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Sample records for 2-chloroethyl vesicants mustard

  1. 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.

  2. 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.

  3. 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.

  4. 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.

    PubMed

    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™). In both systems, administration of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide (CEES, 100-1000μM) 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-β-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.

  5. 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.

  6. 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

    PubMed Central

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

    2012-01-01

    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-FTTM). In both systems, administration of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide (CEES, 100–1000 µM) 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-β-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. PMID:21457723

  7. 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.

  8. 2,6-Dithiopurine blocks toxicity and mutagenesis in human skin cells exposed to sulfur mustard analogs, 2-chloroethyl ethyl sulfide and 2-chloroethyl methyl sulfide

    PubMed Central

    Powell, K. Leslie; Boulware, Stephen; Thames, Howard; Vasquez, Karen M.; MacLeod, Michael C.

    2010-01-01

    Sulfur mustard (bis-(2-chloroethyl)sulfide) is a well known chemical warfare agent that induces debilitating cutaneous toxicity in exposed individuals. It is also known to be carcinogenic and mutagenic due to its ability to damage DNA via electrophilic attack. We previously showed that a nucleophilic scavenger, 2,6-dithiopurine (DTP), reacts chemically with several electrophilic carcinogens, blocking DNA damage in vitro and in vivo and abolishing tumor formation in a two-stage mouse skin carcinogenesis model. To assess the potential of DTP as an antagonist of sulfur mustard, we have utilized monofunctional chemical analogs of sulfur mustard, 2-chloroethyl ethyl sulfide (CEES) and 2-chloroethyl methyl sulfide (CEMS), to induce toxicity and mutagenesis in a cell line, NCTC2544, derived from a human skin tumor. We show that DTP blocks cytotoxicity in CEMS- and CEES-treated cells when present at approximately equimolar concentration. A related thiopurine, 9-methyl-6-mercaptopurine, is similarly effective. Correlated with this, we find that DTP is transported into these cells, and that adducts between DTP and CEES are found intracellularly. Using a shuttle vector-based mutagenesis system, which allows enumeration of mutations induced in the skin cells by a blue/white colony screen, we find that DTP completely abolishes mutagenesis induced by CEMS and CEES in the human cells. PMID:20050631

  9. 2,6-Dithiopurine blocks toxicity and mutagenesis in human skin cells exposed to sulfur mustard analogues, 2-chloroethyl ethyl sulfide and 2-chloroethyl methyl sulfide.

    PubMed

    Powell, K Leslie; Boulware, Stephen; Thames, Howard; Vasquez, Karen M; MacLeod, Michael C

    2010-03-15

    Sulfur mustard (bis-(2-chloroethyl)sulfide) is a well-known chemical warfare agent that induces debilitating cutaneous toxicity in exposed individuals. It is also known to be carcinogenic and mutagenic because of its ability to damage DNA via electrophilic attack. We previously showed that a nucleophilic scavenger, 2,6-dithiopurine (DTP), reacts chemically with several electrophilic carcinogens, blocking DNA damage in vitro and in vivo and abolishing tumor formation in a two-stage mouse skin carcinogenesis model. To assess the potential of DTP as an antagonist of sulfur mustard, we have utilized monofunctional chemical analogues of sulfur mustard, 2-chloroethyl ethyl sulfide (CEES) and 2-chloroethyl methyl sulfide (CEMS), to induce toxicity and mutagenesis in a cell line, NCTC2544, derived from a human skin tumor. We show that DTP blocks cytotoxicity in CEMS- and CEES-treated cells when present at approximately equimolar concentration. A related thiopurine, 9-methyl-6-mercaptopurine, is similarly effective. Correlated with this, we find that DTP is transported into these cells and that adducts between DTP and CEES are found intracellularly. Using a shuttle vector-based mutagenesis system, which allows enumeration of mutations induced in the skin cells by a blue/white colony screen, we find that DTP completely abolishes the mutagenesis induced by CEMS and CEES in human cells.

  10. Mustard gas surrogate, 2-chloroethyl ethylsulfide (2-CEES), induces centrosome amplification and aneuploidy in human and mouse cells : 2-CEES induces centrosome amplification and chromosome instability.

    PubMed

    Bennett, Richard A; Behrens, Elizabeth; Zinn, Ashtyn; Duncheon, Christian; Lamkin, Thomas J

    2014-08-01

    Mustard gas is a simple molecule with a deadly past. First used as a chemical weapon in World War I, its simple formulation has raised concerns over its use by terrorist organizations and unstable governments. Mustard gas is a powerful vesicant and alkylating agent that causes painful blisters on epithelial surfaces and increases the incidence of cancer in those exposed. The mechanism of mustard gas toxicity and tumorigenesis is not well understood but is thought to be mediated by its ability to induce oxidative stress and DNA damage. Interestingly, several proteins that have been shown to either be targets of mustard gas or mediate mustard gas toxicity have also been shown to regulate centrosome duplication. Centrosomes are small nonmembrane-bound organelles that direct the segregation of chromosomes during mitosis through the formation of the bipolar mitotic spindle. Cells with more or less than two centrosomes during mitosis can segregate their chromosomes unequally, resulting in chromosome instability, a common phenotype of cancer cells. In our studies, we show that subtoxic levels of 2-chloroethyl ethylsulfide (2-CEES), a mustard gas analog, induce centrosome amplification and chromosome instability in cells, which may hasten the mutation rate necessary for tumorigenesis. These data may explain why those exposed to mustard gas exhibit higher incidences of cancer than unexposed individuals of the same cohort.

  11. Mustard vesicating agent-induced toxicity in the skin tissue and silibinin as a potential countermeasure.

    PubMed

    Tewari-Singh, Neera; Agarwal, Rajesh

    2016-06-01

    Exposure to the vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) causes severe skin injury with delayed blistering. Depending upon the dose and time of their exposure, edema and erythema develop into blisters, ulceration, necrosis, desquamation, and pigmentation changes, which persist weeks and even years after exposure. Research advances have generated data that have started to explain the probable mechanism of action of vesicant-induced skin toxicity; however, despite these advances, effective and targeted therapies are still deficient. This review highlights studies on two SM analogs, 2-chloroethyl ethyl sulfide (CEES) and NM, and CEES- and NM-induced skin injury mouse models that have substantially added to the knowledge on the complex pathways involved in mustard vesicating agent-induced skin injury. Furthermore, employing these mouse models, studies under the National Institutes of Health Countermeasures Against Chemical Threats program have identified the flavanone silibinin as a novel therapeutic intervention with the potential to be developed as an effective countermeasure against skin injury following exposure to mustard vesicating agents.

  12. Biosynthesis and urinary excretion of methyl sulfonium derivatives of the sulfur mustard analog, 2-chloroethyl ethyl sulfide, and other thioethers

    SciTech Connect

    Mozier, N.M.; Hoffman, J.L. )

    1990-12-01

    Thioether methyltransferase was previously shown to catalyze the S-adenosylmethionine-dependent methylation of diemthyl selenide, dimethyl telluride, and various thioethers to produce the corresponding methyl onium ions. In this paper we show that the following thioethers are also substrates for this enzyme in vitro: 2-hydroxyethyl ethyl sulfide, 2-chloroethyl ethyl sulfide, thiodiglycol, t-butyl sulfide, and isopropyl sulfide. To demonstrate thioether methylation in vivo, mice were injected with (methyl-{sup 3}H)methionine plus different thioethers, and extracts of lungs, livers, kidneys, and urine were analyzed by high-performance liquid chromatography for the presence of ({sup 3}H)methyl sulfonium ions. The following thioethers were tested, and all were found to be methylated in vivo: dimethyl sulfide, diethyl sulfide, methyl n-propyl sulfide, tetrahydrothiophene, 2-(methylthio)ethylamine, 2-hydroxyethyl ethyl sulfide, and 2-chloroethyl ethyl sulfide. This supports our hypothesis that the physiological role of thioether methyltransferase is to methylate seleno-, telluro-, and thioethers to more water-soluble onium ions suitable for urinary excretion. Conversion of the mustard gas analog, 2-chloroethyl ethyl sulfide, to the methyl sulfonium derivative represents a newly discovered mechanism for biochemical detoxification of sulfur mustards, as this conversion blocks formation of the reactive episulfonium ion that is the ultimate alkylating agent for this class of compounds.

  13. 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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:23357548

  15. Efficacy of scalp hair decontamination following exposure to vapours of sulphur mustard simulants 2-chloroethyl ethyl sulphide and methyl salicylate.

    PubMed

    Spiandore, Marie; Piram, Anne; Lacoste, Alexandre; Prevost, Philippe; Maloni, Pascal; Torre, Franck; Asia, Laurence; Josse, Denis; Doumenq, Pierre

    2017-04-01

    Chemical warfare agents are an actual threat and victims' decontamination is a main concern when mass exposure occurs. Skin decontamination with current protocols has been widely documented, as well as surface decontamination. However, considering hair ability to trap chemicals in vapour phase, we investigated hair decontamination after exposure to sulphur mustard simulants methyl salicylate and 2-chloroethyl ethyl sulphide. Four decontamination protocols were tested on hair, combining showering and emergency decontamination (use of Fuller's earth or Reactive Skin Decontamination Lotion RSDL(®)). Both simulants were recovered from hair after treatment, but contents were significantly reduced (42-85% content allowance). Showering alone was the least efficient protocol. Concerning 2-chloroethyl ethyl sulphide, protocols did not display significant differences in decontamination efficacy. For MeS, use of emergency decontaminants significantly increased showering efficacy (10-20% rise), underlining their usefulness before thorough decontamination. Our results highlighted the need to extensively decontaminate hair after chemical exposure. Residual amounts after decontamination are challenging, as their release from hair could lead to health issues.

  16. Induction of neuronal damage in guinea pig brain by intratracheal infusion of 2-chloroethyl ethyl sulfide, a mustard gas analog.

    PubMed

    Gadsden-Gray, Jessica; Mukherjee, Shyamali; Ogunkua, Olugbemiga; Das, Salil K

    2012-01-01

    Intratracheal infusion of 2-chloroethyl ethyl sulfide (CEES), a mustard gas analog and a chemical warfare agent is known to cause massive damage to lung. The purpose of this study was to determine whether intratracheal CEES infusion causes neuronal damage. Histological, immunohistochemical, and Western blot studies indicated that CEES treatment caused dose-dependent increases in blood cell aggregation, microglial cell number, microglial activation, and brain inflammation. In addition, an increased expression of α-synuclein and a decreased expression of the dopamine transporter were observed. The results indicate that intratracheal CEES infusion is associated with changes in brain morphology mediated by an increase in α-synuclein expression, leading to neurotoxicity in a guinea pig model. These changes may be mediated by oxidative stress. Furthermore, the present study indicates for the first time that intratracheal infusion of a single dose of CEES can cause neuroinflammation, which may lead to neurological disorders in later part of life.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Molecular Mechanisms of Sulfur Mustard Vesicant-Induced Cell Death: Early and Late Cell Responses

    DTIC Science & Technology

    2005-10-01

    Mechanisms of Sulfur Mustard Vesicant-Induced Cell Death : Early and late cell responses 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...It possess mutagenic, carcinogenic, cytotoxic, vesicating effects, and results in cell death . However, the biomedical mechanism of cell death induced... cell death via apoptosis: • In early stage, It induces JNK activity and then triggers apoptosis pathway. • In late stage, sulphur mustard attacks the

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

    PubMed

    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 1h 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.

  3. Rotational spectra, nuclear quadrupole hyperfine tensors, and conformational structures of the mustard gas simulent 2-chloroethyl ethyl sulfide

    NASA Astrophysics Data System (ADS)

    Tubergen, M. J.; Lesarri, A.; Suenram, R. D.; Samuels, A. C.; Jensen, J. O.; Ellzy, M. W.; Lochner, J. M.

    2005-10-01

    Rotational spectra have been recorded for both the 35Cl and 37Cl isotopic forms of two structural conformations of 2-chloroethyl ethyl sulfide (CEES). The rotational constants of the 35Cl and 37Cl isotopomers were used to identify the conformational isomers. A total of 236 hyperfine transitions have been assigned for 47 rotational transitions of the 35Cl isotope of a GGT conformer, and 146 hyperfine have been assigned for 37 rotational transitions of the 37Cl isotopomer. For the second conformer, a total of 128 (110) hyperfine and 30 (28) rotational transitions have also been assigned to the 35Cl ( 37Cl) isotopes of a TGT conformation. The extensive hyperfine splitting data, measured to high resolution with a compact Fourier transform microwave spectrometer, were used to determine both the diagonal and off-diagonal elements of the 35Cl and 37Cl nuclear quadrupole coupling tensors in the inertial tensor principal axis system. The experimental rotational constant data, as well as the 35Cl and 37Cl nuclear quadrupole coupling tensors, were compared to the results from 27 optimized ab initio (HF/6-311++G ∗∗ and MP2/6-311++G ∗∗) model structures.

  4. 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.

  5. Characterization of Nitrogen Mustard Formamidopyrimidine Adduct Formation of bis-(2-Chloroethyl)ethylamine with Calf Thymus DNA and a Human Mammary Cancer Cell Line

    PubMed Central

    Gruppi, Francesca; Hejazi, Leila; Christov, Plamen P.; Krishnamachari, Sesha; Turesky, Robert J.; Rizzo, Carmelo J.

    2015-01-01

    A robust, quantitative ultraperformance liquid chromatography ion trap multistage scanning mass spectrometric (UPLC/MS3) method was established to characterize and measure five deoxyguanosine (dG) adducts formed by reaction of the chemotherapeutic nitrogen mustard (NM) bis-(2-chloroethyl)ethylamine with calf thymus (CT) DNA. In addition to the known N7-guanine (NM-G) adduct and its crosslink (G-NM-G), the ring-opened formamidopyrimidine (FapyG) mono-adduct (NM-FapyG) and cross-links in which one (FapyG-NM-G) or both (FapyG-NM-FapyG) guanines underwent ring-opening to FapyG units were identified. Authentic standards of all adducts were synthesized and characterized by NMR and mass spectrometry. These adducts were quantified in CT DNA treated with NM (1 μM) as their deglycosylated bases. A two-stage neutral thermal hydrolysis was developed to mitigate the artifactual formation of ring-opened FapyG adducts involving hydrolysis of the cationic adduct at 37 °C, followed by hydrolysis of the FapyG adducts at 95 °C. The limit of quantification values ranged between 0.3 and 1.6 adducts per 107 DNA bases, when the equivalent of 5 μg DNA hydrolysate was assayed on column. The principal adduct formed was the G-NM-G cross-link, followed by the NM-G mono-adduct; the FapyG-NM-FapyG adduct was at the limit of detection. The NM-FapyG adducts formed in CT DNA at a level of ~20% that of the NM-G adduct. NM-FapyG has not been previously quanitified and the FapyG-NM-G and FapyG-NM-FapyG adducts have not be previously characterized. Our validated analytical method was then applied to measure DNA adduct formation in the MDA-MB-231 mammary tumor cell line exposed to NM (100 μM) for 24 h. The major adduct formed was NM-G (970 adducts per 107 bases), followed by G-NM-G (240 adducts per 107 bases) and NM-FapyG (180 adducts per 107 bases), and lastly the FapyG-NM-G cross-link adduct (6.0 adducts per 107 bases). These lesions are expected to contribute to the NM-mediated toxicity and

  6. Keratinocyte Spray Technology for the Improved Healing of Cutaneous Sulfur Mustard Injuries

    DTIC Science & Technology

    2008-07-01

    of allogeneic keratinocytes in suspension will improve epidermal wound healing of vesicating burns induced by the chemical warfare agent sulfur...improve epidermal wound healing of vesicating burns induced by the chemical warfare agent sulfur mustard (bis (2-chloroethyl) sulfide; HD). The...experiment is being conducted in two Phases. Phase I is a dose ranging study to determine the dose regimen needed to induce a deep dermal/full thickness

  7. 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.

  8. 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.

  9. Mechanisms Mediating the Vesicant Actions of Sulfur Mustard after Cutaneous Exposure

    PubMed Central

    Shakarjian, Michael P.; Heck, Diane E.; Gray, Joshua P.; Sinko, Patrick J.; Gordon, Marion K.; Casillas, Robert P.; Heindel, Ned D.; Gerecke, Donald R.; Laskin, Debra L.; Laskin, Jeffrey D.

    2010-01-01

    Sulfur mustard (SM), a chemical weapon first employed during World War I, targets the skin, eyes, and lung. It remains a significant military and civilian threat. The characteristic response of human skin to SM involves erythema of delayed onset, followed by edema with inflammatory cell infiltration, the appearance of large blisters in the affected area, and a prolonged healing period. Several in vivo and in vitro models have been established to understand the pathology and investigate the mechanism of action of this vesicating agent in the skin. SM is a bifunctional alkylating agent which reacts with many targets including lipids, proteins, and DNA, forming both intra- and intermolecular cross-links. Despite the relatively nonselective chemical reactivity of this agent, basal keratinocytes are more sensitive, and blistering involves detachment of these cells from their basement membrane adherence zones. The sequence and manner in which these cells die and detach is still unresolved. Much has been discovered over the past two decades with respect to the mechanisms of SM-induced cytotoxicity and the intracellular and extracellular targets of this vesicant. In this review, the effects of SM exposure on the skin are described, as well as potential mechanisms mediating its actions. Successful therapy for SM poisoning will depend on following new mechanistic leads to develop drugs that target one or more of its sites of action. PMID:19833738

  10. Vapor Pressure of Bis-(2-chloroethyl)ethylamine (HN1)

    DTIC Science & Technology

    2013-10-01

    Nitrogen mustard Vesicant HN1 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME...compounds for determining vapor pressures. The arrows indicate the direction of flow of the nitrogen carrier gas ...INTRODUCTION The nitrogen mustards (HN1, HN2, and HN3) are similar to sulfur mustard (HD) in their physical properties and physiological effects. All

  11. Cutaneous toxicity of 2-chloroethyl methyl sulfide in isolated perfused porcine skin.

    PubMed

    King, J R; Monteiro-Riviere, N A

    1990-06-01

    Previous research has shown the isolated perfused porcine skin flap (IPPSF) to be a novel in vitro experimental model for investigating xenobiotic percutaneous absorption. In this study, the IPPSF was used to biochemically and morphologically assess the dermatotoxicity of 2-chloroethyl methyl sulfide (CEMS), a monofunctional analog of the vesicant, sulfur mustard. IPPSFs were perfused in a recirculating perfusion system and were treated with 97% CEMS (n = 4) or served as controls (n = 4). Additional IPPSFs were perfused in a nonrecirculating perfusion system and were treated with CEMS (n = 4) or were controls (n = 4). After dosing, each IPPSF was perfused for 8 hr. Cumulative glucose utilization (GU) and lactate production/glucose utilization ratio (L/GU ratio) were used as viability parameters. The average rate of GU for CEMS was significantly lower than control (p less than 0.05) in the recirculating and nonrecirculating IPPSFs. The L/GU ratio for CEMS was not significantly different (p greater than 0.05) from control for either perfusion system. CEMS resulted in a marked increase in vascular resistance versus control in both perfusion systems. Gross vesicles and bullae formation occurred in six of the CEMS-treated IPPSFs. Light microscopy revealed subepidermal vesicle formation above the basement membrane and extensive basal cell pyknosis in all IPPSFs treated with CEMS. No macroscopic or microscopic lesions were noted in the control flaps. Transmission electron microscopy revealed separation between the lamina lucida and the lamina densa of the basal lamina, with intracellular vacuolization and mitochondrial swelling occurring in the stratum basale and stratum spinosum cells of IPPSFs treated with CEMS. These lesions are similar to those described after human exposure to sulfur mustard. Full characterization of the morphological and biochemical changes seen after topical exposure of the IPPSF to vesicants may shed light on the pathogenesis of cutaneous toxicity

  12. Free Radical Production from the Interaction of 2-Chloroethyl Vesicants (Mustard Gas) with Pyridine Nucleotide-Driven Flavoprotein Electron Transport Systems

    DTIC Science & Technology

    2009-01-01

    This mode of toxicant transformation can lead to free radical formation ( Testa , 1995) and lends weight to our earlier speculation about enzymatic...of uncoupling extramitochondrial electron transport and being reduced in place of cytochrome P450 or other terminal electron acceptors ( Testa , 1995... Reyes , E., Mason, R.P., 1979. The reduction of nitroso-spin traps in chemical and biological systems. Tetrahedron Lett. 50, 4809–4812. Kang, S.-I

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

    PubMed Central

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

    2010-01-01

    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 inter-strand crosslinks in DNA. Sulfur and nitrogen mustards are currently of interest as potential chemical threat agents for terrorists due to ease of synthesis. Sulfur mustard and monofunctional analogs (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. PMID:20050632

  14. 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.

  15. Decontamination of 2-chloroethyl ethylsulfide using titanate nanoscrolls

    NASA Astrophysics Data System (ADS)

    Kleinhammes, Alfred; Wagner, George W.; Kulkarni, Harsha; Jia, Yuanyuan; Zhang, Qi; Qin, Lu-Chang; Wu, Yue

    2005-08-01

    Titanate nanoscrolls, a recently discovered variant of TiO 2 nanocrystals, are tested as reactive sorbent for chemical warfare agent (CWA) decontamination. The large surface area of the uncapped tubules provides the desired rapid absorption of the contaminant while water molecules, intrinsic constituents of titanate nanoscrolls, provide the necessary chemistry for hydrolytic reaction. In this study the decomposition of 2-chloroethyl ethylsulfide (CEES), a simulant for the CWA mustard, was monitored using 13C NMR. The NMR spectra reveal reaction products as expected from the hydrolysis of CEES. This demonstrates that titanate nanoscrolls could potentially be employed as a decontaminant for CWAs.

  16. Comparative toxicity of mono- and bifunctional alkylating homologues of sulphur mustard in human skin keratinocytes.

    PubMed

    Sawyer, Thomas W; McNeely, Karin; Louis, Kristen; Lecavalier, Pierre; Song, Yanfeng; Villanueva, Mercy; Clewley, Robin

    2017-03-08

    Sulphur mustard (bis(2-chloroethyl) sulphide; agent H) is a vesicant chemical warfare (CW) agent whose mechanism of action is not known with any certainty and for which there are no effective antidotes. It has a pronounced latent period before signs and symptoms of poisoning appear which it shares with the nitrogen mustards, and that differentiates it from other classes of vesicant agents. Sulphur mustard, the sulphur mustard CW agents Q (1,2-bis(2-chloroethylthio) ethane) and T (1,1 bis(2-chloroethylthioethyl) ether), the H partial hydrolysis product hemi-sulphur mustard (2-chloroethyl 2-hydroxyethyl sulphide; HSM), and the commercially available 2-chloroethyl ethyl sulphide (CEES) were characterized with respect to their toxicity in first passage cultures of proliferating human skin keratinocytes, the target cell of H-induced skin vesication. Agents H and T were equitoxic and half as toxic as agent Q. Hemi-sulphur mustard and CEES were approximately six times and seventeen times, respectively less cytotoxic than H. 2-Chloroethyl ethyl sulphide was only slightly less toxic in confluent cultures compared to actively proliferating cells. In contrast, the toxicity of H, Q, T and HSM significantly decreased as the cultures became confluent, paralleling the decreasing sensitivity of skin keratinocytes to H as they leave the basement membrane of the skin. The toxicity of CEES was maximal by 24h. In contrast, the maximal toxicity of the other four agents occurred at 48h, mirroring the latent period observed for these agents in vivo. The markedly different characteristics of toxicity between CEES and the other four test compounds indicate that it is likely that different mechanisms of action are operative between them. Caution should therefore be taken when interpreting the results of studies utilizing CEES as a simulant for the mechanistic study of H, or in the elucidation of medical countermeasures against this CW agent. It is also notable that the toxicity

  17. 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

  18. Toxicity of vesicant agents scheduled for destruction by the chemical stockpile disposal program

    SciTech Connect

    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. 112 refs., 1 fig., 6 tabs.

  19. Screening hydrolysis products of sulfur mustard agents by high-performance liquid chromatography with inductively coupled plasma mass spectrometry detection.

    PubMed

    Kroening, Karolin K; Richardson, Douglas D; Afton, Scott; Caruso, Joseph A

    2009-04-01

    Sulfur mustard (HD), bis(2-chloroethyl)sulfide, is one of a class of mustard agents which are chemical warfare agents. The main chemical warfare hydrolysis degradation products of sulfur mustards are: thiodiglycol, bis(2-hydroxyethylthio)methane, 1,2-bis(2-hydroxyethylthio)ethane, 1,3-bis(2-hydroxyethylthio)propane, and 1,4-bis(2-hydroxyethylthio)butane. The aim of this study is to identify these five hydrolysis degradation products utilizing reversed-phase high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (ICP-MS) for element-specific sulfur detection using a collision/reaction cell and electrospray ionization mass spectrometry to confirm the identification. To date, this is the first study utilizing ICP-MS with (32)S element-specific detection for the analysis of vesicant chemical warfare agent degradation products.

  20. 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

  1. 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

  2. The Toxicity of Inhaled Sulphur Mustard

    DTIC Science & Technology

    2012-10-01

    BLANK UK UNCLASSIFIED Dstl/TR60201 Page 1 of 92 UK UNCLASSIFIED 1 Introduction The use of sulphur mustard (bis(2-chloroethyl) sulphide ; HD) as a... sulphide ; HD) as a chemical warfare (CW) agent remains of concern to the Armed Forces. Since its first use in World War 1 (WW1; Prentiss, 1937) HD has...Methyl- salicylate (MS); Minute Volume; Model Development; Pig; Porcine; Sulphur Mustard (HD) • Vapor; Bis(2-chloroethyl) sulphide INTRODUCTION Sulphur

  3. 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.

  4. Extraction-spectrophotometric determination of tris(2-chloroethyl)amine using phthaleins.

    PubMed

    Rozsypal, Tomas; Halamek, Emil

    2016-09-20

    Procedures for the extraction-spectrophotometric determination of tris(2-chloroethyl)amine, an alkylating agent known as a drug as well as a chemical warfare agent (nitrogen mustard HN-3), with 7 acid-base indicators of a triphenylmethane lactone type, phthaleins, were developed. Representatives of phthaleins without an oxygen bridge (thymolphthalein, o-cresolphthalein, naphtholphthalein) and with an oxygen bridge (fluorescein, 2',7'-dichlorofluorescein, eosin B and eosin Y) were used. The methods were based on the formation of ion pair complexes. Chloroform was used as a non-polar solvent for an extraction. The conditions to determine were optimized for the optimal pH of the buffer and the concentration of a phthalein as a reagent. The dependence on the reaction time in a water phase and the stoichiometry of extraction products were studied. The detection limits and the limits of the determination of separate procedures and conditional extraction constants were determined. Comparison with the spectrophotometric method of the group determination of alkyl halides and acyl halides using alkaline ethanol-water solution of thymolphthalein, the so-called T-135 agent, was conducted. While studying the selectivity, the possible interference of bis(2-chloroethyl)sulphide and 3 nitrogen mustards in the proposed procedures were verified. Copyright © 2016 John Wiley & Sons, Ltd.

  5. TNF-alpha expression patterns as potential molecular biomarker for human skin cells exposed to vesicant chemical warfare agents: sulfur mustard (HD) and Lewisite (L).

    PubMed

    Arroyo, C M; Burman, D L; Kahler, D W; Nelson, M R; Corun, C M; Guzman, J J; Smith, M A; Purcell, E D; Hackley, B E; Soni, S-D; Broomfield, C A

    2004-11-01

    Studies were conducted to examine the effect of two vesicant chemical warfare agents (VCWA), one of them an arsenical, on cytokine gene expression in normal human epidermal keratinocyte (NHEK) cells. We tested 2,2'-dichlorethylsulfide (sulfur mustard, military designation HD) and 2,chlorovinyldichloroarsine (Lewisite, military designation L), which have significant differences in their chemical, physical, and toxicological properties. Human tumor necrosis factor-alpha (hTNF-alpha) cytokine was detected by using the enzyme-linked immunosorbent assay, a protein multiplex immunoassay, Luminex100, and reverse transcription-polymerase chain reaction (RT-PCR). The messenger RNA expression of hTNF-alpha was determined to provide a semi-quantitative analysis. HD-stimulated NHEK induced secretion of hTNF-alpha in a dose-dependent manner. Dose response effect of Lewisite decreased hTNF-alpha levels. Time-response data indicated that the maximum response for HD occurred at 24 h with an associated cytotoxic concentration of 10(-4) mol/L. NHEK cells stimulated with 10(-4) mol/L HD for 24 h at 37 degrees C increased detectable levels of hTNF-alpha from 5 to 28 ng/ml at an index of cell viability between 85 to 93% as detected by Luminex100. Our results indicated that the increased levels of hTNF-alpha by HD are dependent on the primary cultures, cell densities, and chemical properties of the stimulation. Lewisite under the same conditions as HD caused a reduction of hTNF-alpha from control levels of 1.5 ng/ml to 0.3 ng/ml after stimulation (10(-4) mol/L), with an index of cell viability of reverse similar 34%. We analyzed the transcriptional of hTNF-alpha gene and found that HD (10(-6) to 10(-4) mol/L) activates hTNF-alpha gene in cultured NHEK and that L at 10(-6) to 10(-4) mol/L markedly reduces hTNF-alpha gene. We conclude that the pro-inflammatory mediator, hTNF-alpha, could be a potential biomarker for differentiating between exposure of HD or L.

  6. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25791923

  8. 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.

  9. Quantification by gas chromatography of N,N'-di-(2-chloroethyl)-phosphorodiamidic acid in the plasma of patients receiving isophosphamide.

    PubMed

    Bryant, B M; Jarman, M; Baker, M H; Smith, I E; Smyth, J F

    1980-12-01

    A sensitive method, based on gas chromatography using a phosphorus-specific flame photometric detector, has been developed for quantifying N,N'-di-(2-chloroethyl)phosphorodiamidic acid (isophosphoramide mustard), the putative active metabolite of isophosphamide, in human plasma. Phosphoramide mustard was used as internal standard, and the two compounds were converted into separable trimethyl derivatives by reaction with methyliodide in the presence of silver oxide. The chemistry of the derivatization process has been elucidated using gas chromatography-electron impact mass spectrometry and selected ion monitoring. Levels of isophosphamide and of isophosphoramide mustard were measured in the plasma of patients receiving isophosphamide (2 g/sq m). Peak plasma levels of isophosphoramide mustard of 18.6 to 30.3 nmol/ml occurred at 2 to 4 hr, and levels were still appreciable (6.3 to 11.3 nmol/ml) at 24 hr.

  10. Studies on the Pathogenesis of BIS (2-Chloroethyl) Sulfide (HD) Induced Vesication in Porcine Skin

    DTIC Science & Technology

    1993-05-13

    159-169. Karger. Basel, 1985. 16. Bowman KF, Monteiro-Riviere NA, Riviere JE. Am. I. Vet. Res. 52:75-82. 1991. 17. Yaoita H, Gullino M , Katz SI. J...7. TEM showing nuclear envelope separation in a dark basa t( HD. x5,300 Figure 8. TEM showing coalescing of mitochondria ( M ) in the basale cell layer...Kemppainen, WG Reifenrath). pp. 175-189, CRC Press, 1990. 8. Monteiro-Riviere NA. Fundam. A2, l . Toxicol. 15:174-185, 1990. 9. Riviere JE, Bowman KF

  11. 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

  12. High-throughput sample preparation and simultaneous column regeneration liquid chromatography-tandem mass spectrometry method for determination of nitrogen mustard metabolites in human urine.

    PubMed

    Reddy, Muntha K; Mills, Grier; Nixon, Christopher; Wyatt, Shane A; Croley, Timothy R

    2011-08-15

    Nitrogen mustards (NMs) are known to have DNA alkylation and strong vesicant properties. Their availability to terrorist organizations makes them a potential choice for chemical attacks on civilian populations. After an exposure, it is difficult to measure NMs directly because of their rapid metabolism in the human body. Therefore to determine an individual's level of exposure to NMs, it is necessary to analyze for NM metabolites being excreted by the body. The metabolites of NMs are generated by a hydrolysis reaction, and are easily detectable by liquid chromatography tandem mass spectrometry (LC-MS/MS). This work is focused on the development of a high-throughput assay for the quantitation of N-ethyldiethanolamine (EDEA) and N-methyldiethanolamine (MDEA) metabolites of bis (2-chloroethyl) ethylethanamine (HN1) and bis (2-chloroethyl) methylethanamine (HN2), respectively. The method uses automated 96-well plate sample preparation of human urine samples and a 2-position 10-port switching valve to allow for simultaneous regeneration of the liquid chromatography (LC) columns. Using this method, over 18 h was saved through the reduction of sample preparation and analysis time when compared to a conventional method for 96 samples. The validated method provided excellent accuracy for both EDEA (100.9%) and MDEA (100.6%) with precision better than 5.27% for each analyte.

  13. Photocatalytic degradation of 2-phenethyl-2-chloroethyl sulfide in liquid and gas phases.

    PubMed

    Vorontsov, Alexandre V; Panchenko, Alexander A; Savinov, Evgueni N; Lion, Claude; Smirniotis, Panagiotis G

    2002-12-01

    This work explores the ability of photocatalysis to decontaminate water and air from chemical warfare agent mustard using its simulant 2-phenethyl 2-chloroethyl sulfide (PECES). PECES like mustard slowly dissolves in water with hydrolysis, forming 2-phenethyl 2-hydroxyethyl sulfide (PEHES). Irradiation of TiO2 suspension containing PECES with the unfiltered light of a mercury lamp (lambda > or = 254 nm) decomposed all PECES mostly via photolysis. Reaction under filtered light (lambda > 300 nm) proceeds mainly photocatalytically and requires longer time. Sulfur from starting PECES is completely transformed into sulfuric acid at the end of the reaction. Detected volatile, nonvolatile, surface products, and the suggested scheme of degradation are reported. The main volatile products are styrene and benzaldehyde, nonvolatile--hydroxylated PEHES, surface--2-phenethyl disulfide. Photolysis of PECES produced the same set of volatile products as photocatalysis. Photocatalytic degradation of gaseous PECES in air results in its mineralization but is accompanied by TiO2 deactivation. The highest rate of mineralization with minimum deactivation was observed at about room temperature and a water concentration of 27,500 ppm. No gaseous products except CO2 were detected. The main extracted surface product was styrene. It was concluded that PECES photocatalytic degradation proceeds mainly via C-S bond cleavage and further oxidation of the products. Hydrolysis of the C-S bond was detected only in gas-phase photocatalytic degradation. The quantum efficiency of gas-phase degradation (0.28%) was much higher than that of liquid-phase degradation (0.008%). The results demonstrate the ability of photocatalysis to decontaminate an aqueous and especially an air environment

  14. Role of reactive nitrogen species generated via inducible nitric oxide synthase in vesicant-induced lung injury, inflammation and altered lung functioning

    SciTech Connect

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

    2012-05-15

    Pulmonary toxicity induced by sulfur mustard and related vesicants is associated with oxidative stress. In the present studies we analyzed the role of reactive nitrogen species (RNS) generated via inducible nitric oxide synthase (iNOS) in lung injury and inflammation induced by vesicants using 2-chloroethyl ethyl sulfide (CEES) as a model. C57Bl/6 (WT) and iNOS −/− mice were sacrificed 3 days or 14 days following intratracheal administration of CEES (6 mg/kg) or control. CEES intoxication resulted in transient (3 days) increases in bronchoalveolar lavage (BAL) cell and protein content in WT, but not iNOS −/− mice. This correlated with expression of Ym1, a marker of oxidative stress in alveolar macrophages and epithelial cells. In contrast, in iNOS −/− mice, Ym1 was only observed 14 days post-exposure in enlarged alveolar macrophages, suggesting that they are alternatively activated. This is supported by findings that lung tumor necrosis factor and lipocalin Lcn2 expression, mediators involved in tissue repair were also upregulated at this time in iNOS −/− mice. Conversely, CEES-induced increases in the proinflammatory genes, monocyte chemotactic protein-1 and cyclooxygenase-2, were abrogated in iNOS −/− mice. In WT mice, CEES treatment also resulted in increases in total lung resistance and decreases in compliance in response to methacholine, effects blunted by loss of iNOS. These data demonstrate that RNS, generated via iNOS play a role in the pathogenic responses to CEES, augmenting oxidative stress and inflammation and suppressing tissue repair. Elucidating inflammatory mechanisms mediating vesicant-induced lung injury is key to the development of therapeutics to treat mustard poisoning. -- Highlights: ► Lung injury, inflammation and oxidative stress are induced by the model vesicant CEES ► RNS generated via iNOS are important in the CEES-induced pulmonary toxicity ► iNOS −/− mice are protected from CEES-induced lung toxicity and

  15. Myeloperoxidase deficiency attenuates nitrogen mustard-induced skin injuries

    PubMed Central

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

    2014-01-01

    The pathologic mechanisms of skin injuries, following the acute inflammatory response induced by vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) exposure, are poorly understood. Neutrophils which accumulate at the site of injury, abundantly express myeloperoxidase (MPO), a heme protein that is implicated in oxidant-related antimicrobial and cytotoxic responses. Our previous studies have shown that exposure to SM analog 2-chloroethyl ethyl sulfide (CEES) or NM results in an inflammatory response including increased neutrophilic infiltration and MPO activity. To further define the role of neutrophil-derived MPO in NM-induced skin injury, here we used a genetic approach and examined the effect of NM exposure (12 h and 24 h) on previously established injury endpoints in C57BL/6J wild type (WT) and B6.129X1-MPOtm1Lus/J mice (MPO KO), homozygous null for MPO gene. NM exposure caused a significant increase in skin bi-fold thickness, epidermal thickness, microvesication, DNA damage and apoptosis in WT mice compared to MPO KO mice. MPO KO mice showed relatively insignificant effect. Similarly, NM-induced increases in the expression of inflammatory and proteolytic mediators, including COX-2, iNOS and MMP-9 in WT mice, while having a significantly lower effect in MPO KO mice. Collectively, these results show that MPO, which generates microbicidal oxidants, plays an important role in NM-induced skin injuries. This suggests the development of mechanism-based treatments against NM- and SM-induced skin injuries that inhibit MPO activity and attenuate MPO-derived oxidants. PMID:24631667

  16. Protection against 2-chloroethyl ethyl sulfide (CEES) - induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway

    SciTech Connect

    Abel, Erika L.; Bubel, Jennifer D.; Simper, Melissa S.; Powell, Leslie; McClellan, S. Alex; Andreeff, Michael; MacLeod, Michael C.; DiGiovanni, John

    2011-09-01

    Sulfur mustard (SM or mustard gas) was first used as a chemical warfare agent almost 100 years ago. Due to its toxic effects on the eyes, lungs, and skin, and the relative ease with which it may be synthesized, mustard gas remains a potential chemical threat to the present day. SM exposed skin develops fluid filled bullae resulting from potent cytotoxicity of cells lining the basement membrane of the epidermis. Currently, there are no antidotes for SM exposure; therefore, chemopreventive measures for first responders following an SM attack are needed. Glutathione (GSH) is known to have a protective effect against SM toxicity, and detoxification of SM is believed to occur, in part, via GSH conjugation. Therefore, we screened 6 potential chemopreventive agents for ability to induce GSH synthesis and protect cultured human keratinocytes against the SM analog, 2-chloroethyl ethyl sulfide (CEES). Using NCTC2544 human keratinocytes, we found that both sulforaphane and methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) stimulated nuclear localization of Nrf2 and induced expression of the GSH synthesis gene, GCLM. Additionally, we found that treatment with CDDO-Me elevated reduced GSH content of NCTC2544 cells and preserved their viability by {approx} 3-fold following exposure to CEES. Our data also suggested that CDDO-Me may act additively with 2,6-dithiopurine (DTP), a nucleophilic scavenging agent, to increase the viability of keratinocytes exposed to CEES. These results suggest that CDDO-Me is a promising chemopreventive agent for SM toxicity in the skin. - Highlights: > CDDO-Me treatment increased intracellular GSH in human keratinocytes. > CDDO-Me increased cell viability following exposure to the half-mustard, CEES. > The cytoprotective effect of CDDO-Me was likely due to scavenging with endogenous GSH.

  17. Modified immunoslotblot assay to detect hemi and sulfur mustard DNA adducts.

    PubMed

    Kehe, Kai; Schrettl, Verena; Thiermann, Horst; Steinritz, Dirk

    2013-12-05

    Sulfur mustard (SM) is an old chemical warfare agent causing blisters (vesicant). Skin toxicity is thought to be partly caused by SM induced DNA damage. SM and the hemi mustard 2-chloroethyl ethyl sulfide (CEES) are bi- and monofunctional DNA alkylating agents, respectively. Both chemicals react especially with N7 guanine. The most abundant adducts are 7-hydroxyethylthioethylguanine for SM (61%) and 7-ethyl thioethylguanine for CEES. Thus, DNA alkylation should serve as a biomarker of SM exposure. A specific monoclonal antibody (2F8) was previously developed to detect SM and CEES adducts at N7 position by means of immunoslotblot (ISB) technique (van der Schans et al. (2004) [16]). Nitrogen mustards (HN-1, HN-2, HN-3) are alkylating agents with structural similarities, which can form DNA adducts with N7 guanine. The aim of the presented work was to modify the van der Schans protocol for use in a field laboratory and to test the cross reactivity of the 2F8 antibody against nitrogen mustards. Briefly, human keratinocytes were exposed to SM and CEES (0-300μM, 60min) or HN-1, HN-2, HN-3 (120min). After exposure, cells were scraped and DNA was isolated and normalized. 1μg DNA was transferred to a nitrocellulose membrane using a slotblot technique. After incubation with 2F8 antibody, the DNA adducts were visualized with chromogen staining (3,3'-diaminobenzidine (DAB), SeramunGrün). Blots were photographed and signal intensity was quantified. In general, DAB was superior to SeramunGrün stain. A staining was seen from 30nM to 300μM of SM or CEES, respectively. However, statistically significant DNA adducts were detected after CEES and SM exposure above 30μM which is below the vesicant threshold. No signal was observed after HN-1, HN-2, HN-3 exposure. The total hands-on time to complete the assay was about 36h. Further studies are necessary to validate SM or CEES exposure in blister roofs of exposed patients.

  18. Degradation of the Blister Agent BIS(2-Chloroethyl) Sulfide and Simulant 2-Chloroethyl Phenyl Sulfide on Concrete

    DTIC Science & Technology

    2007-04-01

    Formation of H-2TG from sulfur mustardl’’ 11 Brevett et al. showed that sulfur mustard on wet sand degraded to form TDG, H- 2TG and CH-TG.15 Brevett et...product, CEVS, and the cyclic ether 1,4- 22oxathiane. Wagner et al. demonstrated that on wet CSC at 30 ’C the products CH and TDG were produced in...Figure 7. First-order kinetic plot for HD* loss on ambient concrete C03. 3.3 Aged Concrete with Added Water. The initial spectrum of the CEPS* on wet

  19. Development of an antibody that binds sulfur mustard. (Reannouncement with new availability information)

    SciTech Connect

    Lieske, C.N.; Klopcic, R.S.; Gross, C.L.; Clark, J.H.; Dolzine, T.W.

    1992-12-31

    An antibody that binds bis(2-chloroethyl)sulfide (sulfur mustard) was developed. The immunizing antigen was prepared from the hapten 4-(2-chloroethyl)benzoic acid covalently bound to keyhole limpet hemocyanin (KLH). The antibody was monitored by a solid phase enzyme-linked immunosorbent assay (ELISA). The test antigen consisted of a second hapten, 8-chlorocaprylic acid, covalently bound to bovine serum albumin (BSA). The test antigen was absorbed to the wells of 96-well plates. The immunizing and test antigens contain a common chloroethyl moiety. Thiodiglycol, the principal hydrolysis product of sulfur mustard, does not react with the antibody. This antibody, because of its specificity, has the potential to be a valuable tool for mustard research and forensic detection. Sulfur mustard, sulfur mustard antibody, antibody inhibition haptens.

  20. Reactive removal of 2-chloroethyl ethyl sulfide vapors under visible light irradiation by cerium oxide modified highly porous zirconium (hydr) oxide

    NASA Astrophysics Data System (ADS)

    Mitchell, Joshua K.; Arcibar-Orozco, Javier A.; Bandosz, Teresa J.

    2016-12-01

    Highly porous cerium oxide modified Zr(OH)4 samples were synthesized using a simple one stage urea precipitation method. The amorphicity level of zirconium hydroxide did not change upon addition of cerium oxide particles. A unique aspect of the cerium oxide-modified materials is the presence of both the oxide (CeO2) and hydroxide (Zr(OH)4) phases resulting in a unique microporous structure of the final material. Extensive characterization using various chemical and physical methods revealed significant differences in the surface features. All synthesized materials were microporous and small additions of cerium oxide affected the surface chemistry. These samples were found as effective catalysts for a decontamination of mustard gas surrogate, 2-chloroethyl ethyl sulfide (CEES). Cerium oxide addition significantly decreased the band gap of zirconium hydroxide. Ethyl vinyl sulfide and 1,2-bis (Ethyl thio) ethane were identified as surface reaction products.

  1. Optical "Turn off" based selective detection and concomitant degradation of 2-chloroethyl ethyl sulfide (CEES) via Mg-porphyrazine complex immobilized on glass.

    PubMed

    Neelam; Singh, Vikram; Gupta, Tarkeshwar

    2014-02-17

    Covalently assembled monolayers (CAMs) of Mg-porphyrazine complex on glass and silicon substrates were fabricated and employed as "Turn off" sensor for ppm level detection and degradation of a sulfur mustard analogue: 2-chloroethyl ethyl sulfide (CEES). The detection process was read-out optically via an off-the-shelf UV/Vis spectrophotometer in transmission mode. Monolayer based sensor system was shown to be quite robust and stable, sufficiently accurate and reversible under given experimental conditions. Notably, the sensor system exhibited marked selectivity for CEES when exposed exclusively or in mix to different potent analytes. Moreover, action of KMnO4 on monolayer-CEES complex lead to CEES degradation and resetting of the sensor to its native state for reuse.

  2. 40 CFR 721.10243 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis(2-chloroethyl) ester.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphonic acid, P- ethyl]-, bis(2... Specific Chemical Substances § 721.10243 Phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester. (a... phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester (PMN P-09-193; CAS No. 55088-28-3) is subject...

  3. 40 CFR 721.10243 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis(2-chloroethyl) ester.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphonic acid, P- ethyl]-, bis(2... Specific Chemical Substances § 721.10243 Phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester. (a... phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester (PMN P-09-193; CAS No. 55088-28-3) is subject...

  4. 40 CFR 721.10243 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis(2-chloroethyl) ester.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphonic acid, P- ethyl]-, bis(2... Specific Chemical Substances § 721.10243 Phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester. (a... phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester (PMN P-09-193; CAS No. 55088-28-3) is subject...

  5. Photocatalytic oxidation of gaseous 2-chloroethyl ethyl sulfide over TiO2.

    PubMed

    Martyanov, Igor N; Klabunde, Kenneth J

    2003-08-01

    Photocatalytic oxidation of gaseous 2-chloroethyl ethyl sulfide (2-CEES, ClCH2CH2SCH2CH3) over TiO2 illuminated with UV light and maintained at 25 or 80 degrees C in air has been investigated. 2-CEES was found to suffer progressive oxidation to yield ethylene (CH2CH2), chloroethylene (ClCHCH2), ethanol (CH3CH2OH), acetaldehyde (CH3C(O)H), chloroacetaldehyde (ClCH2C(O)H), diethyl disulfide (CH3CH2S2CH2CH3), 2-chloroethyl ethyl disulfide (ClCH2CH2S2CH2CH3), and bis(2-chloroethyl) disulfide (ClCH2CH2S2CH2CH2Cl) as the main primary intermediates, and water (H2O), carbon dioxide (CO2), sulfur dioxide (SO2), surface sulfate ions (SO4(2-)), and hydrogen chloride (HCl) as the final products. Trace concentrations of gaseous 2-chloroethanol (ClCH2CH2OH), ethanesulfonyl chloride (CH3CH2SO2Cl), ethyl thioacetate (CH3CH2SC(O)CH3), and considerable amounts of acetic acid (CH3C(O)OH), crotonaldehyde (CH3CHCHC(O)H), methyl acetate (CH3C(O)OCH3), and methyl formate (CH3OC(O)H) were also detected in the gas phase during the photooxidation conducted at 80 degrees C. Increase in temperature from 25 to 80 degrees C accelerates formation of gaseous ethanol, acetaldehyde, chloroacetaldehyde, diethyl disulfide, 2-chloroethyl ethyl disulfide, and bis(2-chloroethyl) disulfide but suppresses ethylene and chloroethylene production at initial stages of the process. Some aspects of the possible reaction mechanism leading to this wide array of intermediates and final products are discussed.

  6. Mass spectrometric identification and gas-liquid chromatographic determination of 2-chloroethyl esters of fatty acids in spices and foods.

    PubMed

    Heikes, D L; Griffitt, K R

    1979-07-01

    The 2-chloroethyl esters of 5 fatty acids have been identified in spice and food samples by gas-liquid chromatography-mass spectrometry (GLC/MS). Twenty-four spice samples were analyzed for the 2-chloroethyl esters of fatty acids by AOAC official multiple residues pesticide procedure using GLC with microcoulometric detection. The esters of capric, lauric, myristic, palmitic, and linoleic acids have been identified at levels up to 1400 ppm. 2-Chloroethyl linoleate was the most abundant ester in all samples. Several foods analyzed by the same procedures showed levels of 2-chloroethyl linoleate as high as 35 ppm. Recoveries from fortified samples ranged from 84 to 98% for the various esters. A method using an acid-catalyzed esterification reaction was developed to rapidly determine the fatty acid content of these spices. GLC analysis with microcoulometric detection was used. Recoveries from fortified samples ranged from 92 to 110%. After 2 spice samples found to be free of 2-chloroethyl esters were fumigated with ethylene oxide, the level of 2-chloroethyl linoleate reached 77 ppm. All levels of 2-chloroethyl esters were confirmed by GLC/MS.

  7. Doxycycline loaded poly(ethylene glycol) hydrogels for healing vesicant-induced ocular wounds

    PubMed Central

    Anumolu, SivaNaga S; DeSantis, Andrea S; Menjoge, Anupa R; Hahn, Rita A; Beloni, John A; Gordon, Marion K; Sinko, Patrick J

    2015-01-01

    Half mustard (CEES) and nitrogen mustard (NM) are commonly used surrogates and vesicant analogs of the chemical warfare agent sulfur mustard. In the current study, in situ forming poly(ethylene glycol) (PEG)-based doxycycline hydrogels are developed and evaluated for their wound healing efficacy in CEES and NM exposed rabbit corneas in organ culture. The hydrogels, characterized by UV-Vis spectrophotometry, rheometry, and swelling kinetics, showed that the hydrogels are optically transparent, have good mechanical strength and a relatively low degree of swelling (<7%). In vitro doxycycline release from the hydrogel disks (0.25% w/v) was found to be biphasic with release half times of ~12 and 72 h, respectively, with 80–100% released over a 7-day period. Permeation of doxycycline through vesicant wounded corneas was found to be 2.5 to 3.4 fold higher than non-wounded corneas. Histology and immunofluorescence studies showed a significant reduction of matrix metalloproteinase-9 (MMP-9) and improved healing of vesicant exposed corneas by doxycycline hydrogels compared to a similar dose of doxycycline delivered in phosphate buffered saline (PBS, pH 7.4). In conclusion, the current studies demonstrate that the doxycycline-PEG hydrogels accelerate corneal wound healing after vesicant injury offering a therapeutic option for ocular mustard injuries. PMID:19853296

  8. Doxycycline loaded poly(ethylene glycol) hydrogels for healing vesicant-induced ocular wounds.

    PubMed

    Anumolu, SivaNaga S; DeSantis, Andrea S; Menjoge, Anupa R; Hahn, Rita A; Beloni, John A; Gordon, Marion K; Sinko, Patrick J

    2010-02-01

    Half mustard (CEES) and nitrogen mustard (NM) are commonly used surrogates and vesicant analogs of the chemical warfare agent sulfur mustard. In the current study, in situ forming poly(ethylene glycol) (PEG)-based doxycycline hydrogels are developed and evaluated for their wound healing efficacy in CEES and NM-exposed rabbit corneas in organ culture. The hydrogels, characterized by UV-Vis spectrophotometry, rheometry, and swelling kinetics, showed that the hydrogels are optically transparent, have good mechanical strength and a relatively low degree of swelling (<7%). In vitro doxycycline release from the hydrogel disks (0.25% w/v) was found to be biphasic with release half times of approximately 12 and 72h, respectively, with 80-100% released over a 7-day period. Permeation of doxycycline through vesicant wounded corneas was found to be 2.5 to 3.4 fold higher than non-wounded corneas. Histology and immunofluorescence studies showed a significant reduction of matrix metalloproteinase-9 (MMP-9) and improved healing of vesicant-exposed corneas by doxycycline hydrogels compared to a similar dose of doxycycline delivered in phosphate buffered saline (PBS, pH 7.4). In conclusion, the current studies demonstrate that the doxycycline-PEG hydrogels accelerate corneal wound healing after vesicant injury offering a therapeutic option for ocular mustard injuries.

  9. 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.

  10. Mustard: a potential agent of chemical warfare and terrorism.

    PubMed

    Saladi, R N; Smith, E; Persaud, A N

    2006-01-01

    As one of the most important vesicant agents, the destructive properties of mustards on the skin, eyes and respiratory system, combined with a lack of antidote, makes them effective weapons. Such weapons are inexpensive, easily obtainable and frequently stockpiled. Sulphur mustard (mustard gas) has been used as a chemical warfare agent in at least 10 conflicts. In this article, the use of mustard as a potential agent of chemical warfare and terrorism is outlined. The dose-dependent effects of acute sulphur mustard exposure on the skin, eyes, and respiratory system are described, as well as the possible extents of injuries, the mechanisms of action and the long-term complications. Prevention and management of mustard exposure are briefly discussed. The need for awareness and preparedness in the dermatological community regarding mustard exposure is emphasized.

  11. Mustard gas or sulfur mustard: an old chemical agent as a new terrorist threat.

    PubMed

    Wattana, Monica; Bey, Tareg

    2009-01-01

    Sulfur mustard is a member of the vesicant class of chemical warfare agents that causes blistering to the skin and mucous membranes. There is no specific antidote, and treatment consists of systematically alleviating symptoms. Historically, sulfur mustard was used extensively in inter-governmental conflicts within the trenches of Belgium and France during World War I and during the Iran-Iraq conflict. Longitudinal studies of exposed victims show that sulfur mustard causes long-term effects leading to high morbidity. Given that only a small amount of sulfur mustard is necessary to potentially cause an enormous number of casualties, disaster-planning protocol necessitates the education and training of first-line healthcare responders in the recognition, decontamination, triage, and treatment of sulfur mustard-exposed victims in a large-scale scenario.

  12. Mustard Gas Surrogate, 2-Chloroethyl Ethylsulfide (2-CEES), Induces Centrosome Amplification and Aneuploidy in Human and Mouse Cells

    DTIC Science & Technology

    2014-03-01

    permeabilization    with 1%  Nonidet   P ‐ 40  (Fisher) in PBS for 10 minutes at room temperature.  Cells were blocked   in 15% NGS (Life Technologies) for 1 hour and...in each of at least 100 cells.  p  < 0.05  comparing  treated to untreated cells with more  than 2 centrosomes per cell, except for 50 μM,  which was...00537‐1 [pii]  10.1016/j.freeradbiomed.2009.09.011  Pihan GA, Purohit A, Wallace J, Knecht H, Woda B, Quesenberry  P , Doxsey SJ. 1998. Centrosome

  13. A choline oxidase amperometric bioassay for the detection of mustard agents based on screen-printed electrodes modified with Prussian Blue nanoparticles.

    PubMed

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

    2015-02-13

    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.

  14. Effect of O6-methylguanine on DNA interstrand cross-link formation by chloroethylnitrosoureas and 2-chloroethyl(methylsulfonyl)methanesulfonate.

    PubMed

    Dolan, M E; Pegg, A E; Hora, N K; Erickson, L C

    1988-07-01

    Exposure of HT29 cells in culture to O6-methylguanine is known to result in a reduction in O6-alkylguanine-DNA alkyltransferase (AGT) activity and an enhancement of sensitivity to the cytotoxic effects of chloroethylating agents. Since cytotoxicity of these agents may be mediated by the formation of interstrand cross-links, alkaline elution analysis was performed on HT29 cells treated with 1-(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and Clomesone [2-chloroethyl(methylsulfonyl)methanesulfonate] in the presence or absence of O6-methylguanine pretreatment to determine if the enhanced toxicity was due to an increase in the number of cross-links formed. Interstrand cross-linking by 1-(2-chloroethyl)-1-nitrosourea or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was increased by pretreatment with 0.4 mM O6-methylguanine for 24 h. Cross-linking by Clomesone was observed only in cells exposed to 0.4 mM O6-methylguanine for 24 h prior to administration of the drug and for 12 h after administration, suggesting that the resynthesis of the AGT may prevent the cross-linking by Clomesone. Complete recovery of AGT activity after reduction to 20 to 30% of the basal level upon treatment with 0.4 mM O6-methylguanine required between 8 h and 15 h in both HT29 cells and in Raji cells which were also sensitized to 1-(2-chloro-ethyl)-3-cyclohexyl-1-nitrosourea by exposure to O6-methylguanine. These data suggest that the enhancement of chloroethylnitrosourea toxicity after treatment with O6-methylguanine may be related to an increase in the number of DNA cross-links and that the relatively rapid rate of AGT recovery plays a role in prevention of cross-links resulting from Clomesone.

  15. Surface catalyzed Fenton treatment of bis(2-chloroethyl) ether and bis(2-chloroethoxy) methane.

    PubMed

    Mutuc, Maria D M; Love, Nancy G; Vikesland, Peter J

    2008-02-01

    This study examined the feasibility of using surface catalyzed Fenton treatment to remediate soil and groundwater contaminated by the chlorinated ethers, bis(2-chloroethyl) ether (BCEE) and bis(2-chloroethoxy) methane (BCEM). Parameters that affect the contaminant loss rate such as porewater pH, hydrogen peroxide concentration, and solid/water ratio were systematically evaluated. Batch reactors were set-up utilizing either contaminated or uncontaminated soil, obtained from an industrial site in Moss Point, MS, that was mixed with synthetic groundwater containing the contaminants of interest. The results show an increase in contaminant reduction with a decrease in pH, an increase in hydrogen peroxide concentration, or an increase in the solid/water ratio. For a similar set of conditions, contaminant reduction was greater for systems utilizing contaminated soil as compared to the systems containing uncontaminated soil. In addition, specific oxygen uptake rates (SOURs) were measured for biomass, collected from an activated sludge plant, exposed to different dilutions of untreated and surface catalyzed Fenton treated water to evaluate whether residual BCEE, BCEM, and their co-contaminants as well as their oxidation by-products were potentially inhibitory or can potentially serve as a substrate for the biomass. The measured SOURs show that the surface catalyzed Fenton treatment enhanced the biodegradability of the contaminated groundwater and served as a substrate for the biomass.

  16. 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.

  17. The chemiluminescence determination of 2-chloroethyl ethyl sulfide using luminol-AgNO3-silver nanoparticles system.

    PubMed

    Maddah, Bozorgmehr; Shamsi, Javad; Barsang, Mehran Jam; Rahimi-Nasrabadi, Mehdi

    2015-05-05

    A highly sensitive chemiluminescence (CL) method for the determination of 2-chloroethyl ethyl sulfide (2-CEES) was presented. It was found that 2-chloroethyl ethyl sulfide (2-CEES) could inhibit the CL of the luminol-AgNO3 system in the presence of silver nanoparticles in alkaline solution, which made it applicable for determination of 2-CEES. The presented method is simple, convenient, rapid and sensitive. Under the optimized conditions, the calibration curve was linear in the range of 0.0001-1ngmL(-1), with the correlation coefficient of 0.992; while the limit of detection (LOD), based on signal-to-noise ratio (S/N) of 3, was 6×10(-6)ngmL(-1). Also, the relative standard deviation (RSD, n=5) for determination of 2-CEES (0.50ngmL(-1)) was 3.1%. The method was successfully applied for the determination of 2-CEES in environmental aqueous samples.

  18. 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.

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

    PubMed Central

    Qui, Min; Paromov, Victor M; Yang, Hongsong; Smith, Milton; Stone, William L

    2006-01-01

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

  20. Infrared Spectra of the 2-CHLOROETHYL Radical in Solid Para-Hydrogen

    NASA Astrophysics Data System (ADS)

    Amicangelo, Jay C.; Bahou, Mohammed; Golec, Barbara; Lee, Yuan-Pern

    2011-06-01

    The reaction of chlorine atoms with ethylene and two of its deuterium isotopomers in solid para-hydrogen (p-H2) matrices at 3 K has been studied using infrared spectroscopy. Irradiation at 365 nm of a co-deposited mixture of Cl2, C2H4, and p-H2 at 3 K produces a series of new lines in the infrared spectrum. Several of the new lines are readily assigned to the gauche and trans conformers of 1,2-dichloroethane (CH2ClCH2Cl) resulting from the addition of two Cl atoms to C2H4. Of the remaining lines, a strong line at 664 Cm-1 and three weaker lines at 562, 1070, and 1228 Cm-1 are concluded to be due to a single carrier based on their behavior upon subsequent annealing to 4.5 K and irradiation at 254 and 214 nm. When the positions and intensities of these lines are compared to the MP2/aug-cc-pVDZ predicted vibrational spectra of the possible species that could result from the addition and abstraction reactions of one Cl atom with C2H4, the best agreement is found with the 2-chloroethyl radical (CdotCH2CH2Cl). In order to confirm this assignment, isotopic experiments were performed with C2D4 and t-C2H2D2 and the corresponding infrared bands due to the deuterium isotopomers of this radical (CdotCD2CD2Cl and \\cdotCHDCHDCl) have been observed. A final set of experiments were performed following irradiation of the Cl2/C2H4/p-H2 mixture at 365 nm, in which the matrix was irradiated with filtered infrared light from a globar source, which has been shown to induce a reaction between isolated Cl atoms and matrix H2 to produce HCl and H atoms. In our experiments, the major products observed were HCl and ethyl chloride (CH3CH2Cl) and the possible mechanism of the formation of ethyl chloride will be discussed. P. Brana, B. Menendez, T. Fernandez, and J. A. Sordo, J. Phys. Chem. A 104, 10842 (2000) P. L. Raston and D. T. Anderson, Phys. Chem. Chem. Phys. 8, 3124 (2006)

  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. Characterization and Modulation of Proteins Involved in Sulfur Mustard Vesication

    DTIC Science & Technology

    2000-06-01

    SM may induce apoptosis as well. Recent evidence has revealed that Bcl-2 can complex with both the Caenorhabditis elegans death proteins 3 and 4 (Ced-3...the product of a gene required for programmed Tris-HCl (pH 6.8), and 0.02% bromophenol blue. Samples were re- cell death in Caenorhabditis elegans [17...biochemical or mor- which is required for apoptosis in Caenorhabditis elegans (8). phological changes characteristic of apoptosis when In human

  3. Characterization and Modulation of Proteins Involved in Sulfur Mustard Vesication

    DTIC Science & Technology

    2006-05-01

    µM; (Meier and Millard, 1998 ), KC (50-300 µM; (Rosenthal et al., 1998c; Stoppler et al., 1998 ), and endothelial cells ( µM; (Dabrowska et al...1996), a time- and dose- dependent shift to necrosis at higher doses was observed in SM-treated lymphocytes (Meier and Millard, 1998 ), endothelial...recruitment of FADD was shown to mediate UV apoptosis of HaCaT KC (Aragane et al., 1998 ). Since Fas-neutralizing antibodies were unable to block this

  4. 2-chloroethyl fatty acid esters as indicators of 2-chloroethanol in black walnuts, seasoning mixes, and spices.

    PubMed

    Yurawecz, M P

    1987-01-01

    Residues of 2-chloroethyl fatty acid esters (CEEs) and 2-chloroethanol (ECH), by-products of ethylene oxide fumigation, were determined in black walnuts, seasoning mixes, and spices. Extracts containing ECH and CEE were cleaned up by previously described procedures, and residue levels were quantitatively determined using a gas chromatograph equipped with a halogen-selective electrolytic conductivity detector. All food products that contained CEE residues also contained ECH. ECH residues ranged from less than 0.2 to 880 ppm and were less than 0.2-7 times the CEE levels found.

  5. Induction of specific-locus and dominant lethal mutations in male mice by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU).

    PubMed

    Ehling, U H; Adler, I D; Favor, J; Neuhäuser-Klaus, A

    1997-10-06

    1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) induced dominant lethal and specific-locus mutations in male mice. For both compounds the germ cell stage sensitive to the induction of dominant lethal mutations was dose dependent. A dose of 5 mg BCNU per kg b.wt. induced dominant lethal mutations primarily in spermatocytes, whereas higher doses of BCNU induced dominant lethals in spermatids and spermatocytes. Following doses of 5 and 10 mg CCNU per kg b.wt. dominant lethals were induced in spermatids and spermatocytes similar to the results for higher doses of BCNU. Higher dose exposure to BCNU and CCNU was associated with dominant lethals expressed as pre-implantation loss (reduction in total number of implants). In addition, higher doses of CCNU showed a cytotoxic effect in differentiating spermatogonia. Both compounds induced specific-locus mutations in post-spermatogonial germ cell stages of mice. However, CCNU increased also the specific-locus mutation frequency in spermatogonia in two out of three experiments. We conclude in analogy with criteria developed by IARC, that BCNU and CCNU are potential human mutagens.

  6. 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.

  7. Covalent DNA-Protein Cross-Linking by Phosphoramide Mustard and Nornitrogen Mustard in Human Cells.

    PubMed

    Groehler, Arnold; Villalta, Peter W; Campbell, Colin; Tretyakova, Natalia

    2016-02-15

    N,N-Bis-(2-chloroethyl)-phosphorodiamidic acid (phosphoramide mustard, PM) and N,N-bis-(2-chloroethyl)-amine (nornitrogen mustard, NOR) are the two biologically active metabolites of cyclophosphamide, a DNA alkylating drug commonly used to treat lymphomas, breast cancer, certain brain cancers, and autoimmune diseases. PM and NOR are reactive bis-electrophiles capable of cross-linking cellular biomolecules to form covalent DNA-DNA and DNA-protein cross-links (DPCs). In the present work, a mass spectrometry-based proteomics approach was employed to characterize PM- and NOR-mediated DNA-protein cross-linking in human cells. Following treatment of human fibrosarcoma cells (HT1080) with cytotoxic concentrations of PM, over 130 proteins were found to be covalently trapped to DNA, including those involved in transcriptional regulation, RNA splicing/processing, chromatin organization, and protein transport. HPLC-ESI(+)-MS/MS analysis of proteolytic digests of DPC-containing DNA from NOR-treated cells revealed a concentration-dependent formation of N-[2-[cysteinyl]ethyl]-N-[2-(guan-7-yl)ethyl]amine (Cys-NOR-N7G) conjugates, confirming that it cross-links cysteine thiols of proteins to the N7 position of guanines in DNA. Cys-NOR-N7G adduct numbers were higher in NER-deficient xeroderma pigmentosum cells (XPA) as compared with repair proficient cells. Furthermore, both XPA and FANCD2 deficient cells were sensitized to PM treatment as compared to that of wild type cells, suggesting that Fanconi anemia and nucleotide excision repair pathways are involved in the removal of cyclophosphamide-induced DNA damage.

  8. The chemiluminescence determination of 2-chloroethyl ethyl sulfide using luminol-AgNO3-silver nanoparticles system

    NASA Astrophysics Data System (ADS)

    Maddah, Bozorgmehr; Shamsi, Javad; Barsang, Mehran Jam; Rahimi-Nasrabadi, Mehdi

    2015-05-01

    A highly sensitive chemiluminescence (CL) method for the determination of 2-chloroethyl ethyl sulfide (2-CEES) was presented. It was found that 2-chloroethyl ethyl sulfide (2-CEES) could inhibit the CL of the luminol-AgNO3 system in the presence of silver nanoparticles in alkaline solution, which made it applicable for determination of 2-CEES. The presented method is simple, convenient, rapid and sensitive. Under the optimized conditions, the calibration curve was linear in the range of 0.0001-1 ng mL-1, with the correlation coefficient of 0.992; while the limit of detection (LOD), based on signal-to-noise ratio (S/N) of 3, was 6 × 10-6 ng mL-1. Also, the relative standard deviation (RSD, n = 5) for determination of 2-CEES (0.50 ng mL-1) was 3.1%. The method was successfully applied for the determination of 2-CEES in environmental aqueous samples.

  9. 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).

  10. Sulfur Mustard Toxicity Following Dermal Exposure

    PubMed Central

    Paromov, Victor; Suntres, Zacharias; Smith, Milton; Stone, William L.

    2007-01-01

    Objective: Sulfur mustard (bis-2-(chloroethyl) sulfide) is a chemical warfare agent (military code: HD) causing extensive skin injury. The mechanisms underlying HD-induced skin damage are not fully elucidated. This review will critically evaluate the evidence showing that oxidative stress is an important factor in HD skin toxicity. Oxidative stress results when the production of reactive oxygen (ROS) and/or reactive nitrogen oxide species (RNOS) exceeds the capacity of antioxidant defense mechanisms. Methods: This review will discuss the role of oxidative stress in the pathophysiology of HD skin toxicity in both in vivo and in vitro model systems with emphasis on the limitations of the various model systems. Evidence supporting the therapeutic potential of antioxidants and antioxidant liposomes will be evaluated. Antioxidant liposomes are effective vehicles for delivering both lipophilic (incorporated into the lipid bilayers) and water-soluble (encapsulated in the aqueous inner-spaces) antioxidants to skin. The molecular mechanisms interconnecting oxidative stress to HD skin toxicity are also detailed. Results: DNA repair and inflammation, in association with oxidative stress, induce intracellular events leading to apoptosis or to a programmable form of necrosis. The free radical, nitric oxide (NO), is of considerable interest with respect to the mechanisms of HD toxicity. NO signaling pathways are important in modulating inflammation, cell death, and wound healing in skin cells. Conclusions: Potential future directions are summarized with emphasis on a systems biology approach to studying sulfur mustard toxicity to skin as well as the newly emerging area of redox proteomics. PMID:18091984

  11. 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

  12. 2-Chloroethyl-3-sarcosinamide-1-nitrosourea, a novel chloroethylnitrosourea analogue with enhanced antitumor activity against human glioma xenografts.

    PubMed

    Marcantonio, D; Panasci, L C; Hollingshead, M G; Alley, M C; Camalier, R F; Sausville, E A; Dykes, D J; Carter, C A; Malspeis, L

    1997-09-15

    Nitrosoureas are among the most widely used agents used in the treatment of malignant gliomas. Here, the activity of 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) was compared with that of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), in vivo against s.c. implanted SF-295 and U-251 central nervous system (CNS) tumor xenografts. When given i.v., q4d for 3 doses, to athymic mice bearing s.c. SF-295 tumors, SarCNU, at an optimum of 167 mg/kg/dose, produced 9 tumor-free animals of 10 total animals, 1 regression, and no evidence of overt toxicity (> or =20% body weight loss). With a similar dosing schedule, BCNU produced no tumor-free animals, six regressions, and one drug-related death at its optimum of 30 mg/kg/dose. Furthermore, SarCNU retained high antitumor activity at two lower dose levels, 66 and 45% of the optimal dose, whereas BCNU demonstrated a progressive loss of antitumor activity at lower doses. Following p.o. administration, SarCNU similarly demonstrated antitumor activity that was superior to that of BCNU. In the U-251 CNS tumor model, SarCNU yielded six of six tumor-free animals at 80 mg/kg/dose with i.p. administration q.d. for 5 days, starting on day 14, whereas BCNU, at 9 mg/kg/dose, yielded three of six tumor-free mice and one drug-related death. Again, SarCNU resulted in tumor-free animals at 66 and 45% of its optimal dose and was relatively nontoxic, in contrast to BCNU. Results of testing to date indicate that SarCNU is clearly more effective than BCNU against the human CNS tumors SF-295 and U-251 in vivo. These results encourage the initiation of clinical trials for SarCNU, in an effort to improve therapeutic approaches to glioma, but clinical trials must determine whether superiority of SarCNU in preclinical models can be extrapolated to patients.

  13. 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).

  14. Hybrid anticancer compounds. Steroidal lactam esters of carboxylic derivatives of N,N-bis (2-chloroethyl) aniline (review).

    PubMed

    Catsoulacos, P; Catsoulacos, D

    1991-01-01

    For the rational design of more specific alkylating agents, we suggested new biological platforms able to deliver the alkylating moieties to specific target site and on the other hand we hoped to lead in compounds with synergistic activity. As biological platforms have been used steroidal lactams of A and D- ring and as alkylating agents carboxylic derivatives of N,N-bis (2-Chloroethyl) aniline which combine to the steroid by an easily cleaved ester bond. These homo-aza-steroidal esters gave satisfactory results in early and advanced P388, L1210 leukemias and solid tumors. Whereas unmodified steroidal esters have generally been reported to be inactive in treatment of L1210 leukemia. The steric arrangement of the alkylating moiety greatly effects toxicity and activity of the drugs, while the steric arrangement of the hydrogen atom at position 5 influences these parameters. Isosterism of alkylating agent is the factor for biological action. The amide group of the lactam molecule may be essential for activity.

  15. Identification of alkaline phosphatase genes for utilizing a flame retardant, tris(2-chloroethyl) phosphate, in Sphingobium sp. strain TCM1.

    PubMed

    Takahashi, Shouji; Katanuma, Hiroshi; Abe, Katsumasa; Kera, Yoshio

    2017-03-01

    Tris(2-chloroethyl) phosphate (TCEP) is a haloalkyl phosphate flame retardant and plasticizer that has been recognized as a global environmental contaminant. Sphingobium sp. strain TCM1 can utilize TCEP as a phosphorus source. To identify the phosphomonoesterase involved in TCEP utilization, we identified four putative alkaline phosphatase (APase) genes, named SbphoA, SbphoD1, SbphoD2, and SbphoX-II, in the genome sequence. Following expression of these genes in Escherichia coli, APase activity was confirmed for the SbphoA and SbphoX-II gene products but was not clearly observed for the SbphoD1 and SbphoD2 gene products, owing to their accumulation in inclusion bodies. The single deletion of either SbphoA or SbphoX-II retarded the growth and reduced the APase activity of strain TCM1 cells on medium containing TCEP as the sole phosphorus source; these changes were more marked in cells with the SbphoX-II gene deletion. In contrast, the deletion of either SbphoD1 or SbphoD2 had no effect on cell growth or APase activity. The double deletion of SbphoA and SbphoX-II resulted in the complete loss of cell growth on TCEP. These results show that SbPhoA and SbPhoX-II are involved in the utilization of TCEP as a phosphorus source and that SbPhoX-II is the major phosphomonoesterase involved in TCEP utilization.

  16. Detection of vesicant-induced upper airway mucosa damage in the hamster cheek pouch model using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Hammer-Wilson, Marie J.; Nguyen, Vi; Jung, Woong-Gyu; Ahn, Yehchen; Chen, Zhongping; Wilder-Smith, Petra

    2010-01-01

    Hamster cheek pouches were exposed to 2-chloroethyl ethyl sulfide [CEES, half-mustard gas (HMG)] at a concentration of 0.4, 2.0, or 5.0 mg/ml for 1 or 5 min. Twenty-four hours post-HMG exposure, tissue damage was assessed by both stereomicrography and optical coherence tomography (OCT). Damage that was not visible on gross visual examination was apparent in the OCT images. Tissue changes were found to be dependent on both HMG concentration and exposure time. The submucosal and muscle layers of the cheek pouch tissue showed the greatest amount of structural alteration. Routine light microscope histology was performed to confirm the OCT observations.

  17. Kinetics of the conjugation of aniline mustards with glutathione and thiosulfate.

    PubMed

    Gamcsik, M P; Millis, K K; Hamill, T G

    1997-06-06

    The rates of the non-enzymatic conjugation of the substituted aniline mustards, melphalan, chlorambucil and p-(N,N-bis(2-chloroethyl))toluidine with glutathione and thiosulfate were determined using nuclear magnetic resonance spectroscopy. Using this method, the disappearance of drug and the formation of both the mono-thioether and bis-thioether conjugates can be monitored directly. For glutathione conjugation, the rate constants for the formation of the first and second aziridinium intermediates were similar. With thiosulfate conjugation, the rate constant for the formation of the first aziridinium intermediate is greater than the rate constant for the formation of the second aziridinium. This demonstrates that the type of nucleophile has a significant influence on the overall alkylating activity of these bifunctional mustards. The bisthioether adduct formed from the reaction between p-(N,N-bis([2-13C]-2-chloroethyl))toluidine and glutathione and thiosulfate can be identified and scrambling of the 13C label in the product provides strong evidence that the alkylation must occur through an aziridinium intermediate.

  18. 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

  19. 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.

  20. Silibinin, Dexamethasone, and Doxycycline as Potential Therapeutic Agents for Treating Vesicant-Inflicted Ocular Injuries

    PubMed Central

    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

    2014-01-01

    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. PMID:22841772

  1. 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.

  2. Vesicant chemotherapy extravasation antidotes and treatments.

    PubMed

    Schulmeister, Lisa

    2009-08-01

    Oncology nurses and pharmacists often are given the responsibility of developing or updating institutional policies to manage vesicant chemotherapy extravasations. Antidote and treatment recommendations of vesicant chemotherapy manufacturers, antidotes and treatments approved by the U.S. Food and Drug Administration (FDA), and guidelines and recommendations made by professional oncology organizations are useful resources in this process. This article describes manufacturers' recommendations, lists antidotes and treatments approved by the FDA, and reviews published guidelines and recommendations. Available antidote and treatment formulations and their preparation and administration also are discussed.

  3. 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.

  4. 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

  5. Functional and inflammatory alterations in the lung following exposure of rats to nitrogen mustard

    SciTech Connect

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

    2011-01-01

    Nitrogen mustard is a vesicant that causes damage to the respiratory tract. In these studies, we characterized the acute effects of nitrogen mustard on lung structure, inflammatory mediator expression, and pulmonary function, with the goal of identifying mediators potentially involved in toxicity. Treatment of rats (male Wistar, 200-225 g) with nitrogen mustard (mechlorethamine hydrochloride, i.t., 0.25 mg/kg) resulted in marked histological changes in the respiratory tract, including necrotizing bronchiolitis, thickening of alveolar septa, and inflammation which was evident within 24 h. This was associated with increases in bronchoalveolar lavage protein and cells, confirming injury to alveolar epithelial regions of the lung. Nitrogen mustard administration also resulted in increased expression of inducible nitric oxide synthase and cyclooxygenase-2, pro-inflammatory proteins implicated in lung injury, in alveolar macrophages and alveolar and bronchial epithelial cells. Expression of connective tissue growth factor and matrix metalloproteinase-9, mediators regulating extracellular matrix turnover was also increased, suggesting that pathways leading to chronic lung disease are initiated early in the pathogenic process. Following nitrogen mustard exposure, alterations in lung mechanics and function were also observed. These included decreases in baseline static compliance, end-tidal volume and airway resistance, and a pronounced loss of methacholine responsiveness in resistance, tissue damping and elastance. Taken together, these data demonstrate that nitrogen mustard induces rapid structural and inflammatory changes in the lung which are associated with altered lung functioning. Understanding the nature of the injury induced by nitrogen mustard and related analogs may aid in the development of efficacious therapies for treatment of pulmonary injury resulting from exposure to vesicants.

  6. Preparation and application of the sol-gel-derived acrylate/silicone co-polymer coatings for headspace solid-phase microextraction of 2-chloroethyl ethyl sulfide in soil.

    PubMed

    Liu, Mingming; Zeng, Zhaorui; Fang, Huaifang

    2005-05-27

    Three types of novel acrylate/silicone co-polymer coatings, including co-poly(methyl acrylate/hydroxy-terminated silicone oil) (MA/OH-TSO), co-poly(methyl methacrylate/OH-TSO) (MMA/OH-TSO) and co-poly(butyl methacrylate/OH-TSO) (BMA/OH-TSO), were prepared for the first time by sol-gel method and cross-linking technology and subsequently applied to headspace solid-phase microextraction (HS-SPME) of 2-chloroethyl ethyl sulfide (CEES), a surrogate of mustard, in soil. The underlying mechanisms of the coating process were discussed and confirmed by IR spectra. The selectivity of the three types of sol-gel-derived acrylate/silicone coated fibers was studied, and the BMA/OH-TSO coated fibers exhibited the highest extraction ability to CEES. The concentration of BMA and OH-TSO in sol solution was optimized, and the BMA/OH-TSO (3:1)-coated fibers possessed the highest extraction efficiency. Compared with commercially available polyacrylate (PA) fiber, the sol-gel-derived BMA/OH-TSO (3:1) fibers showed much higher extraction efficiency to CEES. Therefore, the BMA/OH-TSO (3:1)-coated fibers were chosen for the analysis of CEES in soil matrix. The reproducibility of coating preparation was satisfactory, with the RSD 2.39% within batch and 3.52% between batches, respectively. The coatings proved to be quite stable at high temperature (to 350 degrees C) and in different solvents (organic or inorganic), thus their lifetimes (to 150 times) are longer than conventional fibers. Extraction parameters, such as the volume of water added to the soil, extraction temperature and time, and the ionic strength were optimized. The linearity was from 0.1 to 10 microg/g, the limit of detection (LOD) was 2.7 ng/g, and the RSD was 2.19%. The recovery of CEES was 88.06% in agriculture soil, 92.61% in red clay, and 101.95% in sandy soil, respectively.

  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.

  8. 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.

  9. 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.

  10. Site Plan Safety Submission for Sampling, Monitoring, and Decontamination of Mustard Agent - South Plant, Rocky Mountain Arsenal. Volume 1

    DTIC Science & Technology

    1988-10-01

    of Hazard and Physiolo&ical Effects Mustard is an insidious vesicant or blistering agent and has been identified as carcinogenic , mutagenic, and...in laboratory operations involving solvents incompatible with butyl rubber . 0 Nonstandard gloves will be used only in a manner which prohibits...will be monitored before delivery to the laundry. Butyl rubber impermeable protective clothing will burn and does not possess self-extinguishing

  11. Site Plan Safety Submission for Sampling, Monitoring and Decontamination of Mustard Agent, South Plant, Rocky Mountain Arsenal. Volume 1

    DTIC Science & Technology

    1988-10-01

    Mustard is an insidious vesicant or blistering agent and has been identified as carcinogenic , mutagenic, and teratogenic. The agent’s garlic-like odor...butyl rubber . " Nonstandard gloves will be used only in a manner which prohibits intentional contact and has low potential for unintentional contact... rubber impermeable protective clothing will burn and does not possess self-extinguishing properties. Therefore, contact with an SPSS Plan - South Plant

  12. Proceedings of the Vesicant Workshop, February 1987

    DTIC Science & Technology

    1987-12-01

    Rapid detection and decontamination, therefore, become essential in order to permit reduction of MOPP levels. The medical intensity inherent in vesicant...I ~ i Y I " Paipirueister Sum$ary of Presentation I Induction of Glutathione S-Transferase Enhances Detoxification of Aflatoxin I B Control <®, RzW...profiles are shown for aflatoxin B (AFB ) adducts of rat liver DNA. Rats fed 3 control or ethoxyquin-sup~lemented diets were gavaged with I H]AFB 1

  13. 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.

  14. Both extraneuronal monoamine transporter and O(6)-methylguanine-DNA methyltransferase expression influence the antitumor efficacy of 2-chloroethyl-3-sarcosinamide- 1-nitrosourea in human tumor xenografts.

    PubMed

    Chen, Z P; Wang, Z M; Carter, C A; Alley, M C; Mohr, G; Panasci, L C

    2001-03-01

    We previously have found that 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) is a selective cytotoxin that enters cells via the extraneuronal transporter for monoamine transmitters (EMT). Both in vitro and in vivo studies demonstrated that SarCNU was more effective than BCNU against human gliomas. To clarify whether EMT expression correlates with antitumor efficacy of SarCNU, we determined human EMT (EMTh) and O(6)-methylguanine-DNA methyltransferase (MGMT) expression in nine human xenograft models using semiquantitative reverse-transcription polymerase chain reaction. These results were compared with the antitumor effects of SarCNU and the standard chloroethylnitrosourea antitumor agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). There was no significant correlation between EMTh expression and antitumor efficacy of SarCNU or BCNU. Also, there was no significant correlation between MGMT expression and SarCNU efficacy. However, a significant correlation was found between MGMT expression and BCNU antitumor efficacy. Interestingly, multiple regression analysis demonstrated a significant correlation between SarCNU efficacy and EMTh plus MGMT expression, whereas there was no correlation between BCNU efficacy and MGMT plus EMTh expression. Thus, the absence of a linear correlation between SarCNU efficacy and EMTh expression appears to be due, at least in part, to the presence of DNA repair, specifically, MGMT, in these xenograft models. These studies suggest that MGMT expression alone correlates with BCNU activity, whereas both EMTh and MGMT expression are important determinants of SarCNU activity against human tumor xenograft models. SarCNU is in clinical trials and these results may have important clinical implications.

  15. 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.

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

    PubMed

    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.

  17. DOXYCYCLINE HYDROGELS WITH REVERSIBLE DISULFIDE CROSSLINKS FOR DERMAL WOUND HEALING OF MUSTARD INJURIES

    PubMed Central

    Anumolu, SivaNaga S; Menjoge, Anupa R.; Deshmukh, Manjeet; Gerecke, Donald; Stein, Stanley; Laskin, Jeffrey; Sinko, Patrick J.

    2010-01-01

    Doxycycline hydrogels containing reversible disulfide crosslinks were investigated for a dermal wound healing application. Nitrogen mustard (NM) was used as a surrogate to mimic the vesicant effects of the chemical warfare agent sulfur mustard. An 8-arm-poly(ethylene glycol) (PEG) polymer containing multiple thiol (-SH) groups was crosslinked using hydrogen peroxide (H2O2 hydrogel) or 8-arm-S-thiopyridyl (S-TP hydrogel) to form a hydrogel in situ. Formulation additives (glycerin, PVP and PEG 600) were found to promote dermal hydrogel retention for up to 24 h. Hydrogels demonstrated high mechanical strength and a low degree of swelling (<1.5%). Doxycycline release from the hydrogels was biphasic and sustained for up to 10-days in vitro. Doxycycline (8.5 mg/cm3) permeability through NM-exposed skin was elevated as compared to non vesicant-treated controls at 24, 72 and 168 h post exposure with peak permeability at 72 h. The decrease in doxycycline permeability at 168 h correlates to epidermal reepithelialization and wound healing. Histology studies of skin showed that doxycycline-loaded (0.25% w/v) hydrogels provided improved wound healing response on NM-exposed skin as compared to untreated skin and skin treated with placebo hydrogels in a SKH-1 mouse model. In conclusion, PEG-based doxycycline hydrogels are promising for dermal wound healing application of mustard injuries. PMID:20950853

  18. Doxycycline hydrogels with reversible disulfide crosslinks for dermal wound healing of mustard injuries.

    PubMed

    Anumolu, SivaNaga S; Menjoge, Anupa R; Deshmukh, Manjeet; Gerecke, Donald; Stein, Stanley; Laskin, Jeffrey; Sinko, Patrick J

    2011-02-01

    Doxycycline hydrogels containing reversible disulfide crosslinks were investigated for a dermal wound healing application. Nitrogen mustard (NM) was used as a surrogate to mimic the vesicant effects of the chemical warfare agent sulfur mustard. An 8-arm-poly(ethylene glycol) (PEG) polymer containing multiple thiol (-SH) groups was crosslinked using hydrogen peroxide (H(2)O(2) hydrogel) or 8-arm-S-thiopyridyl (S-TP hydrogel) to form a hydrogel in situ. Formulation additives (glycerin, PVP and PEG 600) were found to promote dermal hydrogel retention for up to 24 h. Hydrogels demonstrated high mechanical strength and a low degree of swelling (< 1.5%). Doxycycline release from the hydrogels was biphasic and sustained for up to 10-days in vitro. Doxycycline (8.5 mg/cm(3)) permeability through NM-exposed skin was elevated as compared to non vesicant-treated controls at 24, 72 and 168 h post-exposure with peak permeability at 72 h. The decrease in doxycycline permeability at 168 h correlates to epidermal re-epithelialization and wound healing. Histology studies of skin showed that doxycycline loaded (0.25% w/v) hydrogels provided improved wound healing response on NM-exposed skin as compared to untreated skin and skin treated with placebo hydrogels in an SKH-1 mouse model. In conclusion, PEG-based doxycycline hydrogels are promising for dermal wound healing application of mustard injuries.

  19. 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

  20. Sulfur mustard induces immune sensitization in hairless guinea pigs.

    PubMed

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

    2010-02-01

    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-alpha, IFN-gamma, 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.

  1. Mechanism by which caffeine potentiates lethality of nitrogen mustard.

    PubMed Central

    Lau, C C; Pardee, A B

    1982-01-01

    Caffeine is synergistic with many DNA-damaging agents in increasing lethality to mammalian cells. The mechanism is not well understood. Our results show that caffeine potentiates the lethality of the nitrogen mustard 2-chloro-N-(2-chloroethyl)-N-methylethanamine (HN2) by inducing damaged cells to undergo mitosis before properly repairing lesions in their DNA. Treatment with low doses of HN2 (0.5 microM for 1 hr) caused little lethality in baby hamster kidney cells (90% survival). These cells were arrested in G2 shortly after treatment with HN2 as shown by flow microfluorimetry and autoradiography. After an arrest of 6 hr, HN2-treated cells began to move into mitosis and from then on behaved like normal cells. Repair synthesis was shown to continue during the G2 arrest by using synchronized cells pulse labeled with [3H]thymidine after HN2 treatment and autoradiography. Caffeine (2mM) increased the lethality of HN2 by 5- to 10-fold. It prevented the G2 arrest. Caffeine did not prevent these HN2-treated cells from entering or completing S phase but rather allowed them to divide without finishing the repair processes and as a consequence caused nuclear fragmentation after mitosis. Caffeine-induced nuclear fragmentation and enhanced lethality were proportional, as shown with dose--response curves and time dependence. In addition, both lethality and nuclear fragmentation were abolished by low doses of cycloheximide, an inhibitor of protein synthesis. Images PMID:6953438

  2. Alleviation of mutagenic effects of polycyclic aromatic agents (quinacrine mustard, ICR-191 and ICR-170) by caffeine and pentoxifylline.

    PubMed

    Piosik, Jacek; Ulanowska, Katarzyna; Gwizdek-Wiśniewska, Anna; Czyz, Agata; Kapuściński, Jan; Wegrzyn, Grzegorz

    2003-09-29

    Previous studies performed by others indicated that apart from its other biological effects, caffeine (CAF) may have a role in protection of organisms against cancer. However, biological mechanism of this phenomenon remained unknown. Recent studies suggested that caffeine can form stacking (pi-pi) complexes with polycyclic aromatic chemicals. Therefore, one might speculate that effective concentrations of polycyclic aromatic mutagens could be reduced in the presence of caffeine. Here we demonstrate that caffeine and another xanthine, pentoxifylline (PTX), effectively alleviate mutagenic action of polycyclic aromatic agents (exemplified by quinacrine mustard (QM), 2-methoxy-6-chloro-9-(3-(2-chloroethyl)aminopropylamino)acridine.2HCl (ICR-191) and 1,3,7-propanediamine-N-(2-chloroethyl)-N'-(6-chloro-2-methoxy-9-acridinyl)-N-ethyl.2HCl (ICR-170)), but not of aliphatic mutagens (exemplified by mechlorethamine), in the recently developed mutagenicity test based on bacterium Vibrio harveyi. Biophysical studies indicated that caffeine and pentoxifylline can form stacking complexes with the aromatic agents mentioned above. Molecular modeling also confirmed a possibility of stacking interactions between examined molecules.

  3. 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.

  4. Various concentrations of erucic acid in mustard oil and mustard.

    PubMed

    Wendlinger, Christine; Hammann, Simon; Vetter, Walter

    2014-06-15

    Erucic acid is a typical constituent of mustard or rape. Foodstuff with a high content of erucic acid is considered undesirable for human consumption because it has been linked to myocardial lipidosis and heart lesions in laboratory rats. As a result, several countries have restricted its presence in oils and fats. In this study, the erucic acid content in several mustard oils and prepared mustard samples from Germany and Australia was determined. Seven of nine mustard oil samples exceeded the permitted maximum levels established for erucic acid (range: 0.3-50.8%, limit: 5%). The erucic acid content in mustard samples (n=15) varied from 14% to 33% in the lipids. Two servings (i.e. 20 g) of the mustards with the highest erucic acid content already surpassed the tolerable daily intake established by Food Standards Australia New Zealand. However, a careful selection of mustard cultivars could lower the nutritional intake of erucic acid.

  5. Comparative toxic effect of nitrogen mustards (HN-1, HN-2, and HN-3) and sulfur mustard on hematological and biochemical variables and their protection by DRDE-07 and its analogues.

    PubMed

    Sharma, Manoj; Vijayaraghavan, R; Agrawal, Om Prakash

    2010-07-01

    The chemical warfare agents sulfur mustard (SM) and nitrogen mustards (HN-1, HN-2, and HN-3) are highly reactive vesicants. The study was planned to investigate the protective efficacy of amifostine, DRDE-07 and their analogues, and few conventional antidotes (30 minutes pretreatment) against dermally applied SM and nitrogen mustards in preventing hematological and biochemical changes in mice. Mustard agents (1.0 median lethal dose [LD(50)]) induced a significant decrease in the body weight and spleen weight. A significant decrease in the white blood cell (WBC) count and an increase in serum transaminases and alkaline phosphatases (ALPs) were observed. A significant decrease in reduced (GSH) and oxidized glutathione (GSSG) and an increase in thiobarbituric acid reactive substances were also observed. All the mustard agents increased DNA fragmentation. The effects of SM were significantly ameliorated by DRDE-07 analogues, and with nitrogen mustards the protection was partial. Overall, DRDE-30 (propyl analogue) followed by DRDE-35 (butyl analogue) are favored as safer and better compounds.

  6. Adsorption of 2 Chloroethyl Ethyl Sulfide on Silica: Binding Mechanism and Energy of a Bifunctional Hydrogen-Bond Acceptor at the Gas Surface Interface

    DTIC Science & Technology

    2014-11-19

    in 1997 mandated the destruction of mustard stockpiles worldwide, HD can be readily synthesized by terrorists or militaries who choose to ignore the...Babaeva, M. A. Infrared Spectrum of Ammonia Adsorbed by Si−OH Groups on a Silica Surface. Opt. Spectrosc. 1983, 54, 665−666. (21) Civalleri, B

  7. Solvent effects of N-nitroso, N-(2-chloroethyl), N',N'-dibenzylsulfamid and its copper(II) and cobalt(II) complexes: fluorescence studies.

    PubMed

    Bensouilah, Nadjia; Fisli, Hassina; Dhaoui, Nabila; Benali-Cherif, Nourredine; Abdaoui, Mohamed

    2013-01-01

    The structure of N-nitroso, N-(2-chloroethyl), N',N'-dibenzylsulfamid (CENS) was established by X-ray crystallography. The atomic coordinates, factors of isotropic thermal agitation, bond lengths and valence angles were determined. The solvent effects on the electronic absorption and fluorescence spectra of CENS were investigated at room temperature. The effects of solvent polarity and of hydrogen bonding were interpreted by means of linear solvation energy relationships (LSERs). Multiple linear regression analysis indicated that the hydrogen donation properties of the solvent play an important role in determining the position of the absorption maximum, while the classical polarity of the medium is the only dominating parameter in determining the emission maximum and the Stokes' shift. Complexation of the investigated compound by two different transition metal ions was studied. Fluorescence measurements show that fluorescence quenching by cobalt(II) is more important than that by copper(II). This phenomenon can be attributed to good stereo-structural matching between the electronic configuration of the Co(2+) ion and the active site distribution of CENS in aqueous solution.

  8. 1,3-Bis(2-chloroethyl)-1-nitrosourea-loaded bovine serum albumin nanoparticles with dual magnetic resonance–fluorescence imaging for tracking of chemotherapeutic agents

    PubMed Central

    Wei, Kuo-Chen; Lin, Feng-Wei; Huang, Chiung-Yin; Ma, Chen-Chi M; Chen, Ju-Yu; Feng, Li-Ying; Yang, Hung-Wei

    2016-01-01

    To date, knowing how to identify the location of chemotherapeutic agents in the human body after injection is still a challenge. Therefore, it is urgent to develop a drug delivery system with molecular imaging tracking ability to accurately understand the distribution, location, and concentration of a drug in living organisms. In this study, we developed bovine serum albumin (BSA)-based nanoparticles (NPs) with dual magnetic resonance (MR) and fluorescence imaging modalities (fluorescein isothiocyanate [FITC]-BSA-Gd/1,3-bis(2-chloroethyl)-1-nitrosourea [BCNU] NPs) to deliver BCNU for inhibition of brain tumor cells (MBR 261-2). These BSA-based NPs are water dispersible, stable, and biocompatible as confirmed by XTT cell viability assay. In vitro phantoms and in vivo MR and fluorescence imaging experiments show that the developed FITC-BSA-Gd/BCNU NPs enable dual MR and fluorescence imaging for monitoring cellular uptake and distribution in tumors. The T1 relaxivity (R1) of FITC-BSA-Gd/BCNU NPs was 3.25 mM−1 s−1, which was similar to that of the commercial T1 contrast agent (R1 =3.36 mM−1 s−1). The results indicate that this multifunctional drug delivery system has potential bioimaging tracking of chemotherapeutic agents ability in vitro and in vivo for cancer therapy. PMID:27601895

  9. Effects of atomoxetine on attention in Wistar rats treated with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4).

    PubMed

    Hauser, Joachim; Reissmann, Andreas; Sontag, Thomas-A; Tucha, Oliver; Lange, Klaus W

    2017-03-14

    The aim of the present study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), which allows a depletion of noradrenergic terminals in a dose-dependent manner, on attention in rats as measured using the five-choice serial-reaction time task (5CSRTT). In addition, we investigated whether the effects of DSP4 treatment can be reversed by atomoxetine. Atomoxetine is a selective noradrenaline reuptake inhibitor and has been shown to be effective in the treatment of attention deficit hyperactivity disorder. Wistar rats were trained in the 5CSRTT and treated with one of the three doses of DSP4 (10, 20 or 50 mg/kg) or saline. Following DSP4 treatment, rats were injected with three doses of atomoxetine (0.1, 0.5 or 1 mg/kg) or saline and tested in the 5CSRTT. The treatment with DSP4 caused a reduction in activity and a decline of performance in parameters related to attention in the 5CSRTT. Whether or not these impairments are due to attention deficits or changes in explorative behaviour and activity remains to be investigated. The treatment with atomoxetine had no beneficial effect on the rats' performance regardless of the DSP4 treatment. The present findings support the role of noradrenaline in modulating attentional processes and call for future studies regarding the effects of atomoxetine on attention in rats.

  10. Disposition and metabolism in 1-(2-chloroethyl)-3-(2',3',4'-tri-o-acetyl, ribopyranosyl)-1-nitrosourea in rats.

    PubMed

    Godeneche, D; Moreau, M F; Madelmont, J C; Duprat, J; Plagne, R

    1982-02-01

    The antineoplastic activity in animals of 1-(2-chloroethyl)-3-(2',3',4'-tri-O-acetyl, ribopyranosyl)-1-nitrosourea (RPCNU) has been widely demonstrated. The present study deals with the disposition and the metabolism of three 14C-labeled species of RPCNU. The chemical plasma half-life of the drug was less than 5 min. Within the first min after injections, most of the radioactivity derived from ethyl-14C groups were recovered as volatile products. Among these, 2-chloroethanol was identified as a main component. Analysis of labeled species in urine after administration of [ethyl-14C]RPCNU showed that thiodiacetic acid and its sulfoxide were major metabolites of RPCNU (62% of the urinary radioactivity). Traces of N-acetylcarboxymethyl- and N-acetylhydroxyethylcysteine) were also detected. The only labeled species concentrating in particular tissues was that carrying the chloroethyl moiety. Uptake to high levels of [ethyl-14C]RPCNU did occur in liver, kidney, pancreas, thymus, and Harder's gland.

  11. Neonatal N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) treatment modifies the vulnerability to phenobarbital- and ethanol-evoked sedative-hypnotic effects in adult rats.

    PubMed

    Bortel, Aleksandra; Słomian, Lucyna; Nitka, Dariusz; Swierszcz, Michał; Jaksz, Mirella; Adamus-Sitkiewicz, Beata; Nowak, Przemysław; Jośko, Jadwiga; Kostrzewa, Richard M; Brus, Ryszard

    2008-01-01

    To study the influence of the central noradrenergic system on sensitivity to sedative-hypnotic effects mediated by the aminobutyric acid (GABA) system, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine; 50 mg/kg sc x2, P1 and P3]. At 10 weeks, loss of the righting reflex (LORR) was used as an index to study the acute sedative-hypnotic effects of phenobarbital (100 mg/kg ip) and ethanol (4 g/kg ip, 25% v/v). Additionally, GABA concentration in the medial prefrontal cortex (PFC), hippocampus, cerebellum and brainstem was estimated by an HPLC/ED method. Neonatal DSP-4 treatment diminished the sedative-hypnotic effects of both phenobarbital and ethanol in adult rats. While the endogenous GABA content in the PFC, hippocampus, brainstem and cerebellum of DSP-4-treated rats was not altered, phenobarbital significantly decreased GABA content of both intact and DSP-4-lesioned rats by approximately 40% in the hippocampus and by approximately 20% in other brain regions at 1 h. Ethanol reduced GABA content by approximately 15-30% but only in the hippocampus and brainstem of both intact and lesioned rats. These findings indicate that the noradrenergic system exerts a prominent influence on sedative-hypnotics acting via GABAergic systems in the brain without directly altering GABA levels in the brain.

  12. Noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), treatment eliminates estrogenic effects on song responsiveness in female zebra finches (Taeniopygia guttata).

    PubMed

    Vyas, Akshat; Harding, Cheryl; McGowan, Joseph; Snare, Randall; Bogdan, Diane

    2008-10-01

    Female songbirds use male songs as an important criterion for mate selection. Several studies have reported that female songbirds prefer complex songs to other song types. In a recent study, the authors found that song responsiveness in female zebra finches (Taeniopygia guttata) is strongly modulated by circulating estrogen levels. The behavioral effects of estrogen are often mediated via norepinephrine (NE). The current study administered the noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) to estradiol-treated female zebra finches to investigate if estrogenic effects on song responsiveness are mediated via NE. The authors tested song responsiveness of adult female zebra finches for three acoustically different song types--simple, long-bout, and complex--under three treatment conditions, untreated, estradiol-treated, and estradiol + DSP-4-treated. Females only showed differential song responsiveness when treated with estradiol alone, responding more to complex songs. DSP-4 treatment eliminated this differential responsiveness. The results are discussed in the light of evidence from functional, neurochemical, and neuroanatomical studies that suggest that estrogenic effects on song processing might be mediated by NE.

  13. A new class of nitrosoureas. 4. Synthesis and antitumor activity of disaccharide derivatives of 3,3-disubstituted 1-(2-chloroethyl)-1-nitrosoureas.

    PubMed

    Tsujihara, K; Ozeki, M; Morikawa, T; Kawamori, M; Akaike, Y; Arai, Y

    1982-04-01

    A series of 33 N-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of N-substituted glycosylamines has been prepared and tested for antitumor activities. The compounds were obtained by reaction of glycosylamines with isocyanate, followed by nitrosation with N2O4. Structure-activity relationships of these trisubstituted nitrosoureas were investigated by varying the N-substituents and disaccharide groups and by comparing them with the corresponding disubstituted analogues. A large number of the nitrosoureas bearing a maltosyl group exhibited strong antitumor activities against leukemia L1210 and Ehrlich ascites carcinoma, and 60-day survivors against leukemia L1210 were found at the optimal dose for these derivatives. In contrast, the lactosyl and the melibiosyl derivatives were almost inactive. The most interesting compound in this series, the 3-isobutyl-3-maltosyl derivative (37), was tested against leukemia L1210 by single and multiple treatment. Its therapeutic ratio (96.3) obtained by multiple treatment is 3 times larger than that (31.5) obtained by single treatment, suggesting a possible clinical utility of 37 by multiple treatment. The favorable effect of a maltosyl moiety in this class of compounds is discussed.

  14. Oxidation of a mustard gas analogue using an aldehyde/O2 system catalyzed by V-doped mesoporous silica.

    PubMed

    Livingston, Stephanie R; Landry, Christopher C

    2008-10-08

    Vanadium-doped mesoporous silica was shown to be an effective heterogeneous catalyst for the oxidation of a mustard gas analogue, 2-chloroethyl ethyl sulfide (CEES), in the presence of an aldehyde and molecular oxygen. The oxidation was shown to involve a radical mechanism, which was indicated by the appearance of an induction period when the reaction occurred in the presence of a free radical scavenger. The reaction was initially selective for the oxidation of CEES to the sulfoxide, CEESO, although oxidation of the sulfoxide to the sulfone occurred once all the CEES had been oxidized. Chemical analysis indicated that V species did not leach from the silica support when the reaction was performed in the fluorinated solvent HFE-7100.

  15. 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.

  16. 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.

  17. N-Acetyl-L-cysteine inhibits sulfur mustard-induced and TRPA1-dependent calcium influx.

    PubMed

    Stenger, Bernhard; Popp, Tanja; John, Harald; Siegert, Markus; Tsoutsoulopoulos, Amelie; Schmidt, Annette; Mückter, Harald; Gudermann, Thomas; Thiermann, Horst; Steinritz, Dirk

    2016-10-13

    Transient receptor potential family channels (TRPs) have been identified as relevant targets in many pharmacological as well as toxicological studies. TRP channels are ubiquitously expressed in different tissues and act among others as sensors for different external stimuli, such as mechanical stress or noxious impacts. Recent studies suggest that one member of this family, the transient receptor potential ankyrin 1 cation channel (TRPA1), is involved in pain, itch, and various diseases, suggesting TRPA1 as a potential therapeutic target. As a nociceptor, TRPA1 is mainly activated by noxious or electrophilic compounds, including alkylating substances. Previous studies already revealed an impact of 2-chloroethyl-ethyl sulfide on the ion channel TRPA1. In this study, we demonstrate that sulfur mustard (bis-(2-chloroethyl) sulfide, SM) activates the human TRPA1 (hTRPA1) in a dose-dependent manner measured by the increase in intracellular Ca(2+) concentration ([Ca(2+)]i). Besides that, SM-induced toxicity was attenuated by antioxidants. However, very little is known about the underlying mechanisms. Here, we demonstrate that N-acetyl-L-cysteine (NAC) prevents SM-induced hTRPA1-activation. HEK293-A1-E cells, overexpressing hTRPA1, show a distinct increase in [Ca(2+)]i immediately after SM exposure, whereas this increase is reduced in cells pretreated with NAC in a dose-dependent manner. Interestingly, glutathione, although being highly related to NAC, did not show an effect on hTRPA1 channel activity. Taken together, our results provide evidence that SM-dependent activation of hTRPA1 can be diminished by NAC treatment, suggesting a direct interaction of NAC and the hTRPA1 cation channel. Our previous studies already showed a correlation of hTRPA1-activation with cell damage after exposure to alkylating agents. Therefore, NAC might be a feasible approach mitigating hTRPA1-related dysregulations after exposure to SM.

  18. Implications of Protein Alkyation and Proteolysis on Vesication Caused by Sulfur Mustard

    DTIC Science & Technology

    1999-10-01

    150 mM NaCI, 3 mM EDTA and 0.1% nonidet - P40 (NP40), pH 7.4) and then for 10 min at 4 °C with an ice-cold high salt buffer (10 mM Tris-base, 150 mM...kDa kilodalton KGM keratinocyte growth medium MMP matrix metalloproteinase MT-i MMP membrane type-i matrix metalloproteinase -58- NP40 nonidet - P40

  19. [Determination of tris (2-chloroethyl) phosphate in leather by gas chromatography-mass spectrometry coupled with mixed-mode sorbent solid phase extraction].

    PubMed

    Zhang, Weiya; Zhu, Yuling; Wang, Chengyun; Li, Lixia; Zhang, Junqing; Xing, Jun

    2014-10-01

    Leather is one of the important exporting products to European Union (EU), and tris(2-chloroethyl) phosphate (TCEP) is a commonly used flame retardant in leather and leather products. Recently, TCEP has been classified as a kind of substance of very high concern (SVHC) by EU for its carcinogenicity and reproductive toxicity. But to date, there is not a recognized method for the determination of TCEP in leather and leather products due to the serious matrix interferences and relatively low recovery of TCEP. In this work, a home-made mixed-mode sorbent (Silica-WCX) with carboxyl and alkyl groups was tested as the sorbent of solid phase extraction (SPE) to extract TECP from leather. The results demonstrated that, making the carboxyl groups protonized under acidic condition, Silica-WCX exhibited better extraction performance towards TCEP over some frequently used commercial sorbents tested. After the optimization of the SPE conditions based on Silica-WCX, a method of gas chromatography/mass spectrometry (GC-MS) was established for the determination of TCEP in leather samples. The linear range for TCEP ranged from 0.10 to 100.0 μg/L and the limit of quantification (LOQ, S/N = 10) was 44.46 ng/kg. The recoveries of TCEP spiked in samples at varied levels were in the range of 91.45%-99.98% with the relative standard deviations (RSDs) of 4.33%-5.97%. The method is simple, sensitive and reliable for the analysis of TCEP in leather and leather products.

  20. Activation of H-ras oncogenes in male B6C3F1 mouse liver tumors induced by vinthionine or 2-chloroethyl-methyl sulfide.

    PubMed

    Sohn, Y W; Lee, G H; Liem, A; Miller, J A

    1996-06-01

    Vinthionine (S-vinyl-DL-homocysteine) is hepatocarcinogenic in rats and mice. [Vinyl-14C]vinthionine binds covalently to rat liver DNA, RNA and protein in vivo, but not in vitro. This amino acid is directly mutagenic in Salmonella typhimurium TA100 and TA1535; the mechanism of its metabolic activation in vivo in bacteria and liver is under study. In the present study liver tumors were induced in 12-day-old male B6C3F1 mice by single i.p. injections of vinthionine or the alkylating agent 2-chloroethyl methyl sulfide (CEMS). At 10 months the gross tumors were examined for the presence of activated H-ras oncogenes. DNA was isolated from single tumors per mouse from 37 mice treated with vinthionine and from 31 mice treated with CEMS. These DNAs were screened for codon 61 mutations by restriction fragment length polymorphism of PCR-amplified H-ras gene fragments. Thirty seven of 37 vinthionine-induced hepatomas had H-ras mutations in this codon, which consisted of seven C-->A transversions in the first base, with 29 A-->T transversions and one A-->G transition in the second base. Twenty five of 31 CEMS-induced hepatomas had mutations in the same codon, which consisted of seven C-->A transversions in the first base, with eight A-->T transversions and 10 A-->G transitions in the second base. These mutation spectra are quite different to that noted by others in spontaneous hepatomas in untreated B6C3F1 mice. These data appear to result from the covalent binding of these carcinogens to the liver DNA.

  1. Miscoding properties of 1,N{sup 6}-ethanoadenine, a DNA adduct derived from reaction with antitumor agent 1,3-bis(2-chloroethyl)-1-nitrosourea

    SciTech Connect

    Hang, Bo; Guliaev, Anton B.; Chenna, Ahmed; Singer, B.

    2003-03-05

    1,N{sup 6}-Ethanoadenine (EA) is an exocyclic adduct formed from DNA reaction with the antitumor agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). To understand the role of this adduct in the mechanism of mutagenicity or carcinogenicity by BCNU, an oligonucleotide with a site-specific EA was synthesized using phosphoramidite chemistry. We now report the in vitro miscoding properties of EA in translesion DNA synthesis catalyzed by mammalian DNA polymerases (pols) {alpha}, {beta}, {eta} and {iota}. These data were also compared with those obtained for the structurally related exocyclic adduct, 1,N{sup 6}-ethenoadenine ({var_epsilon}A). Using a primer extension assay, both pols {alpha} and {beta} were primarily blocked by EA or {var_epsilon}A with very minor extension. Pol {eta} a member of the Y family of polymerases, was capable of catalyzing a significant amount of bypass across both adducts. Pol {eta} incorporated all four nucleotides opposite EA and {var_epsilon}A, but with differential preferences and mainly in an error-prone manner. Human pol {iota}, a paralog of human pol {eta}, was blocked by both adducts with a very small amount of synthesis past {var_epsilon}A. It incorporated C and, to a much lesser extent, T, opposite either adduct. In addition, the presence of an A adduct, e.g. {var_epsilon}A, could affect the specificity of pol {iota} toward the template T immediately 3 feet to the adduct. In conclusion, the four polymerases assayed on templates containing an EA or {var_epsilon}A showed differential bypass capacity and nucleotide incorporation specificity, with the two adducts not completely identical in influencing these properties. Although there was a measurable extent of error-free nucleotide incorporation, all these polymerases primarily misincorporated opposite EA, indicating that the adduct, similar to {var_epsilon}A, is a miscoding lesion.

  2. 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.

  3. Vesical nephrogenic adenoma: an unusual presentation of a bladder tumour

    PubMed Central

    Martínez-Sanchíz, Carlos; Martínez-Ruiz, Jesús; Anguita-Fernandez, Pedro J.; Giménez-Bachs, José M.; Atiénzar-Tobarra, Manuel; Rodríguez, Julio Antonio Virseda; Salinas-Sánchez, Antonio S.

    2011-01-01

    Vesical nephrogenic adenoma is a rare, benign entity that appears most commonly in middle-aged males. Its etiology is unknown, but it has been linked to chronic irritating factors, such as infection, trauma, urological surgery, kidney stones, foreign bodies and chemical agents, such as Bacille Calmette-Guerin. We report 2 new cases with a history of transurethral resection of the bladder and the prostate and a history of prolonged voiding symptoms. In both cases, the findings of encysted tubular structures lined with flattened cuboidal cells without atypia were consistent with the diagnosis of vesical nephrogenic adenoma. PMID:21989174

  4. N-(4-iodophenyl)-N′-(2-chloroethyl)urea as a microtubule disrupter: in vitro and in vivo profiling of antitumoral activity on CT-26 murine colon carcinoma cell line cultured and grafted to mice

    PubMed Central

    Borel, M; Degoul, F; Communal, Y; Mounetou, E; Bouchon, B; C-Gaudreault, R; Madelmont, J C; Miot-Noirault, E

    2007-01-01

    The antitumoral profile of the microtubule disrupter N-(4-iodophenyl)-N′-(2-chloroethyl)urea (ICEU) was characterised in vitro and in vivo using the CT-26 colon carcinoma cell line, on the basis of the drug uptake by the cells, the modifications of cell cycle, and β-tubulin and lipid membrane profiles. N-(4-iodophenyl)-N′-(2-chloroethyl)urea exhibited a rapid and dose-dependent uptake by CT-26 cells suggesting its passive diffusion through the membranes. Intraperitoneally injected ICEU biodistributed into the grafted CT-26 tumour, resulting thus in a significant tumour growth inhibition (TGI). N-(4-iodophenyl)-N′-(2-chloroethyl)urea was also observed to accumulate within colon tissue. Tumour growth inhibition was associated with a slight increase in the number of G2 tetraploid tumour cells in vivo, whereas G2 blockage was more obvious in vitro. The phenotype of β-tubulin alkylation that was clearly demonstrated in vitro was undetectable in vivo. Nuclear magnetic resonance analysis showed that cells blocked in G2 phase underwent apoptosis, as confirmed by an increase in the methylene group resonance of mobile lipids, parallel to sub-G1 accumulation of the cells. In vivo, a decrease of the signals of both the phospholipid precursors and the products of membrane degradation occurred concomitantly with TGI. This multi-analysis established, at least partly, the ICEU activity profile, in vitro and in vivo, providing additional data in favour of ICEU as a tubulin-interacting drug accumulating within the intestinal tract. This may provide a starting point for researches for future efficacious tubulin-interacting drugs for the treatment of colorectal cancers. PMID:17486131

  5. 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

    . 2. Vogel, S. Search to Resume near AU for WWI Chemicals; Washington Post, January 24, 1999, page C01. 3. Yperite is a trivial name for sulfur mustard or bis(2-chloroethyl) sulfide. The name honors Ypres, Belgium, where the Germans first used sulfur mustard as a chemical weapon on July 12, 1917. 4. Zhao, L. Two Scenes of Poisonous Shells Left Over by Japan in Dunhua, Jilin Province; presented at the Fifth International Symposium on Sino-Japan relations over the past 100 years, Changchun, PRC, September 23-29, 1998.

  6. The application of ethephon (an ethylene releaser) increases growth, photosynthesis and nitrogen accumulation in mustard (Brassica juncea L.) under high nitrogen levels.

    PubMed

    Khan, N A; Mir, M R; Nazar, R; Singh, S

    2008-09-01

    Ethephon (2-chloroethyl phosphonic acid), an ethylene-releasing compound, influences growth and photosynthesis of mustard (Brassica juncea L. Czern & Coss.). We show the effect of nitrogen availability on ethylene evolution and how this affects growth, photosynthesis and nitrogen accumulation. Ethylene evolution in the control with low N (100 mg N kg(-1) soil) was two-times higher than with high N (200 mg N kg(-1) soil). The application of 100-400 microl x l(-1) ethephon post-flowering, i.e. 60 days after sowing, on plants receiving low or high N further increased ethylene evolution. Leaf area, relative growth rate (RGR), photosynthesis, leaf nitrate reductase (NR) activity and leaf N reached a maximum with application of 200 microl x l(-1) ethephon and high N. The results suggest that the application of ethephon influences growth, photosynthesis and N accumulation, depending on the amount of nitrogen in the soil.

  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. Self-immolative nitrogen mustards prodrugs cleavable by carboxypeptidase G2 (CPG2) showing large cytotoxicity differentials in GDEPT.

    PubMed

    Niculescu-Duvaz, Dan; Niculescu-Duvaz, Ion; Friedlos, Frank; Martin, Jan; Lehouritis, Panos; Marais, Richard; Springer, Caroline J

    2003-04-24

    Nineteen novel potential self-immolative prodrugs and their corresponding drugs have been synthesized for gene-directed enzyme prodrug therapy (GDEPT) with carboxypeptidase G2 (CPG2) as the activating enzyme. The compounds are derived from o- and p-amino and p-methylamino aniline nitrogen mustards. Their aqueous stability, kinetics of drug release by CPG2, and cytotoxicity in the colon carcinoma cell line WiDr, expressing either surface-tethered CPG2 (stCPG2(Q)3) or control beta-galactosidase, are assessed. The effect of various structural features on stability, kinetics of activation, and biological activity is discussed. The p-methylamino prodrugs are the most stable compounds from this series, with the largest cytotoxicity differentials between CPG2-expressing and nonexpressing cells. The most potent compounds in all series are prodrugs of bis-iodo nitrogen mustards. 4-[N-[4'-Bis(2' '-iodoethyl)aminophenyl]-N'-methylcarbamoyloxymethyl]phenylcarbamoyl-l-glutamic acid, compound 39b, is 124-fold more cytotoxic to WiDr cells expressing CPG2 than to cells expressing beta-galactosidase. An additional six compounds show better cytotoxicity differential than the published N-[4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl]-l-glutamic acid (CMDA) prodrug.

  9. 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119): a Cytotoxic Prodrug with Two Stable Conformations Differing in Biological and Physical Properties

    PubMed Central

    Penketh, Philip G.; Baumann, Raymond P.; Shyam, Krishnamurthy; Williamson, Hugh S.; Ishiguro, Kimiko; Zhu, Rui; Eriksson, Emma S. E.; Eriksson, Leif A.; Sartorelli, Alan C.

    2011-01-01

    The anticancer prodrug 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119) selectively releases a short-lived cytotoxin following enzymatic reduction in hypoxic environments found in solid tumors. KS119, in addition to two enantiomers, has two stable atropisomers (conformers differing in structure owing to hindered bond rotation) that interconvert at 37 °C in aqueous solution by first order kinetics with t1/2 values of ~50 and ~64 hours. The atropisomers differ in physical properties such as partition coefficients that allow their chromatographic separation on non-chiral columns. A striking difference in the rate of metabolism of the two atropisomers occurs in intact EMT6 murine mammary carcinoma cells under oxygen deficient conditions. A structurally related molecule, 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(3-hydroxy-4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119WOH), was also found to exist in similar stable atropisomers. The ratio of the atropisomers of KS119 and structurally related agents has the potential to impact the bioavailability, activation and therapeutic activity. Thus, thermally stable atropisomers/conformers in small molecules can result in chemically and enantiomerically pure compounds having differences in biological activities. PMID:21777394

  10. 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.

  11. 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

  12. Ocular Effects of Sulfur Mustard and Therapeutic Approaches: A Review.

    PubMed

    Panahi, Yunes; Rajaee, Seyyed Mahdi; Sahebkar, Amirhossein

    2017-01-20

    Sulfur mustard (SM) is a strong blistering, highly reactive, lipophilic chemical war agent that causes injury in different organs including the skin, eyes and respiratory tract. The Eyes are especially susceptible to the consequences of SM poisoning because of the aqueous and mucosal nature of conjunctiva and cornea. DNA alkylation and depletion of glutathione, are the most important mechanisms of SM action in the eye injuries. Acute clinical symptoms are including decrease in visual acuity, dryness, photophobia, blepharospasm, conjunctivitis and complaints of foreign body sensation and soreness that gradually progress to severe ocular pain. Corneal abrasions, ulcerations, vesication and perforations are common corneal consequences in SM injured victims. Appearance of chronic symptoms has been reported as chronic inflammation of the corneal and conjunctival vasculature, ischemia, lipid and cholesterol deposition, scarring in cornea, corneal thinning, opacification and perforation of the cornea, limbal stem cell deficiency (LSCD) and neovascularization. Different medical and surgical protocols have been documented in the management of SM-induced ocular injuries, including preservative-free artificial tears, topical steroids and antibiotic, mydriatic, antiglaucoma drops, therapeutic contact lenses, dark glasses and punctal plugs/cauterization, N-acetylcysteine, tarsorrhaphy, amniotic membrane transplantation, stem cell transplantation and corneal transplantation. New drugs such as resolvin E1, topical form of essential fatty acids, thymosin β4, 43 amino-acid polypeptides, topical form of curcumin, newly formulated artificial tears, diquafosol, rebamipide, tretinoin and oral uridineseems to be beneficial in the management of ocular lesion associated with sulfur mustard poisoning. Further studies are needed to approve these drugs in SM victims. This article is protected by copyright. All rights reserved.

  13. 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.

  14. Topical sulfur mustard induces changes in prostaglandins and interleukin-1 alpha in isolated perfused porcine skin

    SciTech Connect

    Zhang, Z.; Riviere, J.E.; Monteiro-Rivier, N.A.

    1995-12-01

    Su1fur mustard BIS(2-CHLOROETHYL) SULFIDE, HD is an alkylating agent that causes severe cutaneous injury. The isolated perfused porcine skin flap (IPPSF) is an in vitro model that has been utilized in cutaneous toxicity research. The objective of this study was to characterize the local IPPSF inflammatory response after topical exposure to 5.0 and 10.0 mg/ml of I (n = 5/treatment, n = 5/control). Biochemical markers of viability CUMULATIVE GLUCOSE UTILIZATION (CGU), vascular resistance (VR), morphological parameters, and venous flux of prostaglandin E2 (PGE2), prostaglandin F2% (PGF2%, and interleukin la (IL la)) were determined. HD caused a dose-related response in the formation of gross blisters, and epidermal-dermal separation. Decreases in CGU and an increase in VR were seen in all HD-treated IPPsFs. Increase of both PGE2 and PGF2a was observed only in 5.0 mg/ml HD treatment, which showed the greatest increase in VR, while the 10.0 mg/nil concentration of HD enhanced the release of IL-1a. These results suggest that HD is a potent dermal toxic agent that induces alterations in glucose metabolism and vascular resistance, which resulted in dose-specific patterns of PGE2, PGF2a and IL-la release.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. Validation of a protocol to compare the effectiveness of experimental decontaminants with both components of the M258A1 kit against percutaneous application of undiluted vesicant chemical surety material to the laboratory albino rabbit. Final report, 1 March 1985-24 July 1987

    SciTech Connect

    Joiner, R.L.

    1987-07-24

    A rabbit model was developed and validated for screening noninvasive candidate decontamination systems for their efficacies against topical exposure to the vesicant chemical surety material sulfur mustard (HD). Rabbits were dosed with HD on their shaved dorsa and then decontaminated at varying times with either both components of the M258A1 field kit or twice with distilled water. Lesion lengths were estimated and compared contralaterally. Results revealed statistically shorter lesions for M258A1 decontamination relative to the respective lesions decontaminated with distilled water.

  20. In-Line Ozonation for Sensitive Air-Monitoring of a Mustard-Gas Simulant by Atmospheric Pressure Chemical Ionization Mass Spectrometry.

    PubMed

    Okumura, Akihiko

    2015-09-01

    A highly sensitive method for real-time air-monitoring of mustard gas (bis(2-chloroethyl) sulfide, HD), which is a lethal blister agent, is proposed. Humidified air containing a HD simulant, 2-chloroethyl ethyl sulfide (2CEES), was mixed with ozone and then analyzed by using an atmospheric pressure chemical ionization ion trap tandem mass spectrometer. Mass-spectral ion peaks attributable to protonated molecules of intact, monooxygenated, and dioxygenated 2CEES (MH(+), MOH(+), and MO(2)H(+), respectively) were observed. As ozone concentration was increased from zero to 30 ppm, the signal intensity of MH(+) sharply decreased, that of MOH(+) increased once and then decreased, and that of MO(2)H(+) sharply increased until reaching a plateau. The signal intensity of MO(2)H(+) at the plateau was 40 times higher than that of MH(+) and 100 times higher than that of MOH(+) in the case without in-line ozonation. Twenty-ppm ozone gas was adequate to give a linear calibration curve for 2CEES obtained by detecting the MO(2)H(+) signal in the concentration range up to 60 μg/m(3), which is high enough for hygiene management. In the low concentration range lower than 3 μg/m(3), which is equal to the short-term exposure limit for HD, calibration plots unexpectedly fell off the linear calibration curve, but 0.6-μg/m(3) vapor was actually detected with the signal-to-noise ratio of nine. Ozone was generated from instrumentation air by using a simple and inexpensive home-made generator. 2CEES was ozonated in 1-m extended sampling tube in only 1 s.

  1. In-Line Ozonation for Sensitive Air-Monitoring of a Mustard-Gas Simulant by Atmospheric Pressure Chemical Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Okumura, Akihiko

    2015-09-01

    A highly sensitive method for real-time air-monitoring of mustard gas (bis(2-chloroethyl) sulfide, HD), which is a lethal blister agent, is proposed. Humidified air containing a HD simulant, 2-chloroethyl ethyl sulfide (2CEES), was mixed with ozone and then analyzed by using an atmospheric pressure chemical ionization ion trap tandem mass spectrometer. Mass-spectral ion peaks attributable to protonated molecules of intact, monooxygenated, and dioxygenated 2CEES (MH+, MOH+, and MO2H+, respectively) were observed. As ozone concentration was increased from zero to 30 ppm, the signal intensity of MH+ sharply decreased, that of MOH+ increased once and then decreased, and that of MO2H+ sharply increased until reaching a plateau. The signal intensity of MO2H+ at the plateau was 40 times higher than that of MH+ and 100 times higher than that of MOH+ in the case without in-line ozonation. Twenty-ppm ozone gas was adequate to give a linear calibration curve for 2CEES obtained by detecting the MO2H+ signal in the concentration range up to 60 μg/m3, which is high enough for hygiene management. In the low concentration range lower than 3 μg/m3, which is equal to the short-term exposure limit for HD, calibration plots unexpectedly fell off the linear calibration curve, but 0.6-μg/m3 vapor was actually detected with the signal-to-noise ratio of nine. Ozone was generated from instrumentation air by using a simple and inexpensive home-made generator. 2CEES was ozonated in 1-m extended sampling tube in only 1 s.

  2. Development of a liquid chromatography-multiple reaction monitoring procedure for concurrent verification of exposure to different forms of mustard agents.

    PubMed

    Yeo, Thong-Hiang; Ho, Mer-Lin; Loke, Weng-Keong

    2008-01-01

    A novel liquid chromatography-multiple reaction monitoring (LC-MRM) procedure has been developed for retrospective diagnosis of exposure to different forms of mustard agents. This concise method is able to validate prior exposure to nitrogen mustards (HN-1, HN-2, and HN-3) or sulfur mustard (HD) in a single run, which significantly reduces analysis time compared to separate runs to screen for different mustards' biomarkers based on tandem mass spectrometry. Belonging to one of the more toxic classes of chemical warfare agents, these potent vesicants bind covalently to the cysteine-34 residue of human serum albumin. This results in the formation of stable adducts whose identities were confirmed by a de novo sequencing bioinformatics software package. Our developed technique tracks these albumin-derived adduct biomarkers in blood samples which persist in vitro following exposure, enabling a detection limit of 200 nM of HN-1, 100 nM of HN-2, 200 nM of HN-3, or 50 nM of HD in human blood. The CWA-adducts formed in blood samples can be conveniently and sensitively analyzed by this MRM technique to allow rapid and reliable screening.

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

    PubMed

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

    2013-12-05

    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

  4. Neurotoxic compound N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) depletes endogenous norepinephrine and enhances release of (/sup 3/H)norepinephrine from rat cortical slices

    SciTech Connect

    Landa, M.E.; Rubio, M.C.; Jaim-Etcheverry, G.

    1984-10-01

    The alkylating compound N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) injected to rodents blocks norepinephrine (NE) uptake and reduces endogenous NE levels in the central nervous system and in the periphery. To investigate the processes leading to these alterations, rat cortical slices were incubated in the presence of DSP4. Cortical NE was depleted by 40% after incubation of slices in 10(-5) M DSP4 for 60 min and this was blocked by desipramine. The spontaneous outflow of radioactivity from cortical slices labeled previously with (/sup 3/H)NE was enhanced markedly both during exposure to DSP4 and during the subsequent washings, suggesting that NE depletion could be due to this stimulation of NE release. The radioactivity released by DSP4 was accounted for mainly by NE and its deaminated metabolite 3,4-dihydroxyphenylglycol. The enhanced release, independent of external Ca++, apparently originated from the vesicular pool as it was absent after reserpine pretreatment. Activities of the enzymes related to NE synthesis were not altered by DSP4 in vitro and only monoamine oxidase activity was inhibited at high concentrations. Thus, the depletion of endogenous NE produced by DSP4 is probably due to a persistent enhancement of its release from the vesicular pool. Fixation of DSP4 to the NE transport system is necessary but not sufficient to produce the acute NE depletion and the characteristic long-term actions of the compound.

  5. Synthesis, characterization, crystal structure determination and computational study of a new Cu(II) complex of bis [2-{(E)-[2-chloroethyl)imino]methyl}phenolato)] copper(II) Schiff base complex

    NASA Astrophysics Data System (ADS)

    Grivani, Gholamhossein; Vakili, Mohammad; Khalaji, Aliakbar Dehno; Bruno, Giuseppe; Rudbari, Hadi Amiri; Taghavi, Maedeh

    2016-07-01

    The copper (II) Schiff base complex of [CuL2] (1), HL = 2-{(E)-[2-chloroethyl) imino]methyl}phenol, has been synthesized and characterized by elemental (CHN) analysis, UV-Vis and FT-IR spectroscopy. The molecular structure of 1 was determined by single crystal X-ray diffraction technique. The conformational analysis and molecular structures of CuL2 were investigated by means of density functional theory (DFT) calculations at B3LYP/6-311G* level. An excellent agreement was observed between theoretical and experimental results. The Schiff base ligand of HL acts as a chelating ligand and coordinates via one nitrogen atom and one oxygen atom to the metal center. The copper (II) center is coordinated by two nitrogen atoms and two oxygen atoms from two Schiff base ligands in an approximately square planar trans-[MN2O2] coordination geometry. Thermogravimetric analysis of CuL2 showed that it was decomposed in five stages. In addition, the CuL2 complex thermally decomposed in air at 660 °C and the XRD pattern of the obtained solid showed the formation of CuO nanoparticles with an average size of 34 nm.

  6. N-(2-chloroethyl)-N-nitrosoureas covalently bound to nonionic and monocationic lexitropsin dipeptides. Synthesis, DNA affinity binding characteristics, and reactions with sup 32 P-end-labeled DNA

    SciTech Connect

    Church, K.M.; Wurdeman, R.L.; Zhang, Yi; Chen, Faxian; Gold, B. )

    1990-07-24

    The synthesis and characterization of a series of compounds that contain an N-alkyl-N-nitrosourea functionality linked to DNA minor groove binding bi- and tripeptides (lexitropsins or information-reading peptides) based on methylpyrrole-2-carboxamide subunits are described. The lexitropsins (lex) synthesized have either a 3-(dimethylamino)propyl or propyl substituent on the carboxyl terminus. The preferred DNA affinity binding sequences of these compounds were footprinted in {sup 32}P-end-labeled restriction fragments with methidiumpropyl-EDTA{center dot}Fe(II), and in common with other structural analogues, e.g., distamycin and netropsin, these nitrosoureas recognize A-T-rich runs. The affinity binding of the compound with the dimethylamino terminus, which is ionized at near-neutral pH, appeared stronger than that observed for the neutral dipeptide. The sequence specificity for DNA alkylation by (2-chloroethyl)nitrosourea-lex dipeptides (Cl-ENU-lex), with neutral and charged carboxyl termini, using {sup 32}P-end-labeled restriction fragments, was determined by the conversion of the adducted sites into single-strand breaks by sequential heating at neutral pH and exposure to base. The DNA cleavage sites were visualized by polyacrylamide gel electrophoresis and autoradiography. Linking the Cl-ENU moiety to minor groove binders is a viable strategy to qualitatively and quantitatively control the delivery and release of the ultimate DNA alkylating agent in a sequence-dependent fashion.

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

    PubMed

    Graham, John S; Schoneboom, Bruce A

    2013-12-05

    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

  8. 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.

  9. Locus-specific microemulsion catalysts for sulfur mustard (HD) chemical warfare agent decontamination.

    PubMed

    Fallis, Ian A; Griffiths, Peter C; Cosgrove, Terence; Dreiss, Cecile A; Govan, Norman; Heenan, Richard K; Holden, Ian; Jenkins, Robert L; Mitchell, Stephen J; Notman, Stuart; Platts, Jamie A; Riches, James; Tatchell, Thomas

    2009-07-22

    The rates of catalytic oxidative decontamination of the chemical warfare agent (CWA) sulfur mustard (HD, bis(2-chlororethyl) sulfide) and a range (chloroethyl) sulfide simulants of variable lipophilicity have been examined using a hydrogen peroxide-based microemulsion system. SANS (small-angle neutron scattering), SAXS (small-angle X-ray scattering), PGSE-NMR (pulsed-gradient spin-echo NMR), fluorescence quenching, and electrospray mass spectroscopy (ESI-MS) were implemented to examine the distribution of HD, its simulants, and their oxidation/hydrolysis products in a model oil-in-water microemulsion. These measurements not only present a means of interpreting decontamination rates but also a rationale for the design of oxidation catalysts for these toxic materials. Here we show that by localizing manganese-Schiff base catalysts at the oil droplet-water interface or within the droplet core, a range of (chloroethyl) sulfides, including HD, spanning some 7 orders of octanol-water partition coefficient (K(ow)), may be oxidized with equal efficacy using dilute (5 wt. % of aqueous phase) hydrogen peroxide as a noncorrosive, environmentally benign oxidant (e.g., t(1/2) (HD) approximately 18 s, (2-chloroethyl phenyl sulfide, C(6)H(5)SCH(2)CH(2)Cl) approximately 15 s, (thiodiglycol, S(CH(2)CH(2)OH)(2)) approximately 19 s {20 degrees C}). Our observations demonstrate that by programming catalyst lipophilicity to colocalize catalyst and substrate, the inherent compartmentalization of the microemulsion can be exploited to achieve enhanced rates of reaction or to exert control over product selectivity. A combination of SANS, ESI-MS and fluorescence quenching measurements indicate that the enhanced catalytic activity is due to the locus of the catalyst and not a result of partial hydrolysis of the substrate.

  10. The Determination of Mustard Gas and Related Vesicants in Rubber and Paint by Gas Chromatography-Mass Spectrometry

    DTIC Science & Technology

    1992-12-01

    genomen kunnen worden op een slagveld na gebruik van chemische strijdmiddelen. Binnen bet kader van de opdracbt A84/Y,/159 ’Identificatie van chemische...publicatie gebruikt. TNO-report PML 214492016 Page 4 CONTENTS SUMMARYISAMENVATTING 2 VOORWOORD 3 CONTENTS 4 1 INTRODUCTION 5 2 EXPERIMENTAL 5 2.1...TNO-roport PNI. 2144Q 201 b imgc 12 4 AUTHENTICATION E.R. Wil H.L, Boter (author) (project manager ) TNO-report PML 214492016 Page 13 5 REFERENCES 1

  11. Spontaneous bladder rupture caused by a giant vesical calculus.

    PubMed

    Kaur, Navneet; Attam, Amit; Gupta, Ashish; Amratash

    2006-01-01

    Spontaneous rupture of the urinary bladder is an uncommon occurrence. A 36-year-old man had complaints of pain and progressive distension of abdomen and anuria for 2 days. His abdomen was tense, tender and distended with free fluid. Blood urea was 340 mg% and ascitic fluid urea was 337 mg%. An USG showed massive ascitis, a large vesical calculus and a left renal calculus. The urinary bladder could not be catheterized. Patient underwent hemodialysis and placement of abdominal drains. About 2 l of yellow turbid fluid was drained. Cystolithotomy showed a 6 cm size impacted calculus with a rent in the dome of the bladder, which was repaired. Subsequently patient underwent percutaneous nephrolithotrypsy for left staghorn renal calculus and nephrectomy for right non-functioning kidney.

  12. Activation of DNA damage repair pathways in response to nitrogen mustard-induced DNA damage and toxicity in skin keratinocytes.

    PubMed

    Inturi, Swetha; Tewari-Singh, Neera; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2014-01-01

    Nitrogen mustard (NM), a structural analog of chemical warfare agent sulfur mustard (SM), forms adducts and crosslinks with DNA, RNA and proteins. Here we studied the mechanism of NM-induced skin toxicity in response to double strand breaks (DSBs) resulting in cell cycle arrest to facilitate DNA repair, as a model for developing countermeasures against vesicant-induced skin injuries. NM exposure of mouse epidermal JB6 cells decreased cell growth and caused S-phase arrest. Consistent with these biological outcomes, NM exposure also increased comet tail extent moment and the levels of DNA DSB repair molecules phospho H2A.X Ser139 and p53 Ser15 indicating NM-induced DNA DSBs. Since DNA DSB repair occurs via non homologous end joining pathway (NHEJ) or homologous recombination repair (HRR) pathways, next we studied these two pathways and noted their activation as defined by an increase in phospho- and total DNA-PK levels, and the formation of Rad51 foci, respectively. To further analyze the role of these pathways in the cellular response to NM-induced cytotoxicity, NHEJ and HRR were inhibited by DNA-PK inhibitor NU7026 and Rad51 inhibitor BO2, respectively. Inhibition of NHEJ did not sensitize cells to NM-induced decrease in cell growth and cell cycle arrest. However, inhibition of the HRR pathway caused a significant increase in cell death, and prolonged G2M arrest following NM exposure. Together, our findings, indicating that HRR is the key pathway involved in the repair of NM-induced DNA DSBs, could be useful in developing new therapeutic strategies against vesicant-induced skin injury.

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

    PubMed Central

    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 (IC50 = 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

  14. 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

  15. Pretreatment of primary rat cutaneous epidermal keratinocyte culture with a low concentration of MNNG: Effect on DNA cross-linking measured in situ after challenge with bis-2-chloroethyl sulfide

    SciTech Connect

    Sorsher, D.H.; Conolly, R.B. )

    1989-01-01

    Bis-2-chloroethyl sulfide- (BCES-) induced DNA cross-links in confluent, primary cultures of newborn rat cutaneous epidermal keratinocytes were detected using an assay that includes in situ unwinding of the DNA followed by separation of single-stranded DNA and double-stranded DNA (DSDNA) with hydroxylapatite. DNA cross-links in BCES-challenged cultures were inferred form increases in the percentage of DNA the remained double-stranded, compared with control cultures, after a 60-min alkaline unwinding incubation. The amount of DNA cross-linking after 5 or 10 {mu}M BCES was increased when keratinocytes were first pretreated with 0.05 {mu}M MNNG for 1 h at 8 a.m., 2 p.m., and 8 p.m. for two consecutive days and challenged with BCES the following morning. This increase was statistically significant. For example, after 5{mu}M BCES challenge, cultures not pretreated with MNNG had 114.14% control DSDNA, whereas MNNG pretreated cultures had 122.78% control DSDNA. The level of BCES-induced cross-linking was maximal immediately after 30-min challenge and decreased during postchallenge incubation. At 24 and 48 h post 5, 10, or 20 {mu}M BCES challenge, the level of DSDNA was actually depressed below unchallenged levels. This postchallenge decreased in the level of DSDNA, indicative of SSB in DNA, suggests repair activity by glycosylases and endonucleases. However completion of repair (i.e., a return to control levels of DSDNA) was not seen in these experiments. The activity that resulted in decreases in the level of DSDNA during postchallenge incubation response was unaffected by MNNG pretreatment.

  16. The effect of denervation of the locus coeruleus projections with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on cocaine-induced locomotion and place preference in rats.

    PubMed

    Kõiv, Kadri; Zobel, Rein; Raudkivi, Karita; Kivastik, Toomas; Harro, Jaanus

    2011-01-01

    The potential contribution of locus coeruleus (LC)-derived noradrenaline (NA) in the motor activating and rewarding effects of cocaine (15 mg/kg) were assessed following administration of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). In Experiment 1, administration of 10 mg/kg of DSP-4 similarly to substantial denervation with 50 mg/kg of DSP-4 significantly attenuated the activating effects of cocaine during the first cocaine-paired training session (30 min) in the conditioned place preference (CPP) apparatus. Only administration of the higher dose (50 mg/kg) of DSP-4 attenuated line crossings during the last training, while both doses reduced rearings. Thus, both minor and substantial denervation of LC reduced but did not abolish locomotion activating effect of cocaine. Cocaine CPP as measured by increment of time spent in the previously cocaine-paired chamber during drug-free conditions before and after cocaine-paired trainings was clearly revealed only in animals with intact projections from the LC, and was entirely absent after a large lesion of LC projections by DSP-4 (50 mg/kg). Because recovery of noradrenaline levels by the end of experiment did not allow assessment of the efficacy of the neurotoxin, the effect of DSP-4 pre-treatment on the acute psychomotor effect of cocaine was re-examined in an independent experiment (Experiment 2). Near complete denervation of the LC projections again reduced the effect of cocaine, but the lower dose of DSP-4 had no effect, suggesting that small lesions of the LC do not have a robust impact. Overall, this study demonstrates that both unconditioned and conditioned effects of cocaine depend upon the integrity of LC projections.

  17. Effect of spermine synthase deficiency on polyamine biosynthesis and content in mice and embryonic fibroblasts, and the sensitivity of fibroblasts to 1,3-bis-(2-chloroethyl)-N-nitrosourea.

    PubMed Central

    Mackintosh, C A; Pegg, A E

    2000-01-01

    Mutant Gy male mice, which have previously been described as having disruption of the phosphate-regulating Phex gene and a spermine synthase gene [Meyer, Henley, Meyer, Morgan, McDonald, Mills and Price (1998) Genomics, 48, 289-295; Lorenz, Francis, Gempel, Böddrich, Josten, Schmahl and Schmidt (1998) Hum. Mol. Genet. 7, 541-547], as well as mutant Hyp male mice, which have disruption of the Phex gene only, were examined along with their respective normal male littermates. Biochemical analyses of extracts of brains, hearts and livers of 5-week-old mice showed that Gy males lacked any significant spermine synthase activity as well as spermine content. Organs of Gy males had a higher spermidine content. This was caused not only by the lack of conversion of spermidine into spermine, but also because of compensatory increases in the activities of other polyamine biosynthetic enzymes. Gy males were half the body weight of their normal male littermates at weaning age. Hyp males, however, were no different in size when compared with their controls. High mortality of Gy males occurs by weaning age and this mortality was shown to be largely post-natal. Embryonic fibroblasts were isolated from Gy males and their normal male littermates and were similarly shown to lack any significant spermine synthase activity as well as spermine content. The lack of spermine, however, had no significant effect on the growth of immortalized fibroblasts or of primary fibroblast cultures. Similarly, there was no difference in the time of senescence of primary fibroblast cultures from Gy males compared with cultures derived from normal male littermates. However, the lack of spermine did increase the sensitivity of immortalized fibroblasts to killing by the chloroethylating agent 1, 3-bis(2-chloroethyl)-N-nitrosourea. Therefore both the Gy male mice and derived embryonic fibroblasts provide valuable models to study the importance of spermine and spermine synthase, without the use of inhibitors

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

    PubMed

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

    2013-12-05

    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.

  19. Molecular Strategies Against Sulfur Mustard Toxicity

    DTIC Science & Technology

    2010-04-01

    meiosis . Our current understanding of epigenetic regulation of gene expression involves basically two classes of molecular mechanisms: histone...Molecular Strategies Against Sulfur Mustard Toxicity 30 - 4 RTO-MP-HFM-182 meiosis . Our current understanding of epigenetic gene regulation

  20. 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.

  1. The Toxicity of Inhaled Sulphur Mustard

    DTIC Science & Technology

    2012-03-01

    acetyl -L- cysteine (Mucomyst™; NAC ), in ameliorating inhaled HD-induced lung injury was then assessed in the established model. This work was conducted...J and Sciuto AM. N- acetyl -L- cysteine ( NAC ) Protects Against Inhaled Sulfur Mustard (HD) Poisoning in the Large Swine. Clinical Toxicology, 2012...2012. N- acetyl -L- cysteine ( NAC ) Protects against inhaled sulfur mustard (HD) poisoning in the large swine. Clinical Toxicology; in preparation

  2. 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.

  3. Repeated administration of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) modulates neuroinflammation and amyloid plaque load in mice bearing amyloid precursor protein and presenilin-1 mutant transgenes

    PubMed Central

    Pugh, Perdita L; Vidgeon-Hart, Martin P; Ashmeade, Tracey; Culbert, Ainsley A; Seymour, Zoe; Perren, Marion J; Joyce, Flora; Bate, Simon T; Babin, Anna; Virley, David J; Richardson, Jill C; Upton, Neil; Sunter, David

    2007-01-01

    Background Data indicates anti-oxidant, anti-inflammatory and pro-cognitive properties of noradrenaline and analyses of post-mortem brain of Alzheimer's disease (AD) patients reveal major neuronal loss in the noradrenergic locus coeruleus (LC), the main source of CNS noradrenaline (NA). The LC has projections to brain regions vulnerable to amyloid deposition and lack of LC derived NA could play a role in the progression of neuroinflammation in AD. Previous studies reveal that intraperitoneal (IP) injection of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) can modulate neuroinflammation in amyloid over-expressing mice and in one study, DSP-4 exacerbated existing neurodegeneration. Methods TASTPM mice over-express human APP and beta amyloid protein and show age related cognitive decline and neuroinflammation. In the present studies, 5 month old C57/BL6 and TASTPM mice were injected once monthly for 6 months with a low dose of DSP-4 (5 mg kg-1) or vehicle. At 8 and 11 months of age, mice were tested for cognitive ability and brains were examined for amyloid load and neuroinflammation. Results At 8 months of age there was no difference in LC tyrosine hydroxylase (TH) across all groups and cortical NA levels of TASTPM/DSP-4, WT/Vehicle and WT/DSP-4 were similar. NA levels were lowest in TASTPM/Vehicle. Messenger ribonucleic acid (mRNA) for various inflammatory markers were significantly increased in TASTPM/Vehicle compared with WT/Vehicle and by 8 months of age DSP-4 treatment modified this by reducing the levels of some of these markers in TASTPM. TASTPM/Vehicle showed increased astrocytosis and a significantly larger area of cortical amyloid plaque compared with TASTPM/DSP-4. However, by 11 months, NA levels were lowest in TASTPM/DSP-4 and there was a significant reduction in LC TH of TASTPM/DSP-4 only. Both TASTPM groups had comparable levels of amyloid, microglial activation and astrocytosis and mRNA for inflammatory markers was

  4. Gas chromatography-electron ionization mass spectrometry and liquid chromatography-electrospray tandem mass spectrometry for determination of impurities in the anti-cancer drug isophosphoramide mustard

    NASA Astrophysics Data System (ADS)

    Cole, Richard B.; Chou, Chau-Wen; Boué, Stephen M.; Leblanc, Blaise W.; Rodgers, Andrew H.; Struck, Robert F.; Morgan, Lee Roy

    2004-02-01

    Isophosphoramide mustard (IPM) is known to have substantial anti-cancer activities in various animal models. Liquid chromatography-electrospray mass spectrometry (LC-ES-MS) and LC-ES-MS/MS methodologies have been developed and applied to the analysis of synthesized preparations of IPM. Our studies reveal that the principal impurity in IPM is N-(2-chloroethyl)-N'-ethylphosphorodiamidic acid (MC-IPM) formed by dehydrochlorination of IPM with subsequent hydrogenation during synthesis. This impurity is present at levels in the range of 2-5% depending upon synthesis conditions. In addition, a second IPM derivative has been characterized by LC-ES-MS/MS and has been shown to be the product of a reaction of IPM with the dilute perchloric acid mobile phase used for liquid chromatography separations. The LC-ES-MS/MS method has been successfully employed to detect IPM spiked into a blood plasma sample. This work establishes that LC-ES-MS/MS is a viable tool for the detailed characterization of IPM and related products.

  5. 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.

  6. A New Cross-Link for an Old Cross-Linking Drug: The Nitrogen Mustard Anticancer Agent Mechlorethamine Generates Cross-Links Derived from Abasic Sites in Addition to the Expected Drug-Bridged Cross-Links.

    PubMed

    Nejad, Maryam Imani; Johnson, Kevin M; Price, Nathan E; Gates, Kent S

    2016-12-20

    Nitrogen mustard anticancer drugs generate highly reactive aziridinium ions that alkylate DNA. Monoadducts arising from reaction with position N7 of guanine residues are the major DNA adducts generated by these agents. Interstrand cross-links in which the drug bridges position N7 of two guanine residues are formed in low yields relative to those of the monoadducts but are generally thought to be central to medicinal activity. The N7-alkylguanine residues generated by nitrogen mustards are depurinated to yield abasic (Ap) sites in duplex DNA. Here, we show that Ap sites generated by the nitrogen mustard mechlorethamine lead to interstrand cross-links of a type not previously associated with this drug. Gel electrophoretic data were consistent with early evolution of the expected drug-bridged cross-links, followed by the appearance of Ap-derived cross-links. The evidence is further consistent with a reaction pathway involving alkylation of a guanine residue in a 5'-GT sequence, followed by depurination to generate the Ap site, and cross-link formation via reaction of the Ap aldehyde residue with the opposing adenine residue at this site [Price, N. E., Johnson, K. M., Wang, J., Fekry, M. I., Wang, Y., and Gates, K. S. (2014) J. Am. Chem. Soc. 136, 3483-3490]. The monofunctional DNA-alkylating agents 2-chloro-N,N-diethylethanamine 5, (2-chloroethyl)ethylsulfide 6, and natural product leinamycin similarly were found to induce the formation of Ap-derived cross-links in duplex DNA. This work provides the first characterization of Ap-derived cross-links at sequences in which a cytosine residue is located directly opposing the Ap site. Cross-linking processes of this type could be relevant in medicine and biology because Ap sites with directly opposing cytosine residues occur frequently in genomic DNA via spontaneous or enzymatic depurination of guanine and N7-alkylguanine residues.

  7. 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.

  8. Sulfur Mustard Research—Strategies for the Development of Improved Medical Therapy

    PubMed Central

    Kehe, Kai; Balszuweit, Frank; Emmler, Judith; Kreppel, Helmut; Jochum, Marianne; Thiermann, Horst

    2008-01-01

    Objective: Sulfur mustard (SM) is a bifunctional alkylating substance being used as chemical warfare agent (vesicant). It is still regarded as a significant threat in chemical warfare and terrorism. Exposure to SM produces cutaneous blisters, respiratory and gastrointestinal tract injury, eye lesions, and bone marrow depression. Victims of World War I as well as those of the Iran-Iraq war have suffered from devastating chronic health impairment. Even decades after exposure, severe long-term effects like chronic obstructive lung disease, lung fibrosis, recurrent corneal ulcer disease, chronic conjunctivitis, abnormal pigmentation of the skin, and different forms of cancer have been diagnosed. Methods: This review briefly summarizes the scientific literature and own results concerning detection, organ toxicity of SM, its proposed toxicodynamic actions, and strategies for the development of improved medical therapy. Results: Despite extensive research efforts during the last century, efficient antidotes against SM have not yet been generated because its mechanism of action is not fully understood. However, deeper insights into these mechanisms gained in the last decade and promising developments of new drugs now offer new chances to minimize SM-induced organ damage and late effects. Conclusion: Polymerase inhibitors, anti-inflammatory drugs, antioxidants, matrix metalloproteinase inhibitors, and probably regulators of DNA damage repair are identified as promising approaches to improve treatment. PMID:18615149

  9. Quenching action of monofunctional sulfur mustard on chlorophyll fluorescence: towards an ultrasensitive biosensor.

    PubMed

    Kaur, Simerjit; Singh, Minni; Flora, Swaran Jeet Singh

    2013-11-01

    An ultrasensitive fluorimetric biosensor for the detection of chemical warfare agent sulfur mustard (SM) was developed using its monofunctional analogue. SM is a vesicant and a potent chemical threat owing to its direct toxic effects on eyes, lungs, skin and DNA. This work investigates the quenching action of the analyte on chlorophyll fluorescence as elucidated by nuclear magnetic resonance, Fourier transform infrared spectroscopy and mass spectrometry studies suggesting the electrophilic attack of carbonium ion on nitrogens of the porphyrin moiety of chlorophyll. The properties of immobilisation matrix were optimised and scanning electron microscope observations confirmed improvement in pore size of sol-gels by addition of 32 % (v/v) glycerol, a feature enabling enhanced sensitivity towards the analyte. Chlorophyll embedded sol-gel was treated with increasing concentrations of monofunctional SM and the corresponding drop in maximum fluorescence intensity as measured by emission at 673 nm was observed, which varied linearly and had a detection limit of 7.68 × 10(-16) M. The biosensor was found to be 6 orders of magnitude more sensitive than the glass microfibre-based disc biosensor previously reported by us.

  10. 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.

  11. Sulfur mustard-induced increase in intracellular free calcium level and arachidonic acid release from cell membrane

    SciTech Connect

    Ray, R.; Legere, R.H.; Majerus, B.J.; Petrali, J.P.

    1995-12-31

    The mechanism of action of the alkylating agent bis-(2-chloroethyl)sulfide (sulfur mustard, SM) was studied using the in thai vitro mouse neuroblastoma-rat glioma hybrid NG 108-1 S clonal p cell line model. Following 0.3 mM SM exposure, cell viability remained high (>80% of untreated control) up to 9 hr and then declined steadily to about 40% of control after 20-24 hr. During the early period of SM exposure, when there was no significant cell viability loss, the following effects were observed. The cellular glutathione level decreased 20% after 1 hr and 34% after 6 hr. Between 2 and 6 hr, there was a time-dependent increase (about 10 to 30%) in intracellular free calcium (Ca2+), which was localized to the limiting membrane of swollen endoplasmic reticula and mitochondria, to euchromatin areas of the nucleus, and to areas of the cytosol and plasma membrane. Moreover,there was also a time-dependent increase in the release of isotopically labeled arachidonic acid ((3H)AA) from cellular membranes. Increase in (3H)AA release was 28% at 3 hr and about 60-80% between 6 and 9 hr. This increase in I3HIAA release was inhibited by quinacrine (20 uM), which is a phospholipase (PLA2) inhibitor. At 16 hr after SM exposure, there was a large increase (about 200% of control) in I3HIAA release, which was coincident with a 50% loss of cell viability. These results suggest a Ca2+-mediated toxic mechanism of SM via PLA2 activation and arachidonate release.

  12. Thioredoxin Cross-Linking by Nitrogen Mustard in Lung Epithelial Cells: Formation of Multimeric Thioredoxin/Thioredoxin Reductase Complexes and Inhibition of Disulfide Reduction.

    PubMed

    Jan, Yi-Hua; Heck, Diane E; Casillas, Robert P; Laskin, Debra L; Laskin, Jeffrey D

    2015-11-16

    The thioredoxin (Trx) system, which consists of Trx and thioredoxin reductase (TrxR), is a major cellular disulfide reduction system important in antioxidant defense. TrxR is a target of mechlorethamine (methylbis(2-chloroethyl)amine; HN2), a bifunctional alkylating agent that covalently binds to selenocysteine/cysteine residues in the redox centers of the enzyme, leading to inactivation and toxicity. Mammalian Trx contains two catalytic cysteines; herein, we determined if HN2 also targets Trx. HN2 caused a time- and concentration-dependent inhibition of purified Trx and Trx in A549 lung epithelial cells. Three Trx cross-linked protein complexes were identified in both cytosolic and nuclear fractions of HN2-treated cells. LC-MS/MS of these complexes identified both Trx and TrxR, indicating that HN2 cross-linked TrxR and Trx. This is supported by our findings of a significant decrease of Trx/TrxR complexes in cytosolic TrxR knockdown cells after HN2 treatment. Using purified recombinant enzymes, the formation of protein cross-links and enzyme inhibition were found to be redox status-dependent; reduced Trx was more sensitive to HN2 inactivation than the oxidized enzyme, and Trx/TrxR cross-links were only observed using reduced enzyme. These data suggest that HN2 directly targets catalytic cysteine residues in Trx resulting in enzyme inactivation and protein complex formation. LC-MS/MS confirmed that HN2 directly alkylated cysteine residues on Trx, including Cys32 and Cys35 in the redox center of the enzyme. Inhibition of the Trx system by HN2 can disrupt cellular thiol-disulfide balance, contributing to vesicant-induced lung toxicity.

  13. 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.

  14. Sulfur and nitrogen mustards induce characteristic poly(ADP-ribosyl)ation responses in HaCaT keratinocytes with distinctive cellular consequences.

    PubMed

    Mangerich, Aswin; Debiak, Malgorzata; Birtel, Matthias; Ponath, Viviane; Balszuweit, Frank; Lex, Kirsten; Martello, Rita; Burckhardt-Boer, Waltraud; Strobelt, Romano; Siegert, Markus; Thiermann, Horst; Steinritz, Dirk; Schmidt, Annette; Bürkle, Alexander

    2016-02-26

    Mustard agents are potent DNA alkylating agents with mutagenic, cytotoxic and vesicant properties. They include bi-functional agents, such as sulfur mustard (SM) or nitrogen mustard (mustine, HN2), as well as mono-functional agents, such as "half mustard" (CEES). Whereas SM has been used as a chemical warfare agent, several nitrogen mustard derivatives, such as chlorambucil and cyclophosphamide, are being used as established chemotherapeutics. Upon induction of specific forms of genotoxic stimuli, several poly(ADP-ribose) polymerases (PARPs) synthesize the nucleic acid-like biopolymer poly(ADP-ribose) (PAR) by using NAD(+) as a substrate. Previously, it was shown that SM triggers cellular poly(ADP-ribosyl) ation (PARylation), but so far this phenomenon is poorly characterized. In view of the protective effects of PARP inhibitors, the latter have been proposed as a treatment option of SM-exposed victims. In an accompanying article (Debiak et al., 2016), we have provided an optimized protocol for the analysis of the CEES-induced PARylation response in HaCaT keratinocytes, which forms an experimental basis to further analyze mustard-induced PARylation and its functional consequences, in general. Thus, in the present study, we performed a comprehensive characterization of the PARylation response in HaCaT cells after treatment with four different mustard agents, i.e., SM, CEES, HN2, and chlorambucil, on a qualitative, quantitative and functional level. In particular, we recorded substance-specific as well as dose- and time-dependent PARylation responses using independent bioanalytical methods based on single-cell immuno-fluorescence microscopy and quantitative isotope dilution mass spectrometry. Furthermore, we analyzed if and how PARylation contributes to mustard-induced toxicity by treating HaCaT cells with CEES, SM, and HN2 in combination with the clinically relevant PARP inhibitor ABT888. As evaluated by a novel immunofluorescence-based protocol for the detection of

  15. Histopathological and immunohistochemical evaluation of nitrogen mustard-induced cutaneous effects in SKH-1 hairless and C57BL/6 mice

    PubMed Central

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

    2014-01-01

    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 (3.2 mg) exposure for 12–120 h 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 in 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 (12–24 h); however, at later time points (72 and 120 h), dense collagen staining was observed, indicating either water loss or start of integument repair in both 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

  16. 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.

  17. Medical Management of Cutaneous Sulfur Mustard Injuries

    DTIC Science & Technology

    2009-01-01

    Three of the four sites on each animal were xposed to undiluted liquid sulfur mustard for 8min to produce superficial dermal njuries. The fourth site...previously xposed to HD. If the primary aim of using this technology on a atient is to address hyperpigmentation by applying autologous elanocytes (along with

  18. 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

  19. 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.

  20. 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....

  1. 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....

  2. 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....

  3. 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....

  4. 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

  5. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor

    SciTech Connect

    Malaviya, Rama; Venosa, Alessandro; Hall, LeRoy; Gow, Andrew J.; Sinko, Patrick J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-12-15

    Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d–28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS{sup +} and cyclooxygenase-2{sup +}) and alternatively activated profibrotic (YM-1{sup +} and galectin-3{sup +}) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 ×/day, 1 d–3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ► Nitrogen mustard (NM) induces acute lung injury and fibrosis. ► Pulmonary toxicity is associated with increased expression of iNOS. ► Transient inhibition of iNOS attenuates acute

  6. 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.

  7. Cutaneous injury-related structural changes and their progression following topical nitrogen mustard exposure in hairless and haired mice.

    PubMed

    Tewari-Singh, Neera; Jain, Anil K; 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.

  8. Absence of a p53 allele delays nitrogen mustard-induced early apoptosis and inflammation of murine skin.

    PubMed

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

    2013-09-15

    Bifunctional alkylating agent sulfur mustard (SM) and its analog nitrogen mustard (NM) cause DNA damage leading to cell death, and potentially activating inflammation. Transcription factor p53 plays a critical role in DNA damage by regulating cell cycle progression and apoptosis. Earlier studies by our laboratory demonstrated phosphorylation of p53 at Ser15 and an increase in total p53 in epidermal cells both in vitro and in vivo following NM exposure. To elucidate the role of p53 in NM-induced skin toxicity, we employed SKH-1 hairless mice harboring wild type (WT) or heterozygous p53 (p53+/-). Exposure to NM (3.2mg) caused a more profound increase in epidermal thickness and apoptotic cell death in WT relative to p53+/- mice at 24h. However, by 72h after exposure, there was a comparable increase in NM-induced epidermal cell death in both WT and p53+/- mice. Myeloperoxidase activity data showed that neutrophil infiltration was strongly enhanced in NM-exposed WT mice at 24h persisting through 72h of exposure. Conversely, robust NM-induced neutrophil infiltration (comparable to WT mice) was seen only at 72h after exposure in p53+/- mice. Similarly, NM-exposure strongly induced macrophage and mast cell infiltration in WT, but not p53+/- mice. Together, these data indicate that early apoptosis and inflammation induced by NM in mouse skin are p53-dependent. Thus, targeting this pathway could be a novel strategy for developing countermeasures against vesicants-induced skin injury.

  9. Pretreatment of isolated human peripheral blood lymphocytes with l-oxothiazolidine 4-carboxylate reduces sulfur mustard cytotoxicity

    SciTech Connect

    Gross, C.L.; Smith, W.J.

    1993-05-13

    Despite 70 years of research, there appears to be no satisfactory prophylaxis or treatment for the vesicant chemical warfare agent sulfur mustard (HD). Attempts to modify cytotoxicity of HD are now focusing on the use of intracellular 'scavengers' to interact with sulfur mustard before it can react with critical targets within the cell. Glutathione (GSH) is known to react readily with HD and is involved in the major metabolic pathway to HD detoxification. Glutathione level within the cell was raised 40-60% over control values by pretreatment of quiescent human peripheral blood lymphocytes (PBL) with 10 mM L-oxothiazolidine-4-carboxylate (OTC), a masked cysteine precursor. This increase in glutathione level was not toxic to the cells as judged by trypan blue dye exclusion and reached a maximum level in 48 hrs. PBL pretreated with 10 mM OTC for 48 hrs were harvested, washed, and exposed to 10, 50, or 100 uM HD. After an additional 48 hrs of incubation at 37 deg C, cytotoxicity was measured by propidium iodide dye uptake using flow cytometry. Pretreatment with OTC led to a 20% decrease in cytotoxicity with 10 uM HD, an 11% decrease in cytotoxicity with 50 uM HD, and an 8% decrease in cytotoxicity with 100 uM HD. Cytotoxicity of HD was not influenced by addition of 10 mM OTC 2 hrs after HD exposure. These results suggest that biochemical manipulation of intracellular GSH level may provide an important pretreatment regimen to reduce the cytotoxicity of HD.

  10. 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

  11. Putting some mustard into economic growth.

    PubMed

    Evans, Robert G

    2012-11-01

    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.

  12. Neutralization and Biodegradation of Sulfur Mustard.

    DTIC Science & Technology

    1997-02-01

    obtained from activated sludge (Back River Wastewater Treatment Plant, Baltimore, MD). Initial mixed liquor suspended solids (MLSS) levels were...BIODEGRADATION OF SULFUR MUSTARD Steven P. Harvey Linda L. Szafraniec William T. Beaudry RESEARCH AND TECHNOLOGY DIRECTORATE James T. Earley SBR TECHNOLOGIES, INC... SBR Technologies, Inc.); and Irvine, Robert L. (University of Notre Dame) 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION

  13. Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation.

    PubMed

    Sunil, Vasanthi R; Vayas, Kinal N; Cervelli, Jessica A; Malaviya, Rama; Hall, LeRoy; Massa, Christopher B; Gow, Andrew J; Laskin, Jeffrey D; Laskin, Debra L

    2014-08-01

    Nitrogen mustard (NM) is a toxic alkylating agent that causes damage to the respiratory tract. Evidence suggests that macrophages and inflammatory mediators including tumor necrosis factor (TNF)α contribute to pulmonary injury. Pentoxifylline is a TNFα inhibitor known to suppress inflammation. In these studies, we analyzed the ability of pentoxifylline to mitigate NM-induced lung injury and inflammation. Exposure of male Wistar rats (150-174 g; 8-10 weeks) to NM (0.125 mg/kg, i.t.) resulted in severe histopathological changes in the lung within 3d of exposure, along with increases in bronchoalveolar lavage (BAL) cell number and protein, indicating inflammation and alveolar-epithelial barrier dysfunction. This was associated with increases in oxidative stress proteins including lipocalin (Lcn)2 and heme oxygenase (HO)-1 in the lung, along with pro-inflammatory/cytotoxic (COX-2(+) and MMP-9(+)), and anti-inflammatory/wound repair (CD163+ and Gal-3(+)) macrophages. Treatment of rats with pentoxifylline (46.7 mg/kg, i.p.) daily for 3d beginning 15 min after NM significantly reduced NM-induced lung injury, inflammation, and oxidative stress, as measured histologically and by decreases in BAL cell and protein content, and levels of HO-1 and Lcn2. Macrophages expressing COX-2 and MMP-9 also decreased after pentoxifylline, while CD163+ and Gal-3(+) macrophages increased. This was correlated with persistent upregulation of markers of wound repair including pro-surfactant protein-C and proliferating nuclear cell antigen by Type II cells. NM-induced lung injury and inflammation were associated with alterations in the elastic properties of the lung, however these were largely unaltered by pentoxifylline. These data suggest that pentoxifylline may be useful in treating acute lung injury, inflammation and oxidative stress induced by vesicants.

  14. Pretreatment of human epidermal keratinocytes in vitro with ethacrynic Acid reduces sulfur mustard cytotoxicity.

    PubMed

    Gross, Clark L; Nipwoda, Mary T; Nealley, Eric W; Smith, William J

    2004-01-01

    Sulfur mustard (SM) is a potent alkylating agent, profoundly cytotoxic, and a powerful vesicant. SM reacts quite extensively with glutathione (GSH) and forms GSH conjugates, which are presumably excreted through the mercapturic acid pathway in mammals. It is unknown whether any enzymes, such as the glutathione-S-transferases (GST), are involved in this detoxification of SM by the formation of conjugates. A prototypic inhibitor (ethacrynic acid, EAA) and a prototypic inducer (Oltipraz, OLT) of GSH-S-transferase, have been used as pretreatment compounds in human epidermal keratinocytes (HEK) to investigate the effect of enzyme levels on cytotoxicity following SM challenge from 50 muM to 300 muM. Pretreatment of HEK for 24 h with EAA doubled survival against 200 muM SM (36% viability in non-pretreated cells vs. 81% in EAA-pretreated cells) and quadrupled survival (17% viability in non-pretreated controls vs. 71% in EAA-pretreated cells), while OLT pretreatment had no effect on cytotoxicity at either SM dose. The role of GST in SM cytotoxicity could not be tested because of the lack of an effect on modulation of GST activities by these 2 drugs. Cellular levels of GSH were increased 250-300% over control values using EAA pretreatment, while OLT pretreatment did not lead to any increase in GSH. Pretreatment of HEK with buthionine sulfoximine (BSO), a known depleter of glutathione levels, reduced glutathione levels and increased cytotoxicity. This large increase in GSH appears to be solely responsible for the enhanced survivability of EAA-pretreated HEK.

  15. Use of epr spin-trapping techniques to detect radicals from rat lung lavage fluid following sulfur mustard vapor exposure

    SciTech Connect

    Anderson, D.R.; Yourick, J.J.; Arroyo, C.M.; Young, G.D.; Harris, L.W.

    1993-05-13

    Although well known for skin vesicating properties, pulmonary damage and associated infections account for most of the mortality associated with sulfur mustard (HD). We have employed an in vivo HD vapor exposure model, bronchoalveolar lavage and histopathology in conjunction with electron paramagnetic resonance (EPR) techniques to provide evidence for HD-induced (free radical/lipid peroxidation associated) lung injury. Anesthetized rats were intratracheally intubated and exposed to 0.35 mg HD vapor over 50 min. Immediately, 1 hr or 24 hr after exposure, lungs were lavaged with the spin trap, alpha-phenyl-t-butyl nitrone (PBN; 0.35 mg/ml). Recovered lavage fluid was assayed by EPR spectroscopy for radical spin adducts. Airway lipid extracts were assayed for thiobarbituric acid reactive products (TBARs); while separate groups of rats were used to evaluate histopathology. EPR results show the presence of an ascorbyl radical at 1 and 24 hr, and a carbon centered PBN spin adduct at 24 hr, both indicative of lipid peroxidation. TBAR (A532nm) formation was also detected at 24 hr. Histopathology revealed multifocal separation of the bronchial epithelium from the submucosa with little or no alveolar involvement at 24 hrs. These studies provide evidence that HD may affect lungs by a free radical mechanism which produces membrane and other tissue damage.

  16. 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.

  17. 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

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

    PubMed

    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.

  19. 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

  20. 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…

  1. 7 CFR 201.56-3 - Mustard family, Brassicaceae (Cruciferae).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Mustard family, Brassicaceae (Cruciferae). 201.56-3 Section 201.56-3 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL...-3 Mustard family, Brassicaceae (Cruciferae). Kinds of seed: Broccoli, brussels sprouts,...

  2. Neutralization and biodegradation of sulfur mustard. Final report, October 1995-June 1996

    SciTech Connect

    Harvey, S.P.; Szafraniec, L.L.; Beaudry, W.T.; Earley, J.T.; Irvine, R.L.

    1997-02-01

    The chemical warfare agent sulfur mustard was hydrolyzed to products that were biologically mineralized in sequencing batch reactors seeded with activated sludge. Greater than 90% carbon removal was achieved using laboratory scale bioreactors processing hydrolyzed munitions grade sulfur mustard obtained directly from the U.S. Chemical Stockpile. The bioreactor effluent was nontoxic and contained no detectable sulfur mustard or priority pollutants. The sulfur mustard hydrolysis biodegradation process has potential application to the congressionally mandated disposal of sulfur mustard stockpiles.

  3. Indian mustard [Brassica juncea (L.) Czern.].

    PubMed

    Gasic, Ksenija; Korban, Schuyler S

    2006-01-01

    All economically important Brassica species have been successfully transformed using Agrobacterium tumefaciens. Although different tissues have been used as explants, hypocotyls remain the most desirable explants for Brassica tissue culture owing to their amenability to regeneration. Young explants excised from 3- to 4-d-old seedlings have exhibited optimal regeneration potential; the addition of adjuvants such as silver nitrate to the selection medium is necessary to achieve high efficiency of transformation. This chapter describes an Agrobacterium-mediated transformation protocol for Indian mustard based on inoculation of hypocotyls. The selectable marker gene used encodes for neomycin phosphotransferase II (nptII), and the selection agent is kanamycin.

  4. Comparison of toxicity of selected mustard agents by percutaneous and subcutaneous routes.

    PubMed

    Sharma, Manoj; Vijayaraghavan, R; Ganesan, K

    2008-12-01

    Comparative toxicity of nitrogen mustards (HN-1, HN-2 and HN-3) and sulphur mustard was carried out in mice. Based on LD50, the toxicity pattern was HN-2 < HN-1 < HN-3 < sulphur mustard by percutaneous route whereas, by subcutaneous route the toxicity pattern was sulphur mustard < HN-3 < HN-2 < HN-1. Single dose of 1 LD50 of nitrogen mustards and sulphur mustard was administered percutaneously and various oxidative stress parameters were also evaluated. The weight loss was more in HN-2 on day 3 and in sulphur mustard on day 7. There was a drastic fall of WBC count on day 3 in all groups with a recovery in nitrogen mustard groups on day 7. The RBC count and haemoglobin content showed a significant increase on day 7 in sulphur mustard group. The plasma enzymes (ALT, AST and ALP) showed an increase in all groups on day 3 and day 7. The hepatic GSH and GSSG contents were reduced and MDA content increased in all groups, with a further change in sulphur mustard on 7 day. Extensive DNA fragmentation was observed in all the nitrogen mustard groups compared to sulphur mustard group, on day 3. However, on the day 7 the DNA fragmentation was same in all groups. This study showed that the nitrogen mustards and sulphur mustard were extremely toxic by percutaneous route and caused oxidative stress. Sulphur mustard was more toxic by the percutaneous route and the effects were delayed and progressive.

  5. THE EFFECT OF NITROGEN MUSTARDS ON ENZYMES AND TISSUE METABOLISM

    PubMed Central

    Barron, E. S. Guzman; Bartlett, Grant R.; Miller, Zelma Baker; Meyer, Joe; Seegmiller, J. E.

    1948-01-01

    Nitrogen mustards at a concentration forty times the minimum lethal dose inhibited the respiration of all tissues studied but affected anaerobic glycolysis very little. The inhibiting effect increased with time. The respiration of lymphoid tissue was extremely sensitive to nitrogen mustard, as concentrations below the LD50 definitely inhibited the respiration of rabbit lymph nodes. In tissue slices nitrogen mustards inhibited the oxidation of pyruvate and of l-amino acids and the utilization of NH3. A number of synthesis reactions were also inhibited, such as the synthesis of carbohydrate, of creatine, and of urea. When added to growing seeds, nitrogen mustards inhibited their growth. In rats given lethal doses of nitrogen mustards there were found complete inhibition of choline oxidation and strong inhibition of pyruvate oxidation by the kidney and partial inhibition of urea synthesis by the liver. Inhibition of bone marrow respiration by nitrogen mustards was prevented by the addition of choline, and of dimethylaminoethanol plus methionine The possible mechanism of nitrogen mustard intoxication is discussed. PMID:18858641

  6. General guidelines for medically screening mixed population groups potentially exposed to nerve or vesicant agents

    SciTech Connect

    Watson, A.P.; Munro, N.B. ); Sidell, F.R. ); Leffingwell, S.S. . Center for Environmental Health and Injury Control)

    1992-01-01

    A number of state and local planners have requested guidance on screening protocols and have expressed interest in sampling body fluids from exposed or potentially exposed individuals as a means of estimating agent dose. These guidelines have been developed to provide a clear statement that could be used by state and local emergency response personnel in the event of a nerve or vesicant agent incident resulting in off-post contamination; maximum protection from harm is the goal. The assumption is that any population group so exposed would be heterogeneous for age, gender, reproductive status, and state of health.

  7. 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.

  8. TNF-alpha Expression Patterns as Potential Molecular Biomarker for Human Skin Cells Exposed to Vesicant Chemical Warfare Agents: Sulfur Mustard (HD) and Lewisite (L)

    DTIC Science & Technology

    2004-01-01

    one of the key regulated by Lewisite stimulation (Figures 7) cytokines in irritant dermatitis for HD. at 10--6 to 10-4 mol/L for 24 h, stimulation with...indistinguishable. Microscopically, Irritant contact dermatitis is the clinical result the blister roof is slightly thicker than the of sufficient inflammation...is associated with HD or L, respec- erable necrosis of tissue, gangrene , and slough. tively. The difference in TNF--. induction is not Using RT-PCR

  9. The Mustard Consortium’s Elucidation of the Pathophysiology of Sulfur Mustard and Antidote Development

    DTIC Science & Technology

    2006-09-01

    to the use of CEES. Rat spleen , kidney, and liver that had been exposed to SM (in vivo) were sent to Doctors Stone and Crawford. Dr. Stone’s...expression for potentially several chemical weapons. A protocol is being developed for the isolation of mRNA from blood, spleen , and lung. It is... spleen and lung samples from rats exposed to CEES or mustard gas. In total, tissues from 58 rats have been analyzed for tocopherols (alpha- and gamma

  10. Release of allyl isothiocyanate from mustard seed meal powder.

    PubMed

    Dai, Ruyan; Lim, Loong-Tak

    2014-01-01

    Allyl isothiocyanate (AITC) is a wide-spectrum antimicrobial compound found in mustard seeds, produced when their tissues are disrupted. The formation of AITC in mustard seed is mediated by the myrosinase enzyme which catalyzes the release of volatile AITC from a glucosinolate-sinigrin. Since water is a substrate in the reaction, humidity from the air can be used to activate the release of AITC from mustard seed. In this study, defatted and partially defatted mustard seed meals were ground into powders with particle size ranging from 5 to 300 μm. The mustard seed meal powder (MSMP) samples were enclosed within hermetically sealed glass jars wherein the headspace air was adjusted to 85% or 100% relative humidity at 5, 20, or 35 °C. Data from gas chromatography analysis showed that AITC release rate and amount increased with increasing relative humidity and temperature. Moreover, the release rate can be manipulated by particle size and lipid content of the MSMP samples. The amount of AITC released ranged from 2 to 17 mg/g MSMP within 24 h under the experimental conditions tested. In view of the antimicrobial properties of AITC, the mustard meal powder may be used as a natural antimicrobial material for extending the shelf life of food products.

  11. 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.

  12. Nitrogen and sulphur mustard induced histopathological observations in mouse visceral organs.

    PubMed

    Sharma, Manoj; Pant, S C; Pant, J C; Vijayaraghavan, R

    2010-11-01

    Nitrogen mustards (HN) and sulphur mustard (SM) are potent alkylating blister inducing chemical warfare agents. Single 1.0 LD50 dose produced a progressive fall in body weight from second day onwards in all groups of mustard agents exposed animals. Histological examination of spleen, liver skin and kidney revealed significant histopathological lesions in nitrogen mustards and sulphur mustard. These lesions include granulovascular degeneration with perinuclear clumping of the cytoplasm of hepatocytes and renal parenchymal cells. Renal lesions were characterized by congestion and hemorrhage. The maximum toxic manifestation were noted in spleen and skin of HN-3 exposed mice while sulphur mustard reported maximum toxicity in liver and kidneys. The study suggests both nitrogen mustards and sulphur mustard to be extremely toxic by percutaneous route based on histopathological observation and can contributed to earlier reported free radical generation by these toxicants.

  13. Symptomatic treatment of ascites with a peritoneo-vesical automated fluid shunt system in a dog.

    PubMed

    Venzin, C; Kook, P; Jenni, S; Wilhelm, S; Degen, T; Braun, A; Rütten, M; Glaus, T M

    2012-02-01

    A six-year-old Rottweiler with chronic ascites and moderate panhypoproteinaemia that had been treated with large volume paracentesis over several months duration was diagnosed with a large bi-atrial mass and hepatic fibrosis. For palliative treatment, a peritoneo-vesical automated fluid shunt system with an integrated chargeable battery and an integrated computer to control pump function and to transmit data transcutaneously was implanted by coeliotomy. The pump was left in place for 10 weeks, eliminating the need for further paracentesis during this time. At the end of this period, no ascites was discernible and serum protein concentrations had returned to their respective reference intervals. As a complication, decubitus with skin perforation had developed above the pump. Besides palliative treatment of chronic refractory ascites, this pump may have application in other conditions characterised by chronic cavity effusion or in peritoneal dialysis.

  14. The role of climate on prevalence or eradication of vesical schistosomiasis in Khuzestan Province of Iran.

    PubMed

    Hamidinia, Dariush; Maraghi, Sharif; Azimi, Farideh; Ai, Armin; Shirian, Sadegh

    2016-06-01

    Climate is defined as the combination of climate and air elements of a given region which is usually measured for a period of decades. De-marton climate classification has been established based on many factors, including elements such as temperature and rainfall. Vesicle schistosomiasis is a parasitic disease caused by Schistosoma haematobium. This parasite lives in the blood vessels of the bladder. The parasite can cause hematuria in human and if not treated properly can lead to vesicale carcinoma. The parasite is distributed only in certain parts of the province and it is highly dispersed along the rivers of Dez, Karkheh and Karun with high emissions. In 1970, the prevalence of infection in infected foci was 23.8 %. Campaign against the parasite began in 1958 but it did not encompass all centers of infection. Preventive measures include diagnosis and treatment of patients, public health promotion, health education, drying swamps and ponds, improving the environment, cementing the irrigation canals, and the use of moluscocide eventually leads to changing the ecological and conditions of parasite and snail inhabits. Application of preventive measures resulted in the reduction of infection level to 0.7 % in 1979. By continuing struggle and intensifying preventive measures and changing ecological and climatic environment, in 2008, the examination of 3400 urine samples of students in Andimeshk district revealed no cases of the vesical schistosomiasis. It is concluded that S. haematobium and vesical schistosomiasis is eliminated from Khuzestan province southwest Iran, but the disease is still prevalent in neighboring Iran's western border country (Iraq) and due to the special conditions of its facilities and the traffic between the two countries, it is necessary to control and eradicate the disease in Iraq by using the experiences of Iran in eliminating the disease.

  15. 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

    2015-10-15

    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.

  16. 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...

  17. 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.

  18. [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.

  19. 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.

  20. A novel decontaminant and wound healant formulation of N,N'-dichloro-bis[2,4,6-trichlorophenyl]urea against sulfur mustard-induced skin injury.

    PubMed

    Lomash, Vinay; Pant, Satish C

    2014-01-01

    Sulfur mustard (SM)-induced dermatotoxicity can be prevented by an immediate use of decontamination agents. However, practically due to the time lapse between decontamination and exposure, there is always a possibility of wound formation. In view of this, a hydrophilic decontamination formulation of CC-2 (DRDE/WH-03) was fortified with Aloe vera gel and betaine (DRDE/WH-01) for improving its wound healing ability. Swiss albino mice were exposed to SM percutaneously (5 mg/kg) once, and after 24 hours, DRDE/WH-01, DRDE/WH-03, framycetin, and aloe gel were applied topically, daily for 7 days. Skin sections were subjected to histopathology, histomorphologic grading, tissue leukocytosis, and immunohistochemistry of inflammatory-reparative biomarkers on 3 and 7 days, respectively. DRDE/WH-01, framycetin, and aloe gel showed better reepithelialization, angiogenesis, and fibroplasia compared with DRDE/WH-03 and SM control. On the basis of histomorphologic scale, DRDE/WH-01, framycetin, and aloe gel were found to be equally efficacious. Up-regulation of interleukin-6 and infiltrating leukocytes, endothelial nitric oxide synthase and angiogenesis, fibroblast growth factor, and transforming growth factor-alpha with fibroplasia and reepithelialization were well correlated at various stages of the healing process. DRDE/WH-01 was equally effective as framycetin and has shown improved wound healing efficacy compared with DRDE/WH-03. Thus, DRDE/WH-01 can be recommended as a universal decontaminant and wound healant against vesicant-induced skin injury.

  1. Phytotoxicity of mercury in Indian mustard (Brassica juncea L.).

    PubMed

    Shiyab, Safwan; Chen, Jian; Han, Fengxiang X; Monts, David L; Matta, Frank B; Gu, Mengmeng; Su, Yi

    2009-02-01

    This study investigated the phytotoxicity of mercury to Indian mustard (Brassica juncea L.). Two common cultivars (Florida Broad Leaf and Long-standing) were grown hydroponically in a mercury-spiked solution. Mercury exhibited a significant phytotoxicity in these two cultivars of Indian mustard at elevated concentrations (>or=2 mg L(-1)). Mercury uptake induced a significant reduction in both biomass and leaf relative water content. Microscopy studies indicated that elevated mercury concentrations in plants significantly changed leaf cellular structure: thickly stained areas surrounding the vascular bundles; decreases in the number of palisade and spongy parenchyma cells; and reduced cell size and clotted depositions. The palisade chloroplasts exhibited decreases in their amounts and starch grains as well as a loss of spindle shape. However, due to high accumulation of mercury in plants, especially in the roots, Indian mustard might be a potential candidate plant for phytofiltration of contaminated water and phytostabilization of mercury-contaminated soils.

  2. 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

  3. Selected Physical Properties of 2-Chloroethyl-3-Chloropropyl Sulfide (CECPRS)

    DTIC Science & Technology

    2010-10-01

    EDGEWOOD CHEMICAL BIOLOGICAL CENTER U.S. ARMY RESEARCH, DEVELOPMENT AND ENGINEERING COMMAND ECBC-TR-804 SELECTED PHYSICAL PROPERTIES OF 2...seem. After sample collection, the Tenax collection tube was rapidly heated to 275 °C under a flow rate of 20 seem using ultra high purity ( UHP ) grade...the 10-mm o.d. Tenax collection tube to cool. Then, the focusing trap was rapidly heated to 300 °C under a flow rate of 8.0 seem UHP grade nitrogen

  4. 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).

  5. 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...

  6. Pulmonary complications of mustard gas exposure: a study on cadavers.

    PubMed

    Taghaddosinejad, Fakhreddin; Fayyaz, Amir Farshid; Behnoush, Behnam

    2011-01-01

    Sulfur mustard gas is one of the chemical warfare gases that roughly about 45000 soldiers continue to suffer long-lasting consequences of exposure during the Iran-Iraq war between 1980 and 1988. According to the common pulmonary lesions due to this gas exposure, we studied gross and microscopic pulmonary lesions in cadavers and also assessed the main causes of mortality caused by mustard gas exposure. A case-series study was performed on hospital record files of 100 cadavers that were exposed with documented sulfur mustard gas during the Iran-Iraq war from 1979 to 1988 and autopsied in legal medicine organization In Tehran between 2005 and 2007 and gross and microscopic pathological findings of autopsied organs such as hematological, pulmonary, hepatic, and renal changes were evaluated. All cases were male with the mean age of 43 years. The time interval between the gas exposure and death was almost 20years. The most frequent pulmonary complication was chronic bronchitis in 81% of autopsied cadavers. Other pulmonary findings were progressive pulmonary fibrosis (9%), pulmonary infections and tuberculosis (29%), malignant cellular infiltration (4%), and aspergilloma (1%). According to the chronic progressive lesions caused by mustard gas exposure such as pulmonary lesions and also its high mortality rate, suitable programming for protection of the gas exposed persons and prohibiting chemical warfare are recommended.

  7. 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.

  8. 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

  9. 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

  10. Prospects for Classical Biological Control of Saharan Mustard (Brassica tournefortii)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Saharan mustard (Brassica tournefortii) is a winter annual plant that is native to the Mediterranean Basin and is becoming highly invasive in the Sonoran and Mojave Deserts and adjacent areas and has spread great distances along highways from its original infestation. It is becoming a serious probl...

  11. Mustard oil-induced cutaneous inflammation in the pig.

    PubMed

    Jancsó, G; Pierau, F K; Sann, H

    1993-05-01

    Recent findings indicate that chemical stimulation of the porcine skin with capsaicin evokes a flare response similar to that observed in man. The aim of the present study was to elucidate whether chemical stimulation of cutaneous capsaicin-sensitive nerve endings with mustard oil produces neurogenic inflammatory reactions in the pig. The application of mustard oil onto the abdominal skin of domestic pigs resulted in a pronounced flare response. After a previous intravenous injection of a solution of Evans blue, the skin area in contact with the irritant turned dark blue, indicating a marked extravasation of albumin. Quantitative estimation of the dye content of the skin supported this conclusion. The technique of vascular labelling revealed a delicate network of small subepidermal blood vessels in histological preparations after the application of mustard oil following a previous intravenous injection of colloidal silver. Labelled blood vessels were not noted outside the treated area. The present results show that mustard oil produces a strong cutaneous inflammatory response in the pig, and suggest that the porcine skin provides a valuable model for study of the significance of capsaicin-sensitive sensory nerves in vascular and other cutaneous reactions.

  12. Report on possible routes to breakdown products of mustard gas

    SciTech Connect

    Luman, F.M.

    1983-10-18

    This paper suggests possible routes to the formation of decontamination and breakdown products of the chemical agent Mustard Gas (HD). The terminal decontamination products, CaSO4 and CO2, are harmless to the environment. Oxathiane is formed by hydrolysis and dehydration reactions. Dithiane is formed with the application of heat in a low oxygen or nitrogen environment. (Author).

  13. Mucoadhesion on pig vesical mucosa: influence of polycarbophil/calcium interactions.

    PubMed

    Kerec, M; Bogataj, M; Mugerle, B; Gasperlin, M; Mrhar, A

    2002-07-08

    The influence of polycarbophil/calcium interactions on the mucoadhesive properties of polycarbophil has been examined. Polycarbophil dispersions and films with different concentrations of calcium or sodium ions were prepared and the following parameters were measured: detachment force on pig vesical mucosa, zeta potential, pH and viscosity. Polycarbophil detachment force decreased significantly in the presence of calcium but not sodium. Both ions decrease the pH of polycarbophil dispersions. On the other hand, altering the pH of hydrated polycarbophil films in the absence of added ions had an insignificant effect on detachment force. Both ions reduce the absolute values of polycarbophil zeta potential, calcium more efficiently than sodium. We could conclude that decreased mucoadhesion strength of polycarbophil in the presence of calcium is due to the chelation of polycarbophil carboxylic groups by calcium and crosslinking of polymer. The crosslinked polymer chains would be expected to be less flexible, and therefore, interpenetrate to a lesser extent with the glycosaminoglycans of mucus. Additionally, the interactions between functional groups of polycarbophil and mucus glycosaminoglycans are lowered due to the calcium, blocking the carboxylic groups. The mechanism of calcium influence on viscosity of polycarbophil dispersions appears to be different: repulsion between ionised carboxylic groups of polycarbophil prevails over the crosslinking of polycarbophil by calcium.

  14. The correlation between zeta potential and mucoadhesion strength on pig vesical mucosa.

    PubMed

    Bogataj, Marija; Vovk, Tomaz; Kerec, Mojca; Dimnik, Ales; Grabnar, Iztok; Mrhar, Ales

    2003-05-01

    The detachment forces of various polymers are frequently measured to determine their mucoadhesion strength. As the process of mucoadhesion is a consequence of interactions between the mucus layer on mucosa and mucoadhesive polymers, it is greatly dependent on mucus and polymer structure including their charge. It is also known that the glycosaminoglycan layer, which covers the urinary bladder mucosa surface, is highly negatively charged. Therefore, by measuring the zeta potential of polymer dispersions and mucosal homogenates an insight into electrostatic interactions during mucoadhesion can be obtained. In our experiments we chose three polymers, two anionic (polycarbophil, PC; sodium carboxymethyl cellulose, CMCNa) and one cationic (chitosan hydrochloride, CH), for which we expected different zeta potential values and different mucoadhesion strengths. The correlation between the zeta potential and the detachment force was determined. In addition to that, the zeta potential of the scraped surface layer of pig urinary bladders was measured to confirm its negative value. The mucoadhesion strength decreased in the following order: CH>CMCNa=PC. The zeta potentials for all three polymers and for porcine vesical mucosal homogenates were measured in Tyrode solution and two NaCl solutions with different ionic strengths. The lower values of the detachment force correlated well with the more negative zeta potential of the polymer, which might be a consequence of the greater repulsion between negative charges of polymers and glycosaminoglycans.

  15. Nd:YAG laser incision of the vesical neck in obstructive BPH

    NASA Astrophysics Data System (ADS)

    Gilbert, Peter T. O.

    2003-06-01

    From February, 1995 through June, 2002, 68 patients underwent laser incision of the prostate at our clinic. By means of a 23 F cytoscope and a 600 micrometer lateral firing quartz fiber the vesical neck was incised at the 5 and 7 o'clock position at 60 W power. Total energy averaged 13648 J. Operative time did not exceed 15 minutes. General anesthesia was employed in all but one patient. 38 patients remained catheter-free whereas 30 patients were catheterized for two hours. Except for three cases, all patients were discharged on the same day, usually after the first micturition. Anti-inflammatory treatment was administered for two weeks, Cotrimoxazole for 5 days. No serious complications were encountered. Minor side effects included urinary retention (1 pat.), urinary infection (3 pat.) and retrograde ejaculation (1 pat.). Considering a mean follow-up of 21 months, the average Qmax improved enormously (25.4 ml/s versus 10.9 ml/s), as did residual urine volume (35 ml versus 95 ml) and IPSS (7.1 versus 20.5). Three patients required TUR-P 2-3 years after laser surgery and one patient underwent radical retropubic prostatectomy for prostate cancer 2 years later. In conclusion, Nd:YAG laser incision of the prostate is a simple, safe, reliable and cost-effective outpatient procedure.

  16. 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

  17. 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

  18. 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.

  19. Compatibility and Decontamination of High-Density Polyethylene Exposed to Sulfur Mustard

    DTIC Science & Technology

    2014-05-01

    COMPATIBILITY AND DECONTAMINATION OF HIGH-DENSITY POLYETHYLENE EXPOSED TO SULFUR MUSTARD ECBC-TR-1235...Decontamination of High-Density Polyethylene Exposed to Sulfur Mustard 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...study to determine the compatability of high-density polyethylene (HDPE) with liquid mustard (HD) material and decontamination of HDPE when exposed

  20. 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.

  1. 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.

  2. Synthesis and evaluation of new steroidal lactam conjugates with aniline mustards as potential antileukemic therapeutics.

    PubMed

    Trafalis, Dimitrios; Geromichalou, Elena; Dalezis, Panagiotis; Nikoleousakos, Nikolaos; Sarli, Vasiliki

    2016-11-01

    Alkylating agents are still nowadays one of the most important classes of cytotoxic drugs, which display a wide range of therapeutic use for the treatment of various cancers. We have synthesized and tested four hybrid homo-azasteroidal alkylating esters for antileukemic activity against five sensitive to alkylating agents human leukemia cell lines in vitro and against P388 murine leukemia in vivo. Comparatively, melphalan and 3-(4-(bis(2-chloroethyl)amino)phenoxy)propanoic acid (POPAM) were also examined. All the homo-aza-steroidal alkylators showed relatively lower acute toxicity, very promising and antileukemic activity both in vitro and in vivo.

  3. Absorption and degradation of metalaxyl in mustard plant (Brassica juncea).

    PubMed

    Mehta, N; Saharan, G S; Kathpal, T S

    1997-07-01

    Absorption and degradation of metalaxyl were studied in mustard (Brassica juncea) plants after application as a seed dresser, a foliar spray, and a combination of both under subtropical conditions in India. Results indicated that absorption of metalaxyl increased up to 30 days when it was applied as a seed dresser; thereafter, it started declining and was not detectable after 60 days of sowing. The maximum residues (average, 9.03 ppm) of metalaxyl were found after 1 day of spraying. The dissipation of metalaxyl after initial deposits on mustard plants was almost complete after 15 days of spraying. The safe waiting period of metalaxyl was calculated to be 62 and 8 days for seed dresser and foliar application, respectively. The seeds raised through treatments under study were completely free from any detectable amount of metalaxyl residues.

  4. Microbial responses to mustard gas dumped in the Baltic Sea.

    PubMed

    Medvedeva, Nadezda; Polyak, Yulia; Kankaanpää, Harri; Zaytseva, Tatyana

    2009-08-01

    Microbiological studies were carried out on chemical weapon dump sites in the Baltic Sea. The effect of mustard gas hydrolysis products (MGHPs) on marine microbiota and the ability of microorganisms to degrade MGHPs were studied. Many stations at the dump sites demonstrated reduced microbial diversity, and increased growth of species able to use mustard gas hydrolysis products as sole source of carbon. Significant amounts of MGHP-degrading bacteria were revealed in the near-bottom water. The MGHP-degrading microorganisms identified as Achromobacter sp., Pseudomonas sp., and Arthrobacter sp. were isolated. These microorganisms were capable of utilizing the major product of hydrolysis, thiodiglycol, as the sole source of carbon and energy. The bacteria were capable of metabolizing MGHPs at a low temperature. The metabolic pathway for thiodiglycol degradation was proposed. The results suggest the potential for MGHPs biodegradation by naturally occurring populations of near-bottom-water and sediment microorganisms.

  5. Systemic venous atrium stimulation in transvenous pacing after mustard procedure

    PubMed Central

    Puntrello, Calogero; Lucà, Fabiana; Rubino, Gaspare; Rao, Carmelo Massimiliano; Gelsomino, Sandro

    2014-01-01

    We present the case of a young woman corrected with a Mustard procedure undergoing successful transvenous double chamber pacemaker implantation with the atrial lead placed in the systemic venous channel. The case presented demonstrates that, when the systemic venous atrium is separate from the left atrial appendage, the lead can be easily and safely placed in the systemic venous left atrium gaining satisfactory sensing and pacing thresholds despite consisting partially of pericardial tissue. PMID:25276305

  6. Effect of LED lamping on the chlorophylls of leaf mustard

    NASA Astrophysics Data System (ADS)

    Wu, Shiqiang; Zhu, Liang; Zhao, Fuli; Yang, Bowen; Chen, Zuxin; Cai, Ruhai; Chen, Jiansheng

    The absorption coefficients of chloroplast of leaf mustard were measured by a spectrophotometer. The leaves were collected from seven treatments with different lighting. The chlorophyll content was calculated following Arnon equation. LEDs for filling the light source can increase the conduction of plants. Compared with other treatments, Chlorophyll in the leaves got an higher concentration under the lamping of red LEDS to blue LEDS for 7:1 .

  7. Verification, Dosimetry and Biomonitoring of Mustard Gas Exposure via Immunochemical Detection of Mustard Gas Adducts to DNA and Proteins

    DTIC Science & Technology

    1991-12-01

    of supernatants of hybridomas fox specific antibody activity . Mono- and di-adducts at the N7-position of guanosine-5-phosphate were svthesized for use...antibody activity could be developed and optimized, in which single-stranded calf-thymus DNA exposed to 10 pM mustard gas was used as coating...Figure 11: Chemical shift isuignments and coupling constants for the hydrogen (400 MHz:. a) and carbon atoms (100.6 MHz; b) of t4-(2

  8. Simultaneous determination of four sulfur mustard-DNA adducts in rabbit urine after dermal exposure by isotope-dilution liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Yajiao; Yue, Lijun; Nie, Zhiyong; Chen, Jia; Guo, Lei; Wu, Bidong; Feng, Jianlin; Liu, Qin; Xie, Jianwei

    2014-06-15

    Sulfur mustard (SM) is a classic vesicant agent, which has been greatly employed in several wars or military conflicts. The most lesion mechanism is its strong alkylation of DNAs in vivo. Until now there are four specific DNA adducts of SM identified for further retrospective detection, i.e., N(7)-(2-hydroxyethylthioethyl)-2'-guanine (N(7)-HETEG), bis(2-ethyl-N(7)-guanine)thioether (Bis-G), N(3)-(2-hydroxyethylthioethyl)-2'-adenine (N(3)-HETEA) and O(6)-(2-hydroxyethylthioethyl)-2'-guanine (O(6)-HETEG), respectively. Here, a novel and sensitive method of isotope-dilution ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) combining with solid phase extraction was reported for the simultaneous determination of four SM-DNA adducts. A lower limit of detection of 2-5ngL(-1), and a lower limit of quantitation of 5-10ngL(-1) were achieved, respectively, and the recoveries ranged from 87% to 116%. We applied this method in the determination of four SM-DNA adducts in rabbit urine after dermal exposure by SM in three dose levels (2, 5, 15mgkg(-1)), so as to investigate the related metabolic behavior in vivo. For the first time, in SM exposed rabbit urine, our results revealed the relative accumulation abundance of four SM-DNA adducts, i.e., 67.4% for N(7)-HETEG, 22.7% for Bis-G, 9.8% for N(3)-HETEA, 0.1% for O(6)-HETEG, and significant dose and time dependent responses of these SM-DNA adducts. The four adducts were detectable after 8h, afterwards, their contents continuously increased, achieved maximum in the first two or three days and then gradually decreased till the end of one month. Meanwhile, the amounts of SM-DNA adducts were positively correlated with the exposure doses.

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. 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

  14. The Mexican poppy poisons the Indian mustard facts and figures.

    PubMed

    Thatte, U; Dahanukar, S

    1999-03-01

    Argemone seeds are mixed with mustard seeds either accidentally or purposefully, and, ingestion of this contaminated oil can lead to often fatal "epidemic dropsy". The liver, heart, kidney and lungs are the major target organs of the toxins (the alkaloids, sanguinarine and dihydrosanguinarine) and damage is mostly caused by free radical (singlet oxygen and hydroxyl radical) to the cell membranes. Treatment at present is mainly symptomatic but therapy with anti-secretory agents for glaucoma and anti-oxidants/free radical scavengers for systemic manifestations appear to be logical.

  15. Mustard gas: clinical, toxicological, and mutagenic aspects based on modern experience.

    PubMed

    Aasted, A; Darre, E; Wulf, H C

    1987-10-01

    Based on a study of the literature and our own experience treating fisherman poisoned by mustard gas, this article outlines the clinical effects, and toxicological and mutagenic properties of the agent. Mustards are very persistent chemical agents that easily penetrate clothing. Mustard gas usually causes clinical symptoms after the liquid penetrates the skin or the vapor is inhaled. Skin lesions are similar to first- or second-degree burns and usually heal spontaneously in 4 to 6 weeks. Eye symptoms are photophobia and reduced vision. Following inhalation of the agent, pulmonary edema and long-term dyspnea may be seen. As mustard gas is an alkylating substance, it is conceivable that the risk of developing cancer may be increased, as observed in people who were involved with the production of mustard gas and in animals exposed to the gas. Also, transient significantly increased sister chromatid exchange rates have been found in fishermen exposed to mustard gas. Patients exposed to mustard gas must be treated immediately after exposure. Treatment should consist of cleaning of the exposed skin and clothes with an antigas powder and water and soap. The skin lesions should be treated as burns. Eye lesions and respiratory problems should be treated symptomatically.

  16. Verification, Dosimetry and Biomonitoring of Mustard Gas Exposure via Immunochemical Detection of Mustard Gas Adducts to DNA and Proteins.

    DTIC Science & Technology

    1990-09-01

    thrombocytes and lipids was removed, and the lymphocytes forming a broad band half-way down and the granulocytes banding just above the erythrocytes...on ice. The amount of WBC was counted in a counting-chamber by light microscopy . The cells were irradiated with 0 or 4 Gy 60 Co gamma rays...antibodies against ss- ct-DNA treated with mustard gas were counted by light- microscopy and diluted in HAT-medium to a concentration of 50, 10 and 5

  17. Verification, Dosimetry, and Biomonitoring of Mustard Gas Exposure via Immunochemical Detection of Mustard Gas Adducts to DNA and Proteins

    DTIC Science & Technology

    1993-07-01

    specificity 4- for DNA adducts of mustard gas. With this serum a method for the screening of supernatants of hybridomas for specific antibody activity ...11: Chemical shift assignments and coupling constants for tl-e 1’tdrogen (400 MHz; a) and carbon atoms (100.6 MHz; b) of N7-(2’-hydroxyethylthioethyl...subsequent hydrolysis. 113 Figure 14: Chemical shift assignments and coupling constants for the hydrogen (400 MHz; a) and carbon atoms (100.6 Miz; b) of di-(2

  18. 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.

  19. 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.

  20. In-vitro fermentation characteristics and methane reduction potential of mustard cake (Brassica juncea L.)

    PubMed Central

    Durge, S. M.; Tripathi, M. K.; Dutta, N.

    2016-01-01

    Aim: To assess the effect of mustard cake (Brassica juncea L.) levels in concentrate mixtures and in composite feed mixtures (CFMs) on in-vitro fermentation characteristics and methane production. Materials and Methods: Five concentrate mixtures were prepared with containing 30% oil cake, where linseed cake was replaced by mustard cake at the rate of 0%, 7.5%, 15.0%, 22.5%, and 30% in concentrate mixture. Mustard cake contained glucosinolate 72.58 µmol/g oil free dry matter (DM) and contents in diet were 0, 5.4, 10.9, 16.3, and 21.8 µmol/g of concentrate mixture, respectively. Concentrate mixture containing 15.0% mustard cake was found to produced minimum methane which was then used for the preparation of CFM containing 0%, 25%, 50%, and 75% levels with gram straw. Result: Increased levels of mustard cake in concentrate mixtures had a linear decrease (p<0.05) in the total gas production, and the 15% inclusion showed lowest methane concentration (quadratic, p<0.01). The degradability of DM and organic matter (OM) of concentrate mixtures did not change, however, pH and NH3-N concentrations of the fermentation medium showed linear (p<0.05) reductions with increased mustard cake levels. Increased levels of 15% mustard cake containing concentrate mixture in CFMs exhibited a trend (p=0.052) of increased gas production, whereas methane concentration in total gas, methane produced and degradability of DM and OM were also displayed a linear increase (p<0.05). However, the pH, NH3-N, and total volatile fatty acid levels decreased linearly (p<0.05) with increased levels of concentrate in CFMs. Conclusion: Reduction in methane production was evidenced with the inclusion of mustard cake in concentrate mixture at 15% level, and the CFMs with 25% concentrate, which contained 15% mustard cake, exhibited an improved fermentation and reduced methane production. PMID:27847426

  1. 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.

  2. Eruptive cherry angiomas associated with vitiligo: provoked by topical nitrogen mustard?

    PubMed

    Ma, Hui-Jun; Zhao, Guang; Shi, Fei; Wang, Yi-Xia

    2006-12-01

    We report a 27-year-old man who had suffered with vitiligo for 7 years and with eruptive cherry angiomas within or around the repigmented vitiliginous skin for 2 years. After continual therapy for vitiligo with topical nitrogen mustard in a concentration of 0.001% for 5 years, multiple cherry angiomas erupted within or around the repigmented vitiliginous plaques. The discontinue therapy with nitrogen mustard stopped the appearance of new cherry angiomas. The presence of eruptive cherry angiomas was evident and was confirmed by histopathology. We suggest that the chronic chemical stimuli caused by topical nitrogen mustard might result in the formation of eruptive cherry angiomas.

  3. Bilateral chylothorax complicating Mustard repair of transposition of the great vessels.

    PubMed

    Copeland, J G; Shaut, C

    1982-10-01

    Less than 60 cases of bilateral chylothorax have been previously reported, and only two of these involve complicated Mustard procedures. We describe herein a patient in whom severe bilateral chylothorax developed three weeks after Mustard repair of D transposition. Complete reversal of this condition was obtained with revision of the constricted interatrial baffle and ligation of the thoracic duct. This cases is compared clinically with previously reported instances of chylothorax, and the role of played by obstruction of the superior vena cava after a Mustard procedure for transposition of the great vessels is emphasized.

  4. 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.

  5. Reactions of sulphur mustard and sarin on V 1.02 O 2.98 nanotubes.

    PubMed

    Mahato, T H; Prasad, G K; Singh, Beer; Srivastava, A R; Ganesan, K; Acharya, J; Vijayaraghavan, R

    2009-07-30

    Reactions of sulphur mustard and sarin were studied on the surface of V(1.02)O(2.98) nanotubes by gas chromatography and gas chromatography-mass spectrometry techniques. The V(1.02)O(2.98) nanotube samples were made by using hydrothermal method and characterized by scanning electron microscopy, nitrogen adsorption, X-ray diffractometry and thermogravimetry. Later, they were exposed to sulphur mustard and sarin separately at ambient temperature (30+/-2 degrees C). The data explored the formation of sulphoxide of sulphur mustard, thiodiglycol for sulphur mustard and isopropyl methyl phosphonic acid for sarin on V(1.02)O(2.98) nanotubes illustrating the role of oxidation and hydrolysis reactions in the decontamination.

  6. A Literature Review on the Mechanism of Action of Sulphur and Nitrogen Mustard

    DTIC Science & Technology

    1989-07-01

    skin, Papirmeister et al (1984 a;b) used human skin gmaf onto congenitally athymic nude mice. Papirmeister at al (1984a) exposed the grafts to both...resistance to chlomethylnitroeoizreas, nitrogen mustard and cis-Diam minedichloroplatinumafl) in human glial-derived ceil lines. Cancer Research 47...N,N-Dimethylamiloride. Cancer Research, 48, 2454-2457. 28. Doppler, W., Hof mann, J., Oberhuber, Maly, K. and Grunicke, H. (1985). Nitrogen Mustard

  7. Effects of phosphoramide mustard and acrolein, cytotoxic metabolites of cyclophosphamide, on mouse limb development in vitro.

    PubMed

    Hales, B F

    1989-07-01

    Phosphoramide mustard and acrolein are toxic and reactive metabolites of the widely used anticancer drug and known teratogen cyclophosphamide. To study the mechanism(s) involved and to determine which of the active metabolites of cyclophosphamide is responsible for the production of limb malformations, the effects of exposure of cultured limb buds to phosphoramide mustard and acrolein were investigated. Fore- and hindlimbs were excised from ICR mice on day 12 of gestation and cultured in roller bottles for 6 days. Limbs were exposed to either phosphoramide mustard or acrolein (10 or 50 micrograms/ml) for the first 20 hours of the culture period. Exposure to phosphoramide mustard produced limb reduction malformations in both the fore- and hindlimbs; total limb bone area was greatly reduced, while the relative contribution of the paw to this area in forelimbs was increased. There was a fourfold reduction in both DNA and RNA; protein content was reduced only by one-half. Alkaline phosphatase activity was significantly decreased in fore- and hindlimbs exposed to phosphoramide mustard, whereas creatine phosphokinase activity was only reduced in hindlimbs in the limbs exposed to the higher concentration of phosphoramide mustard. Exposure to acrolein also produced malformed limbs with a mangled appearance; however, total limb bone area and the relative contribution of the long bones versus paw structures were not altered. Acrolein exposure had little effect on growth parameters such as DNA (decreased only in hindlimbs exposed to 50 micrograms/ml), RNA (increased in hindlimbs exposed to 50 micrograms/ml), or protein content. Alkaline phosphatase and creatine phosphokinase activities were not altered in acrolein-exposed fore- or hindlimbs. Thus, phosphoramide mustard and acrolein have dramatically different effects on developing limbs in vitro; this observation may indicate that they have different targets and/or mechanisms of action as teratogens in the limb. The effects

  8. 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

  9. 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.

  10. Covalent sequestration of the nitrogen mustard mechlorethamine by metallothionein.

    PubMed

    Antoine, M; Fabris, D; Fenselau, C

    1998-09-01

    The research reported here demonstrates covalent binding to the metal-binding protein metallothionein (MT) by the therapeutic nitrogen mustard mechlorethamine. The most surprising aspect of this interaction is the selectivity of the alkylating agent for specific residues of MT. A combination of MS and proteolytic and enzymatic methods was used to deduce specific locations of mechlorethamine alkylation. These experiments indicated that alkylation occurs predominantly in the carboxyl domain of MT, with one molecule of mechlorethamine covalently cross-linking two cysteine residues. Electrospray MS revealed the retention of all seven metal ions in the cross-linked MT/mechlorethamine adducts, highlighting the uniqueness of this protein. Computerized docking experiments supported the hypothesis that selective binding precedes selective alkylation, and the structure of the drug indicates the minimal structural requirements for this binding. These results support the idea that MT overexpressed in tumor cells contributes to the inactivation of anticancer drugs.

  11. 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.

  12. NIST-Traceable NMR Method to Determine Quantitative Weight Percentage Purity of Nitrogen Mustard HN-1 Feedstock Samples

    DTIC Science & Technology

    2014-06-01

    ECBC-TR-1251 NIST-TRACEABLE NMR METHOD TO DETERMINE QUANTITATIVE WEIGHT PERCENTAGE PURITY OF NITROGEN MUSTARD HN-1 FEEDSTOCK SAMPLES David J...Determine Quantitative Weight Percentage Purity of Nitrogen Mustard HN-1 Feedstock Samples 5a. CONTRACT NUMBER W911SR-10-D-0004 5b. GRANT NUMBER 5c...using NMR with proton detection is described to determine the weight percent purity of feedstock samples of nitrogen mustard , HN-1. 15. SUBJECT

  13. 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

  14. Accumulation of intact sulfur mustard in adipose tissue and toxicokinetics by chemical conversion and isotope-dilution liquid chromatography-tandem mass spectrometry.

    PubMed

    Xu, Bin; Zong, Cheng; Zhang, Yajiao; Zhang, Tianhong; Wang, Xiaoying; Qi, Meiling; Wu, Jianfeng; Guo, Lei; Wang, Peng; Chen, Jia; Liu, Qin; Xu, Hua; Xie, Jianwei; Zhang, Zhenqing

    2017-02-01

    Sulfur mustard (SM) is a powerful vesicant and one of the most harmful chemical warfare agents. Although having been studied for a long time, it is still difficult to fully elucidate the mechanisms of SM poisoning, and there is no effective antidote or specific treatment for SM injury. The investigations on toxicokinetics and tissue distribution of SM will help to understand its toxicity and provide a theoretical basis for pretreatment and therapy of SM poisoning. But the metabolic trajectory or fate of intact SM in vivo remains unclear, and there are insufficient experimental data to elucidate, due to its high reactivity and difficulty in biomedical sample analysis. In this paper, a sensitive method for the detection and quantification of intact SM in blood or tissues using isotope-dilution LC-MS/MS coupled with chemical conversion was developed. By transforming highly reactive SM into stable derivative product, the real concentration of intact SM in biological samples was obtained accurately. The toxicokinetics and tissue distribution studies of intact SM in rats were successfully profiled by the novel method after intravenous (10 mg/kg) or cutaneous administration (1, 3 and 10 mg/kg). The SM level in blood with peak time at 30-60 min determined in cutaneous exposure experiment was found much higher than previously reported, and the mean residence time in blood extended to 1-1.5 h. A significant accumulation of intact SM was observed in adipose tissues, including the perirenal fat, epididymal fat, subcutaneous fat and brown fat, in which the concentrations of SM were at least 15 times greater than those in non-adipose tissues in cutaneous exposed rats. The recovery of SM in body fat was calculated as 3.3 % of bioavailable SM (the bioavailability after cutaneous exposure was evaluated as 16 %). Thus, the adipose tissue was important for SM distribution and toxicity, which may pioneer a new model for both the prevention and treatment of SM exposure.

  15. Degradation of VX and sulfur mustard by enzymatic haloperoxidation.

    PubMed

    Amitai, G; Adani, R; Hershkovitz, M; Bel, P; Rabinovitz, I; Meshulam, H

    2003-01-01

    Chloroperoxidase (CPO) isolated from Caldariomyces fumago (20 U ml(-1)) together with urea hydrogenperoxide (UPER, 0.5 mM) and sodium chloride as co-substrate (NaCl, 0.5 M) caused rapid breakdown of VX (10 microM) (t((1/2)) = 8 s, 25 C, 50 mM tartarate, pH 2.75). Glucose oxidase (GOX, Aspergillus niger) and glucose were used as an alternative source for H(2)O(2). A mixture of GOX (20 U ml(-1)), glucose (GLU 0.45 M), CPO (20 U ml(-1)) and NaCl (0.5 M) caused a 3.8-fold slower degradation of VX (10 microM) (t((1/2)) = 30 s, 25 C, 50 mM tartarate, pH 2.75). The concentrations of H(2)O(2) and chlorine produced by this enzyme/substrate mixture depended mainly on the GLU concentration. Horseradish peroxidase (HRP) together with UPER (1 mM) and sodium iodide (NaI, 0.05 M) caused progressive degradation of VX that was more than 400-fold slower than with CPO (20 U ml(-1)), UPER (0.5 mM) and NaCl (0.5 M) (t((1/2)) = 55 min, 25 C, pH 8). Skin decontamination of VX by CPO was tested in pig-ear skin in vitro. The chemical agent VX (0.01 M, 100 microl) was degraded by 98% within 3 h of skin diffusion when a mixture of UPER/NaCl/CPO was applied 60 min prior to VX application. A mixture of UPER/NaCl without CPO also caused significant VX degradation (94%) during skin diffusion whereas it did not cause any VX degradation in solution. Degradation of VX in skin, obtained without exogenous CPO, may indicate involvement of endogenous intradermal haloperoxidase-like enzyme. Reagent UPER (1 mM) did not cause any degradation of VX in solution or during its skin diffusion. Furthermore, a mixture of CPO, UPER and NaCl caused rapid degradation of sulfur mustard (HD). Sulfur mustard (50 microM) incubated in the presence of CPO (4 U ml(-1)), UPER (0.05 M) and NaCl (0.5 M) at pH 2.75 and 30 C was oxidized by 97% and 99% within 5 and 10 min, respectively. The oxidation products HD sulfoxide, HD sulfone and HD sulfoxidevinyl were identified by GC/MS in the enzymatic chloroperoxidation mixture.

  16. 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

  17. 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.

  18. Effect of mustard gas exposure on incidence of lung cancer: a longitudinal study.

    PubMed

    Doi, Mihoko; Hattori, Noboru; Yokoyama, Akihito; Onari, Yojiro; Kanehara, Masashi; Masuda, Kenji; Tonda, Tetsuji; Ohtaki, Megu; Kohno, Nobuoki

    2011-03-15

    Sulfur mustard, an agent used in chemical warfare, is an alkylating substance with carcinogenic potential. However, the precise long-term carcinogenic effects of mustard gas are unclear. Since 1952, the authors have conducted health surveys of former workers who were employed from 1929 to 1945 in a poisonous gas factory in Okuno-jima, Hiroshima, Japan. This prospective study was undertaken from 1952 to 2005 to examine the incidence of lung cancer among the workers who were exposed to mustard gas (n=480), lewisite (n=55), and/or diphenylcyanarsine (n=178), as well as the incidence among unexposed workers (n=969). The stochastic relation between exposure and lung cancer was explored on the basis of multistage carcinogenesis by using an accelerated hazard model with a transformed age scale. Mustard gas exposure was found to transform the age scale for developing lung cancer. One year of exposure in subjects ≤18 or >18 years old at first exposure shifted the age scale down by 4.9 years and 3.3 years, respectively. On the basis of the long-term follow-up of former workers in the poisonous gas factory, the authors concluded that sulfur mustard decreased the age at which people were at risk of developing lung cancer and that the effect declined with aging.

  19. Garlic Mustard (Alliaria petiolata) Glucosinolate Content Varies Across a Natural Light Gradient.

    PubMed

    Smith, Lauren M

    2015-05-01

    Garlic mustard is a well-known invader of deciduous forests of North America, yet the influence of environmental factors on garlic mustard allelochemical production is not well understood. Three experiments were conducted to detect interactions between one garlic mustard allelochemical (glucosinolate) production and light availability. First, to detect patterns of glucosinolate production across a natural light gradient, leaves and roots of mature plants and first-year rosettes were sampled in patches ranging from 100 to 2 % of full sun within an Indiana forest. Second, to determine whether genetic variation drives observed correlations between glucosinolate content and light, seed collected across light gradients within six sites was grown in a common garden and glucosinolate production was measured. Finally, to understand whether local adaptation occurred in garlic mustard's response to light, seed collected from defined light environments across six sites was grown under four light treatments. Results of the field sampling showed that mature plants' root glucosinolate content was elevated in high compared to low light. In the common garden experiment, however, there was no correlation between light availability at seed origin and constitutive glucosinolate content. Additionally, in the common light treatments, there was no evidence for local adaptation to light environment. Overall, the results indicate that plasticity in response to light, not genetic variation among plants growing in different light environments, generates correlations between glucosinolate content and light in the field. Since mature garlic mustard populations in high light may exhibit increased glucosinolate content, it makes them potential targets for management.

  20. 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

  1. 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

  2. 40 CFR 180.1167 - Allyl isothiocyanate as a component of food grade oil of mustard; exemption from the requirement...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... used as a component of food grade oil of mustard, in or on all raw agricultural commodities, when... food grade oil of mustard; exemption from the requirement of a tolerance. 180.1167 Section 180.1167... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1167 Allyl...

  3. 40 CFR 180.1167 - Allyl isothiocyanate as a component of food grade oil of mustard; exemption from the requirement...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... used as a component of food grade oil of mustard, in or on all raw agricultural commodities, when... food grade oil of mustard; exemption from the requirement of a tolerance. 180.1167 Section 180.1167... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1167 Allyl...

  4. 40 CFR 180.1167 - Allyl isothiocyanate as a component of food grade oil of mustard; exemption from the requirement...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... used as a component of food grade oil of mustard, in or on all raw agricultural commodities, when... food grade oil of mustard; exemption from the requirement of a tolerance. 180.1167 Section 180.1167... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1167 Allyl...

  5. ‘Carolina Broadleaf’ mustard green (Brassica juncea L.) resistant to the bacterial leaf blight pathogen Pseudomonas cannabina pv. alisalensis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A leafy-green mustard (Brassica juncea L.) cultivar designated ‘Carolina Broadleaf’ has been released by the Agricultural Research Service of the U.S. Dept. of Agriculture in 2015. This released cultivar is a narrow-based population of leafy-green mustard derived from a U.S. plant introduction (PI)...

  6. First report of bacterial leaf blight on mustard greens (Brassica juncea) caused by pseudomonas cannabina pv. alisalensis in Mississippi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2010, a brassica leafy greens grower in Sunflower County, Mississippi, observed scattered outbreaks of a leaf blight disease on mustard greens (Brassica juncea) in a 180-hectare field. A severe outbreak of leaf blight occurred on mustard greens and turnip greens (Brassica rapa) in the same field...

  7. Mechanisms of Cadmium Mobility and Accumulation in Indian Mustard.

    PubMed Central

    Salt, D. E.; Prince, R. C.; Pickering, I. J.; Raskin, I.

    1995-01-01

    Indian mustard (Brassica juncea L.), a high biomass crop plant, accumulated substantial amounts of cadmium, with bioaccumulation coefficients (concentration of Cd in dry plant tissue/concentration in solution) of up to 1100 in shoots and 6700 in roots at nonphytotoxic concentrations of Cd (0.1 [mu]g/mL) in solution. This was associated with a rapid accumulation of phytochelatins in the root, where the majority of the Cd was coordinated with sulfur ligands, probably as a Cd-S4 complex, as demonstrated by x-ray absorption spectroscopy. In contrast, Cd moving in the xylem sap was coordinated predominantly with oxygen or nitrogen ligands. Cd concentrations in the xylem sap and the rate of Cd accumulation in the leaves displayed similar saturation kinetics, suggesting that the process of Cd transport from solution through the root and into the xylem is mediated by a saturable transport system(s). However, Cd translocation to the shoot appeared to be driven by transpiration, since ABA dramatically reduced Cd accumulation in leaves. Within leaves, Cd was preferentially accumulated in trichomes on the leaf surface, and this may be a possible detoxification mechanism. PMID:12228679

  8. Gas chromatographic determination of pesticide residues in white mustard.

    PubMed

    Słowik-Borowiec, Magdalena; Szpyrka, Ewa; Walorczyk, Stanisław

    2015-04-15

    A new analytical method employing gas chromatography coupled to electron capture and nitrogen phosphorus detection (GC-ECD/NPD) has been developed and validated for the screening and quantification of 51 pesticides in a matrix of high chlorophyll content - white mustard (Sinapis alba L.). For preparation of the sample extract, the citrate buffered QuEChERS procedure was followed. However certain changes were made to adapt the method to our needs and available laboratory resources. The sample size was reduced to 5 g, 10 mL water was added and exchange of solvent before GC analysis was done. The samples spiked with the target pesticides at the concentration level 0.01 mg/kg and a higher level (depending on the compound) yielded average recoveries in the range of 70-120% with relative standard deviations (RSDs) 0-19% except for HCB, S-metolachlor and teflubenzuron, and displayed very good linearity (R(2)>0.99) for nearly all the analytes. Limit of quantification was 0.01 mg/kg for the majority of the analytes. The expanded measurement uncertainties were estimated employing a "top-down" empirical model as being between 6% and 32% and yielding an average value of 18% (coverage factor k=2, confidence level 95%).

  9. 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.

  10. Reduction and Coordination of Arsenic in Indian Mustard1

    PubMed Central

    Pickering, Ingrid J.; Prince, Roger C.; George, Martin J.; Smith, Robert D.; George, Graham N.; Salt, David E.

    2000-01-01

    The bioaccumulation of arsenic by plants may provide a means of removing this element from contaminated soils and waters. However, to optimize this process it is important to understand the biological mechanisms involved. Using a combination of techniques, including x-ray absorption spectroscopy, we have established the biochemical fate of arsenic taken up by Indian mustard (Brassica juncea). After arsenate uptake by the roots, possibly via the phosphate transport mechanism, a small fraction is exported to the shoot via the xylem as the oxyanions arsenate and arsenite. Once in the shoot, the arsenic is stored as an AsIII-tris-thiolate complex. The majority of the arsenic remains in the roots as an AsIII-tris-thiolate complex, which is indistinguishable from that found in the shoots and from AsIII-tris-glutathione. The thiolate donors are thus probably either glutathione or phytochelatins. The addition of the dithiol arsenic chelator dimercaptosuccinate to the hydroponic culture medium caused a 5-fold-increased arsenic level in the leaves, although the total arsenic accumulation was only marginally increased. This suggests that the addition of dimercaptosuccinate to arsenic-contaminated soils may provide a way to promote arsenic bioaccumulation in plant shoots, a process that will be essential for the development of an efficient phytoremediation strategy for this element. PMID:10759512

  11. Molecular analysis of the fragile histidine triad (FHIT) tumor suppressor gene in vesical tumors of cattle with chronic enzootic hematuria (CEH).

    PubMed

    Guidi, E; Uboldi, C; Ferretti, L

    2008-01-01

    The FHIT (fragile histidine triad) gene is a tumor suppressor gene known to be inactivated in many tumors including bladder tumors and is spanning FRA3B, a very active common fragile site in the human genome. We have recently isolated the bovine gene, and the aim of this study was to test whether FHIT presents altered expression patterns in vesical tumors of cattle with CEH (chronic enzootic hematuria). CEH is a common syndrome affecting Mediterranean cattle: clastogenic, mutagenic and cancerogenic substances released by the bracken fern (Pteridium spp) grazed by animals induce the formation of neoplastic lesions, among which bladder tumors have a high incidence. We analysed FHIT in 23 bladder tumors of CEH cattle looking at: 1) the methylation status of the CpG island comprising the promoter and part of exon 1; 2) the presence of altered FHIT transcripts; 3) the mRNA expression levels measured with a quantitative real time PCR (QRT-PCR) approach. Our results suggest that unlike in human tumors, FHIT in vesical tumors of CEH cattle is largely unmethylated. Furthermore, the same mRNA isoforms of FHIT were detected in tumors and in healthy tissues, including a novel isoform that was found in this study. Finally, QRT-PCR data did not reveal significantly altered expression profiles of FHIT transcripts. Further studies and larger sets of cases will be useful to confirm this finding, but the data seem to suggest that epigenetic modifications of FHIT and altered expression profiles are not a hallmark of bovine vesical tumors like they are in human tumors.

  12. Microarray gene expression analysis of the human airway in patients exposed to sulfur mustard.

    PubMed

    Najafi, Ali; Masoudi-Nejad, Ali; Imani Fooladi, Abbas Ali; Ghanei, Mostafa; Nourani, Mohamad Reza

    2014-08-01

    There is much data about the acute effects of sulfur mustard gas on humans, animals and cells. But less is known regarding the molecular basics of chronic complications in humans. Basically, mustard gas, as an alkylating agent, causes several chronic problems in the eyes, skin and more importantly in the pulmonary system which is the main cause of death. Although recent proteomic research has been carried out on bronchoalveolar lavage (BAL) and serum, but high-throughput transcriptomics have not yet been applied to chronic airway remodeling. This is the first cDNA-microarray report on the chronic human mustard lung disease, 25 years after exposure during the Iran-Iraq war. Microarray transcriptional profiling indicated that a total of 122 genes were significantly dysregulated in tissues located in the airway of patients. These genes are associated with the extracellular matrix components, apoptosis, stress response, inflammation and mucus secretion.

  13. Safety evaluation of genetically modified mustard (V4) seeds in terms of allergenicity: comparison with native crop.

    PubMed

    Misra, Amita; Kumar, Sandeep; Verma, Alok Kumar; Chanana, Nidhi P; Das, Mukul; Dhawan, Vibha; Dwivedi, Premendra D

    2012-01-01

    Genetically modified (GM) mustard line (V4) with increased carotenoid content was compared with native mustard to find the difference in allergenic potential, if any. Simulated gastric fluid (SGF) digestibility of crude protein extract from GM as well as its native counterpart mustard crop was envisaged to understand the intended or unintended changes in GM crop along with IgE immunoblotting. BALB/c mice were used as model for allergenicity studies for monitoring total and specific IgE, specific IgG1, histamine level, histopathology, and systemic anaphylaxis score. Allergenicity of mustard was checked in humans by clinical history, skin prick test and IgE levels. Similar results were evident by significant increase in total IgE, specific IgE, IgG1, histamine levels, in GM and native mustard in comparison to control group. Prominent anaphylactic symptoms (score 2: 60%; score 3: 20%; score 4: 20% in native mustard and score 2: 40%; score 3: 40%; score 4: 20% in GM mustard) and eruptive histopathological changes were observed in both GM and native mustard when compared with controls. One protein of approximately 16 kDa was found stable up to 1 h in both GM as well as non GM mustard. IgE immunoblotting detected three protein components of approximately 29, 24 and 16 kDa in both GM and non GM varieties. Collectively, our data demonstrate substantially equivalent allergic responses against GM as well as its native counterpart. Therefore, the GM mustard may be as safe as its native counterpart with reference to allergenic responses.

  14. 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.

  15. 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.

  16. Survival of enterohemorrhagic Escherichia coli O157:H7 in retail mustard.

    PubMed

    Mayerhauser, C M

    2001-06-01

    Escherichia coli O157:H7 survival in acid foods such as unpasteurized apple cider and fermented sausage is well documented. Researchers have determined that E. coli O157:H7 can survive in refrigerated acid foods for weeks. The potential of acid foods to serve as a vector of E. coli O157:H7 foodborne illness prompted this study to determine the fate of this organism in retail mustard containing acetic acid when stored at room and refrigerated temperatures. Various retail brands of dijon, yellow, and deli style mustard, pH ranging from 3.17 to 3.63, were inoculated individually with three test strains of E. coli O157:H7. Samples were inoculated with approximately 1.0 x 10(6) CFU/g, incubated at room (25+/-2.5 degrees C) and refrigerated (5+/-3 degrees C) temperatures, and assayed for surviving test strains at predetermined time intervals. An aliquot was appropriately diluted and plated using sorbitol MacConkey agar (SMAC). When the test strain was not recoverable by direct plating, the sample was assayed by enrichment in modified tryptic soy broth and recovered using SMAC. Growth of E. coli O157:H7 test strains was inhibited in all retail mustard styles. E. coli O157:H7 was not detected in dijon style mustard beyond 3 h at room and 2 days at refrigerated temperatures. Survival in yellow and deli style mustard was not detected beyond 1 h. Overall, test strain survival was greater at refrigerated than room temperature. Retail mustard demonstrated the ability to eliminate effectively any chance contamination by this organism within hours to days, suggesting that these products are not a likely factor in E. coli O157:H7 foodborne illness.

  17. Validation and comparison of two commercial ELISA kits and three in-house developed real-time PCR assays for the detection of potentially allergenic mustard in food.

    PubMed

    Palle-Reisch, Monika; Hochegger, Rupert; Štumr, Stepan; Korycanova, Kveta; Cichna-Markl, Margit

    2015-05-01

    The study compares the applicability of two commercial mustard ELISA kits (Mustard ELISA Kit-specific and Mustard ELISA Kit-total) and three in-house developed real-time PCR assays (singleplex assay for white mustard, singleplex assay for black/brown mustard and duplex assay for the detection of white, black and brown mustard). Analyses of raw and brewed model sausages containing white and black/brown mustard in the range from 1 to 50 ppm indicate that both ELISAs and the three real-time PCR assays allow the detection of traces of mustard in raw and in brewed sausages. The ELISAs were found to be more sensitive than the real-time PCR assays. When the ELISAs and real-time PCR assays were applied to the analysis of 15 commercial foodstuffs differing in their labelling concerning mustard, in one sample mustard was detected with both ELISAs and the three real-time PCR assays although mustard was not indicated on the food ingredient list.

  18. Development and validation of a duplex real-time PCR assay for the simultaneous detection of three mustard species (Sinapis alba, Brassica nigra and Brassica juncea) in food.

    PubMed

    Palle-Reisch, Monika; Cichna-Markl, Margit; Hochegger, Rupert

    2014-06-15

    The paper presents a duplex real-time PCR assay for the simultaneous detection of three potentially allergenic mustard species commonly used in food: white mustard (Sinapis alba), black mustard (Brassica nigra) and brown mustard (Brassica juncea). White mustard is detected in the "green" and black/brown mustard in the "yellow" channel. The duplex real-time PCR assay does not show cross-reactivity with other Brassicaceae species including broccoli, cauliflower, radish and rapeseed. Low cross-reactivities (difference in the Ct value ⩾ 11.91 compared with the positive control) were obtained with cumin, fenugreek, ginger, rye and turmeric. When applying 500 ng DNA per PCR tube, the duplex real-time PCR assay allowed the detection of white, black and brown mustard in brewed model sausages down to a concentration of 5mg/kg in 10 out of 10 replicates. The duplex real-time PCR assay was applied to verify correct labelling of commercial foodstuffs.

  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. Apoptotic Cell Death in Rat Lung Following Mustard Gas Inhalation.

    PubMed

    Andres, Devon Katherine; Keyser, Brian M; Melber, Ashley A; Benton, Betty Jean; Hamilton, Tracey A; Kniffin, Denise M; Martens, Magaret E; Ray, Radharaman

    2017-03-30

    To investigate apoptosis as a mechanism of sulfur mustard (SM) inhalation injury in animals, we studied different caspases (caspase-8, -9, -3 and -6) in the lungs from a ventilated rat SM aerosol inhalation model. SM activated all four caspases in cells obtained from bronchoalveolar lavage fluid (BALF) as early as 6 hr after exposure. Caspase-8, which is known to initiate the extrinsic Fas-mediated pathway of apoptosis, was increased 5-fold between 6 to 24 hr, decreasing to the unexposed-control level at 48 hr. The initiator, caspase-9, in the intrinsic mitochondrial pathway of apoptosis as well as the executioner caspases, caspase-3 and -6, all peaked (p<0.01) at 24 hr; caspase-3 and -6 remained elevated, but caspase-9 decreased to unexposed-control level at 48 hr. To study further the Fas pathway, we examined soluble as well as membrane-bound Fas ligand (sFas-L, mFas-L, respectively) and Fas receptor (Fas-R) in both BALF cells and BALF. SFas-L increased significantly at 24 hr after SM exposure in both BALF cells (p<0.01) and BALF (p<0.05). However, mFas-L increased only in BALF cells between 24 to 48 hr (p<0.1, <0.001, respectively). Fas-R increased only in BALF cells by 6 hr (p<0.01) after SM exposure. Apoptosis in SM-inhaled rat lung specimens was also confirmed by both immunohistochemical staining using cleaved caspse-3 and -9 antibodies and TUNEL staining as early as 6 hr in the proximal trachea and bronchi, but not before 48 hr in distal airways. These findings suggest pathogenic mechanisms at the cellular and molecular levels and logical therapeutic target(s) for SM inhalation injury in animals.

  1. Speciation and bioaccessibility of lead and cadmium in soil treated with metal-enriched Indian mustard leaves.

    PubMed

    Cui, Yanshan; Fu, Jin; Chen, Xiaochen

    2011-01-01

    Indian mustard (Brassica juncea (L.) Czern.) has shown good potential for the phytoremediation of soil contaminated with heavy metals. However, there is little information about the speciation and bioaccessibility of heavy metals in soil during the decomposition of metal-rich Indian mustard leaves. Incubation experiments (1-, 3-, and 6-month) were carried out in Beijing and Hunan soil with metal-rich Indian mustard leaves addition (1% and 3%) and the effects of mustard leaves addition on the speciation and bioaccessibility of heavy metals were studied. The results showed that the addition of mustard leaves led to significant increases in pH and DOC in the Hunan soil. Both 1% and 3% of mustard leaf amendment caused the percentage of the exchangeable (F1), precipitated with carbonates (F2), bound to Fe/Mn oxides (F3) and bound to organic matter (F4) fractions of Pb and Cd to increase dramatically, while the percentage of the residual fraction (F5) of Cd and Pb significantly dropped in both Beijing and Hunan soils. Mustard leaf addition caused the bioaccessibility of Pb to decrease in the gastric phase, whereas the values increased in the small intestinal phase. The Cd bioaccessibility increased with mustard leaf addition in both the gastric and small intestinal phases. In conclusion, the metal-enriched mustard leaves addition induces Pb and Cd concentrations and their mobility increasing in the Beijing and Hunan soils. Therefore, heavy metal risk in metal-enriched plant leaves should be considered in phytoremediation system in which heavy metal might be brought back to soil and changed over time.

  2. Evaluation of mustard plants and other products to control sweetpotato whitefly, Bemisia tabaci

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major insect pest of vegetables and horticultural crops in the southeast US is the sweetpotato whitefly.Scientists at the USDA-Agriculture Research Service, Center for Veterinary Entomology, Gainesaville, Florida, evaluated the effect of giant red mustard plants and commercial products to control ...

  3. Glucosinolate content and nematicidal activity of Brazilian wild mustard tissues against Meloidogyne incognita in tomato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The wild mustard (Brassica juncea L.), an invasive weed of winter crops in Brazil, was evaluated for glucosinolate content of its plant tissues and nematicidal activity of its dry leaf meal (LM), whole seed meal (WSM) and hexane defatted seed meal (DSM) against Meloidogyne incognita on tomato plants...

  4. A preliminary investigation of Giant red mustard (Brassica juncea) as a deterrent of silverleaf whitefly oviposition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Different pairs of plants planted in a single pot were tested in the greenhouse for oviposition preference by the silverleaf whitefly (Bemisia argentifolii Bellows & Perring [Homoptera: Aleyrodidae]). Treatments consisted of the following in single pots: 2 giant red mustard plants (Brassica juncea ...

  5. Effectiveness of Defatted Mustard Meals Used to Control Fungus Gnats: 2000-2002

    SciTech Connect

    McCaffrey, J. P.; Morra, M. J.

    2005-07-01

    Our objective is to develop a pesticidal product from mustard meals that can be used to control insect pests. We have focused our efforts on fungus gnats. This report details our current progress in developing a pesticidal product that can be used to control this plant pest.

  6. Efficacy of white mustard and soybean meal as a bioherbicide in organic broccoli and spinach production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Weed control in organic cropping systems generally rely on mechanical or physical methods because of the lack of reliable organically accepted herbicides. Among the several potential bioherbicides being explored, white mustard (Sinapis alba) seed meal is among those bioherbicides that have been sho...

  7. [Toxic mustard plaster dematitis and phototoxic dematitis after application of bergamot oil].

    PubMed

    Weisenseel, P; Woitalla, S

    2005-12-15

    Two cases that illustrate the risks attendant on the therapeutic use of natural medications by laypersons are reported. In the first case, the application of a mustard plaster triggered toxic dermatitis. In the second case, a session in a solarium after the external application of bergamot oil resulted in a phototoxic reaction.

  8. [Relationship between tumorous stem mustard yield and soil fertility in Fuling, Southwest China].

    PubMed

    Zhao, Huan; Qin, Song; Wang, Zheng-Yin; Li, Hui-He; Lü, Hui-Feng

    2013-12-01

    By combining field investigation and indoor chemical analysis, the relationship between tumorous stem mustard yield and soil fertility factors was investigated in the main planting areas of tumorous stem mustard in Fuling, Southwest China. The results showed that available Ca, Mg, Fe, Mn, Cu and Zn in the soil were rich (3034, 260, 11.2, 26.1, 1.15 and 1.50 mg x kg(-1), respectively), available P was moderate (19.3 mg x kg(-1)), and organic matter, available N, available K and available S were deficient (9.05 g x kg(-1), 89.2 mg x kg(-1), 106 mg x kg(-1) and 27.0 mg x kg(-1), respectively). The yield of tumorous stem mustard was significantly positively correlated with soil pH and available Ca, whilst significantly (P < 0.01) negatively correlated with available Fe. The influence order of soil fertility factors on the yield of tumorous stem mustard was available Mn > available Cu > pH > available Fe > available K > available Ca > available Mg > available S > available N > available Zn > organic matter > available P. The linear equation (Y = 31636 + 3.63X(6)) of soil available Ca and the yield, was established by stepwise regression analysis.

  9. Mustard seed meal amendments for suppression of Meloidogyne incognita on tomato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mustard seed meal is applied to soil as a fertilizer and for suppressing weeds and pathogens. Brassica juncea (Bj) ‘Pacific Gold’ and Sinapis alba (Sa) ‘IdaGold’ seed meals were tested for suppression of Meloidogyne incognita on tomato ‘BHN 444’. In greenhouse trials these treatments (all 0.25% weig...

  10. 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...

  11. Wound Healing of Cutaneous Sulfur Mustard Injuries: Strategies for the Development of Improved Therapies

    DTIC Science & Technology

    2005-01-05

    of much greater potency that would likely be very efficacious if used early in the lesion development stage, such as betamethasone dipropionate ...Hunt Valley, MD. pp. 1179- 1186. 108. Miller TL, Graham JS, Hayes TL, Reid FM. Stability of sulfur mustard in vehicles suitable for cutaneous

  12. Mustard gas and American race-based human experimentation in World War II.

    PubMed

    Smith, Susan L

    2008-01-01

    This essay examines the risks of racialized science as revealed in the American mustard gas experiments of World War II. In a climate of contested beliefs over the existence and meanings of racial differences, medical researchers examined the bodies of Japanese American, African American, and Puerto Rican soldiers for evidence of how they differed from whites.

  13. [Fate and balance of bulk blending controlled release fertilizer nitrogen under continuous cropping of mustard].

    PubMed

    Zhang, Pan-Pan; Fan, Xiao-Lin

    2012-10-01

    Under the conditions of applying water soluble fertilizer and its bulk blending with controlled release fertilizer (BB-CRF), and by using micro-lysimeter, this paper quantitatively studied the nitrogen (N) uptake by mustard, the soil N losses from N2O emission, leaching and others, and the N residual in soil in three rotations of continuously cropped mustard. In the treatment of BB-CRF with 25% of controlled release nitrogen, the N uptake by mustard increased with rotations, and the yield by the end of the experiment was significantly higher than that in the treatment of water soluble fertilizer. The cumulated N2O emission loss and the N leaching loss were obviously higher in treatment water soluble fertilizer than in treatment BB-CRF. NO3(-)-N was the primary form of N in the leachate. In relative to water soluble fertilizer, BB-CRF altered the fates of fertilizer nitrogen, i.e., the N uptake by mustard and the N residual in soil increased by 75.4% and 76.0%, and the N leaching loss and other apparent N losses decreased by 27.1% and 66.3%, respectively. The application of BB-CRF could be an effective way to reduce the various losses of fertilizer N while increase the fertilizer N use efficiency, and the controlled release fertilizer is the environmentally friendly fertilizer with the property of high N use efficiency.

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

    SciTech Connect

    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 produced during the synthesis of tris(2-chloroethyl)amine (HN3) that point to 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. Reaction-produced impurities indicative of specific TEA and chloroform stocks were exclusively discovered in HN3 batches made with those reagent stocks. In addition, some reagent impurities were found in the HN3 batches that were presumably not altered during synthesis and believed to be indicative of reagent type regardless of stock. Supervised classification using partial least squares discriminant analysis (PLSDA) on the impurity profiles of chloroform samples from seven stocks resulted in an average classification error by cross-validation of 2.4%. A classification error of zero was obtained using the seven-stock PLSDA model on a validation set of samples from an arbitrarily selected chloroform stock. In a separate analysis, all samples from two of seven chloroform stocks that were purposely not modeled had their samples matched to a chloroform stock rather than assigned a “no class” classification.

  15. 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.

  16. 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.

  17. 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.

  18. pH-dependent toxicity of sulphur mustard in vitro

    SciTech Connect

    Sawyer, Thomas W. . E-mail: Thomas.Sawyer@drdc-rddc.gc.ca; Vair, Cory; Nelson, Peggy; Shei Yimin; Bjarnason, Stephen; Tenn, Catherine; McWilliams, Michael; Villanueva, Mercy; Burczyk, Andrew

    2007-06-15

    The dependence of sulphur mustard (HD) toxicity on intracellular (pH{sub i}) and extracellular pH was examined in CHO-K1 cells. HD produced an immediate and significant concentration-dependent decline in cytosolic pH, and also inhibited the mechanisms responsible for restoring pH{sub i} to physiological values. The concentration-response of HD-induced cytosolic acidification, closely paralleled the acidification of the extracellular buffer through HD hydrolysis. A viability study was carried out in order to assess the importance of HD-induced cytosolic acidification. Cultures were exposed to HD for 1 h in media that were adjusted through a pH range (pH 5.0-10), and the 24 h LC{sub 50} values were assessed using the viability indicator dye alamarBlue{sup TM}. The toxicity of HD was found to be dependent on extracellular pH, with a greater than eight-fold increase in LD{sub 50} obtained in cultures treated with HD at pH 9.5, compared to those treated at pH 5.0. Assays of apoptotic cell death, including morphology, soluble DNA, caspase-3 activity and TUNEL also showed that as pH was increased, much greater HD concentrations were required to cause cell death. The modest decline in HD half-life measured in buffers of increasing pH, did not account for the protective effects of basic pH. The early event(s) that HD initiates to eventually culminate in cell death are not known. However, based on the data obtained in this study, we propose that HD causes an extracellular acidification through chemical hydrolysis and that this, in both a concentration and temporally related fashion, results in cytosolic acidification. Furthermore, HD also acts to poison the antiporter systems responsible for maintaining physiological pH{sub i}, so that the cells are unable to recover from this insult. It is this irreversible decline in pH{sub i} that initiates the cascade of events that results in HD-induced cell death.

  19. Assay techniques for detection of exposure to sulfur mustard, cholinesterase inhibitors, sarin, soman, GF, and cyanide. Technical bulletin

    SciTech Connect

    1996-05-01

    This technical bulletin provides analytical techniques to identify toxic chemical agents in urine or blood samples. It is intended to provide the clinician with laboratory tests to detect exposure to sulfur mustard, cholinesterase inhibitors, sarin, soman, GF, and cyanide.

  20. Effect of sulfur mustard exposure on protease activity in human peripheral blood lymphocytes. (Reannouncement with new availability information)

    SciTech Connect

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

    1991-12-31

    Sulfur mustard is a chemical warfare blistering agent for which neither the mechanism of action nor an antidote is known. Papirmeister et al. (1985) have postulated a biochemical hypothesis for mustard-induced cutaneous injury involving a sequelae of DNA alkylation, metabolic disruption and activation of protease. Human peripheral blood lymphocytes in cell cultures were employed as an in vitro model for alkylating agent toxicity. A chromogenic peptide substrate assay was used for detection of protease in lymphocytes treated with sulfur mustard or chloroethyl sulfide. Exposure of human peripheral blood lymphocytes from normal donors to these alkylating agents resulted in an increase in cell associated protease activity. This increase in protease activity may contribute to the pathology or act as an indicator to predict methods of therapeutic intervention for sulfur mustard toxicity.

  1. 38 CFR 3.316 - Claims based on chronic effects of exposure to mustard gas and Lewisite.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., scar formation, or the following cancers: Nasopharyngeal; laryngeal; lung (except mesothelioma); or squamous cell carcinoma of the skin. (2) Full-body exposure to nitrogen or sulfur mustard or...

  2. 38 CFR 3.316 - Claims based on chronic effects of exposure to mustard gas and Lewisite.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., scar formation, or the following cancers: Nasopharyngeal; laryngeal; lung (except mesothelioma); or squamous cell carcinoma of the skin. (2) Full-body exposure to nitrogen or sulfur mustard or...

  3. 38 CFR 3.316 - Claims based on chronic effects of exposure to mustard gas and Lewisite.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., scar formation, or the following cancers: Nasopharyngeal; laryngeal; lung (except mesothelioma); or squamous cell carcinoma of the skin. (2) Full-body exposure to nitrogen or sulfur mustard or...

  4. Optimization for Reduced-Fat / Low-NaCl Meat Emulsion Systems with Sea Mustard (Undaria pinnatifida) and Phosphate.

    PubMed

    Kim, Cheon-Jei; Hwang, Ko-Eun; Song, Dong-Heon; Jeong, Tae-Jun; Kim, Hyun-Wook; Kim, Young-Boong; Jeon, Ki-Hong; Choi, Yun-Sang

    2015-01-01

    The effects of reducing fat levels from 30% to 20% and salt concentrations from 1.5% to 1.0% by partially substituting incorporated phosphate and sea mustard were investigated based on physicochemical properties of reduced-fat / low-NaCl meat emulsion systems. Cooking loss and emulsion stability, hardness, springiness, and cohesiveness for reduced-fat / low-NaCl meat emulsion systems with 20% pork back fat and 1.2% sodium chloride samples with incorporation of phosphate and sea mustard were similar to the control with 30% pork back fat and 1.5% sodium chloride. Results showed that reduced-fat / low-NaCl meat emulsion system samples containing phosphate and sea mustard had higher apparent viscosity. The results of this study show that the incorporation of phosphate and sea mustard in the formulation will successfully reduce fat and salt in the final meat products.

  5. Optimization for Reduced-Fat / Low-NaCl Meat Emulsion Systems with Sea Mustard (Undaria pinnatifida) and Phosphate

    PubMed Central

    Kim, Cheon-Jei; Hwang, Ko-Eun; Song, Dong-Heon; Jeong, Tae-Jun; Kim, Hyun-Wook

    2015-01-01

    The effects of reducing fat levels from 30% to 20% and salt concentrations from 1.5% to 1.0% by partially substituting incorporated phosphate and sea mustard were investigated based on physicochemical properties of reduced-fat / low-NaCl meat emulsion systems. Cooking loss and emulsion stability, hardness, springiness, and cohesiveness for reduced-fat / low-NaCl meat emulsion systems with 20% pork back fat and 1.2% sodium chloride samples with incorporation of phosphate and sea mustard were similar to the control with 30% pork back fat and 1.5% sodium chloride. Results showed that reduced-fat / low-NaCl meat emulsion system samples containing phosphate and sea mustard had higher apparent viscosity. The results of this study show that the incorporation of phosphate and sea mustard in the formulation will successfully reduce fat and salt in the final meat products. PMID:26761874

  6. Mechanism of Cutaneous Vesication

    DTIC Science & Technology

    1994-02-17

    neurofilibroma. J. Invest. Dermatol. 85:54- 59. Foidart, J.M., Bere, E.W., Yaar, M ., Rennard, S.I., Gullino , M ., Martin, G.R., and Katz, S.I. (1980). Distribution...of animal models for predicting skin penetration in man. Fundam. Appl. Toxicol. 4:S224-S230. Requena, L ., Requena, C., Sanchez, M ., Jaqueti, G...H., Gullino , M ., and Katz, S.I. (1976). Herpes gestationis. Ultrastructure and ultrastructural localization of in vivo-bound complement: Modified

  7. 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.

  8. Aromatic nitrogen mustard-based prodrugs: activity, selectivity, and the mechanism of DNA cross-linking.

    PubMed

    Chen, Wenbing; Han, Yanyan; Peng, Xiaohua

    2014-06-10

    Three novel H2O2-activated aromatic nitrogen mustard prodrugs (6-8) are reported. These compounds contain a DNA alkylating agent connected to a H2O2-responsive trigger by different electron-withdrawing linkers so that they are inactive towards DNA but can be triggered by H2O2 to release active species. The activity and selectivity of these compounds towards DNA were investigated by measuring DNA interstrand cross-link (ICL) formation in the presence or absence of H2O2. An electron-withdrawing linker unit, such as a quaternary ammonia salt (6), a carboxyamide (7), and a carbonate group (8), is sufficient to deactivate the aromatic nitrogen mustard resulting in less than 1.5 % cross-linking formation. However, H2O2 can restore the activity of the effectors by converting a withdrawing group to a donating group, therefore increasing the cross-linking efficiency (>20 %). The stability and reaction sites of the ICL products were determined, which revealed that alkylation induced by 7 and 8 not only occurred at the purine sites but also at the pyrimidine site. For the first time, we isolated and characterized the monomer adducts formed between the canonical nucleosides and the aromatic nitrogen mustard (15) which supported that nitrogen mustards reacted with dG, dA, and dC. The activation mechanism was studied by NMR spectroscopic analysis. An in vitro cytotoxicity assay demonstrated that compound 7 with a carboxyamide linker dramatically inhibited the growth of various cancer cells with a GI50 of less than 1 μM, whereas compound 6 with a charged linker did not show any obvious toxicity in all cell lines tested. These data indicated that a neutral carboxyamide linker is preferable for developing nitrogen mustard prodrugs. Our results showed that 7 is a potent anticancer prodrug that can serve as a model compound for further development. We believe these novel aromatic nitrogen mustards will inspire further and effective applications.

  9. Use of mustard flour to inactivate Escherichia coli O157:H7 in ground beef under nitrogen flushed packaging.

    PubMed

    Nadarajah, D; Han, J H; Holley, R A

    2005-04-01

    This study was undertaken to determine whether the glucosinolates naturally present in non-deheated mustard flour could serve as a source of allyl and other isothiocyanates in sufficient quantity to kill Escherichia coli O157:H7 inoculated in ground beef at three different levels, during refrigerated storage of the meat under nitrogen. Mustard flour was mixed at 5%, 10% or 20% (w/w) with freshly ground beef, then the beef was inoculated with a cocktail of five strains of E. coli O157:H7 at either 3, 6 or < or =1.6 log10 cfu/g. The ground beef was formed into 100 g patties and each was placed in a bag of Nylon/EVOH/PE, which was back-flushed with 100% N2, heat-sealed and stored at 4 degrees C for < or =21 days. During storage, the allyl isothiocyanate (AIT) levels in package headspaces were determined by gas liquid chromatography. By 21 days, the levels present in treatments were not significantly different. After 21 days storage, there were 0.5, 3 and 5.4 log10 decreases in numbers of E. coli O157:H7 from the initial levels of 6 log10 cfu/g in meat containing 5%, 10% and 20% mustard flour, respectively. When inoculated at 3 log10 cfu/g, E. coli O157:H7 was reduced to undetectable levels after 18, 12 and 3 days with 5%, 10% and 20% mustard flour, respectively. When immunomagnetic separation (IMS) was used for E. coli recovery following its inoculation at < or =1.6 log10 cfu/g, 5% mustard did not completely eliminate the pathogen from ground beef stored for 6 days. The natural microflora of the ground beef which developed in vacuum packages was unaffected by the addition of 5% mustard flour but some inhibition was found at higher concentrations. Sensory evaluation of the cooked ground beef showed that there were no significant differences in the acceptability of meat treated with 5 or 10% mustard flour. However, panelists could distinguish untreated controls from mustard treatments, but considered the mustard-treated meat to be acceptable. These results showed that

  10. DNA-directed aniline mustards based on 9-aminoacridine: interaction with DNA.

    PubMed

    O'Connor, C J; Denny, W A; Fan, J Y; Gamage, R S

    1992-11-30

    A series of 4-substituted aniline mustards ArNH(CH2)nOpC6H4N(CH2CH2Cl)2, where Ar is an acridine and n varies from 2 to 5, interact with DNA. Scatchard analysis shows the compounds bind tightly, with a binding site size similar to that of 9-aminoacridine. The rate of hydrolysis of the mustards, measured by HPLC, is essentially constant across the series. With increasing length of the polymethylene linker, non-covalent binding becomes less strong, but the rate of DNA alkylation increases. Viscometric helix extension measurements and electrophoretic analyses using closed circular supercoiled DNA show that all the compounds are DNA intercalating ligands. Despite these similarities, the compounds are known to have quite different patterns of DNA alkylation, switching from guanine to adenine alkylation as the chain length is extended.

  11. Reliable screening technique for evaluation of wild crucifers against mustard aphid Lipaphis erysimi (Kalt.).

    PubMed

    Singh, S P; Kumar, Sandeep; Singh, Y P; Singh, Ram

    2014-12-01

    Wild crucifers namely Arabidopsis thaliana, Brassica fruticulosa, B. rugosa, B. spinescens, B. tournefortii, Camelina sativa, Capsella bursa-pastoris, Crambe abysinnica, Cronopus didymus, Diplotaxis assurgens, D. gomez-campoi, D. muralis, D. siettiana, D. tenuisiliqua, Enatharocarpus lyratus, Lepidium sativum and Sinapis alba along with five cultivated Brassica species including B. rapa (BSH-1), B. juncea (Rohini), B. napus (GSC-6), B. carinata (DLSC-2) and Eruca sativa (T-27) were screened against mustard aphid Lipaphis erysimi (Kalt.) with a standardized technique under definite level of aphid pressure developed using specially designed cages. Observations have revealed that B. fruticulosa, B. spinescens, Camelina sativa, Crambe abysinnica and Lepidium sativum were resistant to mustard aphid L. erysimi with aphid infestation index (AII) ≤ 1. Capsella bursa-pastoris was highly susceptible to bean aphid, Aphis fabae during its vegetative stage (with 100% mortality). Other genotypes were found in the range of 'susceptible' to 'highly susceptible' with AII ranging 3-5.

  12. [Resorcinol-spectrophotometric method for the determination of fructose in mustard leaf's amylose].

    PubMed

    Hasenqimeng; He, Feng-ga

    2002-06-01

    A method using seliwanoff reaction is proposed for the determination of fructose in the amylose of mustard leaves. Fructose reacts with resorcinol forming a red compound with a maximum absorption at 473 nm. The calibration curve is linear over the range of 0-83 micrograms.mL-1 with a correlation coefficient of 0.9998. The content of fructose in the amylose of mustard leaves is found to be 11.41%. Quantitative analysis used for the fructose of syrup include such as volumetric analysis, then layer chromatography, polarimetry, high pressure liquid chromatography and spectrophotometric analysis. According to different color-developing agents, spectrophotometric analysis may be classified as carbazole method, ammonium molybdate way and resorcinol way etc. reported by foreign papers is hard to operate and colored complex is unstable.

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

    PubMed

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

    2014-08-08

    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.

  14. Determination of nitrogen mustard hydrolysis products in rat urine samples using GC-MS.

    PubMed

    Kenar, Levent; Alp, Orkun

    2011-05-01

    A gas chromatographic-mass spectrometric method was developed, validated and demonstrated by measuring the levels of nitrogen mustard hydrolysis products in the urine collected from dosed rats. The recovery values for trimethylsilyl derivatives of EDEA and MDEA are between 82-95% and 88-112%, respectively. In vivo studies performed by using three different doses (0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg) of HN2 base of nitrogen mustard. MDEA concentrations were between 43.1-232.2 ng/mL. The limit of detection (S/N = 3) values are 2.5 ng/mL and 1.6 ng/mL for EDEA and MDEA, respectively, and the precision of the method in terms of RSD is between 5-8%.

  15. Sulfur Mustard Exposure and Non-Ischemic Central Retinal Vein Occlusion

    PubMed Central

    Shoeibi, Nasser; Balali-Mood, Mahdi; Abrishami, Mojtaba

    2016-01-01

    A 41-year-old man was referred with a complaint of visual loss in his left eye and his best corrected visual acuity was 20/80. Slit lamp examination showed arborizing conjunctival vessels and dry eye. Fundus examination and fluorescein angiography revealed a non-ischemic central retinal vein occlusion. Cardiovascular, rheumatologic, and hematologic work up showed no abnormal findings. An ascertained history of exposure to sulfur mustard during the Iran-Iraq war was documented in his medical history. Four sessions of intravitreal bevacizumab injections were done as needed. After two-year follow-up, visual acuity in his left eye improved to 20/25 and macular edema was resolved without any need for further interventions. We conclude that sulfur mustard gas exposure may be considered as a predisposing factor for central retinal vein occlusion, as was found in our patient (an Iranian war veteran) by excluding all yet known etiologies and predisposing factors. PMID:26722147

  16. Sensitivity of mitomycin C and nitrogen mustard crosslinks to extreme alkaline conditions

    SciTech Connect

    Gruenert, D.C.; Cleaver, J.E.

    1984-09-17

    DNA-DNA crosslinks in cells treated with mitomycin C, nitrogen mustard, or decarbamoyl mitomycin C were measured in alkaline isopycnic gradients as a function of pH. Crosslinks from cells treated with mitomycin C and nitrogen mustard, which react with DNA purines, could be detected at pH 12.5 but not at pH 14. No crosslinks from cells treated with decarbamoyl mitomycin C were detected at either pH. Previous studies with cells exposed to psoralen derivatives plus 360 nm light, which produce DNA-DNA crosslinks with pyrimidines, demonstrated stable crosslinks at pH 14. These studies indicate that DNA-DNA crosslinks involving DNA purines are much less stable at high pH than those involving pyrimidines, and that methods involving exposure to extreme alkaline conditions may give inaccurate information for some agents. 25 references, 1 figure.

  17. 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

  18. Intermediate outcome after Mustard and Senning procedures: A study by the Congenital Heart Surgeons Society.

    PubMed

    Wells, Winfield J.; Blackstone, Eugene

    2000-01-01

    Although atrial switch is rarely performed today except as part of a "double switch" operation, there continues to be interest in the long-term outcome of the procedure because of the many Mustard and Senning survivors who are in follow-up. In contrast to most other reported series on atrial switch, this study by the Congenital Heart Surgeons Society (CHSS) is a prospective multiinstitutional study of patients encountered in a relatively short time frame during the late 1980s. Between 1985 to 1989, 20 centers with surgeons belonging to the CHSS prospectively registered patients <15 days of age presenting with simple or complex transposition of the great arteries (TGA). The patients were assigned to protocol groups based on intent to treat (arterial switch, Mustard, or Senning). Data were abstracted in the Data and Analysis Center, which in most cases, conducted the annual follow-up. Among the 281 patients who had an atrial switch, there were 108 Mustard and 173 Senning procedures. For the combined atrial switch population, the survival at 1 month, 5 years and 10 years was 90%, 85%, and 84%, respectively. Results for the Mustard were better than for the Senning with survival at 1 month, 5 years, and 10 years being 96% versus 86%, 95% versus 80%, 93% versus 78%; (P <.001) for Mustard versus Senning. While the major mortality risk occurred in the first postoperative month for both groups, thereafter, the late rate of death from 1 to 10 years after operation was 0.78%/year Senning versus 0.23%/year Mustard (P <.05). TGA/ventricular septal defect (VSD), lower weight, younger age, cardiac positional anomalies, and procedures on the left ventricle (LV) outflow all correlated significantly with poor outcome. There were 19 reoperations including 2 for right ventricle (RV) failure, 12 for pathway obstruction, and 5 for baffle leak with a 36% overall mortality. Freedom from any pathway obstruction at 10 years was 95%. A permanent pacemaker was required in 21 patients with the

  19. 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.

  20. A preliminary report on zinc-induced resistance to nitrogen mustard toxicity in mice

    SciTech Connect

    Shackelford, M.E.; Tobey, R.A.

    1988-12-01

    Previous studies with cultured human normal fibroblasts indicated that treatment of cells with zinc before exposure to alkylating agents enhanced cell survival by seven- to nine-fold. To establish whether a similar zinc-induced protective response could be elicited in vivo, a set of preliminary experiments was carried out in which Balb/cJ mice were treated with zinc chloride (2 mg/kg body weight) or saline by intraperitoneal (ip) injection at 48, 36, 24, and 12 h before ip administration of 4 mg/kg of the alkylating agent nitrogen mustard. Of the animals that received saline before nitrogen mustard, 57% were killed compared with only 20% in the group treated with zinc before administration of the alkylating agent. These results (which almost certainly were achieved with less than optimal induction conditions) provide evidence for the existence, in vivo, of a zinc-inducible process that reduces alkylating agent lethality. 12 refs., 4 figs.

  1. Intervention of Sulfur Mustard Toxicity by Downregulation of Cell Proliferation and Metabolic Rates

    DTIC Science & Technology

    2000-01-01

    attenuating the apop- totic response due to HD.7 We reported that BAPTA AM does not affect the activation of DNA ligase (a DNA repair enzyme) in HD...R. DNA ligase activation fol- lowing sulfur mustard exposure in cultured human epi- dermal keratinocytes. In Vitro Mol. Toxicol. 1998; 11: 45-53. Published in 2000 by John Wiley & Sons, Ltd. J. Appl. Toxicol. 20, S87-S91 (2000)

  2. Pretreatment of Human Epidermal Keratinocytes In Vitro With Ethacrynic Acid Reduces Sulfur Mustard Cytotoxicity

    DTIC Science & Technology

    2004-01-01

    estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the...display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1 . REPORT DATE (DD-MM-YYYY) 2. REPORT TYPE 3. DATES...Ethacrynic Acid Reduces 5b. GRANT NUMBER Sulfur Mustard Toxicity 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Gross, CL, Nipwoda, MT, Nealley

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

    PubMed

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

    2014-09-30

    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.

  4. Architectural and Biochemical Expressions of Mustard Gas Keratopathy: Preclinical Indicators and Pathogenic Mechanisms

    DTIC Science & Technology

    2012-08-10

    Nanoscale topography of the basement membrane underlying the corneal epithelium of the rhesus macaque. Cell Tissue Res 299: 39–46. 28. Pal-Ghosh S...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

  5. 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

  6. Effects of Prednisolone Acetate on Ocular Sulfur Mustard Injury in a Rabbit Model

    DTIC Science & Technology

    2003-12-01

    perforations can be a potential risk. Steriods can greatly potentiate the effects of collagenase activity, resulting in severe destruction (melting...for mustard-induced ocular injury. Steriods are often used in combination but the effects ofjust the steroids alone have only been studied in a...of animals, it seemed likely that the steriod did have a contributing role particularly in corneas that were thinning and attempting to regenerate

  7. Progression of Ocular Sulfur Mustard Injury: Development of a Model System

    DTIC Science & Technology

    2010-01-01

    8923 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Issue: Thymosins in Health and Disease Progression of ocular sulfur mustard injury: development of a...Control corneas have hemidesmosomal- attachments, characteris- tic desmosomal adhesions, and a well-articulated epithelial-stromal architecture (Fig. 3A... desmosomal attachments (white arrow), and a well- articulated epithelial-stromal boundary. (Panel B) One week after exposure, a basal epithelial cell layer

  8. Baseline Serum Clinical Chemistry Values in African Green Monkeys Before and After Sulfur Mustard

    DTIC Science & Technology

    2007-05-01

    COVERED (From - To) March 2001 to June 2003 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Baseline Serum Clinical Chemistry Values in African...models and can serve as an index for future HD AGM studies. 15. SUBJECT TERMS Sulfur mustard, African Green monkey, clinical chemistry , serum 16...Pathology Branch for necropsy histopathology review and clinical chemistry assistance. We also thank Steve Tucker and Dr. John McDonough, Ph.D., for

  9. Production of medium chain fatty acid rich mustard oil using packed bed bioreactor.

    PubMed

    Sengupta, Avery; Roy, Susmita; Mukherjee, Sohini; Ghosh, Mahua

    2015-01-01

    A comparative study was done on the production of different medium chain fatty acid (MCFA) rich mustard oil using a stirred tank batchreactor (STBR) and packed bed bio reactor (PBBR) using three commercially available immobilised lipases viz. Thermomyces lanuginosus, Candida antarctica and Rhizomucor meihe. Three different MCFAs capric, caprylic and lauric acids were incorporated in the mustard oil. Reaction parameters, such as substrate molar ratio, reaction temperature and enzyme concentration were standardized in the STBR and maintained in the PBBR. To provide equal time of residence between the substrate and enzyme in both the reactors for the same amount of substrates, the substrate flow rate in the PBBR was maintainedat 0.27 ml/min. Gas liquid chromatography was used to monitor the incorporation of MCFA in mustard oil. The study showed that the PBBR was more efficient than the STBR in the synthesis of structured lipids with less migration of acyl groups. The physico-chemical parameters of the product along with fatty acid composition in all positions and sn-2 positions were also determined.

  10. GLC analysis of Indian rapeseed-mustard to study the variability of fatty acid composition.

    PubMed

    Kaushik, N; Agnihotri, A

    2000-12-01

    Rapeseed-mustard is one of the most economically important oilseed crops in India. Speciality oils having high amounts of a specific fatty acid are of immense importance for both nutritional and industrial purposes. Oil high in oleic acid has demand in commercial food-service applications due to a long shelf-life and cholesterol-reducing properties. Both linoleic and linolenic acids are essential fatty acids; however, less than 3% linolenic acid is preferred for oil stability. High erucic acid content is beneficial for the polymer industry, whereas low erucic acid is recommended for food purposes. Therefore, it is important to undertake systematic characterization of the available gene pool for its variable fatty acid profile to be utilized for specific purposes. In the present study the Indian rapeseed-mustard germplasm and some newly developed low-erucic-acid strains were analysed by GLC to study the fatty acid composition in these lines. The GLC analysis revealed that the rapeseed-mustard varieties being commonly grown in India are characterized by high erucic acid content (30-51%) in the oil with low levels of oleic acid (13-23%). However, from among the recently developed low-erucic-acid strains, several lines were identified with comparatively high oleic acid (60-70%), moderate to high linoleic acid (13-40%) and low linolenic acid (< 10%) contents. Work is in progress at TERI (New Delhi, India) to utilize these lines for development of strains with particular fatty acid compositions for specific purposes.

  11. 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.

  12. 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.

  13. 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.

  14. IDENTIFICATION OF BIS(2-CHLOROETHYL) ETHER HYDROLYSIS PRODUCTS BY DIRECT AQUEOUS INJECTION GC/FT-IR

    EPA Science Inventory

    Gas chromatography coupled to Fourier-transform infrared spectroscopy (GC/FT-IR) is rapidly becoming an accepted analytical technique complementary to GC/mass spectroscopy for identifying organic compounds in mixtures at low to moderate concentrations. irect aqueous injection (DA...

  15. Acute Environmental Toxicity and Persistence of a Chemical Agent Simulant: 2-Chloroethyl Ethyl Sulfide (CEES)

    DTIC Science & Technology

    1988-11-01

    Isolated Chloroplast Measurements Chloroplasts were isolated from commercially obtained spinach (Spinacea oleracea) leaves according to the methods of...showed an inhibition of photosynthetic capability and elevated respiration rates . Within the photosynthetic apparatus in the chloroplasts , those...Isolated Spinach Chloroplasts ........................................... 49 3.11 Effect of CEES on Dehydrogenase Activities in Burbank and Palouse Soils

  16. 40 CFR 721.10688 - Copper, chloro[tris(2-chloroethyl) phosphite-.kappa.P]-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Copper, chloro -. 721.10688 Section... Substances § 721.10688 Copper, chloro -. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as copper, chloro - (PMN P-13-221; CAS No. 24484-01-3)...

  17. 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.

  18. 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.

  19. [Determination of isothiocyanates and related compounds in mustard extract and horseradish extract used as natural food additives].

    PubMed

    Uematsu, Yoko; Hirata, Keiko; Suzuki, Kumi; Iida, Kenji; Ueta, Tadahiko; Kamata, Kunihiro

    2002-02-01

    Amounts of isothiocyanates and related compounds in a mustard extract and a horseradish extract for food additive use were determined by GC, after confirmation of the identity of GC peaks by GC/MS. Amounts of allyl isothiocyanate, which included that of allyl thiocyanate, because most of the allyl thiocyanate detected in the sample was assumed to have been formed from allyl isothiocyanate during GC analysis, were 97.6% and 85.4%, in the mustard extract and the horseradish extract, respectively. Total amounts of the identified isothiocyanates in the mustard extract and the horseradish extract were 98.5% and 95.4%, respectively. Allyl cyanide, a degradation product of allyl isothiocyanate, was found in the mustard extract and the horseradish extract at the levels of 0.57% and 1.73%, respectively. beta-Phenylethyl cyanide, a possible degradation product of beta-phenylethyl isothiocyanate, and allyl sulfides were found in the horseradish extract, at the levels of 0.13% and 0.46%, respectively. Allylamine, which is another degradation product of allyl isothiocyanate, was determined after acetylation, and was found in the mustard extract and the horseradish extract at the levels of 8 micrograms/g and 67 micrograms/g, respectively.

  20. Rapid monitoring of sulfur mustard degradation in solution by headspace solid-phase microextraction sampling and gas chromatography mass spectrometry.

    PubMed

    Creek, Jo-Anne M; McAnoy, Andrew M; Brinkworth, Craig S

    2010-12-15

    A method using headspace solid-phase microextraction (HS-SPME) followed by gas chromatography/mass spectrometry (GC/MS) analysis has been developed to gain insight into the degradation of the chemical warfare agent sulfur mustard in solution. Specifically, the described approach simplifies the sample preparation for GC/MS analysis to provide a rapid determination of changes in sulfur mustard abundance. These results were found to be consistent with those obtained using liquid-liquid extraction (LLE) GC/MS. The utility of the described approach was further demonstrated by the investigation of the degradation process in a complex matrix with surfactant added to assist solvation of sulfur mustard. A more rapid reduction in sulfur mustard abundance was observed using the HS-SPME approach with surfactant present and was similar to results from LLE experiments. Significantly, this study demonstrates that HS-SPME can simplify the sample preparation for GC/MS analysis to monitor changes in sulfur mustard abundance in solution more rapidly, and with less solvent and reagent usage than LLE.

  1. Childhood physical abnormalities following paternal exposure to sulfur mustard gas in Iran: a case-control study

    PubMed Central

    2010-01-01

    Background Mustard gas, a known chemical weapon, was used during the Iran-Iraq war of 1980-1988. We aimed to determine if exposure to mustard gas among men was significantly associated with abnormalities and disorders among progenies. Methods Using a case-control design, we identified all progenies of Sardasht men (exposed group, n = 498), who were born at least nine months after the exposure, compared to age-matched controls in Rabat, a nearby city (non-exposed group, n = 689). We conducted a thorough medical history, physical examination, and appropriate paraclinical studies to detect any physical abnormality and/or disorder. Given the presence of correlated data, we applied Generalized Estimating Equation (GEE) multivariable models to determine associations. Results The overall frequency of detected physical abnormalities and disorders was significantly higher in the exposed group (19% vs. 11%, Odds Ratio [OR] 1.93, 95% Confidence Interval [CI], 1.37-2.72, P = 0.0002). This was consistent across sexes. Congenital anomalies (OR 3.54, 95% CI, 1.58-7.93, P = 0.002) and asthma (OR, 3.12, 95% CI, 1.43-6.80, P = 0.004) were most commonly associated with exposure. No single abnormality was associated with paternal exposure to mustard gas. Conclusion Our study demonstrates a generational effect of exposure to mustard gas. The lasting effects of mustard gas exposure in parents effects fertility and may impact child health and development in the long-term. PMID:20630096

  2. Kojic acid reduces the cytotoxic effects of sulfur mustard on cultures containing human melanoma cells in vitro.

    PubMed

    Smith, C N; Lindsay, C D

    2001-01-01

    In vivo experiments have shown that melanocytes are more sensitive than keratinocytes to the cytotoxic effects of sulfur mustard when it is applied topically to pig skin.1 It has been hypothesized that this is caused by the uncoupling of the melanogenic pathway by depletion of cellular glutathione, resulting in the uncontrolled production of cytotoxic quinone free-radical species by tyrosinase.2. In the present study, the feasibility of blocking the melanogenic pathway as a means of reducing the cytotoxicity of sulfur mustard was evaluated using kojic acid. Kojic acid is a topically applied depigmenting agent that exerts its effect by acting as a slow-binding, competitive inhibitor of tyrosinase.3 Preincubation of G361 pigmented melanoma cells and mixed cultures of G361 cells and SVK keratinocytes with 2.5 mM kojic acid resulted in significant increases in the viability of these cultures as determined by neutral red (NR) and gentian violet (GV) dye binding assays for up to 48 h following exposure to 50 microM sulfur mustard. The highest levels of protection were seen in the G361 cultures, with a 26.8% increase in culture viability (NR assay) compared with the sulfur-mustard-only controls at 24 h. Preincubation of SVK cells alone with kojic acid resulted in lower increases in viability (2.5% at 24 h by the NR assay). Inhibition of the melanogenic pathway reduces the sensitivity of cultures containing pigment cells to sulfur mustard.

  3. Characterization of a new oriental-mustard (Brassica juncea) allergen, Bra j IE: detection of an allergenic epitope.

    PubMed Central

    Monsalve, R I; Gonzalez de la Peña, M A; Menendez-Arias, L; Lopez-Otin, C; Villalba, M; Rodriguez, R

    1993-01-01

    Bra j IE, a major allergen from oriental-mustard (Brassica juncea) seeds, has been isolated and characterized. Its primary structure has been elucidated. This protein is composed of two chains (37 and 92 amino acids) linked by disulphide bridges. The amino acid sequence obtained is closely related to that previously determined for Sin a I, an allergen isolated from yellow mustard (Sinapis alba). A common epitope has been detected in the large chain of both Bra j IE and Sin a I by means of electroblotting and immunodetection with 2B3, which is a monoclonal antibody raised against the yellow-mustard allergen. A histidine residue of the large chain of both mustard allergens has been found to be essential for the recognition by 2B3 antibody. A synthetic multiantigenic peptide containing this His was recognized by 2B3 as well as by sera of mustard-hypersensitive individuals. Therefore this antigenic determinant must be involved in the allergenicity of these proteins. Images Figure 3 Figure 7 Figure 8 PMID:7688955

  4. '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.

  5. Development and validation of a triplex real-time PCR assay for the simultaneous detection of three mustard species and three celery varieties in food.

    PubMed

    Palle-Reisch, Monika; Hochegger, Rupert; Cichna-Markl, Margit

    2015-10-01

    The paper presents a triplex real-time PCR assay allowing the simultaneous detection of three mustard species (white, black and brown mustard) and three celery varieties (celery roots, celery stalks and leaf celery) in foodstuffs. The triplex assay does not show cross-reactivity with other Brassicaceae. Low cross-reactivities were observed with fenugreek, cumin, ginger, caraway, turmeric, lovage and rye, the ΔCt values were, however, ⩾ 12 compared to positive controls. The triplex assay allows the detection of traces of DNA of the allergenic components in spite of an excess of the other DNA templates. Analysis of extracts from model sausages containing defined concentrations of mustard and celery showed that the triplex assay is applicable to both raw and processed foods. It was found to allow the detection of 1 ppm black/brown mustard and 50 ppm white mustard and celery in raw and brewed sausages with a probability ⩾ 95%.

  6. Comparison of Mustard Oil and Ghee Consumption on the History of Coronary Heart Disease in Urban Population of India

    PubMed Central

    Sharma, Hanjabam Barun; Vyas, Soniya; Kumar, Jayant

    2016-01-01

    Introduction Coronary Heart Disease (CHD) is one of the leading causes of mortality in India, due to high consumption of mustard oil and ghee among urban population. Aim To find out the relationship of mustard oil and ghee consumption on CHD history. Materials and Methods By a random cross-sectional, house-to-house survey in North India, 137 people aged between 40-80 years (70 males and 67 females) were selected by dietary history of Mustard Oil (MO) and Ghee consumption (G), but having no other CHD precipitating factor. Using food frequency questionnaire, the study population was divided into two groups based on the amount of MO and G consumption; Group A (n = 75): MO >1L/month, but G <0.5Kg/month and Group B (n = 62): MO =0.2 to 0.5L/month but G >1.25Kg/month. Serum lipid profile estimation and resting ECGs recording were done from all the subjects. Results There was no statistical significant difference in CHD history between the two groups. Mustard Oil had positive correlation with CHD history. CHD was higher by 50.9% in Group A and was independent of gender. However, the odds of CHD history were higher among males by 32.2% irrespective of the groups. Conclusion The results demonstrated that CHD history was associated with higher relative consumption of mustard oil than ghee and CHD is positively correlated with increase mustard oil intake, blood level of TG, TC, LDL, VLDL, TC/HDL and LDL/HDL ratio. PMID:27891367

  7. 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.

  8. Inhalation and Percutaneous Toxicokinetics of Sulfur Mustard and Its Adducts in Hairless Guinea Pigs and Marmosets. Efficacy of Naval Scavengers

    DTIC Science & Technology

    2005-08-01

    very rapid distribution phase and a very slow elimination phase. The concentration of sulfur mustard in tissues (lung, spleen , liver, and bone marrow...tissue, and spleen . The respiratory tract was isolated from animals that were nose-only exposed to 1 LCt50 of sulfur mustard in 5 min, at 4 h after...detected in spleen , bone marrow and small intestine, while rather low concentrations of N7-HETE-gua were measured in the lung at 10 min and 48 h after

  9. 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

    2009-11-06

    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.

  10. [The implantation of a sequential endocavitary pacemaker in a patient with transposition of the great vessels after the Mustard correction].

    PubMed

    Padró, J M; Montiel, J; Ruyra, X; Subirana, M; Arís, A; Caralps, J M

    1993-08-01

    A 31-year-old male patient, underwent Mustard operation in childhood for complete transposition of the great arteries. He required a sequential (DDD-mode) pacemaker due to a complete symptomatic auriculoventricular block, 25 years after the operation. Wires were inserted through the left cephalic vein and placed in the systemic atrium and ventricle, achieving correct sensing and stimulating thresholds. Atrial rhythm disturbances, specially sinus node dysfunction, are frequent after Mustard's operation and increase through the years following the surgical procedure. Atrioventricular conduction disturbances are rare. Treatment by endocavitary pacemaker implies a correct knowledge of the special anatomy in this congenital disease and its surgical correction.

  11. Adsorption-desorption studies of indigocarmine from industrial effluents by using deoiled mustard and its comparison with charcoal.

    PubMed

    Gupta, Vinod K; Jain, Rajeev; Malathi, S; Nayak, Arunima

    2010-08-15

    Deoiled mustard obtained from local oil mills has been used as an inexpensive and effective adsorbent for the removal of indigocarmine dye from industrial effluents. The influence of various factors on the adsorption capacity has been studied by batch experiments. The adsorption studies validate both Langmuir and Freundlich adsorption isotherms. Thermodynamic parameters such as DeltaG degrees, DeltaH degrees, and DeltaS degrees for the adsorption process were calculated, which indicated the feasibility of the adsorption process. Desorption profiles revealed that a significant portion (85%) could be desorbed from deoiled mustard by using 30% glycerol as eluting agent.

  12. Thermal requirement of indian mustard (Brassica juncea) at different phonological stages under late sown condition.

    PubMed

    Singh, Manoj Pratap; Lallu; Singh, N B

    2014-01-01

    Indian mustard [Brassica juncea (L.) Czern & Coss.] is a long day plant, which requires fairly cool climatic condition during growth and development for obtaining better seed yield. Various workers have correlated crop growth and development with energy requirement parameters, such as growing degree days (GDD), photo-thermal unit (PTU), helios thermal unit (HTU), photo-thermal index (PTI) and heat use efficiency (HUE). Therefore, GDD requirement for different phenological stages of 22 newly developed Indian mustard varieties was studies during winter (rabi) seasons of 2009-10 and 2010-11 at student instructional farm of C.S. Azad University of Agriculture and Technology, Kanpur, (Utter Pradesh). Study revealed that RH-8814, NRCDR-02 and BPR-549-9 recorded higher GDD (1703.0, 1662.9 and 1648.0), PTU (19129.8, 18694.2 and 18379.8), HTU (11397.7, 11072.2 and 10876.0), PTI (13.25, 13.14 and 13.08) and HUE (4.11, 3.84 and 3.71) at physiological maturity, while higher HUE was recorded (9.62, 8.99 and 8.91 kg ha(-1) degrees-day) at days after sowing (DAS) to 50 % flowering. On the basis of study mustard genotypes RH-8814, NRCDR-02 and BPR-549-9 were identified as most heat-tolerant, as they maintained higher values for energy related parameters. Seed yield was highly positively correlated with GDD (r = 0.61, 0.65 and 0.75), PTU (r = 0.66, 0.64 and 0.74), HTU(r = 0.79, 0.68 and 0.73) at the above these three phenological stages, while negatively correlated with PTI at anthesis and at maturity. Hence, these parents could be used in crossing programme for achieving further improvement.

  13. 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.

  14. Environmental Assessment. Proposed Sahara Mustard Control on the Barry M. Goldwater Range - East

    DTIC Science & Technology

    2012-02-01

    dateable) artifacts. Radiocarbon dates , obtained from thermal features indicates that BMGR- 00-D-01 dates to AD 1400-1600 and BMGR-00-D-02 dates to AD...failing to comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE 19 JUL 2012 2...REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Proposed Sahara Mustard Control on the Barry M. Goldwater Range - Easy

  15. Study on evaporation characteristics of a sessile drop of sulfur mustard on glass.

    PubMed

    Jung, Hyunsook; Myung, Sung Min; Park, Myung Kyu; Lee, Hae Wan; Ryu, Sam Gon

    2012-05-01

    The evaporation characteristics (evaporation rates and process) of a sessile drop of sulfur mustard on glass has been studied using a laboratory-sized wind tunnel, gas chromatograph mass spectrometry, and drop shape analysis. It showed that the evaporation rates of the droplet increased with temperature and air flow. The effect of temperature on the rates was more pronounced at lower air flow. Air flow was less effective at lower temperature. The contact angle of the droplet was initially observed as θ = 19.5° ± 0.7 and decreased linearly with time until it switched to a constant mode.

  16. Effect of Sulfur Mustard on Mast Cells in Hairless Guinea Pig Skin

    DTIC Science & Technology

    1993-05-13

    AD-P008 756 EFFECT OF SULFUR MUSTARD ON MAST CELLS IN HAIRLESS GUINEA PIG SKIN JOHN S. GRAHAM, MARK A . BRYANT and ERNEST H. BRAUE U.S. Army Medical...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...histopathology 94-07918 Best Available Copy C0t PONENT PART NOTICE THIS PAPER IS A CCWPOWENT PART OF THE FOLLOWING COIPILATION REPORT: TITLE: Proceedins of the

  17. 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

    1994-12-09

    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.

  18. 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.

  19. Semiquantitative analysis of 3-butenyl isothiocyanate to monitor an off-flavor in mustard seeds and glycosinolates screening for origin identification.

    PubMed

    Frank, Nancy; Dubois, Mathieu; Goldmann, Till; Tarres, Adrienne; Schuster, Elke; Robert, Fabien

    2010-03-24

    The present paper describes the development of an analytical method for the semiquantitative analysis of 3-butenyl isothiocyanate in mustard seeds, this compound being linked to an undesirable (at least for the European palate) off-flavor. 3-Butenyl isothiocyanate is one of the enzymatic degradation products of gluconapin, a member of the glucosinolate family of compounds. A headspace-gas chromatography-mass spectrometry (HS-GC-MS) method has been developed for the rapid analysis of 3-butenyl isothiocyanate in mustard seeds. The cross-check of this HS-GC-MS method has been made on the basis of the analysis of the native gluconapin using liquid chromatography coupled to time-of-flight mass spectrometry (LC-TOF-MS). Both techniques gave comparable results. The HS-GC-MS method was kept as the method of choice as it is rapid and solvent-free. Because yellow mustard seeds do not normally contain gluconapin, its presence in such seeds above the limit of detection was already considered as a criterion for potentially problematic mustard batches. However, "organoleptically" acceptable brown mustard seeds already contained measurable amounts of gluconapin and had to be differentiated from mustard seeds containing nonacceptable levels of gluconapin, as it is typically the case for brown mustard originating from the Indian subcontinent. Thus, a 3-butenyl isothiocyanate content "cut point" has been established to discriminate between batches. This limit could then be applied for the acceptance or rejection of mustard seed batches. In addition, LC-TOF-MS screening of mustard seeds from different geographic origins showed the heterogeneity of the glucosinolate profile and the difficulty to find good origin markers.

  20. Overexpressing both ATP sulfurylase and selenocysteine methyltransferase enhances selenium phytoremediation traits in Indian mustard.

    PubMed

    LeDuc, Danika L; AbdelSamie, Manal; Móntes-Bayon, Maria; Wu, Carol P; Reisinger, Sarah J; Terry, Norman

    2006-11-01

    A major goal of our selenium (Se) phytoremediation research is to use genetic engineering to develop fast-growing plants with an increased ability to tolerate, accumulate, and volatilize Se. To this end we incorporated a gene (encoding selenocysteine methyltransferase, SMT) from the Se hyperaccumulator, Astragalus bisulcatus, into Indian mustard (LeDuc, D.L., Tarun, A.S., Montes-Bayón, M., Meija, J., Malit, M.F., Wu, C.P., AbdelSamie, M., Chiang, C.-Y., Tagmount, A., deSouza, M., Neuhierl, B., Böck, A., Caruso, J., Terry, N., 2004. Overexpression of selenocysteine methyltransferase in Arabidopsis and Indian mustard increases selenium tolerance and accumulation Plant Physiol. 135, 377-383.). The resulting transgenic plants successfully enhanced Se phytoremediation in that the plants tolerated and accumulated Se from selenite significantly better than wild type. However, the advantage conferred by the SMT enzyme was much less when Se was supplied as selenate. In order to enhance the phytoremediation of selenate, we developed double transgenic plants that overexpressed the gene encoding ATP sulfurylase (APS) in addition to SMT, i.e., APSxSMT. The results showed that there was a substantial improvement in Se accumulation from selenate (4 to 9 times increase) in transgenic plants overexpressing both APS and SMT.

  1. Alkylation of nucleic acids by DNA-targeted 4-anilinoquinolinium aniline mustards: kinetic studies.

    PubMed

    O'Connor, C J; Denny, W A; Fan, J Y

    1991-01-01

    The rate of constant for hydrolysis of a series of 4-substituted aniline mustards Ar-X-pC6H4-N(CH2CH2Cl)2, where Ar is 4-anilinoquinolinium and X = O, CH2, CONH and CO, have been measured in water and 0.02 M imidazole buffer at 37 degrees C and in 50% aqueous acetone at 66 degrees C. The equilibrium binding constants of the compounds and their hydrolysis products to nucleic acids of differing base composition have been determined at varying ionic strengths, and the results are consistent with the compounds binding as expected in the DNA minor groove. The alkylating reactivity of the mustards towards these nucleic acids has been measured in water at 37 degrees C and in 0.01 M HEPES buffer over a range of temperatures from 25 degrees C to 60 degrees C. Evaluation of the thermodynamic parameters for these kinetic and equilibrium studies suggests that the interaction with nucleic acids is via an internal SN2 mechanism involving an aziridinium ion.

  2. 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

  3. Influence of biofilm density on anaerobic sequencing batch biofilm reactor treating mustard tuber wastewater.

    PubMed

    Chai, Hongxiang; Kang, Wei

    2012-11-01

    Considering the characteristics of high salinity, high concentration of organic matter, and high biodegradability, a new and efficient anaerobic sequencing batch biofilm reactor (ASBBR) was chosen as an anaerobic pretreatment unit to treat most organic compounds in mustard tuber wastewater. By changing the biofilm density of the reactor, the test was carried out to find out the influence of biofilm density on effluent COD, the content of the sludge dehydrogenase, and gas production rate. Results showed that under the condition of 30 °C, draining ratio of 1/3, and 2 days of hydraulic retention time, COD removal rate increased from 71.5 to 90.5 % when the biofilm density increased from 15 to 50 %; however, COD removal rate increased from 90.5 to 91.3 % when the biofilm density increased from 50 to 70 %. According to the influence of biofilm density on effluent COD, the content of the sludge dehydrogenase, and gas production rate, ASBBR should take 50 % biofilm density in mustard wastewater treatment. At the same time, these design parameters can be used to guide practical engineering.

  4. Ethylene Potentiates Sulfur-Mediated Reversal of Cadmium Inhibited Photosynthetic Responses in Mustard

    PubMed Central

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

    2016-01-01

    The potential of exogenous ethylene and sulfur (S) in reversal of cadmium (Cd)-inhibited photosynthetic and growth responses in mustard (Brassica juncea L. cv. Pusa Jai Kisan) were studied. Plants grown with 50 μM Cd showed increased superoxide and H2O2 accumulation and lipid peroxidation together with increased activity of 1-aminocyclopropane carboxylic acid synthase (ACS) and ethylene production and inhibition of photosynthesis and growth. Application of 1 mM SO42- or 200 μL L-1 ethephon (ethylene source) influenced photosynthetic and growth performance equally in presence or absence of Cd. However, their combined application synergistically improved photosynthetic performance more in presence of Cd and reduced oxidative stress (lower superoxide and H2O2 accumulation) by decreasing ethylene and glucose sensitivity with the increase in cysteine and methionineand a non-proteinogenic thiol (reduced glutathione; GSH) contents. The central role of ethylene in potentiating S-mediated reversal of Cd-induced oxidative stress was evident with the use of ethylene action inhibitor, norbornadiene (NBD). The application of NBD resulted in decreased thiol production and photosynthetic responses. This suggests that ethylene promotes the effects of S in reversal of adverse effects of Cd, and thus, ethylene modulation may be considered as potential tool to substantiate the S effects in reversal of Cd inhibited photosynthesis and growth in mustard. PMID:27853462

  5. Chemical composition, antimicrobial property and microencapsulation of Mustard (Sinapis alba) seed essential oil by complex coacervation.

    PubMed

    Peng, Chao; Zhao, Su-Qing; Zhang, Jun; Huang, Gui-Ying; Chen, Lan-Ying; Zhao, Feng-Yi

    2014-12-15

    In this study, the essential oil from mustard seed was isolated by simultaneous steam distillation and extraction (SDE) and analyzed by gas chromatography-mass spectrometry (GC-MS). Fourteen components were identified in the mustard seed essential oil with allyl isothiocyanate being the main component (71.06%). The essential oil has a broad-spectrum antimicrobial activity with inhibition zones and MIC values in the range of 9.68-15.57 mm and 128-512 μg/mL respectively. The essential oil was subsequently encapsulated in complex coacervation microcapsules with genipin, a natural water-soluble cross-linker. The optimum parameters for the hardening effectiveness of the genipin-hardened essential oil microcapsules were 8h at 40°C and pH 10.0 with a genipin concentration of 0.075 g/g gelatin. The genipin-hardened microcapsules had a particle size of mainly 5-10 μm and strong chemistry stability which is potential for its application in food preservation.

  6. 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.

  7. Effects of lactic acid bacteria isolated from fermented mustard on lowering cholesterol

    PubMed Central

    Wang, Shu Chen; Chang, Chen Kai; Chan, Shu Chang; Shieh, Jiunn Shiuh; Chiu, Chih Kwang; Duh, Pin-Der

    2014-01-01

    Objective To evaluate the ability of lactic acid bacteria (LAB) strains isolated from fermented mustard to lower the cholesterol in vitro. Methods The ability of 50 LAB strains isolated from fermented mustard on lowering cholesterol in vitro was determined by modified o-phtshalaldehyde method. The LAB isolates were analyzed for their resistance to acid and bile salt. Strains with lowering cholesterol activity, were determined adherence to Caco-2 cells. Results Strain B0007, B0006 and B0022 assimilated more cholesterol than BCRC10474 and BCRC 17010. The isolated strains showed tolerance to pH 3.0 for 3 h despite variations in the degree of viability and bile-tolerant strains, with more than 108 CFU/mL after incubation for 24 h at 1% oxigall in MRS. In addition, strain B0007 and B0022 identified as Lactobacillus plantarum with 16S rDNA sequences were able to adhere to the Caco-2 cell lines. Conclusions These strains B0007 and B0022 may be potential functional sources for cholesterol-lowering activities as well as adhering to Caco-2 cell lines. PMID:25183271

  8. Nanoencapsulation Enhances the Post-Emergence Herbicidal Activity of Atrazine against Mustard Plants.

    PubMed

    Oliveira, Halley Caixeta; Stolf-Moreira, Renata; Martinez, Cláudia Bueno Reis; Grillo, Renato; de Jesus, Marcelo Bispo; Fraceto, Leonardo Fernandes

    2015-01-01

    Poly(epsilon-caprolactone) (PCL) nanocapsules have been recently developed as a modified release system for atrazine, an herbicide that can have harmful effects in the environment. Here, the post-emergence herbicidal activity of PCL nanocapsules containing atrazine was evaluated using mustard (Brassica juncea) as target plant species model. Characterization of atrazine-loaded PCL nanocapsules by nanoparticle tracking analysis indicated a concentration of 7.5 x 10(12) particles mL(-1) and an average size distribution of 240.7 nm. The treatment of mustard plants with nanocapsules carrying atrazine at 1 mg mL(-1) resulted in a decrease of net photosynthesis and PSII maximum quantum yield, and an increase of leaf lipid peroxidation, leading to shoot growth inhibition and the development of severe symptoms. Time course analysis until 72 h after treatments showed that nanoencapsulation of atrazine enhanced the herbicidal activity in comparison with a commercial atrazine formulation. In contrast to the commercial formulation, ten-fold dilution of the atrazine-containing nanocapsules did not compromise the herbicidal activity. No effects were observed when plants were treated with nanocapsules without herbicide compared to control leaves sprayed with water. Overall, these results demonstrated that atrazine-containing PCL nanocapsules provide very effective post-emergence herbicidal activity. More importantly, the use of nanoencapsulated atrazine enables the application of lower dosages of the herbicide, without any loss of efficiency, which could provide environmental benefits.

  9. Nanoencapsulation Enhances the Post-Emergence Herbicidal Activity of Atrazine against Mustard Plants

    PubMed Central

    Oliveira, Halley Caixeta; Stolf-Moreira, Renata; Martinez, Cláudia Bueno Reis; Grillo, Renato; de Jesus, Marcelo Bispo; Fraceto, Leonardo Fernandes

    2015-01-01

    Poly(epsilon-caprolactone) (PCL) nanocapsules have been recently developed as a modified release system for atrazine, an herbicide that can have harmful effects in the environment. Here, the post-emergence herbicidal activity of PCL nanocapsules containing atrazine was evaluated using mustard (Brassica juncea) as target plant species model. Characterization of atrazine-loaded PCL nanocapsules by nanoparticle tracking analysis indicated a concentration of 7.5 x 1012 particles mL-1 and an average size distribution of 240.7 nm. The treatment of mustard plants with nanocapsules carrying atrazine at 1 mg mL-1 resulted in a decrease of net photosynthesis and PSII maximum quantum yield, and an increase of leaf lipid peroxidation, leading to shoot growth inhibition and the development of severe symptoms. Time course analysis until 72 h after treatments showed that nanoencapsulation of atrazine enhanced the herbicidal activity in comparison with a commercial atrazine formulation. In contrast to the commercial formulation, ten-fold dilution of the atrazine-containing nanocapsules did not compromise the herbicidal activity. No effects were observed when plants were treated with nanocapsules without herbicide compared to control leaves sprayed with water. Overall, these results demonstrated that atrazine-containing PCL nanocapsules provide very effective post-emergence herbicidal activity. More importantly, the use of nanoencapsulated atrazine enables the application of lower dosages of the herbicide, without any loss of efficiency, which could provide environmental benefits. PMID:26186597

  10. Aquatic toxicity of nitrogen mustard to Ceriodaphina dubia, Daphnia magna, and Pimephales promelas.

    PubMed

    Lan, Cheng-Hang; Lin, Tser-Sheng; Peng, Chiung-Yu

    2005-06-01

    Investigation of toxicity of mustard compounds to aquatic organisms has been limited although their effects on terrestrial mammal species have been well studied. In this study, the 48-h LC50 values of nitrogen mustard (HN2) are reported for two aquatic invertebrate species (Daphnia magna and Ceriodaphnia dubia) and for one fish species (Pimephales promelas). Mean LC50 values to C. dubia, D. magna, and P. promela were 1.12, 2.52, and 98.86 mg/L, respectively. C. dubia was the species most sensitive to HN2. Seven-day lethal and sublethal tests with P. promelas and C. dubia were also conducted. In chronic tests, fathead minnow growth was significantly reduced by 2.50 mg/L HN2, while C. dubia reproduction was significantly affected by 7.81 mug/L HN2. These adverse effects on aquatic organisms caused by lower-level concentrations of HN2 indicate that a possible aquatic ecosystem disaster could occur either after a chemical spill or during chemical warfare.

  11. The EDTA Amendment in Phytoextraction of (134)Cs From Soil by Indian Mustard (Brassica juncea).

    PubMed

    Tjahaja, Poppy Intan; Sukmabuana, Putu; Roosmini, Dwina

    2015-01-01

    Soil contamination with radiocaesium is a significant problem at any countries when a nuclear accident occurred. Recently, phytoextraction technique is developed to remediate the contaminated environment. However, the application is limited by the availability of the contaminant for root uptake. Therefore, a green house trial experiment of soil amendment with ethylene diamine tetraacetic acid (EDTA) has been conducted to examine (134)Cs availability for root uptake. Two groups of Indian mustard (Brassica juncea) were cultivated in (134)Cs contaminated soil. The soil in the first group was treated with EDTA amendment, while the other was not. Plant growth was observed gravimetrically and the (134)Cs concentration in soil as well as plants were determined using gamma spectrometry. The plant uptake capacity was determined as transfer factor (Fv), and the Fv values of 0.22 ± 0.0786 and 0.12 ± 0.039 were obtained for the soil treated with and without EDTA amendment, respectively. The phytoextraction efficiency of the plant cultivated in (134)Cs contaminated soil both with and without EDTA amendment was low. The EDTA amendment to the soil seems to enhance the (134)Cs availability for root uptake of Indian mustard and can still be considered to assist the field phytoremediation of contaminated soil.

  12. Rhizosphere Bacteria Enhance Selenium Accumulation and Volatilization by Indian Mustard1

    PubMed Central

    de Souza, Mark P.; Chu, Dara; Zhao, May; Zayed, Adel M.; Ruzin, Steven E.; Schichnes, Denise; Terry, Norman

    1999-01-01

    Indian mustard (Brassica juncea L.) accumulates high tissue Se concentrations and volatilizes Se in relatively nontoxic forms, such as dimethylselenide. This study showed that the presence of bacteria in the rhizosphere of Indian mustard was necessary to achieve the best rates of plant Se accumulation and volatilization of selenate. Experiments with the antibiotic ampicillin showed that bacteria facilitated 35% of plant Se volatilization and 70% of plant tissue accumulation. These results were confirmed by inoculating axenic plants with rhizosphere bacteria. Compared with axenic controls, plants inoculated with rhizosphere bacteria had 5-fold higher Se concentrations in roots (the site of volatilization) and 4-fold higher rates of Se volatilization. Plants with bacteria contained a heat-labile compound in their root exudate; when this compound was added to the rhizosphere of axenic plants, Se accumulation in plant tissues increased. Plants with bacteria had an increased root surface area compared with axenic plants; the increased area was unlikely to have caused their increased tissue Se accumulation because they did not accumulate more Se when supplied with selenite or selenomethionine. Rhizosphere bacteria also possibly increased plant Se volatilization because they enabled plants to overcome a rate-limiting step in the Se volatilization pathway, i.e. Se accumulation in plant tissues. PMID:9952452

  13. Nonfluoroscopic Imaging as Guidance for Radiofrequency Ablation of Atrioventricular Nodal Reentrant Tachycardia after Mustard Repair

    PubMed Central

    Nguyen, Dinh Q.; Sobczak, Henrik; Brandts, Bodo

    2017-01-01

    Most tachycardias in the pulmonary venous atrium are inaccessible by direct means and require either a retrograde approach or a transseptal approach for ablation. We present a case in which successful radiofrequency ablation of common atrioventricular nodal reentrant tachycardia was accomplished via a retrograde transaortic approach guided by nonfluoroscopic mapping with use of the NavX™ mapping system. The patient was a 49-year-old woman who at the age of 4 years had undergone Mustard repair for complete dextrotransposition of the great arteries. Three-dimensional reconstructions of the ascending aorta, right ventricle, systemic venous atrium, left ventricle, and superior vena cava–inferior vena cava baffle complex were created, and the left-sided His bundle was marked. After a failed attempt at ablation from the systemic venous side, we eliminated the atrioventricular nodal reentrant tachycardia by ablation from the pulmonary venous side. This case is, to our knowledge, the first report of successful radiofrequency ablation of common atrioventricular nodal reentrant tachycardia after Mustard repair for this congenital cardiac malformation in which ablation was guided by 3-dimensional nonfluoroscopic imaging. This imaging technique enabled accurate anatomic location of the ablation catheters in relation to the His bundle marked from the systemic venous side. PMID:28265215

  14. The activation of phosphoramide mustard anticancer drugs from ab initio simulations.

    NASA Astrophysics Data System (ADS)

    Allesch, Markus; Schwegler, Eric; Colvin, Mike; Gygi, Francois; Galli, Giulia

    2007-03-01

    The nitrogen mustard based DNA alkylating agents were the first nonhormonal drugs to be used effectively in the treatment of cancer and remain one of the most important drugs for the chemotherapeutic management of many common malignancies today. An understanding of the activation of these compounds is, in itself, of scientific interest, but also critical in designing improved analogs of greater selectivity and efficacy. We have investigated the activation pathways of one of the most active metabolites, phosphoramide mustard (PM), and its methylated ester (PMME). In particular, we have examined the activation barrier and reaction free energy for the intramolecular cyclization reaction using first principles molecular dynamics simulations with explicit and continuum solvation models. Structural, dynamical and electronic properties along the reaction path have been computed mainly to address the question why de-esterification is required to activate these drugs. This work was performed under the auspices of the U.S. Dept. of Energy at the University of California/Lawrence Livermore National Laboratory under contract no. W-7405-Eng-48.

  15. Growth response modulation by putrescine in Indian mustard Brassica juncea L. under multiple stress.

    PubMed

    Lakra, Nita; Tomar, Pushpa C; Mishra, S N

    2016-04-01

    Plants, in general, are put to various kinds of stress, biotic and abiotic, both natural and manmade. Infestation by insect pests and diseases, and extreme conditions such as salinity, temperature, etc., as well as heavy metal contamination affect their growth performance. Here, we studied the impact of salinity and heavy metal pollution on the growth performance of Indian Mustard Brassica juncea L. and its amelioration by the diamine, putrescine, a known media supplement. We evaluated the putrescine (Put) modulation potential on multiple stress effect in 7-day old Indian mustard. The germination, seedlings length and photosynthetic pigments decline under salinity and metal (Cd/Pb) stress condition, alone or in combination, were checked by putrescine. The stress induced increase in root-shoot ratio, RNA and total amino acids content, as well as Na⁺/K⁺ ratio in leaf tissues were also comparatively less. The increased endogenous Cd/Pb accumulation in plants exposed to either metal further elevated under salinity was also found decelerated. However, the multiple stressed seedlings showed increase in glutathione content, which was further elevated with putrescine application. The increase in protein contents in leaf under single or combined stresses in the presence of putrescine could be a qualitative change. The differential changes in parameters examined here resulted in improved growth (> 10%) suggests stress mitigation by the putrescine up to an extent.

  16. Phenolic component profiles of mustard greens, yu choy, and 15 other brassica vegetables.

    PubMed

    Lin, Long-Ze; Harnly, James M

    2010-06-09

    A liquid chromatography-mass spectrometry (LC-MS) profiling method was used to characterize the phenolic components of 17 leafy vegetables from Brassica species other than Brassica oleracea. The vegetables studied were mustard green, baby mustard green, gai choy, baby gai choy, yu choy, yu choy tip, bok choy, bok choy tip, baby bok choy, bok choy sum, Taiwan bok choy, Shanghai bok choy, baby Shanghai bok choy, rapini broccoli, turnip green, napa, and baby napa. This work led to the tentative identification of 71 phenolic compounds consisting of kaempferol 3-O-diglucoside-7-O-glucoside derivatives, isorhamnetin 3-O-glucoside-7-O-glucoside hydroxycinnamoyl gentiobioses, hydroxycinnamoylmalic acids, and hydroxycinnamoylquinic acids. Ten of the compounds, 3-O-diacyltriglucoside-7-O-glucosides of kaempferol and quercetin, had not been previously reported. The phenolic component profiles of these vegetables were significantly different than those of the leafy vegetables from B. oleracea. This is the first comparative study of these leafy vegetables. Ten of the vegetables had never been previously studied by LC-MS.

  17. Phenolic Component Profiles of Mustard Greens, Yu Choy, and 15 Other Brassica Vegetables

    PubMed Central

    Lin, Long-Ze; Harnly, James M

    2013-01-01

    A liquid chromatography–mass spectrometry (LC-MS) profiling method was used to characterize the phenolic components of 17 leafy vegetables from Brassica species other than Brassica oleracea. The vegetables studied were mustard green, baby mustard green, gai choy, baby gai choy, yu choy, yu choy tip, bok choy, bok choy tip, baby bok choy, bok choy sum, Taiwan bok choy, Shanghai bok choy, baby Shanghai bok choy, rapini broccoli, turnip green, napa, and baby napa. This work led to the tentative identification of 71 phenolic compounds consisting of kaempferol 3-O-diglucoside-7-O-glucoside derivatives, isorhamnetin 3-O-glucoside-7-O-glucoside hydroxycinnamoyl gentiobioses, hydroxycinnamoylmalic acids, and hydroxycinnamoylquinic acids. Ten of the compounds, 3-O-diacyltriglucoside-7-O-glucosides of kaempferol and quercetin, had not been previously reported. The phenolic component profiles of these vegetables were significantly different than those of the leafy vegetables from B. oleracea. This is the first comparative study of these leafy vegetables. Ten of the vegetables had never been previously studied by LC-MS. PMID:20465307

  18. Nitrogen availability regulates proline and ethylene production and alleviates salinity stress in mustard (Brassica juncea).

    PubMed

    Iqbal, Noushina; Umar, Shahid; Khan, Nafees A

    2015-04-15

    Proline content and ethylene production have been shown to be involved in salt tolerance mechanisms in plants. To assess the role of nitrogen (N) in the protection of photosynthesis under salt stress, the effect of N (0, 5, 10, 20 mM) on proline and ethylene was studied in mustard (Brassica juncea). Sufficient N (10 mM) optimized proline production under non-saline conditions through an increase in proline-metabolizing enzymes, leading to osmotic balance and protection of photosynthesis through optimal ethylene production. Excess N (20 mM), in the absence of salt stress, inhibited photosynthesis and caused higher ethylene evolution but lower proline production compared to sufficient N. In contrast, under salt stress with an increased demand for N, excess N optimized ethylene production, which regulates the proline content resulting in recovered photosynthesis. The effect of excess N on photosynthesis under salt stress was further substantiated by the application of the ethylene biosynthesis inhibitor, 1-aminoethoxy vinylglycine (AVG), which inhibited proline production and photosynthesis. Without salt stress, AVG promoted photosynthesis in plants receiving excess N by inhibiting stress ethylene production. The results suggest that a regulatory interaction exists between ethylene, proline and N for salt tolerance. Nitrogen differentially regulates proline production and ethylene formation to alleviate the adverse effect of salinity on photosynthesis in mustard.

  19. Protection of human upper respiratory tract cell lines against sulphur mustard toxicity by hexamethylenetetramine (HMT).

    PubMed

    Andrew, D J; Lindsay, C D

    1998-07-01

    1. Sulphur mustard ('mustard gas', HD) is a highly toxic chemical warfare agent which affects the skin and respiratory tract. The primary targets of inhaled HD are the epithelia of the upper respiratory tract. Hexamethylenetetramine (HMT) has been shown to protect human lung cells against HD toxicity and has also been shown to be effective in vivo against the chemical warfare agent phosgene. The ability of HMT to protect against the toxicity of HD was investigated in the human upper respiratory tract cell lines BEAS-2B and RPMI 2650. 2. HD was highly toxic to both cell lines, with LC50 values of 15-30 microM. HMT, at a concentration of 10 mM, was shown to protect the cell lines against the toxic effects of 20 microM and 40 microM HD. Results demonstrated that it was necessary for HMT to be in situ at the time of exposure to HD for effective cytoprotection. No protection was seen when cells were treated with HMT following exposure to HD, or where HMT was removed prior to HD exposure. 3. Results suggest that HMT may be effective prophylaxis for exposure to HD by inhalation.

  20. A structural basis for a phosphoramide mustard-induced DNA interstrand cross-link at 5'-d(GAC).

    PubMed Central

    Dong, Q; Barsky, D; Colvin, M E; Melius, C F; Ludeman, S M; Moravek, J F; Colvin, O M; Bigner, D D; Modrich, P; Friedman, H S

    1995-01-01

    Phosphoramide mustard-induced DNA interstrand cross-links were studied both in vitro and by computer simulation. The local determinants for the formation of phosphoramide mustard-induced DNA interstrand cross-links were defined by using different pairs of synthetic oligonucleotide duplexes, each of which contained a single potentially cross-linkable site. Phosphoramide mustard was found to cross-link dG to dG at a 5'-d(GAC)-3'. The structural basis for the formation of this 1,3 cross-link was studied by molecular dynamics and quantum chemistry. Molecular dynamics indicated that the geometrical proximity of the binding sites also favored a 1,3 dG-to-dG linkage over a 1,2 dG-to-dG linkage in a 5'-d(GCC)-3' sequence. While the enthalpies of 1,2 and 1,3 mustard cross-linked DNA were found to be very close, a 1,3 structure was more flexible and may therefore be in a considerably higher entropic state. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8618865

  1. Evaluation of Protease Inhibitors and an Antioxidant for Treatment of Sulfur Mustard-Induced Toxic Lung Injury

    DTIC Science & Technology

    2009-01-01

    development of chronic obstructive pulmonary dis- ase (mustard lung), bronchiectasis, asthma , andfibrosis (Emadand ezaian, 1997). Although not fully...inhibitor pre- vents cigarette smoke-induced emphysema in the mouse. COPD 2 (3), 303– 310. utnam, J.B., Royston, D. (Eds.), 2003. Evaluating the Role

  2. First report of natural occurrence of Turnip vein-clearing virus in garlic mustard (Alliaria petiolata) in the United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During 2011-2013 plants of the invasive weed species Alliaria petiolata (garlic mustard) were observed with virus-like disease symptoms in three separate locations in Ramsey and Anoka counties, Minnesota. Symptoms consisted of conspicuous mosaic, leaf deformation and stunting. Numerous virus-like pa...

  3. Use of Se-enriched mustard and canola seed meals as potential bioherbicides and green fertilizers in strawberry production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    New plant-based products can be produced from seed harvested from Brassica species used for phytomanaging selenium (Se) in the westside of central California. We tested Se-enriched seed meals produced from canola (Brassica napus) and mustard (Sinapis alba) plants as potential bio-herbicides and as g...

  4. 38 CFR 3.316 - Claims based on chronic effects of exposure to mustard gas and Lewisite.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... effects of exposure to mustard gas and Lewisite. 3.316 Section 3.316 Pensions, Bonuses, and Veterans... Compensation Ratings and Evaluations; Service Connection § 3.316 Claims based on chronic effects of exposure to... establishes a nonservice-related supervening condition or event as the cause of the claimed condition (See §...

  5. 38 CFR 3.316 - Claims based on chronic effects of exposure to mustard gas and Lewisite.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... effects of exposure to mustard gas and Lewisite. 3.316 Section 3.316 Pensions, Bonuses, and Veterans... Compensation Ratings and Evaluations; Service Connection § 3.316 Claims based on chronic effects of exposure to... establishes a nonservice-related supervening condition or event as the cause of the claimed condition (See §...

  6. Effect of anaerobic soil disinfestation and mustard seed meal for control of charcoal rot in California strawberries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Anaerobic soil disinfestation (ASD) and mustard seed meal (MSM) appear to be promising non-fumigant alternatives for soilborne disease control. However studies of their effect on charcoal rot caused by Macrophomina phaseolina in California strawberry are limited. ASD with rice bran 20 t ha-1 (ASD-RB...

  7. Seed dormancy is modulated in recently evolved chlorsulfuron-resistant Turkish biotypes of wild mustard (sinapis arvensis)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biotypes of the broad-leaved wild mustard (Sinapis arvensis L.) found in wheat fields of the Aegean and Marmara regions of Turkey, were characterized and shown to have developed resistance to sulfonylurea (chlorsulfuron), an inhibitor of acetolactate synthase (ALS). DNA sequence analysis of the ALS...

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

    PubMed

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

    2006-11-01

    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.

  9. Immunomodulatory Properties of Mesenchymal Stem Cells Can Mitigate Oxidative Stress and Inflammation Process in Human Mustard Lung.

    PubMed

    Nejad-Moghaddam, Amir; Ajdary, Sohiela; Tahmasbpour, Eisa; Rad, Farhad Riazi; Panahi, Yunes; Ghanei, Mostafa

    2016-12-01

    Oxidative stress and inflammation are one of the main pathological consequences of sulfur mustard on human lungs. Unfortunately, there is no effective treatment to mitigate pathological effects of sulfur mustard in mustard lungs. Here, we aimed to evaluate potential efficacy of systemic mesenchymal stem cells administration on expression of oxidative stress- and inflammation-related genes in sulfur mustard-exposed patients. Our patient received 100 million cells per injection, which was continued for four injections within 2 months. Sputum samples were provided after each injection. Oxidative stress was evaluated by determining sputum levels of malondialdehyde and glutathione. Furthermore, changes in expression of several oxidative stress- (metallothionein 3, glutathione reductase, oxidative stress responsive 1, glutathione peroxidase 2, lacto peroxidase, forkhead box M1) and inflammation-related genes (matrix metallopeptidase 2, matrix metallopeptidase 9, transforming growth factor-β1, vascular endothelial growth factor, metallopeptidase inhibitor 1, metallopeptidase inhibitor 2) were also evaluated using real-time PCR after treatments. Two-lung epithelial-specific proteins including Clara cell protein 16 and Mucin-1 protein levels were measured using enzyme immunoassay method. No significant differences were found between serum levels of Clara cell protein 16 and serum Mucin-1 protein in patient before and after cell therapy. Most of the oxidative stress responsive genes, particularly oxidative stress responsive 1, were overexpressed after treatments. Expressions of antioxidants genes such as metallothionein 3, glutathione reductase and glutathione peroxidase 2 were increased after cell therapy. Upon comparison of inflammation-related genes, we observed upregulation of vascular endothelial growth factor and matrix metallopeptidase 9 after mesenchymal stem cells therapy. Additionally, a trend for increased value of glutathione and decreased levels of

  10. Identification of genes involved in wild crucifer Rorippa indica resistance response on mustard aphid Lipaphis erysimi challenge.

    PubMed

    Bandopadhyay, Lekha; Basu, Debabrata; Sikdar, Samir Ranjan

    2013-01-01

    Mustard aphid, Lipaphis erysimi (L.) Kaltenbach is a perpetual annual threat in the cultivation of rapeseed- mustard (Brassica spp.) crop in tropical and sub-tropical climate. Cultivated Brassica germplasm has failed so far to provide any source of resistance. Wild germplasm is a potential source of resistance against many threatening herbivores. On wild germplasm screening, we noted that the wild crucifer Rorippa indica (L.) Hiern confers resistance against L. erysimi. In the present study L. erysimi challenged transcriptome of R. indica was compared to un-infested R. indica sample to get a molecular insight about the aphid resistance mechanism and identify the candidate defense response genes. Cloning, sequencing and in silico sequence analysis of complimentary DNA amplified fragment length polymorphism identified 116 differentially expressed transcript derived fragments revealed thirty candidates which are from different functional categories including redox regulation, signalling, photosynthesis, structure, metabolism, defense response as well as a few of unknown function. Twenty four identifications were then studied by quantitative real time RT PCR analysis at 6, 12, 24 and 48 hour time point post infestation to understand the early-to-late defense response through their relative gene expression profiles. Seventeen fragments showed significant up or down regulation at p<0.05 level. The response was influenced by different phytohormonal signalling pathways simultaneously. The candidate defense response expressed sequence tags specifically for the resistance genes identified in this study have implication in building desired mustard aphid resistance in susceptible rapeseed-mustard plants in future. This is the first molecular report on crucifer defense response against mustard aphid L. erysimi.

  11. Identification of Genes Involved in Wild Crucifer Rorippa indica Resistance Response on Mustard Aphid Lipaphis erysimi Challenge

    PubMed Central

    Bandopadhyay, Lekha; Basu, Debabrata; Sikdar, Samir Ranjan

    2013-01-01

    Mustard aphid, Lipaphis erysimi (L.) Kaltenbach is a perpetual annual threat in the cultivation of rapeseed- mustard (Brassica spp.) crop in tropical and sub-tropical climate. Cultivated Brassica germplasm has failed so far to provide any source of resistance. Wild germplasm is a potential source of resistance against many threatening herbivores. On wild germplasm screening, we noted that the wild crucifer Rorippa indica (L.) Hiern confers resistance against L. erysimi. In the present study L. erysimi challenged transcriptome of R. indica was compared to un-infested R. indica sample to get a molecular insight about the aphid resistance mechanism and identify the candidate defense response genes. Cloning, sequencing and in silico sequence analysis of complimentary DNA amplified fragment length polymorphism identified 116 differentially expressed transcript derived fragments revealed thirty candidates which are from different functional categories including redox regulation, signalling, photosynthesis, structure, metabolism, defense response as well as a few of unknown function. Twenty four identifications were then studied by quantitative real time RT PCR analysis at 6, 12, 24 and 48 hour time point post infestation to understand the early-to-late defense response through their relative gene expression profiles. Seventeen fragments showed significant up or down regulation at p<0.05 level. The response was influenced by different phytohormonal signalling pathways simultaneously. The candidate defense response expressed sequence tags specifically for the resistance genes identified in this study have implication in building desired mustard aphid resistance in susceptible rapeseed-mustard plants in future. This is the first molecular report on crucifer defense response against mustard aphid L. erysimi. PMID:24040008

  12. Differential toxicity of cadmium to mustard (Brassica juncia L.) genotypes under higher metal levels.

    PubMed

    Bauddh, Kuldeep; Singh, Rana P

    2011-05-01

    Cadmium application inhibited various growth and biochemical parameters in seedlings of five cultivars of Brassicajuncia L. with different magnitude at lower Cd supply, however, at higher metal applications the variation in Cd toxicity ranged with minor differences. The seedling vigour index (SVI) was inhibited more severely in Gangotri (62.25% over control) and least in Pusa Jai Kisan (8.95%) at 1.0 mM CdCI2. The SVI of all five mustard cultivars, however, severely inhibited (84.29-91.80%) at 5.0 mM Cd. The root and shoot elongation in 7 days old seedlings were inhibited by 32.39-40.38 and 11.83-56.40% respectively at 1.0 mM CdCI2. whereas the varietal differences in root and shoot elongation were 76.71-82.47 and 71.57-78.91 respectively at 5.0 mM CdCI2 The genotypic differences at lower Cd level were more pronounced in shoot elongation than that in the root elongation. The dry weight and moisture content of the seedlings, however, does notshow much varietal differences even at lower Cd level, though the Cd toxicity increased at higher level of Cd application. The metal tolerance index (MTI) and % phytotoxicity of 3 days old seedlings ranged between 43.30-98.37 and 1.63-56.70% respectively at 1.0 mM CdCI2 for different mustard genotypes, whereas at 5.0 mM CdCI2 these factors ranged between 12.26-20.92 and 80.08-87.74% respectively. The varietal differences of MTI and % phytotoxicity was, however, less pronounced at all the metal levels when the seedling attained an age of 7 days. Asimilar trend of genotypic variation was noticed in Cd accumulation in the seedlings at lower and higher levels of Cd supply to the seedlings.Amongst some biochemical parameters e.g. photosynthetic pigments, carbohydrates and proteins in the leaves, the photosynthetic pigments i.e. chlorophylls and carotenoids were decreased more drastically. The carbohydrate content of leaves, however, was the least affected component. Our data indicate that the differential toxicity of cadmium to

  13. Development and validation of a duplex real-time PCR method for the simultaneous detection of celery and white mustard in food.

    PubMed

    Fuchs, Magdalena; Cichna-Markl, Margit; Hochegger, Rupert

    2013-11-01

    The developed duplex real-time PCR method allows the simultaneous detection of traces of potentially allergenic white mustard (Sinapis alba) and celery roots (Apium graveolens var. rapaceum), celery stalks (A. g. var. dulce) and leaf celery (A. g. var. secalinum). The duplex assay does not show any cross-reactivity with 64 different biological species, including various members of the Brassicaceae and Apiaceae family. In raw model sausages spiked with white mustard and celery roots, the LOD was found to be 0.001% white mustard and 0.005% celery. In model sausages brewed at 75-78°C for 15 min the LOD was found to be 0.005% white mustard and 0.005% celery. The duplex real-time PCR assay was applied to check if commercial food products are labelled in compliance with the legal regulations.

  14. 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.

  15. Cancer of the larynx and other occupational hazards of mustard gas workers

    SciTech Connect

    Manning, K.P.; Skegg, D.C.; Stell, P.M.; Doll, R.

    1981-06-01

    An attempt was made to tract 511 men and women who manufactured mustard gas during the 1939-1945 war. Despite limitations in the identifying data available, 428 (84%) were traced to the end of 1974. The numbers of deaths from all neoplasms combined (45) and from all other causes (136) were slightly greater than those expected from national death rates, but not significantly so. Two deaths were attributed to carcinoma of the larynx and one to carcinoma of the trachea, compared with an expected number of 0.40 (P less than 0.02). Carcinoma of the larynx was also mentioned on the death certificate of another man. Seven subjects are known to have developed cancer of the larynx, compared with 0.75 expected (P less than 0.001). Excess mortality was also observed from cancer of the lung, pneumonia and accidents, but the excesses were small and difficult to interpret.

  16. Interaction of a 3' RNA region of the mustard trnK gene with chloroplast proteins.

    PubMed Central

    Nickelsen, J; Link, G

    1989-01-01

    The 3' flanking region of the chloroplast trnK gene for tRNALys of mustard contains a palindromic sequence previously implicated with transcription termination and/or processing of the precursor RNA. Here we have investigated whether RNA sequences from the trnK 3' region are capable of interacting with chloroplast proteins in vitro. We find specific binding to an RNA region which is located further downstream from the palindromic sequence. The approximate length and position of this 3' binding region is reflected by a 41 nt spanning RNA segment which is protected against RNase T1 digestion by chloroplast protein(s). Competition experiments and sequence analyses suggest that U residues play an essential role in the RNA-protein interaction. Only a small number of proteins, possibly one single species, is in contact with the trnK 3' RNA. Images PMID:2481265

  17. Genotypic variation in phytoremediation potential of Indian mustard exposed to nickel stress: a hydroponic study.

    PubMed

    Ansari, Mohd Kafeel Ahmad; Ahmad, Altaf; Umar, Shahid; Zia, Munir Hussain; Iqbal, Muhammad; Owens, Gary

    2015-01-01

    Ten Indian mustard (Brassica juncea L.) genotypes were screened for their nickel (Ni) phytoremediation potential under controlled environmental conditions. All ten genotypes were grown hydroponically in aqueous solution containing Ni concentrations (as nickel chloride) ranging from 0 to 50 μM and changes in plant growth, biomass and total Ni uptake were evaluated. Of the ten genotypes (viz. Agrini, BTO, Kranti, Pusa Basant, Pusa Jai Kisan, Pusa Bahar, Pusa Bold, Vardhan, Varuna, and Vaibhav), Pusa Jai Kisan was the most Ni tolerant genotype accumulating up to 1.7 μg Ni g(-1) dry weight (DW) in its aerial parts. Thus Pusa Jai Kisan had the greatest potential to become a viable candidate in the development of practical phytoremediation technologies for Ni contaminated sites.

  18. Bullous pemphigoid. Occurrence in a patient with mycosis fungoides receiving PUVA and topical nitrogen mustard therapy

    SciTech Connect

    Patterson, J.W.; Ali, M.; Murray, J.C.; Hazra, T.A.

    1985-04-01

    A 57-year-old woman with mycosis fungoides developed blisters within cutaneous plaques while receiving PUVA therapy and topical nitrogen mustard. Direct and indirect immunofluorescence studies showed the findings of bullous pemphigoid. Her bullous disease was controlled after cessation of these therapies and institution of prednisone and methotrexate. During the 5 months following completion of a course of electron-beam therapy, she has been free of the cutaneous manifestations of both diseases. Previous instances of PUVA-related pemphigoid have occurred in psoriatics. The role of ultraviolet light in the induction of pemphigoid is discussed, particularly with regard to its possible interaction with the altered skin of psoriasis or mycosis fungoides. Some of the rare cases of bullous mycosis fungoides might actually have represented ultraviolet-unmasked bullous pemphigoid.

  19. [Long-term results of 156 Mustard operations for simple transposition of the great vessels].

    PubMed

    Landau, J F; Sidi, D; Batisse, A; Kachaner, J

    1978-05-01

    156 children with simple transposition of the great vessels have been operated on by Mustard's technique between 1-6-1967 and 31-12-1976, with an immediate overall mortality rate of 8%. In the longterm, the 9% of late deaths and more especially the complications are regrettable; complications were either of severe arrhythmia (almost 30%) leading to 2 late deaths and 7 pacemaker implantations, or venous obstruction relating to problems with the patch (25%). Despite the improved techniques and consequent reduction in surgical mortality and late complications, longterm prognosis is still unsure because of the unknown fate of the intra-atrial partition, and that of the "passive" rhythms which are so commonly found after this type of surgery.

  20. Adsorption of copper from aqueous solution on Brassica cumpestris (mustard oil cake).

    PubMed

    Ajmal, Mohammad; Rao, Rifaqat Ali Khan; Khan, Moonis Ali

    2005-06-30

    The adsorption behavior of various heavy metals on mustard oil cake (MOC) was studied. The maximum adsorption of Cu(II) was observed followed by Zn(II), Cr(VI), Mn(II), Cd(II), Ni(II) and Pb(II). The adsorption of Cu(II) was found to be dependent on initial concentration of solution, pH, adsorbent dose, temperature and contact time. The adsorption followed pseudo-first-order and second-order kinetics but pseudo-second-order kinetic model was better obeyed since experimental data agreed well with theoretical data. Thermodynamic parameters were also evaluated. The adsorption process was found to be endothermic and spontaneous in nature. Attempts were also made to desorb Cu(II) from the adsorbent and regeneration of the spent adsorbent. The breakthrough and exhaustive capacities were found to be 5 and 10 mg g(-1), respectively.

  1. 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).

  2. Evaluation of risk assessment guideline levels for the chemical warfare agents mustard, GB, and VX.

    PubMed

    Hartmann, Heidi M

    2002-06-01

    The U.S. Army has estimated acute lethality guideline levels for inhalation of the chemical warfare agents mustard, GB, and VX. These levels are expressed as dosages measured in milligram-minutes per cubic meter (mg-min/m(3)). The National Advisory Council has also proposed acute emergency guideline levels (AEGLs) for the agents. The AEGLs are threshold exposure limits for the general public for mild effects, serious adverse effects, and lethality. They are expressed as air concentrations (in units of mg/m(3)) and are applicable to emergency exposure periods ranging from 10 min to 8 h. The report discusses strengths and deficiencies in the levels, important parameters (i.e., exposure time, breathing rate) that need to be explicitly addressed in deriving the guideline levels, and possible impacts that could result from using AEGLs instead of guideline dosages in future assessments.

  3. Whole Genome and Tandem Duplicate Retention Facilitated Glucosinolate Pathway Diversification in the Mustard Family

    PubMed Central

    Hofberger, Johannes A.; Lyons, Eric; Edger, Patrick P.; Chris Pires, J.; Eric Schranz, M.

    2013-01-01

    Plants share a common history of successive whole-genome duplication (WGD) events retaining genomic patterns of duplicate gene copies (ohnologs) organized in conserved syntenic blocks. Duplication was often proposed to affect the origin of novel traits during evolution. However, genetic evidence linking WGD to pathway diversification is scarce. We show that WGD and tandem duplication (TD) accelerated genetic versatility of plant secondary metabolism, exemplified with the glucosinolate (GS) pathway in the mustard family. GS biosynthesis is a well-studied trait, employing at least 52 biosynthetic and regulatory genes in the model plant Arabidopsis. In a phylogenomics approach, we identified 67 GS loci in Aethionema arabicum of the tribe Aethionemae, sister group to all mustard family members. All but one of the Arabidopsis GS gene families evolved orthologs in Aethionema and all but one of the orthologous sequence pairs exhibit synteny. The 45% fraction of duplicates among all protein-coding genes in Arabidopsis was increased to 95% and 97% for Arabidopsis and Aethionema GS pathway inventory, respectively. Compared with the 22% average for all protein-coding genes in Arabidopsis, 52% and 56% of Aethionema and Arabidopsis GS loci align to ohnolog copies dating back to the last common WGD event. Although 15% of all Arabidopsis genes are organized in tandem arrays, 45% and 48% of GS loci in Arabidopsis and Aethionema descend from TD, respectively. We describe a sequential combination of TD and WGD events driving gene family extension, thereby expanding the evolutionary playground for functional diversification and thus potential novelty and success. PMID:24171911

  4. The protective effect of Nigella sativa on lung injury of sulfur mustard-exposed Guinea pigs.

    PubMed

    Hossein, Boskabady Mohammad; Nasim, Vahedi; Sediqa, Amery

    2008-05-01

    The lung is one of the most exposable organs to chemical warfare agents such as sulfur mustard (SM) gas. Airway hyperresponsiveness and lung inflammation are reported in chemical warfare victims. There is no definite treatment for respiratory disorders induced by SM exposure. However, the protective effect of Nigella sativa on inflammatory process was shown. In the present study, the protective effect of Nigella sativa on tracheal responsiveness and lung inflammation of SM exposed guinea pigs was examined. Guinea pigs were exposed to diluent's solution (ethanol, control group), 100 mg/m(3) inhaled sulfur mustard (SME group), and SME treated with Nigella sativa, 0.08 g daily (SME+N), n = 6 for each group. Tracheal responsiveness (TR) to methacholine, total white blood cell (WBC) count of lung lavage, and differential WBC were done 14 days post exposure. The weigh of animal were measured at the beginning, middle (day 7), and the end (day 14) of the study. The TR of SM-exposed guinea pigs was significantly (P < .001) and WBC nonsignificantly higher than those of controls. In SME guinea pigs, there was a weight loss but in the case of SME+N guinea pigs, no obvious weight change thought the study was seen. The eosinophl, monocyte, and lympocytes in SME animals were significantly changed compared to control group (P < .001 for all cases). Monocyte, lymphocyte, and neutrophil number were decreased in SME+N group compared to SME animals, which was significant only for neutrophil (P < .05). These results showed a preventive effect of Nigella sativa on TR of SM-exposed guinea pigs.

  5. Role of micronutrients in defense to white rust and Alternaria blight infecting Indian mustard.

    PubMed

    Rathi, A S; Singh, Dhiraj; Avtar, Ram; Kumar, Pawan

    2015-03-01

    Field experiments were carried out at Oilseeds Research Area of CCS Haryana Agricultural University, Hisar during rabi, 2008-09 to 2011-12 to find out the possible role of soil application of different micronutrients alone and in combinations in defense to white rust and Alternaria blight diseases in Indian mustard [Brassica juncea (L.) Czern & Coss.]. Among the sole application of micronutrients, minimum disease severity of both white rust (35.0%) and Alternaria blight (31.8%) was observed when S @ 40 kg ha in the form of Gypsum was applied as basal dose in the soil. When Gypsum was supplemented with Borax @10 kg ha(-1) or with ZnSO4 @15 kg ha(-1) the level of tolerance seems to be improved for both the diseases as compared to the sole treatment of each nutrient, i.e., ZnSO4 @ 15 kg/ha, Borax @ 10 kg ha' and Gypsum @ 250 kg ha(-1). Furthermore, minimum disease severity of both white rust (31.3 %) and Alternaria blight (26.3 %) was observed with soil application of ZnSO4 @ 15 kg ha(-1) + Borax @ 10 kg ha(-1) + Gypsum @250 kg ha(-1) as basal dose as compared to the severity of white rust (43.6%) and Alternaria blight (38.6%) in untreated check. Significant increase in seed yield (1612 kg ha(-1)) was also recorded in above mentioned treatment as compared to the yield (1337 kg ha(-1)) in untreated check. These findings will also be helpful in maintaining soil health and minimizing the losses due to both the fungal diseases for eco-friendly sustainability of Indian mustard.

  6. Genotypic Variation in the Phytoremediation Potential of Indian Mustard for Chromium

    NASA Astrophysics Data System (ADS)

    Diwan, Hema; Ahmad, Altaf; Iqbal, Muhammad

    2008-05-01

    The term “phytoremediation” is used to describe the cleanup of heavy metals from contaminated sites by plants. This study demonstrates phytoremediation potential of Indian mustard ( Brasicca juncea (L.) Czern. & Coss.) genotypes for chromium (Cr). Seedlings of 10 genotypes were grown hydroponically in artificially contaminated water over a range of environmentally relevant concentrations of Cr (VI), and the responses of genotypes in the presence of Cr, with reference to Cr accumulation, its phytotoxity and anti-oxidative system were investigated. The Cr accumulation potential varied largely among Indian mustard genotypes. At 100 μM Cr treatment, Pusa Jai Kisan accumulated the maximum amount of Cr (1680 μg Cr g-1 DW) whereas Vardhan accumulated the minimum (107 μg Cr g-1 DW). As the tolerance of metals is a key plant characteristic required for phytoremediation purpose, effects of various levels of Cr on biomass were evaluated as the gross effect. The extent of oxidative stress caused by Cr stress was measured as rate of lipid peroxidation. The level of thiobarbituric acid reactive substances (TBARS) was enhanced at all Cr treatments when compared to the control. Inductions of enzymatic and nonenzymatic antioxidants were monitored as metal-detoxifying responses. All the genotypes responded to Cr-induced oxidative stress by modulating nonenzymatic antioxidants [glutathione (GSH) and ascorbate (Asc)] and enzymatic antioxidants [superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR)]. The level of induction, however, differed among the genotypes, being at its maximum in Pusa Jai Kisan and its minimum in Vardhan. Pusa Jai Kisan was grown under natural field conditions with various Cr treatments, and Cr-accumulation capacity was studied. The results confirmed that Pusa Jai Kisan is a hyperaccumulator of Cr and hypertolerant to Cr-induced stress, which makes this genotype a viable candidate for use in the development of

  7. Black and Garlic Mustard Plants Are Highly Suitable for the Development of Two Native Pierid Butterflies.

    PubMed

    Heinen, Robin; Gols, Rieta; Harvey, Jeffrey A

    2016-04-22

    In multivoltine insects that oviposit and develop on short-lived plants, different herbivore generations across a growing season often exploit different plant species. Here, we compare the development time, pupal mass, and survival of two closely related oligophagous herbivore species on two species of brassicaceous plants that grow in different habitats and which exhibit little overlap in temporal growth phenology. In central Europe, the green-veined white butterfly, Pieris napi L., is bivoltine, whereas the small cabbage white butterfly, Pieris rapae L., has two to three generations a year. Moreover, P. napi is primarily found in moist, open (e.g., meadow), and forest habitats, whereas P. rapae prefers drier, open habitats. Both butterflies were reared on Garlic mustard (Alliaria petiolata), which is shade-tolerant and grows early in spring in forest undergrowth, and Black mustard (Brassica nigra), which prefers open disturbed habitats and is most common in summer. Both host plant species differ in other traits such as secondary chemistry. We hypothesized that, owing to habitat preference, P. napi would develop equally well on both plants but that P. rapae would perform better on B. nigra The results provide partial support for this hypothesis, as both herbivores performed equally well on A. petiolata and B. nigra However, there were differences in these parameters that were species-specific: on both plants P. rapae developed faster and had larger pupae than P. napi Our results show that specialized herbivores can exploit different species of related plants that grow at different times of the season, enabling them to have multiple generations.

  8. Nitrogen Mustards

    MedlinePlus

    ... CDC.gov . Specific Hazards Bioterrorism A-Z Anthrax (Bacillus anthracis) Arenaviruses Treatment & Infection Control Specimen Submission & Lab Testing Education & Training Related Bioterrorism Resources Bacillus anthracis (Anthrax) Botulism (Clostridium botulinum toxin) Brucella species ( ...

  9. Sulfur Mustard

    MedlinePlus

    ... CDC.gov . Specific Hazards Bioterrorism A-Z Anthrax (Bacillus anthracis) Arenaviruses Treatment & Infection Control Specimen Submission & Lab Testing Education & Training Related Bioterrorism Resources Bacillus anthracis (Anthrax) Botulism (Clostridium botulinum toxin) Brucella species ( ...

  10. Use of Plackett-Burman design for rapid screening of nitrogen and carbon sources for the production of lipase in solid state fermentation by Yarrowia lipolytica from mustard oil cake (Brassica napus)

    PubMed Central

    Imandi, Sarat Babu; Karanam, Sita Kumari; Garapati, Hanumantha Rao

    2013-01-01

    Mustard oil cake (Brassica napus), the residue obtained after extraction of mustard oil from mustard oil seeds, was investigated for the production of lipase under solid state fermentation (SSF) using the marine yeast Yarrowia lipolytica NCIM 3589. Process parameters such as incubation time, biomass concentration, initial moisture content, carbon source concentration and nitrogen source concentration of the medium were optimized. Screening of ten nitrogen and five carbon sources has been accomplished with the help of Plackett-Burman design. The highest lipase activity of 57.89 units per gram of dry fermented substrate (U/gds) was observed with the substrate of mustard oil cake in four days of fermentation. PMID:24516460

  11. Use of Plackett-Burman design for rapid screening of nitrogen and carbon sources for the production of lipase in solid state fermentation by Yarrowia lipolytica from mustard oil cake (Brassica napus).

    PubMed

    Imandi, Sarat Babu; Karanam, Sita Kumari; Garapati, Hanumantha Rao

    2013-01-01

    Mustard oil cake (Brassica napus), the residue obtained after extraction of mustard oil from mustard oil seeds, was investigated for the production of lipase under solid state fermentation (SSF) using the marine yeast Yarrowia lipolytica NCIM 3589. Process parameters such as incubation time, biomass concentration, initial moisture content, carbon source concentration and nitrogen source concentration of the medium were optimized. Screening of ten nitrogen and five carbon sources has been accomplished with the help of Plackett-Burman design. The highest lipase activity of 57.89 units per gram of dry fermented substrate (U/gds) was observed with the substrate of mustard oil cake in four days of fermentation.

  12. 40 CFR Appendix I to Part 192 - Listed Constituents

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-Naphthalendisulfonic acid, 3,3′- -4,4′-diyl)bis(azo)]bis(5-amino-4-hydroxy-, tetrasodium salt) Uracil mustard (2,4-(1H... vanadate (Vanadic acid, ammonium salt) Aniline (Benzenamine) Antimony and compounds, N.O.S. 1 1 The... listed by name in this appendix. Aramite (Sulfurous acid, 2-chloroethyl 2- -1-methylethyl ester)...

  13. 40 CFR Appendix I to Part 192 - Listed Constituents

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-Naphthalendisulfonic acid, 3,3′- -4,4′-diyl)bis(azo)]bis(5-amino-4-hydroxy-, tetrasodium salt) Uracil mustard (2,4-(1H... vanadate (Vanadic acid, ammonium salt) Aniline (Benzenamine) Antimony and compounds, N.O.S. 1 1 The... listed by name in this appendix. Aramite (Sulfurous acid, 2-chloroethyl 2- -1-methylethyl ester)...

  14. 40 CFR Appendix I to Part 192 - Listed Constituents

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-Naphthalendisulfonic acid, 3,3′- -4,4′-diyl)bis(azo)]bis(5-amino-4-hydroxy-, tetrasodium salt) Uracil mustard (2,4-(1H... vanadate (Vanadic acid, ammonium salt) Aniline (Benzenamine) Antimony and compounds, N.O.S. 1 1 The... listed by name in this appendix. Aramite (Sulfurous acid, 2-chloroethyl 2- -1-methylethyl ester)...

  15. Dissipation kinetics of alpha-cypermethrin and lambda-cyhalothrin residues in aboveground part of white mustard (Sinapis alba L.).

    PubMed

    Słowik-Borowiec, Magdalena

    2016-09-01

    Dissipation of simultaneously applied insecticides alpha-cypermethrin and lambda-cyhalothrin was studied in a minor crop, aboveground part of white mustard (Sinapis alba L.). A validated gas chromatographic method (GC-ECD/NPD) was used to determine insecticide residues. Analytical performances were very satisfactory, with expanded uncertainties not higher than 14% (coverage factor k = 2, confidence level 95%). Dissipation of alpha-cypermethrin and lambda-cyhalothrin in white mustard followed first-order kinetics (R(2) between 0.953 and 0.995), with half-lives of 3.1-4.6 and 2.9-3.7 days respectively. Based on the results of this two-year study and the relevant residue regulation, alpha-cypermethrin and lambda-cyhalothrin treatments can be considered safe for crop protection, feeding animals and the environment.

  16. 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.

  17. 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.

  18. Clinical Outcomes after Anatomic Repair Including Hemi-Mustard Operation in Patients with Congenitally Corrected Transposition of the Great Arteries

    PubMed Central

    Shim, Man-shik; Yang, Ji-Hyuk; Park, Pyo Won; Cho, Yang Hyun; Kang, Seok; Huh, June; Song, Jin Young

    2017-01-01

    Background and Objectives The aims of this study were to determine the early and late outcomes of anatomic repair of congenitally corrected transposition of the great arteries (ccTGA) and to evaluate effectiveness of the hemi-Mustard procedure. Subjects and Methods We conducted a retrospective, single-center study of patients who underwent anatomic repair for ccTGA between July 1996 and December 2013. Sixteen patients were included in the study. The median age at the time of the operation was 3.5 years (range: 0.5-29.7), and the median body weight was 13.3 kg (range: 5.8-54). The median follow-up duration was 7.7 years (range: 0.2-17.4). Results Atrial switch was achieved using the Mustard procedure in 12 patients (hemi-Mustard procedure in 11) or the Senning procedure in four patients. The ventriculoarterial procedure was performed using the Rastelli procedure in 11 patients and arterial switch in five patients. Six patients underwent tricuspid valvuloplasty. The survival rate was 93.8±6.1%. The rate of freedom from reoperation at 5 years was 92.3±7.4% in the Rastelli group. All patients except one were New York Heart Association class I. All patients except one had mild tricuspid regurgitation. Conclusion Anatomic repair can be performed with a low risk of in-hospital mortality. The hemi-Mustard strategy for selected patients is one solution for reducing early mortality and morbidity, and long-term complications such as venous pathway stenosis or sinus node dysfunction. PMID:28382075

  19. Effect of microwave treatment on the efficacy of expeller pressing of Brassica napus rapeseed and Brassica juncea mustard seeds.

    PubMed

    Niu, Yanxing; Rogiewicz, Anna; Wan, Chuyun; Guo, Mian; Huang, Fenghong; Slominski, Bogdan A

    2015-04-01

    A study was conducted to evaluate the effect of microwave heating on the efficacy of expeller pressing of rapeseed and mustard seed and the composition of expeller meals in two types of Brassica napus rapeseed (intermediate- and low-glucosinolate) and in Brassica juncea mustard (high-glucosinolate). Following microwave treatment, the microstructure of rapeseed using transmission electron microscopy showed a significant disappearance of oil bodies and myrosin cells. After 6 min of microwave heating (400 g, 800 W), the oil content of rapeseed expeller meal decreased from 44.9 to 13.5% for intermediate-glucosinolate B. napus rapeseed, from 42.6 to 11.3% for low-glucosinolate B. napus rapeseed, and from 44.4 to 14.1% for B. juncea mustard. The latter values were much lower than the oil contents of the corresponding expeller meals derived from the unheated seeds (i.e., 26.6, 22.6, and 29.8%, respectively). Neutral detergent fiber (NDF) contents showed no differences except for the expeller meal from the intermediate-glucosinolate B. napus rapeseed, which increased from 22.7 to 29.2% after 6 min of microwave heating. Microwave treatment for 4 and 5 min effectively inactivated myrosinase enzyme of intermediate-glucosinolate B. napus rapeseed and B. juncea mustard seed, respectively. In low-glucosinolate B. napus rapeseed the enzyme appeared to be more heat stable, with some activity being present after 6 min of microwave heating. Myrosinase enzyme inactivation had a profound effect on the glucosinolate content of expeller meals and prevented their hydrolysis to toxic breakdown products during the expelling process. It appeared evident from this study that microwave heating for 6 min was an effective method of producing expeller meal without toxic glucosinolate breakdown products while at the same time facilitating high yield of oil during the expelling process.

  20. Study the density, ultrasonic and compressibility of binary mixture of aqueous solution of isopropyl alcohol and mustard oil

    NASA Astrophysics Data System (ADS)

    Monupal, Suthar, B.

    2016-05-01

    The ultrasonic velocities, compressibility and bulk modulus of binary mixtures of aqueous solution of isopropyl alcohol with mustard oil have been measured at different concentrations at room temperature. The results are varied with the concentration in such a way i.e. ultrasonic velocity and Bulk Modulus is decreases with the increase in concentration and compressibility is increases with the increase in concentration of aqueous isopropyl alcohol. It is due to molecular interactions present in the mixtures.

  1. Transport of Cd and Zn to seeds of Indian mustard (Brassica juncea) during specific stages of plant growth and development.

    PubMed

    Sankaran, Renuka P; Ebbs, Stephen D

    2008-01-01

    The accumulation of excess Cd in the seeds of cereal and other crops compromises their commercial value and presents a potential risk to human health. Indian mustard [Brassica juncea (L.) Czern.] is a moderate accumulator of heavy metals such as Cd and Zn, and the seeds are consumed throughout the world, particularly in the Indian subcontinent. The study here examined the transport of Cd into Indian mustard plants and to seeds as a function of external Cd and the stage of the life cycle (vegetative growth, flowering and seed set) to identify critical developmental windows where transport from roots to seeds was the greatest. Plants were also treated simultaneously with Zn to determine if Zn fertilization mitigated the transport of Cd to seeds. Plants treated with Cd during the seed set accumulated the highest concentrations of Cd, exceeding 8 mg kg(-1) dry weight in some instances. Cadmium accumulated during vegetative growth was not highly redistributed to seeds. No effects of Zn were observed with regard to Cd redistribution to seeds. This may be because of the relatively small Zn : Cd ratios tested. However, the results suggest that if Zn fertilization is to be used to reduce the Cd accumulation in seeds of this species, that plants should be treated during the seed set stage. As the seeds of Indian mustard consistently accumulated Cd to concentrations that exceed acceptable limits for food crops, additional study of Cd redistribution in this species is warranted.

  2. 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.

  3. The potential to intensify sulforaphane formation in cooked broccoli (Brassica oleracea var. italica) using mustard seeds (Sinapis alba).

    PubMed

    Ghawi, Sameer Khalil; Methven, Lisa; Niranjan, Keshavan

    2013-06-01

    Sulforaphane, a naturally occurring cancer chemopreventive, is the hydrolysis product of glucoraphanin, the main glucosinolate in broccoli. The hydrolysis requires myrosinase isoenzyme to be present in sufficient activity; however, processing leads to its denaturation and hence reduced hydrolysis. In this study, the effect of adding mustard seeds, which contain a more resilient isoform of myrosinase, to processed broccoli was investigated with a view to intensify the formation of sulforaphane. Thermal inactivation of myrosinase from both broccoli and mustard seeds was studied. Thermal degradation of broccoli glucoraphanin was investigated in addition to the effects of thermal processing on the formation of sulforaphane and sulforaphane nitrile. Limited thermal degradation of glucoraphanin (less than 12%) was observed when broccoli was placed in vacuum sealed bag (sous vide) and cooked in a water bath at 100°C for 8 and 12 min. Boiling broccoli in water prevented the formation of any significant levels of sulforaphane due to inactivated myrosinase. However, addition of powdered mustard seeds to the heat processed broccoli significantly increased the formation of sulforaphane.

  4. Anti-Cytotoxic and Anti-Inflammatory Effects of the Macrolide Antibiotic Roxithromycin in Sulfur Mustard-Exposed Human Airway Epithelial Cells

    DTIC Science & Technology

    2006-11-01

    macrolide antibiotics may serve as potential vesicant respiratory therapeutics through mechanisms independent of their antibacterial activity. 1...macrophages. The subcellular mechanism of the anti-inflammatory effect of macrolides remains unknown. However, it is well known that the expression...effects of macrolides on NF-κB activation. However, it is now held that the molecular mechanism (s) by which macrolides inhibit pro- inflammatory

  5. Teratology studies of lewisite and sulfur mustard agents: effects of lewisite in rats and rabbits. Final report, 15 May 1983-28 February 1987

    SciTech Connect

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

    1987-12-31

    Lewisite, which is a prototype of one of two categories of vesicant war gases, functions by reacting with the sulfhydryl groups of proteins through its arsenic group. Since no information concerning the potential teratogenicity or developmental toxicity of lewisite was available, Pacific Northwest Laboratory, (PNL), under contract with USABRDL, conducted studies to evaluate maternal toxicity, intrauterine mortality, and developmental toxicity in rats and rabbits following the administration of this agent by intragastric intubation.

  6. 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.

  7. Role of Trichoderma harzianum in mitigating NaCl stress in Indian mustard (Brassica juncea L) through antioxidative defense system

    PubMed Central

    Ahmad, Parvaiz; Hashem, Abeer; Abd-Allah, Elsayed Fathi; Alqarawi, A. A.; John, Riffat; Egamberdieva, Dilfuza; Gucel, Salih

    2015-01-01

    Salinity stress affected crop production of more than 20% of irrigated land globally. In the present study the effect of different concentrations of NaCl (0, 100, and 200 mM) on growth, physio-biochemical attributes, antioxidant enzymes, oil content, etc. in Brassica juncea and the protective role of Trichoderma harzianum (TH) was investigated. Salinity stress deteriorates growth, physio-biochemical attributes, that ultimately leads to decreased biomass yield in mustard seedlings. Higher concentration of NaCl (200 mM) decreased the plant height by 33.7%, root length by 29.7% and plant dry weight (DW) by 34.5%. On the other hand, supplementation of TH to NaCl treated mustard seedlings showed elevation by 13.8, 11.8, and 16.7% in shoot, root length and plant DW respectively as compared to plants treated with NaCl (200 mM) alone. Oil content was drastically affected by NaCl treatment; however, TH added plants showed enhanced oil percentage from 19.4 to 23.4% in the present study. NaCl also degenerate the pigment content and the maximum drop of 52.0% was recorded in Chl. ‘a’. Enhanced pigment content was observed by the application of TH to NaCl treated plants. Proline content showed increase by NaCl stress and maximum accumulation of 59.12% was recorded at 200 mM NaCl. Further enhancement to 70.37% in proline content was recorded by supplementation of TH. NaCl stress (200 mM) affirms the increase in H2O2 by 69.5% and MDA by 36.5%, but reduction in the accumulation is recorded by addition of TH to mustard seedlings. 200 mM NaCl elevated SOD, POD, APX, GR, GST, GPX, GSH, and GSSG in the present study. Further enhancement was observed by the application of TH to the NaCl fed seedlings. NaCl stress suppresses the uptake of important elements in both roots and shoots, however, addition of TH restored the elemental uptake in the present study. Mustard seedlings treated with NaCl and TH showed restricted Na uptake as compared to seedlings treated with NaCl alone. In

  8. Survival and Transfer of Murine Norovirus within a Hydroponic System during Kale and Mustard Microgreen Harvesting.

    PubMed

    Wang, Qing; Kniel, Kalmia E

    2015-11-13

    Hydroponically grown microgreens are gaining in popularity, but there is a lack of information pertaining to their microbiological safety. The potential risks associated with virus contamination of crops within a hydroponic system have not been studied to date. Here a human norovirus (huNoV) surrogate (murine norovirus [MNV]) was evaluated for its ability to become internalized from roots to edible tissues of microgreens. Subsequently, virus survival in recirculated water without adequate disinfection was assessed. Kale and mustard seeds were grown on hydroponic pads (for 7 days with harvest at days 8 to 12), edible tissues (10 g) were cut 1 cm above the pads, and corresponding pieces (4 cm by 4 cm) of pads containing only roots were collected separately. Samples were collected from a newly contaminated system (recirculated water inoculated with ∼3 log PFU/ml MNV on day 8) and from a previously contaminated system. (A contaminated system without adequate disinfection or further inoculation was used for production of another set of microgreens.) Viral titers and RNA copies were quantified by plaque assay and real-time reverse transcription (RT)-PCR. The behaviors of MNV in kale and mustard microgreens were similar (P > 0.05). MNV was detected in edible tissues and roots after 2 h postinoculation, and the levels were generally stable during the first 12 h. Relatively low levels (∼2.5 to ∼1.5 log PFU/sample of both edible tissues and roots) of infectious viruses were found with a decreasing trend over time from harvest days 8 to 12. However, the levels of viral RNA present were higher and consistently stable (∼4.0 to ∼5.5 log copies/sample). Recirculated water maintained relatively high levels of infectious MNV over the period of harvest, from 3.54 to 2.73 log PFU/ml. Importantly, cross-contamination occurred easily; MNV remained infectious in previously contaminated hydroponic systems for up to 12 days (2.26 to 1.00 PFU/ml), and MNV was detected in both

  9. Survival and Transfer of Murine Norovirus within a Hydroponic System during Kale and Mustard Microgreen Harvesting

    PubMed Central

    Wang, Qing

    2015-01-01

    Hydroponically grown microgreens are gaining in popularity, but there is a lack of information pertaining to their microbiological safety. The potential risks associated with virus contamination of crops within a hydroponic system have not been studied to date. Here a human norovirus (huNoV) surrogate (murine norovirus [MNV]) was evaluated for its ability to become internalized from roots to edible tissues of microgreens. Subsequently, virus survival in recirculated water without adequate disinfection was assessed. Kale and mustard seeds were grown on hydroponic pads (for 7 days with harvest at days 8 to 12), edible tissues (10 g) were cut 1 cm above the pads, and corresponding pieces (4 cm by 4 cm) of pads containing only roots were collected separately. Samples were collected from a newly contaminated system (recirculated water inoculated with ∼3 log PFU/ml MNV on day 8) and from a previously contaminated system. (A contaminated system without adequate disinfection or further inoculation was used for production of another set of microgreens.) Viral titers and RNA copies were quantified by plaque assay and real-time reverse transcription (RT)-PCR. The behaviors of MNV in kale and mustard microgreens were similar (P > 0.05). MNV was detected in edible tissues and roots after 2 h postinoculation, and the levels were generally stable during the first 12 h. Relatively low levels (∼2.5 to ∼1.5 log PFU/sample of both edible tissues and roots) of infectious viruses were found with a decreasing trend over time from harvest days 8 to 12. However, the levels of viral RNA present were higher and consistently stable (∼4.0 to ∼5.5 log copies/sample). Recirculated water maintained relatively high levels of infectious MNV over the period of harvest, from 3.54 to 2.73 log PFU/ml. Importantly, cross-contamination occurred easily; MNV remained infectious in previously contaminated hydroponic systems for up to 12 days (2.26 to 1.00 PFU/ml), and MNV was detected in both

  10. Effect of ionic strength and cationic DNA affinity binders on the DNA sequence selective alkylation of guanine N7-positions by nitrogen mustards

    SciTech Connect

    Hartley, J.A.; Forrow, S.M.; Souhami, R.L. )

    1990-03-27

    Large variations in alkylation intensities exist among guanines in a DNA sequence following treatment with chemotherapeutic alkylating agents such as nitrogen mustards, and the substituent attached to the reactive group can impose a distinct sequence preference for reaction. In order to understand further the structural and electrostatic factors which determine the sequence selectivity of alkylation reactions, the effect of increase ionic strength, the intercalator ethidium bromide, AT-specific minor groove binders distamycin A and netropsin, and the polyamine spermine on guanine N7-alkylation by L-phenylalanine mustard (L-Pam), uracil mustard (UM), and quinacrine mustard (QM) was investigated with a modification of the guanine-specific chemical cleavage technique for DNA sequencing. The result differed with both the nitrogen mustard and the cationic agent used. The effect, which resulted in both enhancement and suppression of alkylation sites, was most striking in the case of netropsin and distamycin A, which differed from each other. DNA footprinting indicated that selective binding to AT sequences in the minor groove of DNA can have long-range effects on the alkylation pattern of DNA in the major groove.

  11. 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

  12. Use of Immunohistochemistry Techniques in Patients Exposed to Sulphur Mustard Gas

    PubMed Central

    Ghanei, Mostafa; Chilosi, Marco; Mohammad Hosseini Akbari, Hassan; Motiei-Langroudi, Rouzbeh; Harandi, Ali Amini; Shamsaei, Hassan; Bahadori, Moslem; Tazelaar, Henry D.

    2011-01-01

    We performed a pathologic study with further using an immunohistochemical technique (using anti-p63 and anti-CK5) on tissues obtained by open lung biopsy from 18 patients with previous exposure to sulphur mustard (SM) as case group and 8 unexposed patients (control group). The most frequent pathologic diagnosis was constrictive bronchiolitis (44.4%), followed by respiratory (22.2%) and chronic cellular bronchiolitis (16.7%) in the case group, and hypersensitivity bronchiolitis (50%) in the control group. The pathologic diagnoses were significantly different in the case and control groups (P = 0.042). In slides stained by anti-p63 and anti-CK5, the percent of stained cells and the mean number of epithelial cells were lower in the case group in comparison to the control group. This difference was significant for the mean number of cells stained by anti-CK5 (P = 0.042). Furthermore, there was a significant correlation between pathologic diagnosis and total number of cells and mean number of cells stained with anti-p63 and anti-CK5 (P  value = 0.002, <0.001, 0.044). These results suggest that constrictive bronchiolitis may be the major pathologic consequence of exposure to SM. Moreover, decrease of p63 in respiratory tissues affected by SM may suggest the lack of regenerative capacity in these patients. PMID:21776342

  13. Mustard tuber wastewater treatment and simultaneous electricity generation using microbial fuel cells.

    PubMed

    Guo, Fei; Fu, Guokai; Zhang, Zhi; Zhang, Chunling

    2013-05-01

    Mustard tuber wastewater (MTWW) was utilized as fuel in the typical dual-chamber microbial fuel cells (MFCs) to recover bio-energy and to obtain effluent treatment simultaneously. The whole experiment was divided into four phases characterized by increasing contents of primary clarifier effluent (PCE). Results showed substrate1, with which MFC generated a maximum power density of 246 mW/m(2), was the most appropriate fuel in terms of power recovery and the internal resistance and columbic efficiency were 121 Ω and 67.7±1%, respectively. When feeding MFCs with substrate4, 85±0% of COD could be removed, which was the highest COD removal, however, the power retrieve efficiency was much lower. Interestingly, significantly negative correlation (P<0.01, F-test) between contents of PCE and maximum cell voltages and positive correlation between the contents and internal resistances were found. It was the complexity and colloidal particulates present in PCE that gradually increased internal resistance and accordingly decreased power-generating performance.

  14. Dermal and ocular exposure systems for the development of models of sulfur mustard-induced injury.

    PubMed

    Weber, Waylon M; Kracko, Dean A; Lehman, Mericka R; Cox, Christopher E; Cheng, Yung-Sung; Grotendorst, Gary R; McDonald, Jacob D

    2011-09-01

    Sulfur mustard (SM) is a chemical threat agent for which the effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present article details the techniques used to develop SM laboratory exposure systems for the development of animal models of ocular and dermal injury. These models are critical to enable evaluation of SM injury and therapeutics against that injury. Iterative trials were conducted to optimize dermal and ocular injury models in guinea pigs and rabbits respectively. The goal was a homogeneous and diffuse ocular and dermal injury that compares to the human injury. Dermal exposures were conducted by either a flow-past or static vapor cup system. Ocular exposures were conducted by a static exposure system. Ocular and dermal exposures were conducted with vaporized SM. Vapor concentrations increased with time in the dermal and ocular exposure systems but were stable with varying amounts of applied SM. A dermal deposition estimation study was also conducted. Deposited volumes increased with exposure time.

  15. The capsaicin receptor TRPV1 is a crucial mediator of the noxious effects of mustard oil.

    PubMed

    Everaerts, Wouter; Gees, Maarten; Alpizar, Yeranddy A; Farre, Ricard; Leten, Cindy; Apetrei, Aurelia; Dewachter, Ilse; van Leuven, Fred; Vennekens, Rudi; De Ridder, Dirk; Nilius, Bernd; Voets, Thomas; Talavera, Karel

    2011-02-22

    Mustard oil (MO) is a plant-derived irritant that has been extensively used in experimental models to induce pain and inflammation. The noxious effects of MO are currently ascribed to specific activation of the cation channel TRPA1 in nociceptive neurons. In contrast to this view, we show here that the capsaicin receptor TRPV1 has a surprisingly large contribution to aversive and pain responses and visceral irritation induced by MO. Furthermore, we found that this can be explained by previously unknown properties of this compound. First, MO has a bimodal effect on TRPA1, producing current inhibition at millimolar concentrations. Second, it directly and stably activates mouse and human recombinant TRPV1, as well as TRPV1 channels in mouse sensory neurons. Finally, physiological temperatures enhance MO-induced TRPV1 stimulation. Our results refute the dogma that TRPA1 is the sole nocisensor for MO and motivate a revision of the putative roles of these channels in models of MO-induced pain and inflammation. We propose that TRPV1 has a generalized role in the detection of irritant botanical defensive traits and in the coevolution of multiple mammalian and plant species.

  16. 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.

  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. Inhalation Exposure Systems for the Development of Rodent Models of Sulfur Mustard-Induced Pulmonary Injury

    PubMed Central

    Weber, Waylon M.; Kracko, Dean A.; Lehman, Mericka R.; Irvin, Clinton M.; Blair, Lee F.; White, Richard K.; Benson, Janet M.; Grotendorst, Gary R.; Cheng, Yung-Sung; McDonald, Jacob D.

    2011-01-01

    Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury. These models are critical for evaluating SM injury and developing therapeutics against that injury. Iterative trials were conducted to optimize a lung injury model. The resulting pathology was used as a guide, with a goal of effecting homogeneous and diffuse lung injury comparable to that of human injury. Inhalation exposures were conducted by either nose-only inhalation or intubated inhalation. The exposures were conducted to either directly vaporized SM or SM that was nebulized from an ethanol solution. Inhalation of SM by nose-only inhalation resulted in severe nasal epithelial degeneration and minimal lung injury. The reactivity of SM did not permit it to transit past the upper airways to promote lower airway injury. Intratracheal inhalation of SM vapors at a concentration of 5400 mg · min/m3 resulted in homogeneous lung injury with no nasal degeneration. PMID:20025432

  19. The immunostatus of natural killer cells in people exposed to sulfur mustard.

    PubMed

    Ghotbi, Ladan; Hassan, Zuhair

    2002-06-01

    Sulfur mustard (2,2-dichloroethyl sulfide, SM) has been documented as an alkylating agent. It has been widely used as a chemical weapon during the last two decades. Despite extensive worldwide research, no effective therapy has yet been devised for the treatment of patients exposed to SM. A severe suppression of the immune system still remains as the major cause of opportunistic infections, septicemia and death in such patients. The aim of this study was to determine the possible effect of SM on natural killer (NK) cells in patients suffering from SM injuries. Patients were classified into three groups: mild, moderate and severe. Blood sample obtained from each patient was examined using flowcytometric technique. Results showed that the percentage of NK cells (CD45+/CD56+) is significantly lower in severe patients than that of the control group (P<0.05). It was also observed that the activity of NK cells (CD56+/CD25+) in severe alkylating group is noticeably higher compared with the control group (P<0.1).

  20. Pollinators, "mustard oil" volatiles, and fruit production in flowers of the dioecious tree Drypetes natalensis (Putranjivaceae).

    PubMed

    Johnson, Steven D; Griffiths, Megan E; Peter, Craig I; Lawes, Michael J

    2009-11-01

    The Putranjivaceae is an enigmatic family, notable for being the only lineage outside the Capparales to possess the glucosinolate biochemical pathway, which forms the basis of an induced chemical defense system against herbivores (the "mustard oil bomb"). We investigated the pollination biology and floral scent chemistry of Drypetes natalensis (Putranjivaceae), a dioecious subcanopy tree with flowers borne on the stem (cauliflory). Flowering male trees were more abundant than female ones and produced about 10-fold more flowers. Flowers of both sexes produce copious amounts of nectar on disc-like nectaries accessible to short-tongued insects. The main flower visitors observed were cetoniid beetles, bees, and vespid wasps. Pollen load analysis indicated that these insects exhibit a high degree of fidelity to D. natalensis flowers. Insects effectively transfer pollen from male to female plants resulting in about 31% of female flowers developing fruits with viable seeds. Cetoniid beetles showed significant orientation toward the scent of D. natalensis flowers in a Y-maze olfactometer. The scents of male and female flowers are similar in chemical composition and dominated by fatty acid derivatives and isothiocyanates from the glucosinolate pathway. The apparent constitutive emission of isothiocyanates raises interesting new questions about their functional role in flowers.

  1. 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

  2. Genetic Analysis of Reduced γ-Tocopherol Content in Ethiopian Mustard Seeds

    PubMed Central

    García-Navarro, Elena; Fernández-Martínez, José M.; Pérez-Vich, Begoña

    2016-01-01

    Ethiopian mustard (Brassica carinata A. Braun) line BCT-6, with reduced γ-tocopherol content in the seeds, has been previously developed. The objective of this research was to conduct a genetic analysis of seed tocopherols in this line. BCT-6 was crossed with the conventional line C-101 and the F1, F2, and BC plant generations were analyzed. Generation mean analysis using individual scaling tests indicated that reduced γ-tocopherol content fitted an additive-dominant genetic model with predominance of additive effects and absence of epistatic interactions. This was confirmed through a joint scaling test and additional testing of the goodness of fit of the model. Conversely, epistatic interactions were identified for total tocopherol content. Estimation of the minimum number of genes suggested that both γ- and total tocopherol content may be controlled by two genes. A positive correlation between total tocopherol content and the proportion of γ-tocopherol was identified in the F2 generation. Additional research on the feasibility of developing germplasm with high tocopherol content and reduced concentration of γ-tocopherol is required. PMID:27275005

  3. 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

  4. Inhalation exposure systems for the development of rodent models of sulfur mustard-induced pulmonary injury.

    PubMed

    Weber, Waylon M; Kracko, Dean A; Lehman, Mericka R; Irvin, Clinton M; Blair, Lee F; White, Richard K; Benson, Janet M; Grotendorst, Gary R; Cheng, Yung-Sung; McDonald, Jacob D

    2010-01-01

    Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury. These models are critical for evaluating SM injury and developing therapeutics against that injury. Iterative trials were conducted to optimize a lung injury model. The resulting pathology was used as a guide, with a goal of effecting homogeneous and diffuse lung injury comparable to that of human injury. Inhalation exposures were conducted by either nose-only inhalation or intubated inhalation. The exposures were conducted to either directly vaporized SM or SM that was nebulized from an ethanol solution. Inhalation of SM by nose-only inhalation resulted in severe nasal epithelial degeneration and minimal lung injury. The reactivity of SM did not permit it to transit past the upper airways to promote lower airway injury. Intratracheal inhalation of SM vapors at a concentration of 5400 mg x min/m(3) resulted in homogeneous lung injury with no nasal degeneration.

  5. Fate of sulfur mustard on soil: Evaporation, degradation, and vapor emission.

    PubMed

    Jung, Hyunsook; Kah, Dongha; Chan Lim, Kyoung; Lee, Jin Young

    2017-01-01

    After application of sulfur mustard to the soil surface, its possible fate via evaporation, degradation following absorption, and vapor emission after decontamination was studied. We used a laboratory-sized wind tunnel, thermal desorber, gas chromatograph-mass spectrometry (GC-MS), and (13)C nuclear magnetic resonance ((13)C NMR) for systematic analysis. When a drop of neat HD was deposited on the soil surface, it evaporated slowly while being absorbed immediately into the matrix. The initial evaporation or drying rates of the HD drop were found to be power-dependent on temperature and initial drop volume. Moreover, drops of neat HD, ranging in size from 1 to 6 μL, applied to soil, evaporated at different rates, with the smaller drops evaporating relatively quicker. HD absorbed into soil remained for a month, degrading eventually to nontoxic thiodiglycol via hydrolysis through the formation of sulfonium ions. Finally, a vapor emission test was performed for HD contaminant after a decontamination process, the results of which suggest potential risk from the release of trace chemical quantities of HD into the environment.

  6. Genetic Analysis of Reduced γ-Tocopherol Content in Ethiopian Mustard Seeds.

    PubMed

    García-Navarro, Elena; Fernández-Martínez, José M; Pérez-Vich, Begoña; Velasco, Leonardo

    2016-01-01

    Ethiopian mustard (Brassica carinata A. Braun) line BCT-6, with reduced γ-tocopherol content in the seeds, has been previously developed. The objective of this research was to conduct a genetic analysis of seed tocopherols in this line. BCT-6 was crossed with the conventional line C-101 and the F1, F2, and BC plant generations were analyzed. Generation mean analysis using individual scaling tests indicated that reduced γ-tocopherol content fitted an additive-dominant genetic model with predominance of additive effects and absence of epistatic interactions. This was confirmed through a joint scaling test and additional testing of the goodness of fit of the model. Conversely, epistatic interactions were identified for total tocopherol content. Estimation of the minimum number of genes suggested that both γ- and total tocopherol content may be controlled by two genes. A positive correlation between total tocopherol content and the proportion of γ-tocopherol was identified in the F2 generation. Additional research on the feasibility of developing germplasm with high tocopherol content and reduced concentration of γ-tocopherol is required.

  7. Biorefinery process for protein extraction from oriental mustard (Brassica juncea (L.) Czern.) using ethanol stillage

    PubMed Central

    2012-01-01

    Large volumes of treated process water are required for protein extraction. Evaporation of this water contributes greatly to the energy consumed in enriching protein products. Thin stillage remaining from ethanol production is available in large volumes and may be suitable for extracting protein rich materials. In this work protein was extracted from ground defatted oriental mustard (Brassica juncea (L.) Czern.) meal using thin stillage. Protein extraction efficiency was studied at pHs between 7.6 and 10.4 and salt concentrations between 3.4 × 10-2 and 1.2 M. The optimum extraction efficiency was pH 10.0 and 1.0 M NaCl. Napin and cruciferin were the most prevalent proteins in the isolate. The isolate exhibited high in vitro digestibility (74.9 ± 0.80%) and lysine content (5.2 ± 0.2 g/100 g of protein). No differences in the efficiency of extraction, SDS-PAGE profile, digestibility, lysine availability, or amino acid composition were observed between protein extracted with thin stillage and that extracted with NaCl solution. The use of thin stillage, in lieu of water, for protein extraction would decrease the energy requirements and waste disposal costs of the protein isolation and biofuel production processes. PMID:22239856

  8. Synthesis and characterization of water-soluble carbon nanotubes from mustard soot

    NASA Astrophysics Data System (ADS)

    Dubey, Prashant; Muthukumaran, Devarajan; Dash, Subhashis; Mukhopadhyay, Rupa; Sarkar, Sabyasachi

    2005-10-01

    Carbon nanotubes (CNT) has been synthesized by pyrolysing mustard oil using an oil lamp. It was made water-soluble (wsCNT) through oxidative treatment by dilute nitric acid and was characterized by SEM, AFM, XRD, Raman and FTIR spectroscopy. The synthesized wsCNT showed the presence of several junctions and defects in it. The presence of curved graphene structure (sp^{2}) with frequent sp^{3} hybridized carbon is found to be responsible for the observed defects. These defects along with the presence of di- and tri-podal junctions showed interesting magnetic properties of carbon radicals formed by spin frustration. This trapped carbon radical showed ESR signal in aqueous solution and was very stable even under drastic treatment by strong oxidizing or reducing agents. Oxidative acid treatment of CNT introduced several carboxylic acid group functionalities in wsCNT along with the nicking of the CNT at different lengths with varied molecular weight. To evaluate molecular weights of these wsCNTs, an innovative method like gel electrophoresis using high molecular weight DNA as marker was introduced.

  9. Evaluation of candidate decontaminants against percutaneous sulfur mustard and thickened soman challenges

    SciTech Connect

    Blank, J.A.; Hobson, D.W.; Menton, R.G.; Olson, C.T.; Korte, D.W.

    1993-05-13

    Studies were conducted to evaluate the efficacy of candidate skin decontaminants relative to a standard control decontaminant, XE-555 resin, against percutaneous sulfur mustard (HD) or thickened soman (TGD) challenge. Male, New Zealand White rabbits were used as the model system with lesion area as the end point for HD exposures and erythrocyte acetylcholinesterase (AChE) inhibition as the endpoint for TGD exposure. Initial studies were performed to establish assay parameters for, and to validate the use of, AChE inhibition as an endpoint for assessing candidate decontaminant efficacy against nerve agent exposures. XE-555 resin was concurrently evaluated with each candidate decontaminant for both assay control and comparative purpose. Decontamination was initiated at 1, 3, or 5 min after HD exposures and 2 min after TGD exposures. U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) compounds 1513, 1514, 1515, 1516, and 1517 were evaluated against HD and against TGD. Results from these studies demonstrated the utility of AChE inhibition for evaluating skin decontaminants. None of the candidate decontaminants evaluated was more effective than the standard control decontaminant against HD or TGD exposures.

  10. DNA damage in internal organs after cutaneous exposure to sulphur mustard.

    PubMed

    Batal, Mohamed; Boudry, Isabelle; Mouret, Stéphane; Cléry-Barraud, Cécile; Wartelle, Julien; Bérard, Izabel; Douki, Thierry

    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 60mg/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.

  11. 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.

  12. The chemical toxicity of cesium in Indian mustard (Brassica juncea L.) seedlings.

    PubMed

    Lai, Jin-Long; Tao, Zong-Ya; Fu, Qian; Han, Na; Wu, Guo; Zhang, Hong; Lu, Hong; Luo, Xue-Gang

    2016-08-01

    To distinguish between the radiological and chemical effects of radiocesium, we study the chemical toxicity of cesium in the seedlings of Indian mustard (Brassica juncea L.). In this study, the experiment was designed in two factors and five levels random block design to investigate the interaction effects of Cs and K. Results showed that excessive Cs was one of the main factors influence the growth of Brassica juncea seedlings. And the toxicity of Cs in Brassica juncea is likely to be caused by Cs interacts with K-binding sites in essential K-dependent protein, either competes with K for essential biochemical functions, causing intracellular metabolic disturbance. To test the hypothesis that the toxicity of Cs might cause intracellular metabolic disturbance, next-generation sequencing (NGS)-based Illumina paired-end Solexa sequencing platform was employed to analysis the changes in gene expression, and understand the key genes in B. juncea seedlings responding to the toxicity of Cs. Based on the assembled de novo transcriptome, 2032 DEGs that play significant roles in the response to the toxicity of Cs were identified. Further analysis showed that excessive Cs is disturbance the auxin signal transduction pathway, and inhibited the indoleacetic acid-induced protein (AUX/IAA) genes expression eventually lead the seedlings growth and development be inhibited. The results suggest that disturbances to tryptophan metabolism might be linked to changes in growth.

  13. GERD related micro-aspiration in chronic mustard-induced pulmonary disorder

    PubMed Central

    Aliannejad, Rasoul; Hashemi-Bajgani, Seyed-Mehdi; Karbasi, Asharaf; Jafari, Mahvash; Aslani, Jafar; Salehi, Maryam; Ghanei, Mostafa

    2012-01-01

    Background and Aim: Bronchiolitis obliterans (BO) is the main pulmonary involvement resulting from sulfur mustard (SM) gas exposure that was used against Iranian civilians and military forces during the Iran-Iraq war. The present study aimed to investigate the prevalence of gastro-esophageal reflux (GER) and gastric micro-aspiration in SM gas injured patients with chronic pulmonary diseases and recurrent episodes of exacerbations. Materials and Methods: This cross-sectional study was done at Baqiyatallah University of Medical Sciences, Tehran, Iran. Gastric micro-aspiration and GER were assessed in the enrolled patients by assessing bile acids, pepsin and trypsin in their bronchoalveolar lavage fluid. Results: Our result showed that bile acids were found to be high in 21.4% patients, and low in 53.6% of patients. Only in 16% patients, no bile was detected in the BALF. Trypsin and pepsin were detected in BAL fluid of all patients. Conclusion: Most of BO patients after exposure to SM suffer GER, while none the etiologic factors of GER in post lung transplant BO are present. It would be hypothesized that GER per se could be considered as an aggregative factor for exacerbations in patients. Further studies will provide more advances to better understanding of pathophysiological mechanism regarding GER and BO and treatment. PMID:23798946

  14. The effect of vitamin E on lung pathology in sulfur mustard-exposed guinea pigs.

    PubMed

    Gholamnezhad, Zahra; Boskabady, Mohammad Hossein; Amery, Sediqa; Vahedi, Nassim; Tabatabaei, Abass; Boskabady, Morteza; Shahriary, Alireza

    2016-12-01

    Pulmonary complications of exposure to sulfur mustard (SM) gas range from no effect or mild symptoms to severe bronchial stenosis. In the present study, the protective effect of vitamin E on the lung inflammation of SM-exposed guinea pigs was examined. Guinea pigs (n = 5 for each group) were exposed to ethanol (control group), 40 mg/m(3) inhaled SM (SME group), SME treated with vitamin E (SME + E), SME treated with dexamethasone (SME + D), and SME treated with both treatments (SME + E + D). Pathological evaluation of the lung was done 14 days postexposure. The epithelial desquamation of trachea and other pathologic changes in the lung of the SME group were significantly higher than those in the control group. Furthermore, the pathological changes of trachea and lung in the SME + E and SME + E + D groups were significantly improved compared with those of SME group. In addition, the pathological changes of trachea and lung of SME + E and SME + E + D animals were significantly less than those of SME + D group.

  15. Plasma concentrations of 4-hydroxycyclophosphamide and phosphoramide mustard in patients repeatedly given high doses of cyclophosphamide in preparation for bone marrow transplantation.

    PubMed

    Sladek, N E; Doeden, D; Powers, J F; Krivit, W

    1984-10-01

    Plasma half-life and area under the curve (AUC) values for cyclophosphamide were determined in patients given this agent iv at doses of 50-60 mg/kg/infusion. Apparent plasma half-life and AUC values for the metabolites 4-hydroxycyclophosphamide and phosphoramide mustard were also determined in some of these patients. Disappearance from the plasma of the parent compound as well as that of the metabolites was approximately first-order. Plasma half-life values for cyclophosphamide ranged from 45 to 480 mins; AUC values ranged from 10 to 188 mM X min. As expected, AUC values for cyclophosphamide increased approximately linearly with an increase in its plasma half-life. Apparent plasma half-life values for 4-hydroxycyclophosphamide and phosphoramide mustard increased approximately linearly with an increase in plasma half-life values for cyclophosphamide; the slopes of these relationships were 1.35 and 1.97, respectively, but did not quite extrapolate to zero. AUC values for 4-hydroxycyclophosphamide and phosphoramide mustard remained approximately constant at about 5 and 15 mM X min, respectively, over the relatively wide range of plasma half-life and AUC values obtained for cyclophosphamide. On the basis of these observations we suggest that (a) changes in the rate of cyclophosphamide hydroxylation, effected by whatever means, will not alter the systemic therapeutic and toxic responses to a given dose of cyclophosphamide, given that the cytotoxic effects of this agent are directly proportional to AUC values of 4-hydroxycyclophosphamide and/or phosphoramide mustard, and (b) in most cases, 4-hydroxycyclophosphamide, and not phosphoramide mustard, is likely to be the circulating metabolite of therapeutic importance in humans since the AUC values for phosphoramide mustard exceeded those for 4-hydroxycyclophosphamide by only a factor of 3 and tumor and bone marrow cells proliferating in culture are generally substantially (8-25-fold) more sensitive to 4

  16. Construction of a genetic linkage map and QTL analysis of erucic acid content and glucosinolate components in yellow mustard (Sinapis alba L.)

    PubMed Central

    2013-01-01

    Background Yellow mustard (Sinapis alba L.) is an important condiment crop for the spice trade in the world. It has lagged behind oilseed Brassica species in molecular marker development and application. Intron length polymorphism (ILP) markers are highly polymorphic, co-dominant and cost-effective. The cross-species applicability of ILP markers from Brassica species and Arabidopsis makes them possible to be used for genetic linkage mapping and further QTL analysis of agronomic traits in yellow mustard. Results A total of 250 ILP and 14 SSR markers were mapped on 12 linkage groups and designated as Sal01-12 in yellow mustard. The constructed map covered a total genetic length of 890.4 cM with an average marker interval of 3.3 cM. The QTL for erucic content co-localized with the fatty acid elongase 1 (FAE1) gene on Sal03. The self-(in)compatibility gene was assigned to Sal08. The 4-hydroxybenzyl, 3-indolylmethyl and 4-hydroxy-3-indolylmethyl glucosinolate contents were each controlled by one major QTL, all of which were located on Sal02. Two QTLs, accounting for the respective 20.4% and 19.2% of the total variation of 2-hydroxy-3-butenyl glucosinolate content, were identified and mapped to Sal02 and Sal11. Comparative synteny analysis revealed that yellow mustard was phylogenetically related to Arabidopsis thaliana and had undergone extensive chromosomal rearrangements during speciation. Conclusion The linkage map based on ILP and SSR markers was constructed and used for QTL analysis of seed quality traits in yellow mustard. The markers tightly linked with the genes for different glucosinolate components will be used for marker-assisted selection and map-based cloning. The ILP markers and linkage map provide useful molecular tools for yellow mustard breeding. PMID:24066707

  17. Metal accumulation, biochemical response and yield of Indian mustard grown in soil amended with rural roadside pond sediment.

    PubMed

    Karak, Tanmoy; Bhattacharyya, Pradip; Kumar Paul, Ranjit; Das, D K

    2013-06-01

    This present study aims to discern the effect of roadside pond sediments on Brassica juncea (L.) Czern. (cv. Rohini) by examining heavy metal uptake by different parts of the plant and its influence on biochemical properties, biomass, yield and oil content in plant. Although the treated soils were clearly contaminated with heavy metals (HMs) after application of pond sediments and chemical fertilizers, but the metal content in mustard leaves and seeds are below the permissible limit of consumable food. HMs accumulation was proportionally lesser in grains than in shoots and roots. All the biochemical characteristics were significantly (p<0.05) responded to the pond sediments application as compared to the control. Increase in photosynthetic pigment was also observed during growing period while pond sediment was used as amendment. This study revealed that Brassica juncea is well adapted to tolerate and accumulate high quantities of HMs due to increased level of antioxidants (cysteine and ascorbic acid) in roots, shoots and leaves. Multivariate techniques like principal component analysis and cluster analysis (CA) were used as classification techniques. On the basis of factor loadings and principal component scores, different parameters were grouped based on their similarity or closeness, separately in leaves, roots and seeds. A very similar grouping was also obtained using CA. However, pond sediment did not thwart the enhancement of mustard yield and oil content. Therefore, pond sediment would be a valuable resource for mustard as an alternative soil amendment for nutrients, but long-term use may require the cessation to restrict HMs contamination in soils.

  18. Vapor-phase toxicity of butylbenzyl phthalate to three plant species: white mustard, chinese cabbage, and white clover.

    PubMed

    Gorsuch, J W; Staples, C A; Brown, D; Enste-Diefenbach, R

    2008-08-01

    During the manufacture of products containing butylbenzyl phthalate (BBP), low emissions to the air may occur. Due to potential exposure of terrestrial communities to BBP vapors, phytotoxicity tests were conducted using Chinese cabbage, white mustard, and white clover. No significant effects on shoot growth were observed at the higher BBP vapor-phase concentration tested, which measured 5.7 microg/m(3). The overall practicality of vapor-phase testing of chemicals with very low vapor pressures is reviewed. These study results suggest that environmental risk from exposure to BBP vapor is negligible for plants.

  19. Delayed neurological complications of sulphur mustard and tabun poisoning in 43 Iranian veterans.

    PubMed

    Darchini-Maragheh, Emadodin; Nemati-Karimooy, Habibollah; Hasanabadi, Hosein; Balali-Mood, Mahdi

    2012-12-01

    Delayed neurotoxic complications of chemical warfare agents (CWA), such as sulphur mustard (SM) and tabun, in human beings have not been reported in detail. We thus aimed to investigate possible neurotoxic complications of these agents in Iranian veterans 22-27 years after exposure. After co-ordination with the veteran foundation and obtaining the approval of the medical research ethics committee, 43 Iranian veterans with late complications of CWA exposure during the Iran-Iraq conflict were studied after obtaining signed written informed consent. Demographic and clinical findings were recorded on pre-designed forms. Neurological examination was performed by a neurologist. Routine biochemical tests were performed for all the patients. Electromyography (EMG), nerve conduction velocity (NCV) and electroencephalography (EEG) were carried out as clinically indicated. The majority of the patients (38) had been exposed to SM and only five patients to tabun. Hyperaesthesia was the most objective finding (72.1%). Fatigue (93%), paraesthesia (88.3%) and headache (83.7%) were the most common subjective findings in the patients. Sensory nerve impairments, including paraesthesia (88.3%), hyperaesthesia (72.1%) and hypoesthesia (11.6%), were the most common observed clinical complications. EMG and NCV were impaired in seven patients (16.3%) who were all SM-exposed patients but did not show any significant correlation with organ complications. EEG was negative even in the seized patients. Cholesterol, LDL and triglyceride levels were significantly above the normal ranges. Late neurological complications of CWA, particularly SM poisoning, are considerable even after three decades of exposure and require medical attention.

  20. Hedge mustard (Sisymbrium officinale): chemical diversity of volatiles and their antimicrobial activity.

    PubMed

    Blazević, Ivica; Radonić, Ani; Mastelić, Josip; Zekić, Marina; Skocibusić, Mirjana; Maravić, Ana

    2010-08-01

    Volatile compounds of hedge mustard (Sysimbrium officinale) have been investigated for the first time. Forthy-two compounds were identified after hydrodistillation (without or upon autolysis) after gas chromatography and gas chromatography/mass spectrometry analyses. In addition, after decoction and hydrolysis of O-glycosides, 18 volatile O-aglycones were identified. In general, the main volatiles found in hydrodistillates were: isopropyl isothiocyanate (27.6-48.9%), 2-methylpropanenitrile (0.5-18.8%), (Z)-hex-3-en-1-ol (0.5-18.0%), sec-butyl isothiocyanate (4.9-9.4%), (E)-hex-2-enal (3.5-8.6%), (Z)-hex-2-en-1-ol (0.3-8.4%), octanoic (0.5-8.6%) and dodecanoic acid (0-5.0%), 2-methylbutanenitrile (0-4.6%), dibutyl phthalate (0-4.5%), and ethyl linolenate (0-3.6%). The main volatile O-aglycones were: 2-phenylethyl alcohol (21.5%), 6,7-dehydro-7,8-dihydro-3-oxo-alpha-ionol (9.3%), eugenol (8.3%), benzyl alcohol (7.0%), ethyl vanillate (5.2%), 6-(tert-butyl)-5-methylphenol (5.1%), vanillin acetone (4.7%), ethyl 4-hydroxybenzoate (4.3%), and 2-hydroxy-beta-ionone (3.8%). All hydrodistillates exhibited great potential of antibacterial activity against five Gram-positive bacteria, nine ampicillin-resistant Gram-negative bacteria, and four fungi at a concentration of 500 microg/ml using the disc diffusion method.