformly set at 200% of stoichiometric requirements for the parent compounds.

  1. Immunochemical analysis of poly(ADP-ribosyl)ation in HaCaT keratinocytes induced by the mono-alkylating agent 2-chloroethyl ethyl sulfide (CEES): Impact of experimental conditions.

    PubMed

    Debiak, Malgorzata; Lex, Kirsten; Ponath, Viviane; Burckhardt-Boer, Waltraud; Thiermann, Horst; Steinritz, Dirk; Schmidt, Annette; Mangerich, Aswin; Bürkle, Alexander

    2016-02-26

    Sulfur mustard (SM) is a bifunctional alkylating agent with a long history of use as a chemical weapon. Although its last military use is dated for the eighties of the last century, a potential use in terroristic attacks against civilians remains a significant threat. Thus, improving medical therapy of mustard exposed individuals is still of particular interest. PARP inhibitors were recently brought into the focus as a potential countermeasure for mustard-induced pathologies, supported by the availability of efficient compounds successfully tested in cancer therapy. PARP activation after SM treatment was reported in several cell types and tissues under various conditions; however, a detailed characterization of this phenomenon is still missing. This study provides the basis for such studies by developing and optimizing experimental conditions to investigate poly(ADP-ribosyl)ation (PARylation) in HaCaT keratinocytes upon treatment with the monofunctional alkylating agent 2-chloroethyl ethyl sulfide ("half mustard", CEES). By using an immunofluorescence-based approach, we show that optimization of experimental conditions with regards to the type of solvent, dilution factors and treatment procedure is essential to obtain a homogenous PAR staining in HaCaT cell cultures. Furthermore, we demonstrate that different CEES treatment protocols significantly influence the cytotoxicity profiles of treated cells. Using an optimized treatment protocol, our data reveals that CEES induces a dose- and time-dependent dynamic PARylation response in HaCaT cells that could be completely blocked by treating cells with the clinically relevant pharmacological PARP inhibitor ABT888 (also known as veliparib). Finally, siRNA experiments show that CEES-induced PAR formation is predominantly due to the activation of PARP1. In conclusion, this study provides a detailed analysis of the CEES-induced PARylation response in HaCaT keratinocytes, which forms an experimental basis to study the

  2. Bacterial mutagenicity studies of DNA-intercalating aniline mustards: an insight into the mode of action of a novel class of anti-tumour drugs.

    PubMed

    Ferguson, L R; Gourdie, T A; Valu, K K; Denny, W A

    1989-10-01

    Bifunctional alkylating agents are reactive compounds which work by crosslinking DNA, but which have no special affinity for it. A series of acridine-linked aniline mustards of widely-varying alkylator reactivity (5-11), designed as DNA-directed alkylating agents, have been evaluated in various strains of Salmonella typhimurium with differing DNA repair capabilities to obtain information about their mechanism of action. The compounds showed greatly increased potency (determined as D37 values) compared with the corresponding untargeted mustards, in the repair-proficient strain TA1978+. All but the most unreactive mustards were considerably more potent (greater than 10-fold) in the corresponding repair-deficient strain TA98, indicating that DNA-crosslinking is the major cytotoxic mechanism. However, the mutagenic profile of the compounds in four Salmonella strains, particularly in the excision repair-deficient strains TA98 and TA100, suggest the compounds also form substantial levels of mutagenic monoadducts. The possibility that intercalative binding by the acridine chromophore provides an additional geometrical restraint on cross-linking by the mustard is an important facet of design which needs further study.

  3. Development and validation of a real-time PCR method for the simultaneous detection of black mustard (Brassica nigra) and brown mustard (Brassica juncea) in food.

    PubMed

    Palle-Reisch, Monika; Wolny, Martina; Cichna-Markl, Margit; Hochegger, Rupert

    2013-05-01

    The paper presents a real-time PCR method allowing the simultaneous detection of traces of black mustard (Brassica nigra) and brown mustard (Brassica juncea) in food. The primers and the probe target the B. nigra partial RT gene for reverse transcriptase from gypsy-like retroelement 13G42-26. The real-time PCR method does not show any cross-reactivity with other Brassicaceae species with the exception of white mustard. Low cross-reactivities with cinnamon, cumin, fenugreek, ginger, rye and turmeric can be ignored because in common mustard containing foodstuffs these biological species are present in very low amounts. By analysing serially diluted DNA extracts from black and brown mustard, the DNA of both mustard species could be detected down to 0.1 pg. With 10 ng DNA per PCR tube the real-time PCR method allows the detection of 5 ppm black and brown mustard in brewed sausages. PMID:23265498

  4. Comparison of cake compositions, pepsin digestibility and amino acids concentration of proteins isolated from black mustard and yellow mustard cakes.

    PubMed

    Sarker, Ashish Kumar; Saha, Dipti; Begum, Hasina; Zaman, Asaduz; Rahman, Md Mashiar

    2015-01-01

    As a byproduct of oil production, black and yellow mustard cakes protein are considered as potential source of plant protein for feed applications to poultry, fish and swine industries. The protein contents in black and yellow mustard cakes were 38.17% and 28.80% and their pepsin digestibility was 80.33% and 77.43%, respectively. The proteins were extracted at different pH and maximum proteins (89.13% of 38.17% and 87.76% of 28.80% respectively) isolated from black and yellow mustard cakes at pH 12. The purity of isolated proteins of black and yellow mustard cakes was 89.83% and 91.12% respectively and their pepsin digestibility was 89.67% and 90.17% respectively which assigned the absence of antinutritional compounds. It was found that essential amino acids isoleucine, lysine, methionine, threonine and tryptophan and non essential amino acids arginine and tyrosine were present in greater concentration in black mustard cake protein whereas other amino acids were higher in yellow mustard cake protein.

  5. Estimated general population control limits for unitary agents in drinking water, milk, soil, and unprocessed food items

    SciTech Connect

    Watson, A.P.; Adams, J.D.; Cerar, R.J.; Hess, T.L.; Kistner, S.L.; Leffingwell, S.S.; MacIntosh, R.G.; Ward, J.R.

    1992-01-01

    In the event of an unplanned release of chemical agent during any stage of the Chemical Stockpile Disposal Program (CSDP), the potential exists for contamination of drinking water, forage crops, grains, garden produce, and livestock. Persistent agents such as VX or sulfur mustard pose the greatest human health concern for reentry. This White Paper has been prepared to provide technical bases for these decisions by developing working estimates of agent control limits in selected environmental media considered principal sources of potential human exposure. To date, control limits for public exposure to unitary agents have been established for atmospheric concentrations only. The current analysis builds on previous work to calculate working estimates of control limits for ingestion and dermal exposure to potentially contaminated drinking water, milk, soil, and unprocessed food items such as garden produce. Information characterizing agent desorption from, and detection on or in, contaminated porous media are presently too developed to permit reasonable estimation of dermal exposure from this source. Thus, dermal contact with potentially contaminated porous surfaces is not considered in this document.

  6. Direct gas-phase detection of nerve and blister warfare agents utilizing active capillary plasma ionization mass spectrometry.

    PubMed

    Wolf, J-C; Schaer, M; P Siegenthaler, P; Zenobi, R

    2015-01-01

    Ultrasensitive direct gas-phase detection of chemical warfare agents (CWAs) is demonstrated utilizing active capillary plasma ionization and triple quadrupole mass spectrometry (MS) instrumentation. Four G- agents, two V-agents and various blistering agents [including sulfur mustard (HD)] were detected directly in the gas phase with limits of detection in the low parts per trillion (ng m(-3)) range. The direct detection of HD was shown for dry carrier gas conditions, but signals vanished when humidity was present, indicating a possible direct detection of HD after sufficient gas phase pretreatment. The method provided sufficient sensitivity to monitor directly the investigated volatile CWAs way below their corresponding minimal effect dose, and in most cases even below the eight hours worker exposure concentration. In general, the ionization is very soft, with little to no in-source fragmentation. Especially for the G-agents, some dimer formation occurred at higher concentrations. This adds complexity, but also further selectivity, to the corresponding mass spectra. Our results show that the active capillary plasma ionization is a robust, sensitive, "plug and play" ambient ionization source suited (but not exclusively) to the very sensitive detection of CWAs. It has the potential to be used with portable MS instrumentation. PMID:26307710

  7. Clastogenic effects of transplacental exposure of mouse embryos to nitrogen mustard of cyclophosphamide

    SciTech Connect

    Meyne, J.; Legator, M.S.

    1983-01-01

    Embryos from day 12 pregnant Swiss mice given intraperitoneal injections of nitrogen mustard (HN/sub 2/) or cyclophosphamide (CP) were evaluated for chromosomal aberrations. Both agents induced dose-dependent increases in the frequency of cells with aberrations observed in embryos from females treated 6 hr before sacrifice. The highest frequencies of cells with aberrations were observed when females were injected 15 or 18 hr before sacrifice on day 12. A teratogenic dose of HN/sub 2/ (1.0 mg/kg) induced significantly higher frequencies of damaged cells than a teratogenic dose of CP (20 mg/kg). Cytogenetic analysis of rodent embryos from pregnant females exposed to xenobiotic agents may be an effective screening test for evaluation of genetic effects induced by transplacental exposure.

  8. [Mustard gas bombs found astray in the Faxaflói bay. Mustard gas: usage and poisonings].

    PubMed

    Kristinsson, Jakop; Jóhannesson, Thorkell

    2009-05-01

    The finding in 1972 of two World War II mustard gas artillery shells in crushed shell sediment dredged in the Faxaflói Bay and transported as raw material for cement production at Akranes (Western Iceland) is reported. One of the shells was wedged in a stone crusher in the raw material processing line and was ruptured. As a result dark fluid with a garlic like smell seeped out from the metal canister. The attending employees believed the metal object to be inert and tried to cut it out with a blow torch. This resulted in the explosion of the shell charge and in the exposure of four employees to mustard gas. All suffered burns on their hands and two of them in the eyes also. The second shell was detonated in the open at a distance from the factory. Emphasis is given to the fact that instant, or at least as soon as possible, cleansing and washing is the most efficient measure to be taken against the debilitating effects of mustard gas. It is also pointed out that the active principle in mustard gas (dichlorodiethyl sulphide) can easily be synthesized and none of the precursor substances are subjected to any restrictions of use. The authors conclude that mustard gas bombs may still be found in the arsenals of some military powers in spite of an international convention that prohibits the production, stockpiling and the use of chemical weapons. Terrorist groups have also seemingly tried to aquire mustard gas bombs and other chemical weapons. Therefore cases of mustard gas poisoning might still occur. PMID:19430031

  9. Mustard seed meal for management of root-knot nematode and weeds in tomato production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mustard seed meals of indian mustard [InM (Brassica juncea)] and yellow mustard [YeM (Sinapis alba)], alone and combined, were tested for effects on tomato (Solanum lycopersicum) plants and for suppression of southern root-knot nematode [RKN (Meloidogyne incognita)] and weed populations. In the gree...

  10. Pacific Northwest Condiment Yellow Mustard (Sinapis alba L.) Grower Guide: 2000-2002

    SciTech Connect

    Brown, J.; Davis, J. B.; Esser, A.

    2005-07-01

    This report is a grower guide for yellow mustard. Yellow mustard (Sinapis alba L.), synonymous with white mustard, is a spring annual crop and well adapted to hot, dry growing conditions. It has shown potential as an alternative crop in rotations with small grain cereals and has fewer limitations compared to other traditional alternative crops.

  11. Long-term effects of mustard gas on respiratory system of Iranian veterans after Iraq-Iran war: a review.

    PubMed

    Razavi, Seyed-Mansour; Ghanei, Mostafa; Salamati, Payman; Safiabadi, Mehdi

    2013-01-01

    To review long-term respiratory effects of mustard gas on Iranian veterans having undergone Iraq-Iran war. Electronic databases of Scopus, Medline, ISI, IranMedex, and Irandoc sites were searched. We accepted articles published in scientific journals as a quality criterion.The main pathogenic factors are free radical mediators. Prevalence of pulmonary involvement is approximately 42.5%. The most common complaints are cough and dyspnea. Major respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, and asthma. Spirometry results can reveal restrictive and obstructive pulmonary disease. Plain chest X-ray does not help in about 50% of lung diseases. High-resolution CT of the lung is the best modality for diagnostic assessment of parenchymal lung and bronchi. There is no definite curative treatment for mustard lung. The effective treatment regimens consist of oxygen administration, use of vaporized moist air, respiratory physiotherapy, administration of mucolytic agents, bronchodilators, corticosteroids, and long-acting beta-2 agonists, antioxidants, surfactant, magnesium ions, therapeutic bronchoscopy, laser therapy, placement of respiratory stents, early tracheostomy in laryngospasm, and ultimately lung transplantation. High-resolution CT of the lung is the most accurate modality for the evaluation of the lung parenchyma and bronchi. The treatment efficacy of patients exposed to mustard gas depends on patient conditions (acute or chronic, upper or lower respiratory tract involvement). There are various treatment protocols, but unfortunately none of them is definitely curable. PMID:23735551

  12. Long-term effects of mustard gas on respiratory system of Iranian veterans after Iraq-Iran war: a review.

    PubMed

    Razavi, Seyed-Mansour; Ghanei, Mostafa; Salamati, Payman; Safiabadi, Mehdi

    2013-01-01

    To review long-term respiratory effects of mustard gas on Iranian veterans having undergone Iraq-Iran war. Electronic databases of Scopus, Medline, ISI, IranMedex, and Irandoc sites were searched. We accepted articles published in scientific journals as a quality criterion.The main pathogenic factors are free radical mediators. Prevalence of pulmonary involvement is approximately 42.5%. The most common complaints are cough and dyspnea. Major respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, and asthma. Spirometry results can reveal restrictive and obstructive pulmonary disease. Plain chest X-ray does not help in about 50% of lung diseases. High-resolution CT of the lung is the best modality for diagnostic assessment of parenchymal lung and bronchi. There is no definite curative treatment for mustard lung. The effective treatment regimens consist of oxygen administration, use of vaporized moist air, respiratory physiotherapy, administration of mucolytic agents, bronchodilators, corticosteroids, and long-acting beta-2 agonists, antioxidants, surfactant, magnesium ions, therapeutic bronchoscopy, laser therapy, placement of respiratory stents, early tracheostomy in laryngospasm, and ultimately lung transplantation. High-resolution CT of the lung is the most accurate modality for the evaluation of the lung parenchyma and bronchi. The treatment efficacy of patients exposed to mustard gas depends on patient conditions (acute or chronic, upper or lower respiratory tract involvement). There are various treatment protocols, but unfortunately none of them is definitely curable.

  13. Treatment of sulphur mustard skin injury.

    PubMed

    Jenner, John; Graham, Stuart J

    2013-12-01

    Since its first use in 1917, sulphur mustard (SM) has been used virtually exclusively as a weapon of war.SM is a volatile liquid that damages any tissue it contacts as a vapour or liquid. SM primarily damages the skin, eyes and lungs producing massive inflammation culminating in the characteristic blistering of the skin which classifies SM as a vesicant. Several mechanisms of action at the cellular level have been proposed for SM, but none has ever been convincingly linked to the production of blisters or vesication. First aid for those contaminated with liquid SM consists of the rapid removal (within a few minutes) of liquid from the surface of the skin, as once penetrated into the stratum corneum it is very difficult to remove. In the absence of a mechanistically based specific therapy, SM skin injury is normally treated in a similar way to thermal and chemical burns, which it resembles pathologically. Effective therapy consist of treating the inflammation and where necessary removal of the dead eschar to facilitate healing. Post surgical care comprises the use of one of a number of available dressings used in thermal burn care and antibiotic creams should infection be present.

  14. Cysteine S-conjugate β-lyases: Important roles in the metabolism of naturally occurring sulfur and selenium-containing compounds, xenobiotics and anticancer agents

    PubMed Central

    Cooper, Arthur J. L.; Krasnikov, Boris F.; Niatsetskaya, Zoya V.; Pinto, John T.; Callery, Patrick S.; Villar, Maria T.; Artigues, Antonio; Bruschi, Sam A.

    2010-01-01

    Summary Cysteine S-conjugate β-lyases are pyridoxal 5′-phosphate-containing enzymes that catalyze β-elimination reactions with cysteine S-conjugates that possess a good leaving group in the β-position. The end products are aminoacrylate and a sulfur-containing fragment. The aminoacrylate tautomerizes and hydrolyzes to pyruvate and ammonia. The mammalian cysteine S-conjugate β-lyases thus far identified are enzymes involved in amino acid metabolism that catalyze β-lyase reactions as non-physiological side reactions. Most are aminotransferases. In some cases the lyase is inactivated by reaction products. The cysteine S-conjugate β-lyases are of much interest to toxicologists because they play an important key role in the bioactivation (toxication) of halogenated alkenes, some of which are produced on an industrial scale and are environmental contaminants. The cysteine S-conjugate β-lyases have been reviewed in this journal previously [Cooper and Pinto, 2006]. Here we focus on more recent findings regarding: 1) the identification of enzymes associated with high-Mr cysteine S-conjugate β-lyases in the cytosolic and mitochondrial fractions of rat liver and kidney; 2) the mechanism of syncatalytic inactivation of rat liver mitochondrial aspartate aminotransferase by the nephrotoxic β-lyase substrate S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (the cysteine S-conjugate of tetrafluoroethylene); 3) toxicant channeling of reactive fragments from the active site of mitochondrial aspartate aminotransferase to susceptible proteins in the mitochondria; 4) the involvement of cysteine S-conjugate β-lyases in the metabolism/bioactivation of drugs and natural products; and 5) the role of cysteine S-conjugate β-lyases in the metabolism of selenocysteine Se-conjugates. This review emphasizes the fact that the cysteine S-conjugate β-lyases are biologically more important than hitherto appreciated. PMID:20306345

  15. Cysteine S-conjugate β-lyases: important roles in the metabolism of naturally occurring sulfur and selenium-containing compounds, xenobiotics and anticancer agents.

    PubMed

    Cooper, Arthur J L; Krasnikov, Boris F; Niatsetskaya, Zoya V; Pinto, John T; Callery, Patrick S; Villar, Maria T; Artigues, Antonio; Bruschi, Sam A

    2011-06-01

    Cysteine S-conjugate β-lyases are pyridoxal 5'-phosphate-containing enzymes that catalyze β-elimination reactions with cysteine S-conjugates that possess a good leaving group in the β-position. The end products are aminoacrylate and a sulfur-containing fragment. The aminoacrylate tautomerizes and hydrolyzes to pyruvate and ammonia. The mammalian cysteine S-conjugate β-lyases thus far identified are enzymes involved in amino acid metabolism that catalyze β-lyase reactions as non-physiological side reactions. Most are aminotransferases. In some cases the lyase is inactivated by reaction products. The cysteine S-conjugate β-lyases are of much interest to toxicologists because they play an important key role in the bioactivation (toxication) of halogenated alkenes, some of which are produced on an industrial scale and are environmental contaminants. The cysteine S-conjugate β-lyases have been reviewed in this journal previously (Cooper and Pinto in Amino Acids 30:1-15, 2006). Here, we focus on more recent findings regarding: (1) the identification of enzymes associated with high-M(r) cysteine S-conjugate β-lyases in the cytosolic and mitochondrial fractions of rat liver and kidney; (2) the mechanism of syncatalytic inactivation of rat liver mitochondrial aspartate aminotransferase by the nephrotoxic β-lyase substrate S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (the cysteine S-conjugate of tetrafluoroethylene); (3) toxicant channeling of reactive fragments from the active site of mitochondrial aspartate aminotransferase to susceptible proteins in the mitochondria; (4) the involvement of cysteine S-conjugate β-lyases in the metabolism/bioactivation of drugs and natural products; and (5) the role of cysteine S-conjugate β-lyases in the metabolism of selenocysteine Se-conjugates. This review emphasizes the fact that the cysteine S-conjugate β-lyases are biologically more important than hitherto appreciated.

  16. Treating exposure to chemical warfare agents: Implications for health care providers and community emergency planning

    SciTech Connect

    Munro, N.B.; Watson, A.P.; Ambrose, K.R.; Griffin, G.D. )

    1990-11-01

    Current treatment protocols for exposure to nerve and vesicant agents found in the US stockpile of unitary chemical weapons are summarized, and the toxicities of available antidotes are evaluated. The status of the most promising of the new nerve agent antidotes is reviewed. In the US, atropine and pralidoxime compose the only approved antidote regimen for organophosphate nerve agent poisoning. Diazepam may also be used if necessary to control convulsions. To avoid death, administration must occur within minutes of substantial exposure together with immediate decontamination. Continuous observation and repeated administration of antidotes are necessary as symptoms warrant. Available antidotes do not necessarily prevent respiratory failure or incapacitation. The toxicity of the antidotes themselves and the individualized nature of medical care preclude recommending that autoinjectors be distributed to the general public. In addition, precautionary administration of protective drugs to the general population would not be feasible or desirable. No antidote exists for poisoning by the vesicant sulfur mustard (H, HD, HT); effective intervention can only be accomplished by rapid decontamination followed by palliative treatment of symptoms. British anti-Lewisite (BAL) (2,3-dimercapto-1-propanol) is the antidote of choice for treatment of exposure to Lewisite, another potent vesicant. Experimental water-soluble BAL analogues have been developed that are less toxic than BAL. Treatment protocols for each antidote are summarized in tabular form for use by health care providers.

  17. Efficacy of liquid and foam decontamination technologies for chemical warfare agents on indoor surfaces.

    PubMed

    Love, Adam H; Bailey, Christopher G; Hanna, M Leslie; Hok, Saphon; Vu, Alex K; Reutter, Dennis J; Raber, Ellen

    2011-11-30

    Bench-scale testing was used to evaluate the efficacy of four decontamination formulations on typical indoor surfaces following exposure to the liquid chemical warfare agents sarin (GB), soman (GD), sulfur mustard (HD), and VX. Residual surface contamination on coupons was periodically measured for up to 24h after applying one of four selected decontamination technologies [0.5% bleach solution with trisodium phosphate, Allen Vanguard Surface Decontamination Foam (SDF™), U.S. military Decon Green™, and Modec Inc. and EnviroFoam Technologies Sandia Decontamination Foam (DF-200)]. All decontamination technologies tested, except for the bleach solution, performed well on nonporous and nonpermeable glass and stainless-steel surfaces. However, chemical agent residual contamination typically remained on porous and permeable surfaces, especially for the more persistent agents, HD and VX. Solvent-based Decon Green™ performed better than aqueous-based bleach or foams on polymeric surfaces, possibly because the solvent is able to penetrate the polymer matrix. Bleach and foams out-performed Decon Green for penetrating the highly polar concrete surface. Results suggest that the different characteristics needed for an ideal and universal decontamination technology may be incompatible in a single formulation and a strategy for decontaminating a complex facility will require a range of technologies. PMID:21944706

  18. Efficacy of liquid and foam decontamination technologies for chemical warfare agents on indoor surfaces.

    PubMed

    Love, Adam H; Bailey, Christopher G; Hanna, M Leslie; Hok, Saphon; Vu, Alex K; Reutter, Dennis J; Raber, Ellen

    2011-11-30

    Bench-scale testing was used to evaluate the efficacy of four decontamination formulations on typical indoor surfaces following exposure to the liquid chemical warfare agents sarin (GB), soman (GD), sulfur mustard (HD), and VX. Residual surface contamination on coupons was periodically measured for up to 24h after applying one of four selected decontamination technologies [0.5% bleach solution with trisodium phosphate, Allen Vanguard Surface Decontamination Foam (SDF™), U.S. military Decon Green™, and Modec Inc. and EnviroFoam Technologies Sandia Decontamination Foam (DF-200)]. All decontamination technologies tested, except for the bleach solution, performed well on nonporous and nonpermeable glass and stainless-steel surfaces. However, chemical agent residual contamination typically remained on porous and permeable surfaces, especially for the more persistent agents, HD and VX. Solvent-based Decon Green™ performed better than aqueous-based bleach or foams on polymeric surfaces, possibly because the solvent is able to penetrate the polymer matrix. Bleach and foams out-performed Decon Green for penetrating the highly polar concrete surface. Results suggest that the different characteristics needed for an ideal and universal decontamination technology may be incompatible in a single formulation and a strategy for decontaminating a complex facility will require a range of technologies.

  19. Biodetector of organophosphorous and other nerve agents. Contractor report, May 1984-July 1987

    SciTech Connect

    Eldefrawi, M.E.; Valdes, J.J.

    1987-09-01

    The nicotinic ACh receptor obtained from the electric organ of Torpedo was used successfully to detect OP nerve agents but had low sensitivity for cyanide and sulfur mustard. Use of ACh receptor-regulated binding of the allosteric probe was more efficient than monitoring changes in fluorescent receptor complexes. The most-effective and practical strategy for developing a biodetector of nerve agents was to pursue receptor-based capacitance biosensors. The receptor embedded in lipid bilayer was interfaced with a microsensor and its activation by ACh increased the capacitance and this was inhibited by curare. The ACh-receptor-based biosensor was very sensitive in detecting the effects of OP nerve agents on receptor responses. The preliminary success that was achieved with the ACh-receptor-based biosensor establishes the principle and suggests that other receptors should also work to detect a wide variety of toxicants. A receptor-based biodetector is no longer simply a hypothesis but is a reality and a practical one can be developed.

  20. Treating exposure to chemical warfare agents: implications for health care providers and community emergency planning.

    PubMed Central

    Munro, N B; Watson, A P; Ambrose, K R; Griffin, G D

    1990-01-01

    Current treatment protocols for exposure to nerve and vesicant agents found in the U.S. stockpile of unitary chemical weapons are summarized, and the toxicities of available antidotes are evaluated. The status of the most promising of the new nerve agent antidotes is reviewed. In the U.S. atropine and pralidoxime compose the only approved antidote regimen for organophosphate nerve agent poisoning. Diazepam may also be used if necessary to control convulsions. To avoid death, administration must occur within minutes of substantial exposure together with immediate decontamination. Continuous observation and repeated administration of antidotes are necessary as symptoms warrant. Available antidotes do not necessarily prevent respiratory failure or incapacitation. The toxicity of the antidotes themselves and the individualized nature of medical care preclude recommending that autoinjectors be distributed to the general public. In addition, precautionary administration of protective drugs to the general population would not be feasible or desirable. No antidote exists for poisoning by the vesicant sulfur mustard (H, HD, HT); effective intervention can only be accomplished by rapid decontamination followed by palliative treatment of symptoms. British anti-Lewisite (BAL) (2,3-dimercapto-1-propanolol) is the antidote of choice for treatment of exposure to Lewisite, another potent vesicant. Experimental water-soluble BAL analogues have been developed that are less toxic than BAL. Treatment protocols for each antidote are summarized in tabular form for use by health care providers. PMID:2088748

  1. Cyclic process for the removal of sulfur dioxide and the recovery of sulfur from gases

    SciTech Connect

    Lo, C.L.

    1991-11-19

    This patent describes a process for the removal of sulfur dioxide from a gas containing sulfur dioxide. It comprises contacting a gas containing sulfur dioxide with an aqueous solution comprising water, ferric chloride and a salt selected from the group consisting of barium chloride and calcium chloride to form ferrous chloride, hydrochloric acid and a precipitate selected from the group consisting of barium sulfate and calcium sulfate; and treating the aqueous solution with an oxidizing agent to convert ferrous chloride to ferric chloride.

  2. Cytotoxicity of aniline mustard glucuronide alone or in a combination with glucose in Walker cells in culture and sarcoma-180 tumour bearing animals.

    PubMed

    Deliconstantinos, G; Ramantanis, G; Todorou, D K

    1983-01-01

    The effect of aniline mustard glucuronide (AMG), p-hydroxyaniline mustard (HAM), and aniline mustard (AM), on Walker ascites tumour cells in vitro showed that AM in about 80 times more toxic than its glucuronide but HAM is at least 800 times more toxic. A non toxic dose of AMG became completely lethal to Walker tumour cells in vitro, if bovine liver beta-glucuronidase was added to the incubation medium. Prior treatment of Walker tumour cells in vitro with glucose, increased the breakdown of AMG to HAM within the intact cells, while a non-toxic dose of the glucuronide became completely lethal to cells pretreated with glucose. The administration of AMG in combination with glucose to animals bearing the highly resistant to alkylating agents Sarcoma-180 tumour, increased the toxicity of the glucuronide but produced a slight effect on tumour growth. Glucose administration in Sarcoma-180 and ADJ/PC6 tumour bearing animals did not alter the tumour intracellular pH determined in vivo indirectly from the distribution of the weak non-metabolizable organic acid 5,5-dimethyl-2,4-oxazolinedione (DMO) between intra- and extra-cellular water. The present data suggest that the combination of aniline mustard glucuronide with glucose, could be effective in those tumours which have a high beta-glucuronidase activity and a lower tumour intracellular pH could be induced by glucose.

  3. Architectural and Biochemical Expressions of Mustard Gas Keratopathy: Preclinical Indicators and Pathogenic Mechanisms

    PubMed Central

    McNutt, Patrick; Lyman, Megan; Swartz, Adam; Tuznik, Kaylie; Kniffin, Denise; Whitten, Kim; Milhorn, Denise; Hamilton, Tracey

    2012-01-01

    A subset of victims of ocular sulfur mustard (SM) exposure develops an irreversible, idiotypic keratitis with associated secondary pathologies, collectively referred to as mustard gas keratopathy (MGK). MGK involves a progressive corneal degeneration resulting in chronic ocular discomfort and impaired vision for which clinical interventions have typically had poor outcomes. Using a rabbit corneal vapor exposure model, we previously demonstrated a clinical progression with acute and chronic sequelae similar to that observed in human casualties. However, a better understanding of the temporal changes that occur during the biphasic SM injury is crucial to mechanistic understanding and therapeutic development. Here we evaluate the histopathologic, biochemical and ultrastructural expressions of pathogenesis of the chronic SM injury over eight weeks. We confirm that MGK onset exhibits a biphasic trajectory involving corneal surface regeneration over the first two weeks, followed by the rapid development and progressive degeneration of corneal structure. Preclinical markers of corneal dysfunction were identified, including destabilization of the basal corneal epithelium, basement membrane zone abnormalities and stromal deformation. Clinical sequelae of MGK appeared abruptly three weeks after exposure, and included profound anterior edema, recurring corneal erosions, basement membrane disorganization, basal cell necrosis and stromal degeneration. Unlike resolved corneas, MGK corneas exhibited frustrated corneal wound repair, with significantly elevated histopathology scores. Increased lacrimation, disruption of the basement membrane and accumulation of pro-inflammatory mediators in the aqueous humor provide several mechanisms for corneal degeneration. These data suggest that the chronic injury is fundamentally distinct from the acute lesion, involving injury mechanisms that operate on different time scales and in different corneal tissues. Corneal edema appears to be the

  4. Impacts of mustard gas exposure on veterans mental health: A study on the role of education

    PubMed Central

    Karami, Gholam-Reza; Ameli, Javad; Roeintan, Rahim; Jonaidi-Jafari, Nematollah; Saburi, Amin

    2013-01-01

    Background: The mustard gas (MG) exposure can impair physical health and therefore increase the probability of the posttraumatic stress disorder (PTSD) and psychological disorders. Aim: The aim of this study was to investigate long-term effects of MG exposure on veterans’ mental health. Materials and Methods: This was a cross-sectional study. In order to assess prevalence of mental health and PTSD of 100 MG victims 25 years after the exposure to MG in Iran-Iraq conflict, the general health questionnaire (GHQ-28) and Impact of Event Scale-Revised, respectively was administered. Results: The mean (±standard deviation (SD)) age of participants was 40.63 (±5.86) years. The mean GHQ-28 (47.34) of the study group was higher compared to standardized cutoff point (23) of the Iranian community. Also, it was found that 38 participants (38%) suffer from PTSD. The results of this study showed that academic education in the PTSD group was less than that in the non-PTSD group (P=0.03). In addition, in multivariate analysis it was found that only education level of the veterans and their wives were effective on the mental health score (adjusted P=0.036 and 0.041, respectively). The mean score of depression and psychosocial activity subscale in patients at higher education level was lower than patients at lower education level (P<0.05). Conclusion: This study found that sulfur mustard (SM) exposure can be effect on mental health even 25 years after exposure. Therefore, the psychological state should be more considered in chemical injured veterans and it is important that providing more mental health centers for this community. PMID:24459369

  5. Novel liquid chromatography-mass spectrometry method for sensitive determination of the mustard allergen Sin a 1 in food.

    PubMed

    Posada-Ayala, Maria; Alvarez-Llamas, Gloria; Maroto, Aroa S; Maes, Xavier; Muñoz-Garcia, Esther; Villalba, Mayte; Rodríguez, Rosalía; Perez-Gordo, Marina; Vivanco, Fernando; Pastor-Vargas, Carlos; Cuesta-Herranz, Javier

    2015-09-15

    Mustard is a condiment added to a variety of foodstuffs and a frequent cause of food allergy. A new strategy for the detection of mustard allergen in food products is presented. The methodology is based on liquid chromatography analysis coupled to mass spectrometry. Mustard allergen Sin a 1 was purified from yellow mustard seeds. Sin a 1 was detected with a total of five peptides showing a linear response (lowest LOD was 5ng). Sin a 1 was detected in mustard sauces and salty biscuit (19±3mg/kg) where mustard content is not specified. Sin a 1, used as an internal standard, allowed quantification of this mustard allergen in foods. A novel LC/MS/MS SRM-based method has been developed to detect and quantify the presence of mustard. This method could help to detect mustard allergen Sin a 1 in processed foods and protect mustard-allergic consumers. PMID:25863610

  6. Novel liquid chromatography-mass spectrometry method for sensitive determination of the mustard allergen Sin a 1 in food.

    PubMed

    Posada-Ayala, Maria; Alvarez-Llamas, Gloria; Maroto, Aroa S; Maes, Xavier; Muñoz-Garcia, Esther; Villalba, Mayte; Rodríguez, Rosalía; Perez-Gordo, Marina; Vivanco, Fernando; Pastor-Vargas, Carlos; Cuesta-Herranz, Javier

    2015-09-15

    Mustard is a condiment added to a variety of foodstuffs and a frequent cause of food allergy. A new strategy for the detection of mustard allergen in food products is presented. The methodology is based on liquid chromatography analysis coupled to mass spectrometry. Mustard allergen Sin a 1 was purified from yellow mustard seeds. Sin a 1 was detected with a total of five peptides showing a linear response (lowest LOD was 5ng). Sin a 1 was detected in mustard sauces and salty biscuit (19±3mg/kg) where mustard content is not specified. Sin a 1, used as an internal standard, allowed quantification of this mustard allergen in foods. A novel LC/MS/MS SRM-based method has been developed to detect and quantify the presence of mustard. This method could help to detect mustard allergen Sin a 1 in processed foods and protect mustard-allergic consumers.

  7. Mugwort-Mustard Allergy Syndrome due to Broccoli Consumption.

    PubMed

    Sugita, Yuri; Makino, Teruhiko; Mizawa, Megumi; Shimizu, Tadamichi

    2016-01-01

    Pollen-food allergy syndrome (PFAS) is a relatively rare form of food allergy which develops in individuals who are sensitized to pollen. Tree pollens, especially birch pollen, frequently induce PFAS; however, the incidence of PFAS due to grass or weed pollens such as ragweed or mugwort is relatively rare. Mugwort-mustard allergy syndrome (MMAS) is an example of a PFAS in which individuals sensitized to mugwort may develop an allergy to mustard and experience severe reactions. We herein describe a case of MMAS due to broccoli consumption. PMID:27478657

  8. Ion chromatographic determination of chloride in mustard sauces.

    PubMed

    López Agüero, E; Bosch Bosch, N; Barrera Vázquez, C; López Ruiz, B

    1999-11-01

    A new, simple, precise, and rapid ion chromatography (IC) method has been developed to determine chloride in mustard sauces using a mixture of phthalic acid, acetone, and water adjusted to pH 5.0 as eluent. Conductometric detection was carried out. The retention time for chloride was 1.5 min. Linearity was obtained up to a concentration level of 100 mg/L NaCl. The method was statistically evaluated for accuracy and precision after being used to assay the chloride from mustard sauces. Within the same samples, the chloride levels obtained by IC were compared with the sodium concentrations quantified by atomic absorption spectrophotometry.

  9. Mugwort-Mustard Allergy Syndrome due to Broccoli Consumption

    PubMed Central

    2016-01-01

    Pollen-food allergy syndrome (PFAS) is a relatively rare form of food allergy which develops in individuals who are sensitized to pollen. Tree pollens, especially birch pollen, frequently induce PFAS; however, the incidence of PFAS due to grass or weed pollens such as ragweed or mugwort is relatively rare. Mugwort-mustard allergy syndrome (MMAS) is an example of a PFAS in which individuals sensitized to mugwort may develop an allergy to mustard and experience severe reactions. We herein describe a case of MMAS due to broccoli consumption. PMID:27478657

  10. Measurement of breakthrough volumes of volatile chemical warfare agents on a poly(2,6-diphenylphenylene oxide)-based adsorbent and application to thermal desorption-gas chromatography/mass spectrometric analysis.

    PubMed

    Kanamori-Kataoka, Mieko; Seto, Yasuo

    2015-09-01

    To establish adequate on-site solvent trapping of volatile chemical warfare agents (CWAs) from air samples, we measured the breakthrough volumes of CWAs on three adsorbent resins by an elution technique using direct electron ionization mass spectrometry. The trapping characteristics of Tenax(®) TA were better than those of Tenax(®) GR and Carboxen(®) 1016. The latter two adsorbents showed non-reproducible breakthrough behavior and low VX recovery. The specific breakthrough values were more than 44 (sarin) L/g Tenax(®) TA resin at 20°C. Logarithmic values of specific breakthrough volume for four nerve agents (sarin, soman, tabun, and VX) showed a nearly linear correlation with the reciprocals of their boiling points, but the data point of sulfur mustard deviated from this linear curve. Next, we developed a method to determine volatile CWAs in ambient air by thermal desorption-gas chromatography (TD-GC/MS). CWA solutions that were spiked into the Tenax TA(®) adsorbent tubes were analyzed by a two-stage TD-GC/MS using a Tenax(®) TA-packed cold trap tube. Linear calibration curves for CWAs retained in the resin tubes were obtained in the range between 0.2pL and 100pL for sarin, soman, tabun, cyclohexylsarin, and sulfur mustard; and between 2pL and 100pL for VX and Russian VX. We also examined the stability of CWAs in Tenax(®) TA tubes purged with either dry or 50% relative humidity air under storage conditions at room temperature or 4°C. More than 80% sarin, soman, tabun, cyclohexylsarin, and sulfur mustard were recovered from the tubes within 2 weeks. In contrast, the recoveries of VX and Russian VX drastically reduced with storage time at room temperature, resulting in a drop to 10-30% after 2 weeks. Moreover, we examined the trapping efficiency of Tenax TA(®) adsorbent tubes for vaporized CWA samples (100mL) prepared in a 500mL gas sampling cylinder. In the concentration range of 0.2-2.5mg/m(3), >50% of sarin, soman, tabun, cyclohexylsarin, and HD were

  11. Measurement of breakthrough volumes of volatile chemical warfare agents on a poly(2,6-diphenylphenylene oxide)-based adsorbent and application to thermal desorption-gas chromatography/mass spectrometric analysis.

    PubMed

    Kanamori-Kataoka, Mieko; Seto, Yasuo

    2015-09-01

    To establish adequate on-site solvent trapping of volatile chemical warfare agents (CWAs) from air samples, we measured the breakthrough volumes of CWAs on three adsorbent resins by an elution technique using direct electron ionization mass spectrometry. The trapping characteristics of Tenax(®) TA were better than those of Tenax(®) GR and Carboxen(®) 1016. The latter two adsorbents showed non-reproducible breakthrough behavior and low VX recovery. The specific breakthrough values were more than 44 (sarin) L/g Tenax(®) TA resin at 20°C. Logarithmic values of specific breakthrough volume for four nerve agents (sarin, soman, tabun, and VX) showed a nearly linear correlation with the reciprocals of their boiling points, but the data point of sulfur mustard deviated from this linear curve. Next, we developed a method to determine volatile CWAs in ambient air by thermal desorption-gas chromatography (TD-GC/MS). CWA solutions that were spiked into the Tenax TA(®) adsorbent tubes were analyzed by a two-stage TD-GC/MS using a Tenax(®) TA-packed cold trap tube. Linear calibration curves for CWAs retained in the resin tubes were obtained in the range between 0.2pL and 100pL for sarin, soman, tabun, cyclohexylsarin, and sulfur mustard; and between 2pL and 100pL for VX and Russian VX. We also examined the stability of CWAs in Tenax(®) TA tubes purged with either dry or 50% relative humidity air under storage conditions at room temperature or 4°C. More than 80% sarin, soman, tabun, cyclohexylsarin, and sulfur mustard were recovered from the tubes within 2 weeks. In contrast, the recoveries of VX and Russian VX drastically reduced with storage time at room temperature, resulting in a drop to 10-30% after 2 weeks. Moreover, we examined the trapping efficiency of Tenax TA(®) adsorbent tubes for vaporized CWA samples (100mL) prepared in a 500mL gas sampling cylinder. In the concentration range of 0.2-2.5mg/m(3), >50% of sarin, soman, tabun, cyclohexylsarin, and HD were

  12. Characterization of mustard seeds and paste by DART ionization with time-of-flight mass spectrometry.

    PubMed

    Prchalová, Jana; Kovařík, František; Ševčík, Rudolf; Čížková, Helena; Rajchl, Aleš

    2014-09-01

    Direct analysis in real time (DART) is a novel technique with great potential for rapid screening analysis. The DART ionization method coupled with high-resolution time-of-flight mass spectrometry (TOF-MS) has been used for characterization of mustard seeds and table mustard. The possibility to use DART to analyse glucosinolates was confirmed on determination of sinalbin (4-hydroxybenzyl glucosinolate). The DART-TOF-MS method was optimized and validated. A set of samples of mustard seeds and mustard products was analyzed. High-performance liquid chromatography and DART-TOF-MS were used to determine glucosinolates in mustard seeds and compared. The correlation equation between these methods was DART = 0.797*HPLC + 6.987, R(2)  = 0.972. The DART technique seems to be a suitable method for evaluation of the quality of mustard seeds and mustard products. PMID:25230177

  13. Identification of chemical warfare agents from vapor samples using a field-portable capillary gas chromatography/membrane-interfaced electron ionization quadrupole mass spectrometry instrument with Tri-Bed concentrator.

    PubMed

    Nagashima, Hisayuki; Kondo, Tomohide; Nagoya, Tomoki; Ikeda, Toru; Kurimata, Naoko; Unoke, Shohei; Seto, Yasuo

    2015-08-01

    A field-portable gas chromatograph-mass spectrometer (Hapsite ER system) was evaluated for the detection of chemical warfare agents (CWAs) in the vapor phase. The system consisted of Tri-Bed concentrator gas sampler (trapping time: 3s(-1)min), a nonpolar low thermal-mass capillary gas chromatography column capable of raising temperatures up to 200°C, a hydrophobic membrane-interfaced electron ionization quadrupole mass spectrometer evacuated by a non-evaporative getter pump for data acquisition, and a personal computer for data analysis. Sample vapors containing as little as 22μg sarin (GB), 100μg soman (GD), 210μg tabun (GA), 55μg cyclohexylsarin (GF), 4.8μg sulfur mustard, 390μg nitrogen mustard 1, 140μg of nitrogen mustard 2, 130μg nitrogen mustard 3, 120μg of 2-chloroacetophenone and 990μg of chloropicrin per cubic meter could be confirmed after Tri-Bed micro-concentration (for 1min) and automated AMDIS search within 12min. Using manual deconvolution by background subtraction of neighboring regions on the extracted ion chromatograms, the above-mentioned CWAs could be confirmed at lower concentration levels. The memory effects were also examined and we found that blister agents showed significantly more carry-over than nerve agents. Gasoline vapor was found to interfere with the detection of GB and GD, raising the concentration limits for confirmation in the presence of gasoline by both AMDIS search and manual deconvolution; however, GA and GF were not subject to interference by gasoline. Lewisite 1, and o-chlorobenzylidene malononitrile could also be confirmed by gas chromatography, but it was hard to quantify them. Vapors of phosgene, chlorine, and cyanogen chloride could be confirmed by direct mass spectrometric detection at concentration levels higher than 2, 140, and 10mg/m(3) respectively, by bypassing the micro-concentration trap and gas chromatographic separation. PMID:26118803

  14. Identification of chemical warfare agents from vapor samples using a field-portable capillary gas chromatography/membrane-interfaced electron ionization quadrupole mass spectrometry instrument with Tri-Bed concentrator.

    PubMed

    Nagashima, Hisayuki; Kondo, Tomohide; Nagoya, Tomoki; Ikeda, Toru; Kurimata, Naoko; Unoke, Shohei; Seto, Yasuo

    2015-08-01

    A field-portable gas chromatograph-mass spectrometer (Hapsite ER system) was evaluated for the detection of chemical warfare agents (CWAs) in the vapor phase. The system consisted of Tri-Bed concentrator gas sampler (trapping time: 3s(-1)min), a nonpolar low thermal-mass capillary gas chromatography column capable of raising temperatures up to 200°C, a hydrophobic membrane-interfaced electron ionization quadrupole mass spectrometer evacuated by a non-evaporative getter pump for data acquisition, and a personal computer for data analysis. Sample vapors containing as little as 22μg sarin (GB), 100μg soman (GD), 210μg tabun (GA), 55μg cyclohexylsarin (GF), 4.8μg sulfur mustard, 390μg nitrogen mustard 1, 140μg of nitrogen mustard 2, 130μg nitrogen mustard 3, 120μg of 2-chloroacetophenone and 990μg of chloropicrin per cubic meter could be confirmed after Tri-Bed micro-concentration (for 1min) and automated AMDIS search within 12min. Using manual deconvolution by background subtraction of neighboring regions on the extracted ion chromatograms, the above-mentioned CWAs could be confirmed at lower concentration levels. The memory effects were also examined and we found that blister agents showed significantly more carry-over than nerve agents. Gasoline vapor was found to interfere with the detection of GB and GD, raising the concentration limits for confirmation in the presence of gasoline by both AMDIS search and manual deconvolution; however, GA and GF were not subject to interference by gasoline. Lewisite 1, and o-chlorobenzylidene malononitrile could also be confirmed by gas chromatography, but it was hard to quantify them. Vapors of phosgene, chlorine, and cyanogen chloride could be confirmed by direct mass spectrometric detection at concentration levels higher than 2, 140, and 10mg/m(3) respectively, by bypassing the micro-concentration trap and gas chromatographic separation.

  15. Estimated general population control limits for unitary agents in drinking water, milk, soil, and unprocessed food items. For use in reentry decision-making

    SciTech Connect

    Watson, A.P.; Adams, J.D.; Cerar, R.J.; Hess, T.L.; Kistner, S.L.; Leffingwell, S.S.; MacIntosh, R.G.; Ward, J.R.

    1992-01-01

    In the event of an unplanned release of chemical agent during any stage of the Chemical Stockpile Disposal Program (CSDP), the potential exists for contamination of drinking water, forage crops, grains, garden produce, and livestock. Persistent agents such as VX or sulfur mustard pose the greatest human health concern for reentry. This White Paper has been prepared to provide technical bases for these decisions by developing working estimates of agent control limits in selected environmental media considered principal sources of potential human exposure. To date, control limits for public exposure to unitary agents have been established for atmospheric concentrations only. The current analysis builds on previous work to calculate working estimates of control limits for ingestion and dermal exposure to potentially contaminated drinking water, milk, soil, and unprocessed food items such as garden produce. Information characterizing agent desorption from, and detection on or in, contaminated porous media are presently too developed to permit reasonable estimation of dermal exposure from this source. Thus, dermal contact with potentially contaminated porous surfaces is not considered in this document.

  16. Effects of sulfur-based hemostatic agents and gingival retraction cords handled with latex gloves on the polymerization of polyvinyl siloxane impression materials

    PubMed Central

    MACHADO, Carlos Eduardo Palhares; GUEDES, Carlos Gramani

    2011-01-01

    Objectives This study investigated the possible interactions between three addition silicone materials (Express®, Aquasil Ultra® and Adsil®), three hemostatic agents (ferric sulfate, StatGel FS®; aluminum sulfate, GelCord®; and aluminum chloride, Hemostop®) and gingival retraction cords previously handled with latex gloves to determine whether direct contact with medicaments or indirect contamination by latex in conditions similar to those found in clinical practice inhibit or affect the setting of the impression materials. Material and Methods A portable device for the simultaneous test of several specimens was specifically developed for this study. Polymerization inhibition was analyzed by examination of the impressions and the molded surface. Ten trials were performed for each addition silicone material used in the study, at a total of 240 study samples. Results All the samples tested (N=240) were nonreactive regardless of the type of combination used. Conclusions Aluminum sulfate, ferric sulfate and aluminum chloride hemostatic solutions did not show any inhibitory potential on the addition silicone samples under study, and there were no changes in polymerization as a result of contact between addition silicone and retraction cords handled with latex gloves. PMID:22230998

  17. Onion and weed response to mustard (Sinapis alba) seed meal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Weed control in organic onion production is often difficult and expensive, requiring numerous cultivations and extensive hand-weeding. Onion safety and weed control with mustard seed meal (MSM) derived from Sinapis alba was evaluated in greenhouse and field trials. MSM applied at 110, 220, and 440 g...

  18. Onion and weed response to mustard (Sinapis alba) seed meal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Onion and weed response to mustard seed meal (MSM) were tested in greenhouse and field trials in 2007-2009. MSM was applied to the soil surface at rates of 1.1, 2.2, and 4.4 MT/ha. In greenhouse trials, onions were severely injured and stands reduced with all rates of MSM applied prior to onion emer...

  19. Mustard Seed Meal suppresses Weeds in Potato and Peppermint

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seed meal is a co-product remaining after pressing mustard seed to remove the oil. Seed meals containing high glucosinolates have been reported to have herbicidal activity. Weed suppression with seed meal of Sinapis alba, variety Ida Gold was evaluated in field trials on potatoes and peppermint in ...

  20. β-Amylase from Mustard (Sinapis alba L.) Cotyledons 1

    PubMed Central

    Subbaramaiah, Kotha; Sharma, Rameshwar

    1989-01-01

    A polyclonal antiserum against mustard (Sinapis alba L.) β-amylase was obtained by injecting a homogeneously purified enzyme preparation in rabbits. The formation of β-amylase specific antibodies was confirmed by staining the precipitin line in double diffusion gel for β-amylase activity. The monospecificity of antiserum against mustard β-amylase was also ascertained by Western blotting. The antiserum efficiently recognised both the denatured and the native form of β-amylase, but it did not cross-react with other higher plant β-amylase. The mode of photoregulation of β-amylase activity in mustard cotyledons was investigated by a variety of immunochemical techniques. Immunotitration experiments ruled out the possible contribution of enzyme activation/inactivation in photoregulation of β-amylase activity. The use of single radial immunodiffusion, rocket immunoelectrophoresis, and immunotitration confirmed that the light mediated increase in β-amylase activity quantitatively corresponds with the increase in β-amylase protein level. The in vivo labeling with l-[35S] methionine and pulse chase studies of in vivo labeled β-amylase protein revealed that the photoregulated increase in β-amylase activity in mustard cotyledon exclusively results from an increase in the rate of de novo synthesis of β-amylase protein against a very low background rate of enzyme degradation. Images Figure 1 Figure 2 PMID:16666633

  1. 87. EAST SECTION OF SOUTH PLANT, SHOWING MUSTARD FILLING BUILDING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    87. EAST SECTION OF SOUTH PLANT, SHOWING MUSTARD FILLING BUILDING (BUILDING 728) AT LEFT AND INCINERATOR/PRECIPITATOR (BUILDING 724) AT CENTER, FROM CHEMICAL STORAGE TANK. VIEW TO SOUTHWEST. - Rocky Mountain Arsenal, Bounded by Ninety-sixth Avenue & Fifty-sixth Avenue, Buckley Road, Quebec Street & Colorado Highway 2, Commerce City, Adams County, CO

  2. 14. SOUTH PLANT MUSTARD FILLING BUILDING (BUILDING 728) AND WAREHOUSE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. SOUTH PLANT MUSTARD FILLING BUILDING (BUILDING 728) AND WAREHOUSE (BUILDING 729) FROM CHEMICAL STORAGE TANK. VIEW TO NORTHEAST. - Rocky Mountain Arsenal, Bounded by Ninety-sixth Avenue & Fifty-sixth Avenue, Buckley Road, Quebec Street & Colorado Highway 2, Commerce City, Adams County, CO

  3. 23. SOUTH PLANT MUSTARD FILLING BUILDING (BUILDING 728) AND WAREHOUSE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    23. SOUTH PLANT MUSTARD FILLING BUILDING (BUILDING 728) AND WAREHOUSE (BUILDING 729) FROM ROOF OF TON CONTAINER RECONDITIONING BUILDING, SHOWING FACILITIES MAINTENANCE BUILDING AT FOREGROUND AND BUILDING 741, 742 AND 743 AT CENTER BACKGROUND. VIEW TO SOUTHEAST. - Rocky Mountain Arsenal, Bounded by Ninety-sixth Avenue & Fifty-sixth Avenue, Buckley Road, Quebec Street & Colorado Highway 2, Commerce City, Adams County, CO

  4. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., and marketing of the mustard; except, if the salvage price can be increased by conditioning, we may..., each will be considered a separate price election that will be multiplied by the number of insurable... production based processor contracts which specify a maximum number of acres, the lesser of: (i)......

  5. Uses of lunar sulfur

    NASA Technical Reports Server (NTRS)

    Vaniman, D.; Pettit, D.; Heiken, G.

    1992-01-01

    Sulfur and sulfur compounds have a wide range of applications for their fluid, electrical, chemical, and biochemical properties. Although known abundances on the Moon are limited (approximately 0.1 percent in mare soils), sulfur is relatively extractable by heating. Coproduction of sulfur during oxygen extraction from ilmenite-rich mare soils could yield sulfur in masses up to 10 percent of the mass of oxygen produced. Sulfur deserves serious consideration as a lunar resource.

  6. Effects of native herbs and light on garlic mustard (Alliaria petiolata) invasion

    USGS Publications Warehouse

    Phillips-Mao, Laura; Larson, Diane L.; Jordan, Nicholas R.

    2014-01-01

    The degree to which invasive species drive or respond to environmental change has important implications for conservation and invasion management. Often characterized as a driver of change in North American woodlands, the invasive herb garlic mustard may instead respond to declines in native plant cover and diversity. We tested effects of native herb cover, richness, and light availability on garlic mustard invasion in a Minnesota oak woodland. We planted 50 garlic mustard seeds into plots previously planted with 0 to 10 native herb species. We measured garlic mustard seedling establishment, survival to rosette and adult stages, and average (per plant) and total (per plot) biomass and silique production. With the use of structural equation models, we analyzed direct, indirect, and net effects of native cover, richness, and light on successive garlic mustard life stages. Native plant cover had a significant negative effect on all life stages. Species richness had a significant positive effect on native cover, resulting in indirect negative effects on all garlic mustard stages, and net negative effects on adult numbers, total biomass, and silique production. Light had a strong negative effect on garlic mustard seedling establishment and a positive effect on native herb cover, resulting in significant negative net effects on garlic mustard rosette and adult numbers. However, light's net effect on total garlic mustard biomass and silique production was positive; reproductive output was high even in low-light/high-cover conditions. Combined effects of cover, richness, and light suggest that native herbs provide biotic resistance to invasion by responding to increased light availability and suppressing garlic mustard responses, although this resistance may be overwhelmed by high propagule pressure. Garlic mustard invasion may occur, in part, in response to native plant decline. Restoring native herbs and controlling garlic mustard seed production may effectively reduce

  7. Sulfuric acid-sulfur heat storage cycle

    DOEpatents

    Norman, John H.

    1983-12-20

    A method of storing heat is provided utilizing a chemical cycle which interconverts sulfuric acid and sulfur. The method can be used to levelize the energy obtained from intermittent heat sources, such as solar collectors. Dilute sulfuric acid is concentrated by evaporation of water, and the concentrated sulfuric acid is boiled and decomposed using intense heat from the heat source, forming sulfur dioxide and oxygen. The sulfur dioxide is reacted with water in a disproportionation reaction yielding dilute sulfuric acid, which is recycled, and elemental sulfur. The sulfur has substantial potential chemical energy and represents the storage of a significant portion of the energy obtained from the heat source. The sulfur is burned whenever required to release the stored energy. A particularly advantageous use of the heat storage method is in conjunction with a solar-powered facility which uses the Bunsen reaction in a water-splitting process. The energy storage method is used to levelize the availability of solar energy while some of the sulfur dioxide produced in the heat storage reactions is converted to sulfuric acid in the Bunsen reaction.

  8. [Preparation, in vitro and in vivo evaluation of cataplasm of white mustard seed varnish to prevent asthma].

    PubMed

    Du, Li-Na; Zhu, Wei-Nan; Liu, Xiao-Yan; Chen, Wen-Yang; Yu, Xiang; Li, Miao; Jin, Yi-Guang

    2014-12-01

    The aim of the manuscript was to optimize formulations and preparation technologies of cataplasm of white mustard seed varnish, and to evaluate its anti-asthma effect on rats. The single factor experiments included spreading thickness, types of crosslinking agents, dihydroxyaluminum aminoacetate amount, sodium polyacrylate amount, types of adhesive agents with human sense as the evaluation index. Blank cataplasm matrix was optimized by the orthogonal experiment with the amount of glycerine, citric acid, and sodium carboxymethylcellulose as the major influential factors. Initial adhesive force, peeling strength and human sense were as the evaluation index. The optimized formulation of blank cataplasm were as followings: glycerine-water-ethanol-PEG400-dihydroxyaluminum aminoacetate-citric acid-sodium carboxymethylcellulose-sodium carboxymethylcellulose 2 : 8 : 0.8 : 0.4 : 0.07: 0.15 : 0.1 : 0.5. The active ingredients of white mustard seed, corydalis, and gansui root were extracted by alcohol extraction method. Asiasarum volatile oil was extracted by oil extractor. The optimized drug loading amount was 11% with initial adhesive force, peeling strength and human sense as the evaluation index. Asthma rats model were established by sensitized with ovalbumin and nose-scratching time as the evaluation index. High dose (17%) group of drug-loaded cataplasm had the obvious inhibition effect on nose-scratching time of rats (P = 0.037 < 0.05). In comparison, middle dose (11%), low dose (4%) and positive-control groups had no obvious inhibitive effect on rats. White mustard seed cataplasm supplied a novel choice for anti-asthma therapy. And the overall pharmacodynamics assessment will be carried out on molecular level in near future. PMID:25911808

  9. Shrubby Reed-Mustard Habitat: Parent Material, Soil, and Landscape Characteristics

    NASA Astrophysics Data System (ADS)

    Kelly, L. S.; Boettinger, J. L.

    2012-12-01

    Shrubby reed-mustard (Glaucocarpum suffrutescens, a.k.a. Schoenocrambe suffrutescens, Glaucocarpum suffrutescens, or Hesperidanthus suffrutescens) is an endangered perennial shrub endemic to the southern Uinta Basin in northeast Utah. Only seven populations of shrubby reed-mustard have been identified. The arid area where the plant grows is rich in natural gas and oil deposits, as well as oil shale. Oil wells already dot the landscape, and there is significant concern that further development of these resources will threaten the continued existence of shrubby reed-mustard. Determination of the parent material, soil and landscape characteristics associated with shrubby reed-mustard habitat is imperative to facilitate conservation management. Shrubby reed-mustard grows where little else does and, based on field observations and remotely sensed spectral data, appears to occur in a particular type of strata. Our objective is to identify the physical and chemical characteristics of shrubby reed-mustard's environment. Site characteristics such as parent material and associated vegetation have been identified and documented. Soil properties such as water-soluble and total leachable elements, particle-size distribution, organic carbon, cation exchange capacity, total nitrogen, and available phosphorus and potassium are being determined. During the course of this investigation, soils within four shrubby reed-mustard habitat areas were sampled. Soils from non-shrubby reed-mustard areas adjacent to the four shrubby reed-mustard populations were also sampled. Soil samples were collected from a total of twenty-five shrubby reed-mustard soil pits and twenty-four non-shrubby reed-mustard soil pits. The soil horizons of each pedon were delineated, and samples were collected from each horizon. Field data indicate that shrubby reed-mustard occurs exclusively in shale-derived, shallow soils on bedrock-controlled uplands. Although there is some overlap of plant species on both types

  10. The effects of atorvastatin on mustard-gas-exposed patients with chronic obstructive pulmonary disease: A randomized controlled trial

    PubMed Central

    Ghobadi, Hassan; Lari, Shahrzad M.; Pourfarzi, Farhad; Mahmoudpour, Afsoun; Ghanei, Mostafa

    2014-01-01

    Background: Statins have anti-inflammatory effects in patients with chronic obstructive pulmonary disease (COPD). This study designed to evaluate the effects of atorvastatin on serum highly sensitive C-reactive protein (hs-CRP) and pulmonary function in sulfur mustard exposed patients with COPD. Materials and Methods: Fifty patients with chronic obstructive pulmonary disease due to sulfur mustard and high serum hs-CRP entered in this study. Participants were randomized to receive 40 mg atorvastatin or placebo in a double-blind clinical trial. Forty-five patients completed the study (n = 23 atorvastatin and n = 22 placebo). Pulse oximetry (SpO2), pulmonary function test (PFT), and 6 min walk distance test (6MWD) was measured. COPD assessment test (CAT) and St. George's respiratory questionnaire (SGRQ) were also completed by patients at the beginning of trial and after 9 weeks of prescription of 40 mg/day atorvastatin or placebo. At fourth week, SpO2, PFT, and 6MWD were again measured. After 9 weeks serum hs-CRP was re-measured. Results: There was no significant difference between atorvastatin and the placebo group in SpO2, FEV1, and 6MWD after fourth week (P = 0.79, P = 0.12, P = 0.12, respectively). The difference between baseline and ninth week was calculated for two groups of trial and control in term of serum hs-CRP, SpO2, FEV1, and 6MWD. Significant improvement was not observed between two groups in above mentioned variables (P = 0.35, P = 0.28, P = 0.94, P = 0.43, respectively). However, the quality of life was improved by administration of atorvastatin using the CAT score (P < 0.001) and SGRQ total score (P = 0.004). Conclusion: Atorvastatin does not alter serum hs-CRP and lung functions but may improve quality of life in SM-injured patients with COPD. PMID:24778661

  11. Competitive Interactions of Garlic Mustard (Alliaria petiolata) and Damesrocket (Hesperis matronalis)

    USGS Publications Warehouse

    Leicht-Young, Stacey A.; Pavlovic, Noel B.; Adams, Jean V.

    2012-01-01

    Competitive interactions between native plants and nonnative, invasive plant species have been extensively studied; however, within degraded landscapes, the effect of interspecific interactions among invasive plants is less explored. We investigated a competitive interaction between two sympatric, invasive mustard species that have similar life history strategies and growth forms: garlic mustard and damesrocket. Greenhouse experiments using a full range of reciprocal density ratios were conducted to investigate interspecific competition. Garlic mustard had a negative effect on the final biomass, number of leaves, and relative growth rate in height of damesrocket. Survival of damesrocket was not negatively affected by interspecific competition with garlic mustard; however, garlic mustard showed higher mortality because of intraspecific competition. These results indicated that although garlic mustard has been observed to be the dominant species in this landscape, it may not completely outcompete damesrocket in all situations. Studies of invasive species in competition are important in degraded landscapes because this is the common situation in many natural areas.

  12. Occurrence and possible sources of arsenic in seafloor sediments surrounding sea-disposed munitions and chemical agents near O´ahu, Hawai´i

    NASA Astrophysics Data System (ADS)

    Tomlinson, Michael S.; De Carlo, Eric Heinen

    2016-06-01

    The Department of Defense disposed of conventional and chemical munitions as well as bulk containers of chemical agents in US coastal waters including those surrounding the State of Hawai´i. The Hawai´i Undersea Military Munitions Assessment has been collecting biota, water, and sediment samples from two disposal areas south of the island of O´ahu in waters 500 to 600 m deep known to have received both conventional munitions and chemical agents (specifically sulfur mustard). Unlike a number of other sea-disposed munitions investigations which used grabs or corers lowered from surface vessels, we used manned submersibles to collect the samples. Using this approach, we were able to visually identify the munitions and precisely locate our samples in relation to the munitions on the seafloor. This paper focuses on the occurrence and possible sources of arsenic found in the sediments surrounding the disposed military munitions and chemical agents. Using nonparametric multivariate statistical techniques, we looked for patterns in the chemical data obtained from these sediment samples in order to determine the possible sources of the arsenic found in these sediments. The results of the ordination technique nonmetric multidimensional scaling indicate that the arsenic is associated with terrestrial sources and not munitions. This was not altogether surprising given that: (1) the chemical agents disposed of in this area supposedly did not contain arsenic, and (2) the disposal areas studied were under terrestrial influence or served as dredge spoil disposal sites. The sediment arsenic concentrations during this investigation ranged from <1.3 to 40 mg/kg-dry weight with the lower concentrations typically found around control sites and munitions (not located in dredge disposal areas) and the higher values found at dredge disposal sites (with or without munitions). During the course of our investigation we did, however, discover that mercury appears to be loosely associated

  13. DNA sequence-specific adenine alkylation by the novel antitumor drug tallimustine (FCE 24517), a benzoyl nitrogen mustard derivative of distamycin.

    PubMed Central

    Broggini, M; Coley, H M; Mongelli, N; Pesenti, E; Wyatt, M D; Hartley, J A; D'Incalci, M

    1995-01-01

    FCE 24517, a novel distamycin derivative possessing potent antitumor activity, is under initial clinical investigation in Europe. In spite of the presence of a benzoyl nitrogen mustard group this compound fails to alkylate the N7 position of guanine, the major site of alkylation by conventional nitrogen mustards. Characterisation of DNA-drug adducts revealed only a very low level of adenine adduct formation. Using a modified Maxam-Gilbert sequencing method the consensus sequence for FCE 24517-adenine adduct formation was found to be 5'-TTTTGA-3'. A single base modification in the hexamer completely abolishes the alkylation of adenine. Using a Taq polymerase stop assay alkylations were confirmed at the A present in the hexamer TTTTGA and, in addition, in one out of three TTTTAA sequences present in the plasmid utilized. The sequence specificity of alkylation by FCE 24517 is therefore the most striking yet observed for an alkylating agent of small molecular weight. Images PMID:7870593

  14. Potent antitumor 9-anilinoacridines and acridines bearing an alkylating N-mustard residue on the acridine chromophore: synthesis and biological activity.

    PubMed

    Su, Tsann-Long; Lin, Yi-Wen; Chou, Ting-Chao; Zhang, Xiuguo; Bacherikov, Valeriy A; Chen, Ching-Huang; Liu, Leroy F; Tsai, Tsong-Jen

    2006-06-15

    A series of 9-anilinoacridine and acridine derivatives bearing an alkylating N-mustard residue at C4 of the acridine chromophore were synthesized. The N-mustard pharmacophore was linked to the C4 of the acridine ring with an O-ethyl (O-C(2)), O-propyl (O-C(3)), or O-butyl (O-C(4)) spacer. It revealed that all newly synthesized compounds were very potent cytotoxic agents against human leukemia and various solid tumors in vitro. These agents did not exhibit cross-resistance against vinblastine-resistant (CCRF-CEM/VBL) or taxol-resistant (CCRF-CEM/taxol) cells. It also showed that these agents were DNA cross-linking agents rather than topoisomerase II inhibitors. Of these agents, compounds 27a and 27c were shown to have potent antitumor activity in nude mice bearing the human breast carcinoma MX-1 xenograft. The therapeutic efficacies of these two agents are comparable to that of taxol.

  15. Sensory evaluation of dry-fermented sausage containing ground deodorized yellow mustard.

    PubMed

    Li, Shuliu; Aliani, Michel; Holley, Richard A

    2013-10-01

    Ground deodorized yellow mustard is used as a binder and meat protein substitute in cooked processed meat products. Recent studies have shown that it has the potential to be used in uncooked processed meat products because of its natural antimicrobial properties. In the present study, ground deodorized yellow mustard was added to uncooked dry-fermented sausage during manufacture at 1% to 4% (w/w) and analyzed for its effects on starter cultures, physico-chemical properties, and consumer acceptability. Mustard had a nondose-dependent inhibitory effect on the Staphylococcus starter culture, had no effect on water activity or instrumental texture, and tended to accelerate sausage pH reduction. At 3% and 4% mustard, consumer scores on all sensory attributes as well as overall acceptability were significantly lower. The appearance and color of 3% and 4% mustard-treated sausages were liked slightly, whereas flavor, texture, and overall acceptability scores were reduced. The control without mustard and 1% mustard-treated sausages had similar sensory properties and were the most acceptable, while 2% mustard-treated sausages were given "like moderately" and "like slightly" descriptors. Sensory results mean that at concentrations necessary for mandated regulatory control of Escherichia coli O157:H7 in dry sausages, mustard may have a negative effect on consumer acceptance.

  16. Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans

    PubMed Central

    Balali-Mood, M; Mousavi, SH; Balali-Mood, B

    2008-01-01

    The widespread use of sulphur mustard (SM) as an incapacitating chemical warfare agent in the past century has proved its long-lasting toxic effects. It may also be used as a chemical terrorist agent. Therefore, all health professionals should have sufficient knowledge and be prepared for any such chemical attack. SM exerts direct toxic effects on the eyes, skin, and respiratory tissue, with subsequent systemic action on the nervous, immunological, haematological, digestive, and reproductive systems. SM is an alkylating agent that affects DNA synthesis, and, thus, delayed complications have been seen since the First World War. Cases of malignancies in the target organs, particularly in haematopoietic, respiratory, and digestive systems, have been reported. Important delayed respiratory complications include chronic bronchitis, bronchiectasis, frequent bronchopneumonia, and pulmonary fibrosis, all of which tend to deteriorate with time. Severe dry skin, delayed keratitis, and reduction of natural killer cells with subsequent increased risk of infections and malignancies are also among the most distressing long-term consequences of SM intoxication. However, despite a lot of research over the past decades on Iranian veterans, there are still major gaps in the SM literature. Immunological and neurological dysfunction, as well as the relationship between SM exposure and mutagenicity, carcinogenicity, and teratogenicity are important fields that require further studies, particularly on Iranian veterans with chronic health effects of SM poisoning. There is also a paucity of information on the medical management of acute and delayed toxic effects of SM poisoning—a subject that greatly challenges health care specialists. PMID:22460216

  17. Effect of temperature on the desorption and decomposition of mustard from activated carbon

    SciTech Connect

    Karwacki, C.J.; Buchanan, J.H.; Mahle, J.J.; Buettner, L.C.; Wagner, G.W.

    1999-12-07

    Experimental data are reported for the desorption of bis-2-chloroethyl sulfide, (a sulfur mustard or HD) and its decomposition products from activated coconut shell carbon (CSC). The results show that under equilibrium conditions changes in the HD partial pressure are affected primarily by its loading and temperature of the adsorbent. The partial pressure of adsorbed HD is found to increase by about a decade for each 25 C increase in temperature for CSC containing 0.01--0.1 g/g HD. Adsorption equilibria of HD appear to be little affected by coadsorbed water. Although complicated by its decomposition, the distribution of adsorbed HD (of known amount) appears to occupy pores of similar energy whether dry or in the presence of adsorbed water. On dry CSC adsorbed HD appears stable, while in the presence of water its decomposition is marked by hydrolysis at low temperature and thermal decomposition at elevated temperatures. The principal volatile products desorbed are 1,4-thioxane, 2-chloroethyl vinyl sulfide and 1,4-dithiane, with the latter favoring elevated temperatures.

  18. Early indicators of survival following exposure to mustard gas: Protective role of 25(OH)D.

    PubMed

    Das, Lopa M; Binko, Amy M; Traylor, Zachary P; Duesler, Lori R; Dynda, Scott M; Debanne, Sara; Lu, Kurt Q

    2016-04-25

    The use of sulfur mustard (SM) as a chemical weapon for warfare has once again assumed center stage, endangering civilian and the military safety. SM causes rapid local skin vesication and late-onset systemic toxicity. Most studies on SM rely on obtaining tissue and blood for characterizing burn pathogenesis and assessment of systemic pathology, respectively. However the present study focuses on developing a non-invasive method to predict mortality from high dose skin SM exposure. We demonstrate that exposure to SM leads to a dose dependent increase in wound area size on the dorsal surface of mice that is accompanied by a progressive loss in body weight loss, blood cytopenia, bone marrow destruction, and death. Thus our model utilizes local skin destruction and systemic outcome measures as variables to predict mortality in a novel skin-based model of tissue injury. Based on our recent work using vitamin D (25(OH)D) as an intervention to treat toxicity from SM-related compounds, we explored the use of 25(OH)D in mitigating the toxic effects of SM. Here we show that 25(OH)D offers protection against SM and is the first known demonstration of an intervention that prevents SM-induced mortality. Furthermore, 25(OH)D represents a safe, novel, and readily translatable potential countermeasure following mass toxic exposure. PMID:26940683

  19. Cyanide in the chemical arsenal of garlic mustard, Alliaria petiolata.

    PubMed

    Cipollini, Don; Gruner, Bill

    2007-01-01

    Cyanide production has been reported from over 2500 plant species, including some members of the Brassicaceae. We report that the important invasive plant, Alliaria petiolata, produces levels of cyanide in its tissues that can reach 100 ppm fresh weight (FW), a level considered toxic to many vertebrates. In a comparative study, levels of cyanide in leaves of young first-year plants were 25 times higher than in leaves of young Arabidopsis thaliana plants and over 150 times higher than in leaves of young Brassica kaber, B. rapa, and B. napus. In first-year plants, cyanide levels were highest in young leaves of seedlings and declined with leaf age on individual plants. Leaves of young plants infested with green peach aphids (Myzus persicae) produced just over half as much cyanide as leaves of healthy plants, suggesting that aphid feeding led to loss of cyanide from intact tissues before analysis, or that aphid feeding inhibited cyanide precursor production. In a developmental study, levels of cyanide in the youngest and oldest leaf of young garlic mustard plants were four times lower than in the youngest and oldest leaf of young Sorghum sudanense (cv. Cadan 97) plants, but cyanide levels did not decline in these leaves with plant age as in S. sudanense. Different populations of garlic mustard varied moderately in the constitutive and inducible expression of cyanide in leaves, but no populations studied were acyanogenic. Although cyanide production could result from breakdown products of glucosinolates, no cyanide was detected in vitro from decomposition of sinigrin, the major glucosinolate of garlic mustard. These studies indicate that cyanide produced from an as yet unidentified cyanogenic compound is a part of the battery of chemical defenses expressed by garlic mustard.

  20. Activity of quinone alkylating agents in quinone-resistant cells.

    PubMed

    Begleiter, A; Leith, M K

    1990-05-15

    The role of the quinone group in the antitumor activity of quinone alkylating agents, such as mitomycin C and 2,5-diaziridinyl-3,5-bis(carboethoxyamino)-1,4-benzoquinone, is still uncertain. The quinone group may contribute to antitumor activity by inducing DNA strand breaks through the formation of free radicals and/or by influencing the alkylating activity of the quinone alkylators. The cytotoxic activity and DNA damage produced by the model quinone alkylating agents, benzoquinone mustard and benzoquinone dimustard, were compared in L5178Y murine lymphoblasts sensitive and resistant to the model quinone antitumor agent, hydrolyzed benzoquinone mustard. The resistant cell lines, L5178Y/HBM2 and L5178Y/HBM10, have increased concentrations of glutathione and elevated catalase, superoxide dismutase, glutathione S-transferase, and DT-diaphorase activity. L5178Y/HBM2 and L5178Y/HBM10 cells were 7.4- and 8.5-fold less sensitive to benzoquinone mustard and 1.7- and 4.3-fold less sensitive to benzoquinone dimustard, respectively, compared with sensitive cells, but showed no resistance to the non-quinone alkylating agent, aniline mustard. The formation of DNA double strand breaks by benzoquinone mustard was reduced by 2- and 8-fold in L5178Y/HBM2 and L5178Y/HBM10 cells, respectively, while double strand break formation by benzoquinone dimustard was reduced only in the L5178Y/HBM10 cells. The number of DNA-DNA cross-links produced by benzoquinone mustard was 3- and 6-fold lower, and the number produced by benzoquinone dimustard was 35% and 2-fold lower in L5178Y/HBM2 and L5178Y/HBM10 cells, respectively, compared with L5178Y parental cells. In contrast, cross-linking by aniline mustard was unchanged in sensitive and resistant cells. Dicoumarol, an inhibitor of DT-diaphorase, increased the cytotoxic activity of both benzoquinone mustard and benzoquinone dimustard in L5178Y/HBM10 cells. This study provides evidence that elevated DT-diaphorase activity in the resistant cells

  1. Solubility of Sulfur Dioxide in Sulfuric Acid

    NASA Technical Reports Server (NTRS)

    Chang, K. K.; Compton, L. E.; Lawson, D. D.

    1982-01-01

    The solubility of sulfur dioxide in 50% (wt./wt.) sulfuric acid was evaluated by regular solution theory, and the results verified by experimental measurements in the temperature range of 25 C to 70 C at pressures of 60 to 200 PSIA. The percent (wt./wt.) of sulfur dioxide in 50% (wt./wt.) sulfuric acid is given by the equation %SO2 = 2.2350 + 0.0903P - 0.00026P 10 to the 2nd power with P in PSIA.

  2. The Sulfur Cycle

    ERIC Educational Resources Information Center

    Kellogg, W. W.; And Others

    1972-01-01

    A model estimating the contributions of sulfur compounds by natural and human activities, and the rate of removal of sulfur from the atmosphere, is based on a review of the existing literature. Areas requiring additional research are identified. (AL)

  3. Effect of mustard seed meal on early weed emergence in peppermint and potato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seed meal is the by-product remaining after pressing/crushing mustard seed to remove the majority of the oil. Trials to evaluate weed suppression were conducted at several locations on peppermint and potatoes using seed meal obtained from Sinapis alba, variety Ida Gold. White mustard seed meal appl...

  4. Suppression of bacterial blight on mustard greens with host plant resistance and Acibenzolar-S-Methyl

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial blight, caused by Pseudomonas cannabina pv. alisalensis, attacks the leaves of most brassica vegetables, including mustard greens (Brassica juncea). ‘Carolina Broadleaf,’ a new mustard cultivar, is resistant to bacterial blight. Acibenzolar-S-methyl (trade name Actigard) has been used to m...

  5. Comparative study on the effect of chemicals on Alternaria blight in Indian mustard--a multi-location study in India.

    PubMed

    Meena, P D; Chattopadhyay, C; Kumar, A; Awasthi, R P; Singh, R; Kaur, S; Thomas, L; Goyal, P; Chand, P

    2011-05-01

    High severity of Altemaria blight disease is a major constraint in production of rapeseed-mustard in India. The aim of this study was to investigate the suppressive potential of chemicals viz., zinc sulphate, borax, sulphur, potash and calcium sulphate, aqueous extracts viz., Eucalyptus globosus (50 g l-1) leaf extract and garlic (Allium sativum) bulb (20 g l-1) extract, cow urine and bio-agents Trichoderma harzianum, Pseudomonas fluorescence in comparison with the recommended chemical fungicide (mancozeb), against foliar disease Alternaria blight of Indian mustard [Brassica juncea (L.) Czern. and Coss] under five different geographical locations of India. Mancozeb recorded the lowest mean severity (leaf: 33.1%; pod: 26.3%) of Alternaria blight with efficacy of garlic bulb extract alone (leaf = 34.4%; pod = 27.3%) or in combination with cow urine (leaf = 34.2%; pod = 28.6%) being statistically at par with the recommended chemical fungicide. Chemicals also proved effective in reducing Alternaria blight severity on leaves and pods of Indian mustard (leaf = 36.3-37.9%; pod = 27.5-30.1%). The effective treatments besides providing significant reduction in disease severity also enabled increase in dry seed yield of the crop (mancozeb = 2052 kg ha-1; garlic = 2006 kg ha-1; control = 1561 kg ha-1).

  6. Attenuation of Nitrogen Mustard-Induced Pulmonary Injury and Fibrosis by Anti-Tumor Necrosis Factor-α Antibody.

    PubMed

    Malaviya, Rama; Sunil, Vasanthi R; Venosa, Alessandro; Verissimo, Vivianne L; Cervelli, Jessica A; Vayas, Kinal N; Hall, LeRoy; Laskin, Jeffrey D; Laskin, Debra L

    2015-11-01

    Nitrogen mustard (NM) is a bifunctional alkylating agent that causes acute injury to the lung that progresses to fibrosis. This is accompanied by a prominent infiltration of macrophages into the lung and upregulation of proinflammatory/profibrotic cytokines including tumor necrosis factor (TNF)α. In these studies, we analyzed the ability of anti-TNFα antibody to mitigate NM-induced lung injury, inflammation, and fibrosis. Treatment of rats with anti-TNFα antibody (15 mg/kg, iv, every 9 days) beginning 30 min after intratracheal administration of NM (0.125 mg/kg) reduced progressive histopathologic alterations in the lung including perivascular and peribronchial edema, macrophage/monocyte infiltration, interstitial thickening, bronchiolization of alveolar walls, fibrin deposition, emphysema, and fibrosis. NM-induced damage to the alveolar-epithelial barrier, measured by bronchoalveolar lavage (BAL) protein and cell content, was also reduced by anti-TNFα antibody, along with expression of the oxidative stress marker, heme oxygenase-1. Whereas the accumulation of proinflammatory/cytotoxic M1 macrophages in the lung in response to NM was suppressed by anti-TNFα antibody, anti-inflammatory/profibrotic M2 macrophages were increased or unchanged. Treatment of rats with anti-TNFα antibody also reduced NM-induced increases in expression of the profibrotic mediator, transforming growth factor-β. This was associated with a reduction in NM-induced collagen deposition in the lung. These data suggest that inhibiting TNFα may represent an efficacious approach to mitigating lung injury induced by mustards.

  7. The cytotoxicity of benzaldehyde nitrogen mustard-2-pyridine carboxylic acid hydrazone being involved in topoisomerase IIα inhibition.

    PubMed

    Fu, Yun; Zhou, Sufeng; Liu, Youxun; Yang, Yingli; Sun, Xingzhi; Li, Changzheng

    2014-01-01

    The antitumor property of iron chelators and aromatic nitrogen mustard derivatives has been well documented. Combination of the two pharmacophores in one molecule in drug designation is worth to be explored. We reported previously the syntheses and preliminary cytotoxicity evaluation of benzaldehyde nitrogen mustard pyridine carboxyl acid hydrazones (BNMPH) as extended study, more tumor cell lines (IC50 for HepG2: 26.1 ± 3.5 μM, HCT-116: 57.5 ± 5.3 μM, K562: 48.2 ± 4.0 μM, and PC-12: 19.4 ± 2.2 μM) were used to investigate its cytotoxicity and potential mechanism. In vitro experimental data showed that the BNMPH chelating Fe(2+) caused a large number of ROS formations which led to DNA cleavage, and this was further supported by comet assay, implying that ROS might be involved in the cytotoxicity of BNMPH. The ROS induced changes of apoptosis related genes, but the TFR1 and NDRG1 metastatic genes were not obviously regulated, prompting that BNMPH might not be able to deprive Fe(2+) of ribonucleotide reductase. The BNMPH induced S phase arrest was different from that of iron chelators (G1) and alkylating agents (G2). BNMPH also exhibited its inhibition of human topoisomerase IIα. Those revealed that the cytotoxic mechanism of the BNMPH could stem from both the topoisomerase II inhibition, ROS generation and DNA alkylation.

  8. Consumer acceptability and sensory profile of cooked broccoli with mustard seeds added to improve chemoprotective properties.

    PubMed

    Ghawi, Sameer Khalil; Shen, Yuchi; Niranjan, Keshavan; Methven, Lisa

    2014-09-01

    Broccoli, a rich source of glucosinolates, is a commonly consumed vegetable of the Brassica family. Hydrolysis products of glucosinolates, isothiocyanates, have been associated with health benefits and contribute to the flavor of Brassica. However, boiling broccoli causes the myrosinase enzyme needed for hydrolysis to denature. In order to ensure hydrolysis, broccoli must either be mildly cooked or active sources of myrosinase, such as mustard seed powder, can be added postcooking. In this study, samples of broccoli were prepared in 6 different ways; standard boiling, standard boiling followed by the addition of mustard seeds, sous vide cooking at low temperature (70 °C) and sous vide cooking at higher temperature (100 °C) and sous vide cooking at higher temperature followed by the addition of mustard seeds at 2 different concentrations. The majority of consumers disliked the mildly cooked broccoli samples (70 °C, 12 min, sous vide) which had a hard and stringy texture. The highest mean consumer liking was for standard boiled samples (100 °C, 7 min). Addition of 1% mustard seed powder developed sensory attributes, such as pungency, burning sensation, mustard odor, and flavor. One cluster of consumers (32%) found mustard seeds to be a good complement to cooked broccoli; however, the majority disliked the mustard-derived sensory attributes. Where the mustard seeds were partially processed, doubling the addition to 2% led to only the same level of mustard and pungent flavors as 1% unprocessed seeds, and mean consumer liking remained unaltered. This suggests that optimization of the addition level of partially processed mustard seeds may be a route to enhance bioactivity of cooked broccoli without compromising consumer acceptability. PMID:25156799

  9. Consumer acceptability and sensory profile of cooked broccoli with mustard seeds added to improve chemoprotective properties.

    PubMed

    Ghawi, Sameer Khalil; Shen, Yuchi; Niranjan, Keshavan; Methven, Lisa

    2014-09-01

    Broccoli, a rich source of glucosinolates, is a commonly consumed vegetable of the Brassica family. Hydrolysis products of glucosinolates, isothiocyanates, have been associated with health benefits and contribute to the flavor of Brassica. However, boiling broccoli causes the myrosinase enzyme needed for hydrolysis to denature. In order to ensure hydrolysis, broccoli must either be mildly cooked or active sources of myrosinase, such as mustard seed powder, can be added postcooking. In this study, samples of broccoli were prepared in 6 different ways; standard boiling, standard boiling followed by the addition of mustard seeds, sous vide cooking at low temperature (70 °C) and sous vide cooking at higher temperature (100 °C) and sous vide cooking at higher temperature followed by the addition of mustard seeds at 2 different concentrations. The majority of consumers disliked the mildly cooked broccoli samples (70 °C, 12 min, sous vide) which had a hard and stringy texture. The highest mean consumer liking was for standard boiled samples (100 °C, 7 min). Addition of 1% mustard seed powder developed sensory attributes, such as pungency, burning sensation, mustard odor, and flavor. One cluster of consumers (32%) found mustard seeds to be a good complement to cooked broccoli; however, the majority disliked the mustard-derived sensory attributes. Where the mustard seeds were partially processed, doubling the addition to 2% led to only the same level of mustard and pungent flavors as 1% unprocessed seeds, and mean consumer liking remained unaltered. This suggests that optimization of the addition level of partially processed mustard seeds may be a route to enhance bioactivity of cooked broccoli without compromising consumer acceptability.

  10. Sulfuric acid on Europa and the radiolytic sulfur cycle

    NASA Technical Reports Server (NTRS)

    Carlson, R. W.; Johnson, R. E.; Anderson, M. S.

    1999-01-01

    A comparison of laboratory spectra with Galileo data indicates that hydrated sulfuric acid is present and is a major component of Europa's surface. In addition, this moon's visually dark surface material, which spatially correlates with the sulfuric acid concentration, is identified as radiolytically altered sulfur polymers. Radiolysis of the surface by magnetospheric plasma bombardment continuously cycles sulfur between three forms: sulfuric acid, sulfur dioxide, and sulfur polymers, with sulfuric acid being about 50 times as abundant as the other forms. Enhanced sulfuric acid concentrations are found in Europa's geologically young terrains, suggesting that low-temperature, liquid sulfuric acid may influence geological processes.

  11. Sulfur tolerant anode materials

    SciTech Connect

    Not Available

    1988-05-01

    The goal of this program is the development of a molten carbonate fuel cell (MCFC) anode which is more tolerant of sulfur contaminants in the fuel than the current state-of-the-art nickel-based anode structures. This program addresses two different but related aspects of the sulfur contamination problem. The primary aspect is concerned with the development of a sulfur tolerant electrocatalyst for the fuel oxidation reaction. A secondary issue is the development of a sulfur tolerant water-gas-shift reaction catalyst and an investigation of potential steam reforming catalysts which also have some sulfur tolerant capabilities. These two aspects are being addressed as two separate tasks.

  12. Biochemistry of sulfur

    SciTech Connect

    Huxtable, R.J.; LaFranconi, W.M.

    1986-01-01

    This book presents information on the following topics: the chemistry of sulfur; the oxidation states of sulfur; the reduction of sulfate and the oxidation of sulfide; the sulfur cycle; oxidation of inorganic sulfide; the metabolism and functions of methionine; taurine and the oxidative metabolism of cysteine; thiols, disulfides, and thioesters; thioethers; thiamine; biotin; sulfates; inherited disorders of sulfur metabolism; cystinuria; sulfur and the metabolism of xenobiotics; general aspects of xenobiotic metabolism; glutathione and sulfation of xenobiotics; and metabolic activation as a result of sulfate conjugation.

  13. Sulfur tolerant anode materials

    SciTech Connect

    Not Available

    1988-02-01

    The goal of this program is the development of a molten carbonate fuel cell (MCFC) anode which is more tolerant of sulfur contaminants in the fuel than the current state-of-the-art nickel-based anode structures. This program addresses two different but related aspects of the sulfur contamination problem. The primary aspect is concerned with the development of a sulfur tolerant electrocatalyst for the fuel oxidation reaction. A secondary issue is the development of a sulfur tolerant water-gas-shift reaction catalyst and an investigation of potential steam reforming catalysts which also have some sulfur tolerant capabilities. These two aspects are being addressed as two separate tasks.

  14. Sulfur tolerant anode materials

    SciTech Connect

    Not Available

    1987-02-01

    The goal of this program is the development of a molten carbonate fuel cell (MCFC) anode which is more tolerant of sulfur contaminants in the fuel than the current state-of-the-art nickel-based anode structures. This program addresses two different but related aspects of the sulfur contamination problem. The primary aspect is concerned with the development of a sulfur tolerant electrocatalyst for the fuel oxidation reaction. A secondary issue is the development of a sulfur tolerant water-gas-shift reaction catalyst and an investigation of potential steam reforming catalysts which also have some sulfur tolerant capabilities. These two aspects are being addressed as two separate tasks.

  15. Sulfur rate control system

    SciTech Connect

    Bell, T.A.; Mullendore, M.G.; Kleinfeldt, T.E.; Walker, H.G. Jr.

    1993-07-20

    A sulfur rate control system is described for substantially optimizing particulate removal performance of an electrostatic precipitator in fluid communication with a flue carrying combustion products of a fossil fuel, comprising: an electrostatic precipitator having an inlet for receiving a flue gas: means for injecting sulfur trioxide into a flue for mixing with said flue gas at a location preceding entry of said flue gas into said electrostatic precipitator, said injection of sulfur trioxide being varied responsive to a proportional control signal; and, control means coupled to both said flue and said sulfur trioxide injection means for generating said proportional control signal, said control means including (1) means for measuring a sulfur dioxide concentration quantity in said flue gas at a location preceding said sulfur trioxide injection means, (2) means for measuring a flow rate of particulates in said flue gas at a location preceding said sulfur trioxide injection means, and (3) a controller for calculating a ratio between said sulfur dioxide concentration quantity and said flow rate of particulates, said ratio calculating controller having a first input coupled to said sulfur dioxide measuring means and a second input coupled to said particulate flow rate measuring means for generating said proportional control signal in proportion to a difference between a predetermined value and said ratio between said sulfur dioxide concentration quantity and said flow rate of particulates, said ratio controller having an output coupled to said sulfur trioxide injection means for maximizing particulate removal efficiency of said electrostatic precipitator.

  16. Evaluation of cranial capacity by mustard seed technique.

    PubMed

    Howale, D S; Shah, J V; Iyer, K; Patel, V H; Patel, D C

    2011-12-01

    The volume of the cranium is used as a rough indicator of the size of the brain. In the present study Breitinger's mustard seeds technique was applied for the measurement of cranial capacity. Grossly normal 75 male skulls of Gujarat population were studied at Kesar SAL Medical College, Ahmedabad (Gujarat) in the year 2010. The mean cranial capacity among the study group was recorded to be 1256 cc with a minimum of 1110 cc and maximum of 1430 cc. The results were compared with the similar studies by different authors from different geographical areas. PMID:23469572

  17. A novel polynuclear Cu(I)-sulfur cluster with 1,2-dithiolate-o-carborane ligands as a potential in vitro antitumour agent and its DNA binding properties.

    PubMed

    Han, Zhong; Jiang, Jin; Lu, Jing; Li, Dacheng; Cheng, Shuang; Dou, Jianmin

    2013-04-14

    A novel polynuclear Cu(I)-sulfur cluster, (C54H62B30Cu6N8S6), bearing 1,2-dithiolate-o-carborane and 1,10-phenanthroline ligands was synthesized. The complex displayed rapid, low micromolar in vitro cytotoxicity against a range of epithelial tumour cells and efficient CT-DNA binding. PMID:23426331

  18. Membrane-associated Sulfur Oxidation by the Autotroph Thiobacillus thiooxidans

    PubMed Central

    Adair, Frank W.

    1966-01-01

    Adair, Frank W. (Rutgers, The State University, New Brunswick, N. J.). Membrane-associated sulfur oxidation by the autotroph Thiobacillus thiooxidans. J. Bacteriol. 92:899–904. 1966.—Washed cell wall-membrane fragments derived from sulfur-grown cells of the strictly autotrophic bacterium, Thiobacillus thiooxidans, oxidized elemental sulfur to sulfate without the addition of cofactors. The oxidation was optimal at pH 7.0 and was increased by the presence of wetting agents. Oxygen uptake was inhibited by cyanide, azide, and thiol-binding agents. Sulfite was also oxidized, and both the sulfur- and sulfite-oxidizing systems were heat-labile. Neither thiosulfate nor tetrathionate was oxidized by soluble or membrane preparations. The fragments fixed C14O2 in the presence of ribose-5-phosphate, Mg++, and adenosine triphosphate. Sulfur oxidation did not provide energy for C14O2 fixation in this system. PMID:5926757

  19. Thermal and pressure stability of myrosinase enzymes from black mustard (Brassica nigra L. W.D.J. Koch. var. nigra), brown mustard (Brassica juncea L. Czern. var. juncea) and yellow mustard (Sinapsis alba L. subsp. maire) seeds.

    PubMed

    Okunade, Olukayode Adediran; Ghawi, Sameer Khalil; Methven, Lisa; Niranjan, Keshavan

    2015-11-15

    This study investigates the effects of temperature and pressure on inactivation of myrosinase extracted from black, brown and yellow mustard seeds. Brown mustard had higher myrosinase activity (2.75 un/mL) than black (1.50 un/mL) and yellow mustard (0.63 un/mL). The extent of enzyme inactivation increased with pressure (600-800 MPa) and temperature (30-70° C) for all the mustard seeds. However, at combinations of lower pressures (200-400 MPa) and high temperatures (60-80 °C), there was less inactivation. For example, application of 300 MPa and 70 °C for 10 min retained 20%, 80% and 65% activity in yellow, black and brown mustard, respectively, whereas the corresponding activity retentions when applying only heat (70° C, 10 min) were 0%, 59% and 35%. Thus, application of moderate pressures (200-400 MPa) can potentially be used to retain myrosinase activity needed for subsequent glucosinolate hydrolysis. PMID:25977054

  20. Mustard catch crop enhances denitrification in shallow groundwater beneath a spring barley field.

    PubMed

    Jahangir, M M R; Minet, E P; Johnston, P; Premrov, A; Coxon, C E; Hackett, R; Richards, K G

    2014-05-01

    Over-winter green cover crops have been reported to increase dissolved organic carbon (DOC) concentrations in groundwater, which can be used as an energy source for denitrifiers. This study investigates the impact of a mustard catch crop on in situ denitrification and nitrous oxide (N2O) emissions from an aquifer overlain by arable land. Denitrification rates and N2O-N/(N2O-N+N2-N) mole fractions were measured in situ with a push-pull method in shallow groundwater under a spring barley system in experimental plots with and without a mustard cover crop. The results suggest that a mustard cover crop could substantially enhance reduction of groundwater nitrate NO3--N via denitrification without significantly increasing N2O emissions. Mean total denitrification (TDN) rates below mustard cover crop and no cover crop were 7.61 and 0.002 μg kg(-1) d(-1), respectively. Estimated N2O-N/(N2O-N+N2-N) ratios, being 0.001 and 1.0 below mustard cover crop and no cover crop respectively, indicate that denitrification below mustard cover crop reduces N2O to N2, unlike the plot with no cover crop. The observed enhanced denitrification under the mustard cover crop may result from the higher groundwater DOC under mustard cover crop (1.53 mg L(-1)) than no cover crop (0.90 mg L(-1)) being added by the root exudates and root masses of mustard. This study gives insights into the missing piece in agricultural nitrogen (N) balance and groundwater derived N2O emissions under arable land and thus helps minimise the uncertainty in agricultural N and N2O-N balances.

  1. Isophosphoramide mustard, a metabolite of ifosfamide with activity against murine tumours comparable to cyclophosphamide.

    PubMed Central

    Struck, R. F.; Dykes, D. J.; Corbett, T. H.; Suling, W. J.; Trader, M. W.

    1983-01-01

    Isophosphoramide mustard was synthesized and was found to demonstrate activity essentially comparable to cyclophosphamide and ifosfamide against L1210 and P388 leukaemia. Lewis lung carcinoma, mammary adenocarcinoma 16/C, ovarian sarcoma M5076, and colon tumour 6A, in mice and Yoshida ascitic sarcoma in rats. At doses less than, or equivalent to, the LD10, isophosphoramide mustard retained high activity against cyclophosphamide-resistant L1210 and P388 leukaemias, but was less active against intracerebrally-implanted P388 leukaemia while cyclophosphamide produced a 4 log10 tumour cell reduction. It was also less active (one log10 lower cell kill) than cyclophosphamide against the B16 melonoma. Metabolism studies on ifosfamide in mice identified isophosphoramide mustard in blood. In addition, unchanged drug, carboxyifosfamide, 4-ketoifosfamide, dechloroethyl cyclophosphamide, dechloroethylifosfamide, and alcoifosfamide were identified. The latter 4 metabolites were also identified in urine from an ifosfamide-treated dog. In a simulated in vitro pharmacokinetic experiment against L1210 leukaemia in which drugs were incubated at various concentrations for various times, both 4-hydroxycyclophosphamide and isophosphoramide mustard exhibited significant cytoxicity at concentration times time values of 100-1000 micrograms X min ml-1, while acrolein was significantly cytotoxic at 10 micrograms X min ml-1. Treatment of mice with drug followed by L1210 cells demonstrated a shorter duration of effective levels of cytotoxic activity for isophosphoramide mustard and phosphoramide mustard in comparison with cyclophosphamide and ifosfamide. Isophosphoramide mustard and 2-chloroethylamine, a potential hydrolysis product of isophosphoramide mustard and carboxyifosfamide, were less mutagenic in the standard Ames test than the 2 corresponding metabolites of cyclophosphamide [phosphoramide mustard and bis(2-chloroethyl)amine]. PMID:6821629

  2. Selenium Assimilation and Volatilization from Selenocyanate-Treated Indian Mustard and Muskgrass1

    PubMed Central

    de Souza, Mark P.; Pickering, Ingrid J.; Walla, Michael; Terry, Norman

    2002-01-01

    Selenocyanate (SeCN−) is a major contaminant in the effluents from some oil refineries, power plants, and in mine drainage water. In this study, we determined the potential of Indian mustard (Brassica juncea) and muskgrass (a macroalga, Chara canescens) for SeCN− phytoremediation in upland and wetland situations, respectively. The tolerance of Indian mustard to toxic levels of SeCN− was similar to or higher than other toxic forms of Se. Indian mustard treated with 20 μm SeCN− removed 30% (w/v) of the Se supplied in 5 d, accumulating 554 and 86 μg of Se g−1 dry weight in roots and shoots, respectively. Under similar conditions, muskgrass removed approximately 9% (w/v) of the Se supplied as SeCN− and accumulated 27 μg of Se g−1 dry weight. A biochemical pathway for SeCN− degradation was proposed for Indian mustard. Indian mustard and muskgrass efficiently degraded SeCN− as none of the Se accumulated by either organism remained in this form. Indian mustard accumulated predominantly organic Se, whereas muskgrass contained Se mainly as selenite and organic Se forms. Indian mustard produced volatile Se from SeCN− in the form of less toxic dimethylselenide. Se volatilization by Indian mustard accounted for only 0.7% (w/v) of the SeCN− removed, likely because the biochemical steps in the production of dimethylselenide from organic Se were rate limiting. Indian mustard is promising for the phytoremediation of SeCN−-contaminated soil and water because of its remarkable abilities to phytoextract SeCN− and degrade all the accumulated SeCN− to other Se forms. PMID:11842165

  3. Exogenous salicylic acid improves photosynthesis and growth through increase in ascorbate-glutathione metabolism and S assimilation in mustard under salt stress.

    PubMed

    Nazar, Rahat; Umar, Shahid; Khan, Nafees A

    2015-01-01

    Ascorbate (AsA)-glutathione (GSH) cycle metabolism has been regarded as the most important defense mechanism for the resistance of plants under stress. In this study the influence of salicylic acid (SA) was studied on ascorbate-glutathione pathway, S-assimilation, photosynthesis and growth of mustard (Brassica juncea L.) plants subjected to 100 mM NaCl. Treatment of SA (0.5 mM) alleviated the negative effects of salt stress and improved photosynthesis and growth through increase in enzymes of ascorbate-glutathione pathway which suggest that SA may participate in the redox balance under salt stress. The increase in leaf sulfur content through higher activity of ATP sulfurylase (ATPS) and serine acetyl transferase (SAT) by SA application was associated with the increased accumulation of glutathione (GSH) and lower levels of oxidative stress. These effects of SA were substantiated by the findings that application of SA-analog, 2,6, dichloro-isonicotinic acid (INA) and 1 mM GSH treatment produced similar results on rubisco, photosynthesis and growth of plants establishing that SA application alleviates the salt-induced decrease in photosynthesis mainly through inducing the enzyme activity of ascorbate-glutathione pathway and increased GSH production. Thus, SA/GSH could be a promising tool for alleviation of salt stress in mustard plants.

  4. Effect of nitroreduction on the alkylating reactivity and cytotoxicity of the 2,4-dinitrobenzamide-5-aziridine CB 1954 and the corresponding nitrogen mustard SN 23862: distinct mechanisms of bioreductive activation.

    PubMed

    Helsby, Nuala A; Wheeler, S James; Pruijn, Frederik B; Palmer, Brian D; Yang, Shangjin; Denny, William A; Wilson, William R

    2003-04-01

    The dinitrobenzamide aziridine CB 1954 (1) and its nitrogen mustard analogue SN 23862 (6) are prodrugs that are activated by enzymatic nitroreduction in tumors. Bioactivation of 1 is considered to be due to reduction of its 4-nitro group to the hydroxylamine and subsequent formation of the N-acetoxy derivative; this acts as a reactive center, in concert with the aziridine moiety, to provide a bifunctional DNA cross-linking agent (Knox model). It is currently unclear whether bioactivation of 6 occurs by the same mechanism or results from the electronic effects of nitroreduction on reactivity of the nitrogen mustard moiety. To discriminate between these mechanisms, we have synthesized the hydroxylamine and amine derivatives of 1 and 6, plus related compounds, and determined their alkylating reactivities in aqueous solution, using LC/MS to identify reaction pathways. The relationships between substituent electronic effects, reactivity, and cytotoxicity were determined using the UV4 cell line, which is defective in nucleotide excision repair (thus avoiding differences in repair kinetics). Alkylating reactivity correlated with the electron-donating character of the ortho or para substituent in the case of the mustards, with a less marked electronic effect for the aziridines. Importantly, there was a highly significant linear relationship between cytotoxic potency and alkylating reactivity in both the aziridine and the mustard series, with the notable exception of 4, the 4-hydroxylamine of 1, which was 300-fold more toxic than predicted by this relationship. This demonstrates that the high potency of 4 does not result from activation of the aziridine ring, supporting the Knox model. The single-step bioactivation of 6, to amino or hydroxylamine metabolites with similar potency to 4, is a potential advantage in the use of dinitrobenzamide mustards as prodrugs for activation by nitroreductases.

  5. The global sulfur cycle

    NASA Technical Reports Server (NTRS)

    Sagan, D. (Editor)

    1985-01-01

    The results of the planetary biology microbial ecology's 1984 Summer Research Program, which examined various aspects of the global sulfur cycle are summarized. Ways in which sulfur flows through the many living and chemical species that inhabit the surface of the Earth were investigated. Major topics studied include: (1) sulfur cycling and metabolism of phototropic and filamentous sulfur bacteria; (2) sulfur reduction in sediments of marine and evaporite environments; (3) recent cyanobacterial mats; (4) microanalysis of community metabolism in proximity to the photic zone in potential stromatolites; and (5) formation and activity of microbial biofilms on metal sulfides and other mineral surfaces. Relationships between the global sulfur cycle and the understanding of the early evolution of the Earth and biosphere and current processes that affect global habitability are stressed.

  6. DSRP, Direct Sulfur Production

    SciTech Connect

    Gangwal, S.K.; McMichael, W.J.; Agarwal, S.K.; Jang, B.L.; Howe, G.B.; Chen, D.H.; Hopper, J.R.

    1993-08-01

    Hot-gas desulfurization processes for IGCC and other advanced power applications utilize regenerable mixed-metal oxide sorbents to remove hydrogen sulfide (H{sub 2}S) from raw coal gas. Regeneration of these sorbents produces an off-gas typically containing I to 3 percent sulfur dioxide (SO{sub 2}). Production of elemental sulfur is a highly desirable option for the ultimate disposal of the SO{sub 2} content of this off-gas. Elemental sulfur, an essential industrial commodity, is easily stored and transported. As shown in Figure 1, the DSRP consists of two catalytic reactors, each followed by a sulfur condenser. Hot regenerator off-gas is mixed with a hot coal-gas slip stream and fed to the first DSRP reactor. Approximately 95 percent of the sulfur gas in the inlet stream of the first reactor is converted to elemental sulfur. The outlet gas of the first DSRP reactor is cooled, condensing out sulfur. The gas could be recycled after the Stage I condenser. Alteratively, by adjusting the proportion of coal gas to regenerator off-gas, the effluent composition of the first reactor can be controlled to produce an H{sub 2}S-to-SO{sub 2} ratio of 2 to 1 at 95 percent sulfur conversion. The cooled gas stream is then passed to the second DSRP reactor where 80 to 90 percent of the remaining sulfur compounds are converted to elemental sulfur via the modified Claus reaction at high pressure. The total efficiency of the two reactors for the conversion of sulfur compounds to elemental sulfur is projected to be about 99.5 percent.

  7. Skin decontamination of mustards and organophosphates: comparative efficiency of RSDL and Fuller's earth in domestic swine.

    PubMed

    Taysse, L; Daulon, S; Delamanche, S; Bellier, B; Breton, P

    2007-02-01

    Research in skin decontamination and therapy of chemical warfare agents has been a difficult problem due to the simultaneous requirement of rapid action and non-aggressive behaviour. The aim of this study was to compare the performance of two decontaminating systems: the Canadian Reactive Skin Decontaminant Lotion (RSDL) and the Fuller's Earth (FE). The experiment was conducted with domestic swine, as a good model for extrapolation to human skin. RSDL and FE were tested against sulphur mustard (SM), a powerful vesicant, and VX, a potent and persistent cholinesterase inhibitor. When used 5 min after contamination, the results clearly showed that both systems were active against SM (10.1 mg/cm(2)) and VX (0.06 mg/cm(2)). The potency of the RSDL/sponge was statistically better than FE against skin injury induced by SM, observed 3 days post-exposure. RSDL was rather more efficient than FE in reducing the formation of perinuclear vacuoles and inflammation processes in the epidermis and dermis. Against a severe inhibition (67%) of plasmatic cholinesterases induced by VX poisoning, the potencies of the RSDL/sponge and FE were similar. Both systems completely prevented cholinesterase inhibition, which indirectly indicates a prevention of toxic absorption through the skin.

  8. Skin decontamination of mustards and organophosphates: comparative efficiency of RSDL and Fuller's earth in domestic swine.

    PubMed

    Taysse, L; Daulon, S; Delamanche, S; Bellier, B; Breton, P

    2007-02-01

    Research in skin decontamination and therapy of chemical warfare agents has been a difficult problem due to the simultaneous requirement of rapid action and non-aggressive behaviour. The aim of this study was to compare the performance of two decontaminating systems: the Canadian Reactive Skin Decontaminant Lotion (RSDL) and the Fuller's Earth (FE). The experiment was conducted with domestic swine, as a good model for extrapolation to human skin. RSDL and FE were tested against sulphur mustard (SM), a powerful vesicant, and VX, a potent and persistent cholinesterase inhibitor. When used 5 min after contamination, the results clearly showed that both systems were active against SM (10.1 mg/cm(2)) and VX (0.06 mg/cm(2)). The potency of the RSDL/sponge was statistically better than FE against skin injury induced by SM, observed 3 days post-exposure. RSDL was rather more efficient than FE in reducing the formation of perinuclear vacuoles and inflammation processes in the epidermis and dermis. Against a severe inhibition (67%) of plasmatic cholinesterases induced by VX poisoning, the potencies of the RSDL/sponge and FE were similar. Both systems completely prevented cholinesterase inhibition, which indirectly indicates a prevention of toxic absorption through the skin. PMID:17370872

  9. Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse. (I) Development of a model for screening studies in skin decontamination and protection.

    PubMed

    Dorandeu, F; Taysse, L; Boudry, I; Foquin, A; Hérodin, F; Mathieu, J; Daulon, S; Cruz, C; Lallement, G

    2011-06-01

    Exposure to lethal chemical warfare agents (CWAs) is no longer only a military issue due to the terrorist threat. Among the CWAs of concern are the organophosphorus nerve agent O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX) and the vesicant sulfur mustard (SM). Although efficient means of decontamination are available, most of them lose their efficacy when decontamination is delayed after exposure of the bare skin. Alternatively, CWA skin penetration can be prevented by topical skin protectants. Active research in skin protection and decontamination is thus paramount. In vivo screening of decontaminants or skin protectants is usually time consuming and may be expensive depending on the animal species used. We were thus looking for a suitable, scientifically sound and cost-effective model, which is easy to handle. The euthymic hairless mouse Crl: SKH-1 (hr/hr) BR is widely used in some skin studies and has previously been described to be suitable for some experiments involving SM or SM analogs. To evaluate the response of this species, we studied the consequences of exposing male anaesthetized SKH-1 mice to either liquid VX or to SM, the latter being used in liquid form or as saturated vapours. Long-term effects of SM burn were also evaluated. The model was then used in the companion paper (Taysse et al.(1)).

  10. Impact of the preparation conditions in the sulfur distribution of a new sulfurized porous adsorbent

    SciTech Connect

    Guijarro, M.I.; Mendioroz, S. . Inst. Catalisis y Petroleoquimica); Munoz, V. . Dept. de Quimica Inorganica y Quimica Tecnica)

    1994-02-01

    Fibrous natural silicates (sepiolite), instead of more conventional active carbon, have been sulfurized to be used as remover agents of mercury vapors from contaminated industrial waste gases. The Claus reaction, 2nH[sub 2]S + nSO[sub 2] [r arrow] (3n/x)S[sub x] + 2nH[sub 2]O, at low temperature (<400 K) and reactant concentration (2--3% molar) has been used as the sulfur source, thus being an additional way of eliminating SO[sub 2] from metallurgical processes and urban areas. The process has been carried out in a fluidized bed reactor of the semicontinuous type, and various homogeneous materials with sulfur contents in the range 3--40% S were generated. Sulfur condensation results in catalyst deactivation but, prior to its stabilization as monoclinic sulfur, also acts as cocatalyst of the reaction contributing to its overall kinetics. A study of the operating conditions, temperature, reactant concentration, and textural properties of the solid on the yield of sulfur deposited has been made. Different pore-plugging mechanisms have been applied, and from them, the influence of temperature in sulfur distribution has been concluded. In this paper, TA, N[sub 2] adsorption at 77 K, and mercury-intrusion porosimetry were used to characterize the resulting adsorbents.

  11. ADVANCED SULFUR CONTROL CONCEPTS

    SciTech Connect

    Apostolos A. Nikolopoulos; Santosh K. Gangwal; William J. McMichael; Jeffrey W. Portzer

    2003-01-01

    Conventional sulfur removal in integrated gasification combined cycle (IGCC) power plants involves numerous steps: COS (carbonyl sulfide) hydrolysis, amine scrubbing/regeneration, Claus process, and tail-gas treatment. Advanced sulfur removal in IGCC systems involves typically the use of zinc oxide-based sorbents. The sulfides sorbent is regenerated using dilute air to produce a dilute SO{sub 2} (sulfur dioxide) tail gas. Under previous contracts the highly effective first generation Direct Sulfur Recovery Process (DSRP) for catalytic reduction of this SO{sub 2} tail gas to elemental sulfur was developed. This process is currently undergoing field-testing. In this project, advanced concepts were evaluated to reduce the number of unit operations in sulfur removal and recovery. Substantial effort was directed towards developing sorbents that could be directly regenerated to elemental sulfur in an Advanced Hot Gas Process (AHGP). Development of this process has been described in detail in Appendices A-F. RTI began the development of the Single-step Sulfur Recovery Process (SSRP) to eliminate the use of sorbents and multiple reactors in sulfur removal and recovery. This process showed promising preliminary results and thus further process development of AHGP was abandoned in favor of SSRP. The SSRP is a direct Claus process that consists of injecting SO{sub 2} directly into the quenched coal gas from a coal gasifier, and reacting the H{sub 2}S-SO{sub 2} mixture over a selective catalyst to both remove and recover sulfur in a single step. The process is conducted at gasifier pressure and 125 to 160 C. The proposed commercial embodiment of the SSRP involves a liquid phase of molten sulfur with dispersed catalyst in a slurry bubble-column reactor (SBCR).

  12. The presence of Bt-transgenic oilseed rape in wild mustard populations affects plant growth.

    PubMed

    Liu, Yongbo; Stewart, C Neal; Li, Junsheng; Huang, Hai; Zhang, Xitao

    2015-12-01

    The adventitious presence of transgenic plants in wild plant populations is of ecological and regulatory concern, but the consequences of adventitious presence are not well understood. Here, we introduced Bacillus thuringiensis Cry1Ac (Bt)-transgenic oilseed rape (Bt OSR, Brassica napus) with various frequencies into wild mustard (Brassica juncea) populations. We sought to better understand the adventitious presence of this transgenic insecticidal crop in a wild-relative plant population. We assessed the factors of competition, resource availability and diamondback moth (Plutella xylostella) infestation on plant population dynamics. As expected, Bt OSR performed better than wild mustard in mixed populations under herbivore attack in habitats with enough resources, whereas wild mustard had higher fitness when Bt OSR was rarer in habitats with limited resources. Results suggest that the presence of insect-resistant transgenic plants could decrease the growth of wild mustard and Bt OSR plants and their populations, especially under high herbivore pressure.

  13. The presence of Bt-transgenic oilseed rape in wild mustard populations affects plant growth.

    PubMed

    Liu, Yongbo; Stewart, C Neal; Li, Junsheng; Huang, Hai; Zhang, Xitao

    2015-12-01

    The adventitious presence of transgenic plants in wild plant populations is of ecological and regulatory concern, but the consequences of adventitious presence are not well understood. Here, we introduced Bacillus thuringiensis Cry1Ac (Bt)-transgenic oilseed rape (Bt OSR, Brassica napus) with various frequencies into wild mustard (Brassica juncea) populations. We sought to better understand the adventitious presence of this transgenic insecticidal crop in a wild-relative plant population. We assessed the factors of competition, resource availability and diamondback moth (Plutella xylostella) infestation on plant population dynamics. As expected, Bt OSR performed better than wild mustard in mixed populations under herbivore attack in habitats with enough resources, whereas wild mustard had higher fitness when Bt OSR was rarer in habitats with limited resources. Results suggest that the presence of insect-resistant transgenic plants could decrease the growth of wild mustard and Bt OSR plants and their populations, especially under high herbivore pressure. PMID:26338267

  14. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1.

    PubMed

    Jordt, Sven-Eric; Bautista, Diana M; Chuang, Huai-Hu; McKemy, David D; Zygmunt, Peter M; Högestätt, Edward D; Meng, Ian D; Julius, David

    2004-01-15

    Wasabi, horseradish and mustard owe their pungency to isothiocyanate compounds. Topical application of mustard oil (allyl isothiocyanate) to the skin activates underlying sensory nerve endings, thereby producing pain, inflammation and robust hypersensitivity to thermal and mechanical stimuli. Despite their widespread use in both the kitchen and the laboratory, the molecular mechanism through which isothiocyanates mediate their effects remains unknown. Here we show that mustard oil depolarizes a subpopulation of primary sensory neurons that are also activated by capsaicin, the pungent ingredient in chilli peppers, and by Delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Both allyl isothiocyanate and THC mediate their excitatory effects by activating ANKTM1, a member of the TRP ion channel family recently implicated in the detection of noxious cold. These findings identify a cellular and molecular target for the pungent action of mustard oils and support an emerging role for TRP channels as ionotropic cannabinoid receptors. PMID:14712238

  15. Role of MAP kinases in regulating expression of antioxidants and inflammatory mediators in mouse keratinocytes following exposure to the half mustard, 2-chloroethyl ethyl sulfide

    SciTech Connect

    Black, Adrienne T.; Joseph, Laurie B.; Casillas, Robert P.; Heck, Diane E.; Gerecke, Donald R.; Sinko, Patrick J.; Laskin, Debra L.; Laskin, Jeffrey D.

    2010-06-15

    Dermal exposure to sulfur mustard causes inflammation and tissue injury. This is associated with changes in expression of antioxidants and eicosanoids which contribute to oxidative stress and toxicity. In the present studies we analyzed mechanisms regulating expression of these mediators using an in vitro skin construct model in which mouse keratinocytes were grown at an air-liquid interface and exposed directly to 2-chloroethyl ethyl sulfide (CEES), a model sulfur mustard vesicant. CEES (100-1000 {mu}M) was found to cause marked increases in keratinocyte protein carbonyls, a marker of oxidative stress. This was correlated with increases in expression of Cu,Zn superoxide dismutase, catalase, thioredoxin reductase and the glutathione S-transferases, GSTA1-2, GSTP1 and mGST2. CEES also upregulated several enzymes important in the synthesis of prostaglandins and leukotrienes including cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-2 (mPGES-2), prostaglandin D synthase (PGDS), 5-lipoxygenase (5-LOX), leukotriene A{sub 4} (LTA{sub 4}) hydrolase and leukotriene C{sub 4} (LTC{sub 4}) synthase. CEES readily activated keratinocyte JNK and p38 MAP kinases, signaling pathways which are known to regulate expression of antioxidants, as well as prostaglandin and leukotriene synthases. Inhibition of p38 MAP kinase suppressed CEES-induced expression of GSTA1-2, COX-2, mPGES-2, PGDS, 5-LOX, LTA{sub 4} hydrolase and LTC{sub 4} synthase, while JNK inhibition blocked PGDS and GSTP1. These data indicate that CEES modulates expression of antioxidants and enzymes producing inflammatory mediators by distinct mechanisms. Increases in antioxidants may be an adaptive process to limit tissue damage. Inhibiting the capacity of keratinocytes to generate eicosanoids may be important in limiting inflammation and protecting the skin from vesicant-induced oxidative stress and injury.

  16. Distribution of chemical warfare agent, energetics, and metals in sediments at a deep-water discarded military munitions site

    NASA Astrophysics Data System (ADS)

    Briggs, Christian; Shjegstad, Sonia M.; Silva, Jeff A. K.; Edwards, Margo H.

    2016-06-01

    There is a strong need to understand the behavior of chemical warfare agent (CWA) at underwater discarded military munitions (DMM) sites to determine the potential threat to human health or the environment, yet few studies have been conducted at sites in excess of 250 m, the depth at which most U.S. chemical munitions were disposed. As part of the Hawai'i Undersea Military Munitions Assessment (HUMMA), sediments adjacent to chemical and conventional DMM at depths of 400-650 m were sampled using human occupied vehicles (HOVs) in order to quantify the distribution of CWA, energetics, and select metals. Sites in the same general area, with no munitions within 50 m in any direction were sampled as a control. Sulfur mustard (HD) and its degradation product 1,4-dithiane were detected at each CWA DMM site, as well as a single sample with the HD degradation product 1,4-thioxane. An energetic compound was detected in sediment to a limited extent at one CWA DMM site. Metals common in munitions casings (i.e., Fe, Cu, and Pb) showed similar trends at the regional and site-wide scales, likely reflecting changes in marine sediment deposition and composition. This study shows HD and its degradation products can persist in the deep-marine environment for decades following munitions disposal.

  17. Human health risk screening due to consumption of fish contaminated with chemical warfare agents in the Baltic Sea.

    PubMed

    Sanderson, Hans; Fauser, Patrik; Thomsen, Marianne; Sørensen, Peter B

    2009-02-15

    Chemical warfare agents (CWAs) have been disposed of in various fashions over the past decades. Significant amounts of CWA, roughly 11,000ton, have been dumped in the Baltic Sea east of the island Bornholm following the disarmament of Germany after World War II. This has caused concerns over potential human and environmental health risks, and resulted in restrictions on fishing in the dumpsite area. The purpose of this paper is to assess the potential indirect human health risks due to consumption of CWA-contaminated fish from the dumpsite area east of Bornholm. Earlier studies suggest that the fish community may be at risk from CWA exposure in the Bornholm basin. Moreover, elevated frequencies of lesions on fish caught in a CWA dumpsite in the Mediterranean Sea have been observed. The fish at the Mediterranean dumpsite had elevated total arsenic (As) concentrations in their tissue, and elevated total As levels were also observed in the sediment. Elevated total sediment As concentrations have also been recorded in CWA dumpsites in the Skagerrak and the Baltic Sea. Triphenylarsine and sulfur mustard gas (Yperite) are the CWAs with the greatest indirect human health risk potential. There are recognized uncertainties concerning Yperite's and CWA-derived arsenical's fate and speciation in the environment, as well as their inherent toxicity, warranting caution and further site-specific environmental and human health risk assessments of CWAs dumped in the Bornholm basin.

  18. Advanced sulfur control concepts

    SciTech Connect

    Gangwal, S.K.; Turk, B.S.; Gupta, R.P.

    1995-11-01

    Regenerable metal oxide sorbents, such as zinc titanate, are being developed to efficiently remove hydrogen sulfide (H{sub 2}S) from coal gas in advanced power systems. Dilute air regeneration of the sorbents produces a tailgas containing a few percent sulfur dioxide (SO{sub 2}). Catalytic reduction of the SO{sub 2} to elemental sulfur with a coal gas slipstream using the Direct Sulfur Recovery Process (DSRP) is a leading first-generation technology. Currently the DSRP is undergoing field testing at gasifier sites. The objective of this study is to develop second-generation processes that produce elemental sulfur without coal gas or with limited use. Novel approaches that were evaluated to produce elemental sulfur from sulfided sorbents include (1) sulfur dioxide (SO{sub 2}) regeneration, (2) substoichiometric (partial) oxidation, (3) steam regeneration followed by H{sub 2}S oxidation, and (4) steam-air regeneration. Preliminary assessment of these approaches indicated that developing SO{sub 2} regeneration faced the fewest technical and economic problems among the four process options. Elemental sulfur is the only likely product of SO{sub 2} regeneration and the SO{sub 2} required for the regeneration can be obtained by burning a portion of the sulfur produced. Experimental efforts have thus been concentrated on SO{sub 2}-based regeneration processes. Results from laboratory investigations are presented and discussed.

  19. Sulfur isotopic data

    SciTech Connect

    Rye, R.O.

    1987-01-01

    Preliminary sulfur isotope data have been determined for samples of the Vermillion Creek coal bed and associated rocks in the Vermillion Creek basin and for samples of evaporites collected from Jurassic and Triassic formations that crop out in the nearby Uinta Mountains. The data are inconclusive, but it is likely that the sulfur in the coal was derived from the evaporites.

  20. The Phases of Sulfur.

    ERIC Educational Resources Information Center

    Birdwhistell, Kurt R.

    1995-01-01

    Presents a demonstration that illustrates the dramatic changes that sulfur undergoes upon heating to 200 degrees centigrade and then cooling to room temperature. Supplements the demonstration of the rubberlike properties of catenasulfur made by rapid cooling of the sulfur melt in ice water. (JRH)