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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.

    PubMed

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

    2010-09-01

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

  2. 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.

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

    PubMed

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

    2010-09-01

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

  4. 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.

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

    SciTech Connect

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

    2011-02-01

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

  6. 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.

  7. 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.

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

    SciTech Connect

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

    1995-10-01

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

  9. 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.

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

    PubMed

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

    2007-02-01

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

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

    PubMed

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

    2007-02-01

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

  12. 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.

  13. 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.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2013-05-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2016-08-15

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

  18. 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.

  19. The cytotoxicity, DNA crosslinking ability and DNA sequence selectivity of the aniline mustards melphalan, chlorambucil and 4-[bis(2-chloroethyl)amino] benzoic acid.

    PubMed

    Sunters, A; Springer, C J; Bagshawe, K D; Souhami, R L; Hartley, J A

    1992-07-01

    Three aniline derivatives melphalan (L-PAM), chlorambucil (CHL) and 4-[bis(2-chloroethyl)amino] benzoic acid (BAM) have been compared on the basis of their in vitro cytotoxicities, DNA interstrand crosslinking ability and DNA sequence selectivity. Cytotoxicity was assessed in the human colonic adenocarcinoma LS174T and leukaemic K562 cell lines using the sulpho-rhodamine B and tetrazolium dye reduction assays. The order of cytotoxicities was L-PAM greater than CHL greater than BAM in both cell lines with K562 being less sensitive than LS174T. This was different from the order CHL greater than L-PAM greater than BAM which would be predicted from simple chemical reactivity or rate of hydrolysis, parameters which have been used previously as indicators of biological potency for aromatic nitrogen mustards. DNA interstrand crosslinking in cells as determined by alkaline elution showed a correlation with IC50 values. The ranking order of activity was further predicted by the ability of the agents to produce interstrand crosslinks in isolated DNA. The extent of guanine N-7 alkylation, assessed using a modified DNA sequencing technique, mirrored cytotoxicity and crosslinking ability, but at equivalent levels of alkylation there was no significant difference in DNA sequence selectivity. These data demonstrates that simple chemical reactivity or hydrolysis rate is not a good indicator of DNA reactivity or cytotoxicity for a number of aniline mustards, whereas DNA interstrand crosslinking ability either measured directly in cells or in isolated DNA, gives a good indication of biological activity.

  20. CO2 laser debridement of sulphur mustard (bis-2-chloroethyl sulphide) induced cutaneous lesions accelerates production of a normal epidermis with elimination of cytological atypia.

    PubMed

    Smith, K J; Skelton, H G; Martin, J L; Hurst, C G; Hackley, B E

    1997-10-01

    Sulphur mustard (bis-2-chloroethyl sulphide; HD) exposure acutely produces lesions that vary from mild erythema, to blister formation, to necrosis. When blisters occur, with or without necrosis, healing of the lesions is delayed. Weanling pigs exposed to a mild erythema-producing dose of HD and to a moderate erythema-producing dose that consistently gave microblister formation were treated with CO2 laser (Tru-Pulse) debridement at 6, 24 or 48 h after exposure. The histopathological features observed at 14 days after exposure in control skin and skin exposed to both HD doses were compared with the features observed in CO2 laser-debrided skin in non-exposed and HD-exposed skin sites. The overlying epidermis in the non-laser treated lesions was thin, with cytological atypia and squamoid changes within the basal cell layer, as well as scattered apoptotic/necrotic keratinocytes. An increased inflammatory infiltrate and necrobiotic changes in the dermis were seen at the higher HD dose. All laser-treated lesions appeared identical, with a thick, differentiated epidermis and a well-formed basal cell layer. There was minimal inflammatory infiltrate. In the papillary dermis there were increased stromal cells. Laser debridement of mild clinical lesions induced by HD produced a more functional epidermis by 14 days as well as clearing the epidermis of damaged keratinocytes.

  1. 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.

  2. 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

  3. Steroidal esters of the aromatic nitrogen mustard 2-[4-N,N-bis(2-chloroethyl)amino-phenyl]butanoic acid (2-PHE-BU): synthesis and in-vivo biological evaluation.

    PubMed

    Papaconstantinou, Ioanna C; Fousteris, Manolis A; Koutsourea, Anna I; Pairas, Georgios N; Papageorgiou, Athanasios D; Nikolaropoulos, Sotiris S

    2013-01-01

    On the basis of the results of in-silico predictions and in an effort to extend our structure-activity relationship studies, the aromatic nitrogen mustard 2-[4-N,N-bis(2-chloroethyl) amino-phenyl]butanoic acid (2-PHE-BU) was synthesized and conjugated with various steroidal alcohols. The resulting steroidal esters were evaluated for their in-vivo toxicity and antileukemic activity in P388-leukemia-bearing mice. The new derivatives showed significantly reduced toxicity and marginally improved antileukemic activity compared with free 2-PHE-BU. Nevertheless, they did not prove to be superior either to the template steroidal ester used for in-silico predictions or to previously synthesized steroidal esters of aromatic nitrogen mustards. The results obtained indicate that in-silico design predictions may guide the design and synthesis of new bioactive steroidal esters, but further parameters should be considered aiming at the discovery of compounds with optimum activity.

  4. 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.

  5. 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.

  6. Gene expressions in Jurkat cells poisoned by a sulphur mustard vesicant and the induction of apoptosis.

    PubMed

    Zhang, Peng; Ng, Patrick; Caridha, Diana; Leach, Richard A; Asher, Ludmila V; Novak, Mark J; Smith, William J; Zeichner, Steven L; Chiang, Peter K

    2002-09-01

    1. The sulphur mustard vesicant 2-chloroethylethyl sulphide (CEES) induced apoptosis in Jurkat cells. 2. Akt (PKB), a pivotal protein kinase which can block apoptosis and promotes cell survival, was identified to be chiefly down-regulated in a dose-dependent manner following CEES treatment. Functional analysis showed that the attendant Akt activity was simultaneously reduced. 3. PDK1, an upstream effector of Akt, was also down-regulated following CEES exposure, but two other upstream effectors of Akt, PI3-K and PDK2, remained unchanged. 4. The phosphorylation of Akt at Ser(473) and Thr(308) was significantly decreased following CEES treatment, reflecting the suppressed kinase activity of both PDK1 and PDK2. 5. Concurrently, the anti-apoptotic genes, Bcl family, were down-regulated, in sharp contrast to the striking up-regulation of some death executioner genes, caspase 3, 6, and 8. 6. Based on these findings, a model of CEES-induced apoptosis was established. These results suggest that CEES attacked the Akt pathway, directly or indirectly, by inhibiting Akt transcription, translation, and post-translation modification. 7. Taken together, upon exposure to CEES, apoptosis was induced in Jurkat cells via the down-regulation of the survival factors that normally prevent the activation of the death executioner genes, the caspases. PMID:12208782

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

    PubMed

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

    2010-03-15

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

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

    PubMed

    Watson, A P; Griffin, G D

    1992-11-01

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

  9. 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

  10. 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

  11. 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

  12. 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.

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

    PubMed

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

    2015-05-15

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

  14. 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.

  15. Vesicant burns.

    PubMed

    Mellor, S G; Rice, P; Cooper, G J

    1991-01-01

    (1) Of the 120,000 victims of sulphur mustard gas in World War I there were only 2-3% fatalities, and few long term effects. (2) The interactions of sulphur mustard with the skin are complete within a few minutes of exposure. Once the victim has been decontaminated there is no risk to the attendant and there is no active agent in the blister fluid. (3) The rate of wound healing is slow for sulphur mustard burns, but in general the wounds heal satisfactorily. (4) There is no specific therapy for poisoning by sulphur mustard.

  16. Use of the mouse ear vesicant model to evaluate the effectiveness of ebselen as a countermeasure to the nitrogen mustard mechlorethamine.

    PubMed

    Lulla, Anju; Reznik, Sandra; Trombetta, Louis; Billack, Blase

    2014-12-01

    Previous studies in this and other laboratories have demonstrated that ebselen (EB-1), an organoselenium compound, spares cells from mechlorethamine (HN2) toxicity in vitro. In the present study, the hypothesis that EB-1 will reduce dermal toxicity of HN2 in vivo is put forward and found to have merit. Using the mouse ear vesicant model (MEVM), HN2, applied topically, showed a dose-dependent effect upon ear swelling and thickness 24 h after treatment; whereas tissue injury consistent with vesication was observed at the higher test doses of HN2 (≥ 0.250 µmol per ear). To examine HN2 countermeasure activity using the MEVM, either hydrocortisone (HC), as a positive control, or EB-1, the test countermeasure, was administered as three topical treatments 15 min, 4 and 8 h after HN2 exposure. Using this approach, both HC and EB-1 were found to reduce tissue swelling associated with HN2 toxicity 24 h after exposure to the vesicant. Taken together, these data demonstrate for the first time the effectiveness of EB-1 as a vesicant countermeasure in a relevant in vivo model.

  17. 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

  18. 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

  19. Treatability studies of groundwater contaminated with bis(2-chloroethyl) ether

    SciTech Connect

    Huang, F.Y.C.; Li, K.Y.; Liu, C.C.

    1999-05-01

    The groundwater aquifer underneath a chemical manufacturing plant in Southeast Texas has been contaminated with the leachate from its landfill. There are 17 major chlorinated hydrocarbon contaminants found in the groundwater with concentrations ranging from 1 ppm to 1,200 ppm. An air-stripping unit followed by a thermal catalytic oxidation unit is currently operating on-site to remove all of the chlorinated compounds from the contaminated groundwater. One of the contaminants, bis(2-chloroethyl)ether (DCEE), has a fairly low Henry`s Law constant; therefore, a high air flow rate is employed in the stripping unit to improve the overall stripping efficiency. Nevertheless, the treated groundwater still contains a fair amount of DCEE. An UV-peroxidation reactor is set up to study its feasibility for oxidizing DCEE. The treatability data indicate that DCEE at a concentration of 200 ppm can be oxidized effectively in the presence of H{sub 2}O{sub 2} and the effective UV wavelengths lie between 200 and 280 nm. No noticeable reduction of the oxidation rate is observed at low temperature ({approximately} 11 C). Apparent oxidation rate equations of DCEE are determined and several process design parameters are discussed.

  20. 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.

  1. Respiratory Complications Due to Sulfur Mustard Exposure

    PubMed Central

    Rahmani, Hossein; Shirali, Saeed

    2016-01-01

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

  2. Respiratory Complications Due to Sulfur Mustard Exposure

    PubMed Central

    Rahmani, Hossein; Shirali, Saeed

    2016-01-01

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

  3. Decontamination of 2-Chloroethyl Ethyl Sulfide by Pulsed Corona Plasma

    NASA Astrophysics Data System (ADS)

    Li, Zhanguo; Hu, Zhen; Cao, Peng; Zhao, Hongjie

    2014-11-01

    Decontamination of 2-chloroethyl ethyl sulfide (2-CEES, CH3CH2SCH2CH2Cl) by pulsed corona plasma was investigated. The results show that 212.6 mg/m3 of 2-CEES, with the gas flow rate of 2 m3/h, can be decontaminated to 0.09 mg/m3. According to the variation of the inlet and outlet concentration of 2-CEES vapor with retention time, it is found that the reaction of 2-CEES in a pulsed corona plasma system follows the first order reaction, with the reaction rate constant of 0.463 s-1. The decontamination mechanism is discussed based on an analysis of the dissociation energy of chemical bonds and decontamination products. The C-S bond adjacent to the Cl atom will be destroyed firstly to form CH3CH2S· and ·CH2CH2Cl radicals. CH3CH2S· can be decomposed to ·C2H5 and ·S. ·S can be oxidized to SO2, while ·C2H5 can be finally oxidized to CO2 and H2O. The C-Cl bond in the ·CH2CH2Cl radical can be destroyed to form ·CH2CH2. and ·Cl, which can be mineralized to CO2, H2O and HCl. The H atom in the ·CH2CH2Cl radical can also be substituted by ·Cl to form CHCl2-CHCl2.

  4. Inflammatory mechanisms of pulmonary injury induced by mustards.

    PubMed

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

    2016-02-26

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

  5. 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...

  6. 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...

  7. 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...

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

    PubMed

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

    2016-06-01

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

  9. Kinetic study of UV peroxidation of bis(2-chloroethyl) ether in aqueous solution

    SciTech Connect

    Li, K.Y.; Liu, C.C.; Ni, Q.; Colapret, J.A.; Liu, Z.F.; Huang, F.Y.C.

    1995-06-01

    The groundwater aquifer underneath a chemical manufacturing plant in Southeast Texas has been contaminated by the leachate from its landfill. Based on computer simulations, the current air flow rate used in the air-stripping unit is about 10 times higher than the calculated flow rate if bis(2-chloroethyl) ether (DCEE) is excluded. This excessive air flow rate has caused maintenance problems and a higher energy consumption. It was proposed to treat the contaminated groundwater by air stripping to remove the volatile compounds and by UV/H{sub 2}O{sub 2} oxidation to destruct the low-volatility compounds such as DCEE. Experimental data from the UV peroxidation of DCEE in aqueous solution indicated the rate equation is 0.163[DCEE]{sup 0.61}[H{sub 2}O{sub 2}]{sup 0.54}. Important intermediates identified are 2-chloroethyl acetate, an enolic tautomer of 2-chloroethyl acetate, 2-chloroethoxyethene, 2-chloroethanol, acetaldehyde, ethylene oxide, and chloroethene. All the intermediates could be reduced to undetectable levels after 30 min of irradiation when DCEE/H{sub 2}O{sub 2} initial ratio of 1/10 was used. A reaction mechanism with complex pathways through both the attack of hydroxy free radical and the direct photolysis on DCEE was proposed. Intermediate identification and the rate equation suggested that the pathways in which DCEE is attacked by hydroxy free radicals are predominant. The rate equation derived from this mechanism predicted the peroxidation of DCEE is half-order with respect to both DCEE and H{sub 2}O{sub 2} concentrations.

  10. DNA damage induced by a new 2-chloroethyl nitrosourea on malignant melanoma cells.

    PubMed

    Godeneche, D; Rapp, M; Thierry, A; Laval, F; Madelmont, J C; Chollet, P; Veyre, A

    1990-09-15

    Different biological aspects of a novel 2-chloroethyl nitrosourea derived from cysteamine, N'-(2-chloroethyl)-N-[2-(methylsulfinyl)ethyl]-N'- nitrosourea (CMSOEN2), were studied. Drug-induced cytotoxic effects, uptake kinetics, DNA damage, and O6-alkylguanine-DNA alkyltransferase activity were determined in 3 melanoma cell lines: the murine B16 and 2 human metastatic-derived cell lines (M4 Beu and M3 Dau). We found that radioactivity uptake and incorporation in acido-precipitable material was inversely proportional to cell drug viability. The highly CMSOEN2-sensitive B16 line showed the lowest total radioactivity uptake. In fact, among the melanoma cell parameters studied, 3 of them were well correlated: (a) cytotoxicity as reflected by the colony-forming assay; (b) DNA cross-link frequency estimated by the alkaline elution technique; and (c) O6-alkylguanine-DNA alkyltransferase activity (Mer phenotype), defined as the ability of cell extracts to remove O6-methylguanine from N-methyl-N-nitrosourea-alkylated DNA. The 2 human cell lines (M4 Beu and M3 Dau), the most resistant to the cytostatic drug effects, showed little or no ability to form DNA lethal cross-links. These results correspond to the higher O6-alkylguanine-DNA alkyltransferase activity found in human-derived cell lines compared with that present in murine B16 cell lines. This study confirms that the cell content in this repair DNA protein is certainly one of the important factors implicated in the variability of response to 2-chloroethyl nitrosourea treatment observed in a number of established malignant cell lines. It has been shown that pretreatment of derived cell lines with methylating agents (N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine) or O6-methylguanine used as a free base, increased cytotoxic effects of this class of anticancer agents, likely by saturating receptor sites (sulfhydryl groups) of this specific DNA repair enzyme. Nevertheless, in preliminary Phase I and II clinical

  11. [Cutaneous and systemic toxicology of vesicants used in warfare].

    PubMed

    Pita, R; Vidal-Asensi, S

    2010-01-01

    Vesicants are a group of chemicals used in warfare. The most representative agent is yperite, also known as mustard gas. The blisters that appeared on those exposed to yperite during combat in the First World War are responsible for the current name--vesicants--for this group of chemicals. Their affects are produced mainly through localized action of liquid or vapor forms on the skin, eyes, and respiratory tract. However, the high absorption of the liquid form through the skin or the vapor form on inhalation may cause substantial systemic effects. Here we analyze these effects, treatment of intoxication, and long-term sequelae, drawing on our experience and a review of the literature.

  12. 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.

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

    PubMed

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

    2011-10-01

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

  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. Sulfur Mustard

    MedlinePlus

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

  16. Relationships between structure, toxicity and genetic effects in Salmonella typhimurium and Saccharomyces cerevisiae for substituted aniline mustards.

    PubMed

    Ferguson, L R; Palmer, B D; Denny, W A

    1989-09-01

    A series of 4-substituted aniline mustards of widely varying reactivities have been evaluated for their mutagenic effects in Salmonella typhimurium strains of varying uvrB gene and plasmid status, and for their ability to cause mitotic crossing-over in Saccharomyces cerevisiae. The 4-methyl aniline mustard N,N-bis(2-chloroethyl)-4-methylaniline and its corresponding half-mustard N-(2-chloroethyl)-4-methylaniline showed widely different effects in the various bacterial strains, with the half-mustard being much less toxic than the full mustard in the uvrB- strain TA100. However, in the uvrB+ strain TA1978+, possessing an intact excision repair system, both compounds were equally toxic and the full mustard was the more mutagenic. Both compounds were equally effective in promoting mitotic crossing-over in yeast. For a series of 4-substituted full mustards, the toxicity in S. typhimurium strain TA100 correlated with substituent electronic parameters in the same way as does mammalian cell toxicity, supporting the view that the primary mode of toxicity is via DNA cross-linking, even for unreactive analogues. However, there were no obvious correlations between substituent physiochemical properties and mutagenic potential in bacteria, suggesting that mutagenic events are subject to a variety of influences other than the reactivity of the mustard group. In contrast, the most chemically reactive compounds were the most toxic and most recombinogenic in yeast.

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

    PubMed

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

    1998-01-01

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

  18. Biodegradation of Bis(2-Chloroethyl) Ether by Xanthobacter sp. Strain ENV481▿

    PubMed Central

    McClay, Kevin; Schaefer, Charles E.; Vainberg, Simon; Steffan, Robert J.

    2007-01-01

    Degradation of bis(2-chloroethyl) ether (BCEE) was observed to occur in two bacterial strains. Strain ENV481, a Xanthobacter sp. strain, was isolated by enrichment culturing of samples from a Superfund site located in the northeastern United States. The strain was able to grow on BCEE or 2-chloroethylethyl ether as the sole source of carbon and energy. BCEE degradation in strain ENV481 was facilitated by sequential dehalogenation reactions resulting in the formation of 2-(2-chloroethoxy)ethanol and diethylene glycol (DEG), respectively. 2-Hydroxyethoxyacetic acid was detected as a product of DEG catabolism by the strain. Degradation of BCEE by strain ENV481 was independent of oxygen, and the strain was not able to grow on a mixture of benzene, ethylbenzene, toluene, and xylenes, other prevalent contaminants at the site. Another bacterial isolate, Pseudonocardia sp. strain ENV478 (S. Vainberg et al., Appl. Environ. Microbiol. 72:5218-5224, 2006), degraded BCEE after growth on tetrahydrofuran or propane but was not able to grow on BCEE as a sole carbon source. BCEE degradation by strain ENV478 appeared to be facilitated by a monooxygenase-mediated O-dealkylation mechanism, and it resulted in the accumulation of 2-chloroacetic acid that was not readily degraded by the strain. PMID:17873075

  19. Mobility and sorption of bis-2-chloroethyl ether in an aquifer material.

    PubMed

    Bednar, A J; Kirgan, R A; Karn, R A; Donovan, B; Mohn, M F; Sirkis, D M

    2009-09-15

    Active treatment of BCEE (bis-2-chloroethyl ether) is being currently performed in the on-site Cohansey Aquifer at the Lipari Superfund Site. Remediation of BCEE in the underlying Kirkwood aquifer is being considered, necessitating investigations of BCEE geochemistry in aquifer material from the site. It is currently unknown to what extent BCEE is present in the dissolved, sorbed, or free-product phase in the Kirkwood Sand aquifer material. A series of partition coefficient sorption, column leach, and column loading tests were conducted to determine BCEE sorption to, and mobility in, the Kirkwood Sand aquifer material. The leach studies indicated that up to 50% of BCEE spiked (as free-phase product) onto two aquifer material column designs could be leached in approximately 18h, due to the high aqueous solubility of BCEE. Dissolved BCEE concentrations then began to plateau as sorption reactions hindered further leaching, resulting in up to 80% removal after 48h. Column loading and batch sorption experiments suggest that BCEE mobility is limited by sorption rather than solubility factors. Tracer tests in both column loading and batch sorption tests indicate sorption hinders leaching of BCEE from the Kirkwood Sand material.

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

    PubMed Central

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

    2015-01-01

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

  1. 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.

  2. 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.

  3. 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

  4. 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).

  5. 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.

  6. 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

    2015-05-01

    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 0.0001-1ngmL(-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. PMID:25703367

  7. Nitrogen Mustards

    MedlinePlus

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

  8. Capillary gas chromatography and thermionic N-P-specific detection of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in stability and pharmacokinetic studies.

    PubMed

    El-Yazigi, A; Martin, C R

    1988-04-01

    An expedient, rapid, and sensitive capillary gas chromatographic method for the analysis of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in plasma is described. Separation of the underivatized nitrosourea compounds was performed on a 0.33-mm-i.d., 25-m fused-silica, SE-30 capillary column, and detection was carried out using a thermionic N-P-specific detector. The compounds were extracted from plasma with benzene with a yield of greater than 87%. The assay was linear in the ranges of 0.001 to 0.5 and 0.5 to 25 micrograms/ml for CCNU or 0.003 to 0.50 and 0.5 to 25 micrograms/ml for BCNU, with correlation coefficients from 0.9914 to 0.9999 and coefficients of variation (CV) of less than 3.3%. Other antineoplastic agents did not interfere in the assay. The method was employed to study the pharmacokinetics of BCNU in rabbits. The plasma concentration-time curves were fit to a two-compartment model with a mean (SE) alpha, beta, and total-body clearance of 2.898 (0.913) hr-1, 0.1228 (0.0179) hr-1, and 7.211 (2.862) liters/hr.kg, respectively. Further, the stability of BCNU and CCNU in solution was examined at different temperatures. Both compounds were stable in benzene or acetone (4 to 37 degrees C) but labile in plasma even if refrigerated. The apparent rate constants for degradation of BCNU and CCNU were 0.09921 and 0.02853 hr-1 at 4 degrees C and 5.998 and 2.553 hr-1 at 37 degrees C, respectively.

  9. 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.

  10. The use of laser Doppler imaging as an aid in clinical management decision making in the treatment of vesicant burns.

    PubMed

    Brown, R F; Rice, P; Bennett, N J

    1998-12-01

    Vesicants are a group of chemicals recognised, under the terms of the Chemical Weapons Convention, as potential chemical warfare agents whose prime effect on the skin is to cause burns and blistering. Experience of the clinical management of these injuries is not readily available and therefore an accurate assessment of the severity of the lesion and extent of tissue involvement is an important factor when determining the subsequent clinical management strategy for such lesions. This study was performed to assess the use of laser Doppler imaging (LDI) as a noninvasive means of assessing wound microvascular perfusion following challenge with the vesicant agents (sulphur mustard or lewisite) by comparing the images obtained with histopathological analysis of the lesion. Large white pigs were challenged with sulphur mustard (1.91 mg cm(-2)) or lewisite (0.3 mg.cm(-2)) vapour for periods of up to 6 h At intervals of between 1 h and 7 days following vesicant challenge, LDI images were acquired and samples for routine histopathology were taken. The results from this study suggest that LDI was: (i) a simple, reproducible and noninvasive means of assessing changes in tissue perfusion, and hence tissue viability, in developing and healing vesicant burns; (ii) the LDI images correlates well with histopathological assessment of the resulting lesions and the technique was sufficiently sensitive enough to discriminate between skin lesions of different aetiology. These attributes suggest that LDI would be a useful investigative tool that could aid clinical management decision making in the early treatment of vesicant agent-induced skin burns.

  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. 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

  13. 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.

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

    PubMed

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

    2012-11-28

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

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

    PubMed

    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. PMID:20210463

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

    PubMed Central

    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. PMID:20210463

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

    PubMed

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

    2003-12-01

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

  18. In vivo potentiation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea by the radiation sensitizer benznidazole

    SciTech Connect

    Siemann, D.W.; Morrissey, S.; Wolf, K.

    1983-03-01

    Recent studies in mouse tumor systems have indicated a potential therapeutic advantage in combining the radiosensitizer misonidazole (MISO) with cancer chemotherapy drugs. One agent the antitumor activity of which has been enhanced to a greater extent than its hematological or gastrointestinal toxicities is the nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). Recently, sensitizers more lipophylic than MISO have been reported to give greater tumor response enhancement when combined with CCNU. The present studies compared the potential therapeutic benefit of combining MISO (partition coefficient, 0.43) or benznidazole (BENZO) (partition coefficient, 8.5) in KHT sarcoma or RIF-1 tumor-bearing C3H mice. Both sensitizers were administered i.p. and given either 30 min before (BENZO) or simultaneously with (MISO) the chemotherapeutic agent. Survival of clonogenic tumor cells assessed 22 to 24 hr after treatment or in situ tumor growth delay were used as assays of tumor response. Normal tissue toxicity was determined using the drug dose yielding 50% animal lethality in 30 days end point. When combined with CCNU, doses of MISO (5.0 mmol/kg) or BENZO (0.3 mmol/kg) were found to yield approximately equivalent increases in both the tumor effect (enhancement ratio, approximately 1.8 to 2.0) and normal tissue toxicity (enhancement ratio approximately 1.3 to 1.4). Both sensitizers therefore led to a therapeutic benefit. However, although a approximately 10-fold lower dose of the more lipophylic sensitizer BENZO proved to be as effective as MISO at enhancing the tumoricidal effects of CCNU, this dose reduction did not result in a greater therapeutic gain for BENZO.

  19. Isophosphoramide mustard, a metabolite of ifosfamide with activity against murine tumours comparable to cyclophosphamide.

    PubMed Central

    Struck, R. F.; Dykes, D. J.; Corbett, T. H.; Suling, W. J.; Trader, M. W.

    1983-01-01

    Isophosphoramide mustard was synthesized and was found to demonstrate activity essentially comparable to cyclophosphamide and ifosfamide against L1210 and P388 leukaemia. Lewis lung carcinoma, mammary adenocarcinoma 16/C, ovarian sarcoma M5076, and colon tumour 6A, in mice and Yoshida ascitic sarcoma in rats. At doses less than, or equivalent to, the LD10, isophosphoramide mustard retained high activity against cyclophosphamide-resistant L1210 and P388 leukaemias, but was less active against intracerebrally-implanted P388 leukaemia while cyclophosphamide produced a 4 log10 tumour cell reduction. It was also less active (one log10 lower cell kill) than cyclophosphamide against the B16 melonoma. Metabolism studies on ifosfamide in mice identified isophosphoramide mustard in blood. In addition, unchanged drug, carboxyifosfamide, 4-ketoifosfamide, dechloroethyl cyclophosphamide, dechloroethylifosfamide, and alcoifosfamide were identified. The latter 4 metabolites were also identified in urine from an ifosfamide-treated dog. In a simulated in vitro pharmacokinetic experiment against L1210 leukaemia in which drugs were incubated at various concentrations for various times, both 4-hydroxycyclophosphamide and isophosphoramide mustard exhibited significant cytoxicity at concentration times time values of 100-1000 micrograms X min ml-1, while acrolein was significantly cytotoxic at 10 micrograms X min ml-1. Treatment of mice with drug followed by L1210 cells demonstrated a shorter duration of effective levels of cytotoxic activity for isophosphoramide mustard and phosphoramide mustard in comparison with cyclophosphamide and ifosfamide. Isophosphoramide mustard and 2-chloroethylamine, a potential hydrolysis product of isophosphoramide mustard and carboxyifosfamide, were less mutagenic in the standard Ames test than the 2 corresponding metabolites of cyclophosphamide [phosphoramide mustard and bis(2-chloroethyl)amine]. PMID:6821629

  20. 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).

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

    PubMed

    Rice, Paul

    2003-01-01

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

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

    PubMed

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

    1997-06-01

    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.

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

    PubMed

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

    1994-01-01

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

  4. 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.

  5. Antioxidants countermeasures against sulfur mustard.

    PubMed

    Pohanka, M

    2012-07-01

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

  6. 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.

  7. Treatment of sulphur mustard skin injury.

    PubMed

    Jenner, John; Graham, Stuart J

    2013-12-01

    Since its first use in 1917, sulphur mustard (SM) has been used virtually exclusively as a weapon of war.SM is a volatile liquid that damages any tissue it contacts as a vapour or liquid. SM primarily damages the skin, eyes and lungs producing massive inflammation culminating in the characteristic blistering of the skin which classifies SM as a vesicant. Several mechanisms of action at the cellular level have been proposed for SM, but none has ever been convincingly linked to the production of blisters or vesication. First aid for those contaminated with liquid SM consists of the rapid removal (within a few minutes) of liquid from the surface of the skin, as once penetrated into the stratum corneum it is very difficult to remove. In the absence of a mechanistically based specific therapy, SM skin injury is normally treated in a similar way to thermal and chemical burns, which it resembles pathologically. Effective therapy consist of treating the inflammation and where necessary removal of the dead eschar to facilitate healing. Post surgical care comprises the use of one of a number of available dressings used in thermal burn care and antibiotic creams should infection be present.

  8. 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.

  9. Sulphur mustard degradation on zirconium doped Ti-Fe oxides.

    PubMed

    Štengla, Václav; Grygar, Tomáš Matys; Opluštil, František; Němec, Tomáš

    2011-09-15

    Zirconium doped mixed nanodispersive oxides of Ti and Fe were prepared by homogeneous hydrolysis of sulphate salts with urea in aqueous solutions. Synthesized nanodispersive metal oxide hydroxides were characterised as the Brunauer-Emmett-Teller (BET) surface area and Barrett-Joiner-Halenda porosity (BJH), X-ray diffraction (XRD), infrared (IR) spectroscopy, scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) microanalysis, and acid-base titration. These oxides were taken for an experimental evaluation of their reactivity with sulphur mustard (chemical warfare agent HD or bis(2-chloroethyl)sulphide). The presence of Zr(4+) dopant tends to increase both the surface area and the surface hydroxylation of the resulting doped oxides in such a manner that it can contribute to enabling the substrate adsorption at the oxide surface and thus accelerate the rate of degradation of warfare agents. The addition of Zr(4+) to the hydrolysis of ferric sulphate with urea shifts the reaction route and promotes formation of goethite at the expense of ferrihydrite. We discovered that Zr(4+) doped oxo-hydroxides of Ti and Fe exhibit a higher degradation activity towards sulphur mustard than any other yet reported reactive sorbents. The reaction rate constant of the slower parallel reaction of the most efficient reactive sorbents is increased with the increasing amount of surface base sites.

  10. 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.

  11. 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.

  12. Sulfur mustard-induced ocular surface disorders.

    PubMed

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

    2011-07-01

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

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

    PubMed

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

    2015-08-01

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

  14. 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

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2009-02-15

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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. The effect of mustard gas on the biological activity of soil.

    PubMed

    Medvedeva, N; Polyak, Yu; Kuzikova, I; Orlova, O; Zharikov, G

    2008-03-01

    A special group of substances that are very dangerous for the biosphere includes war gases such as mustard gas (bis(2-chloroethyl)sulphide). The influence of mustard gas hydrolysis products (MGHPs) on soil microbiota has been investigated. These substances bear numerous toxic effects on soil microorganisms. They change significantly the number and the specific composition of soil microbiota and inhibit the enzyme activity of soils. The main "ecological targets" of mustard and its hydrolysis products' toxic action have been determined. MGHPs affect the growth and reproduction of soil micromycetes, as well as their morphological and cultural properties. Increase in number and size of mitochondria in the fungal cells is accompanied by increase in dehydrogenases activity. Cell permeability influenced by MGHPs grows in connection with concentration of toxicants. Increase of permeability corresponds to growth of the amount of unsaturated fatty acids. The changes in the fatty acid composition of lipids in the cells of the soil micromycetes display their adaptation to adverse impact of the substances studied. MGHPs and thiodiglycol enhance synthesis of polysaccharides and pigments.

  3. The effect of mustard gas on the biological activity of soil.

    PubMed

    Medvedeva, N; Polyak, Yu; Kuzikova, I; Orlova, O; Zharikov, G

    2008-03-01

    A special group of substances that are very dangerous for the biosphere includes war gases such as mustard gas (bis(2-chloroethyl)sulphide). The influence of mustard gas hydrolysis products (MGHPs) on soil microbiota has been investigated. These substances bear numerous toxic effects on soil microorganisms. They change significantly the number and the specific composition of soil microbiota and inhibit the enzyme activity of soils. The main "ecological targets" of mustard and its hydrolysis products' toxic action have been determined. MGHPs affect the growth and reproduction of soil micromycetes, as well as their morphological and cultural properties. Increase in number and size of mitochondria in the fungal cells is accompanied by increase in dehydrogenases activity. Cell permeability influenced by MGHPs grows in connection with concentration of toxicants. Increase of permeability corresponds to growth of the amount of unsaturated fatty acids. The changes in the fatty acid composition of lipids in the cells of the soil micromycetes display their adaptation to adverse impact of the substances studied. MGHPs and thiodiglycol enhance synthesis of polysaccharides and pigments. PMID:17537425

  4. 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.

  5. 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.

  6. 1,3-Bis(2-chloroethyl)-1-nitrosourea-loaded bovine serum albumin nanoparticles with dual magnetic resonance-fluorescence imaging for tracking of chemotherapeutic agents.

    PubMed

    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

  7. Tris(2-chloroethyl)phosphate-induced cell growth arrest via attenuation of SIRT1-independent PI3K/Akt/mTOR pathway.

    PubMed

    Zhang, Wenjuan; Zhang, Youjian; Wang, Zhiyuan; Xu, Tian; Huang, Cheng; Yin, Wenjun; Wang, Jing; Xiong, Wei; Lu, Wenhong; Zheng, Hongyan; Yuan, Jing

    2016-07-01

    Tris(2-chloroethyl)phosphate (TCEP) as an organophosphorus flame retardant and plasticizer has been widely used in industrial and household products. It not only was detected in residential indoor air and dust, surface and drinking water, but also in human plasma and breast milk, and tissue samples of liver, kidneys and brain from rodents. TCEP is classified as carcinogenic category 2 and toxic for reproduction category 1B. Sufficient evidence from experimental animals indicated carcinogenicity of TCEP in the liver, and kidneys as well as cell loss in the brain. However, the underlying mechanisms of TCEP-induced hepatotoxicity are mostly unknown. We investigated the in vitro effects of TCEP as well as TCEP-induced cell growth in the L02 and HepG2 cells through the PI3K/Akt/mTOR pathway. We found that TCEP reduced cell viability of these cell lines, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the PI3K/Akt/mTOR pathway. However, growth arrest of the L02 and HepG2 cells were aggravated after inhibiting the SIRT1 expression with EX-527. The findings above suggested that TCEP induced the cell growth arrest of L02 and HepG2 cells via attenuation of the SIRT1-independent PI3K/Akt/mTOR pathway. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26378621

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

    SciTech Connect

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

    1993-05-13

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

  10. 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

  11. 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.

  12. Detection and monitoring of early airway injury effects of half-mustard (2-chloroethylethylsulfide) exposure using high-resolution optical coherence tomography.

    PubMed

    Kreuter, Kelly A; Mahon, Sari B; Mukai, David S; Su, Jianping; Jung, Woong-Gyu; Narula, Navneet; Guo, Shuguang; Wakida, Nicole; Raub, Chris; Berns, Michael W; George, Steven C; Chen, Zhongping; Brenner, Matthew

    2009-01-01

    Optical coherence tomography (OCT) is a noninvasive, high-resolution imaging technology capable of delivering real-time, near-histologic images of tissues. Mustard gas is a vesicant-blistering agent that can cause severe and lethal damage to airway and lungs. The ability to detect and assess airway injury in the clinical setting of mustard exposure is currently limited. The purpose of this study is to assess the ability to detect and monitor progression of half-mustard [2-chloroethylethylsulfide (CEES)] airway injuries with OCT techniques. A ventilated rabbit mustard exposure airway injury model is developed. A flexible fiber optic OCT probe is introduced into the distal trachea to image airway epithelium and mucosa in vivo. Progression of airway injury is observed over eight hours with OCT using a prototype time-domain superluminescent diode OCT system. OCT tracheal images from CEES exposed animals are compared to control rabbits for airway mucosal thickening and other changes. OCT detects the early occurrence and progression of dramatic changes in the experimental group after exposure to CEES. Histology and immunofluorescence staining confirms this finding. OCT has the potential to be a high resolution imaging modality capable of detecting, assessing, and monitoring treatment for airway injury following mustard vesicant agent exposures. PMID:19725748

  13. Detection and monitoring of early airway injury effects of half-mustard (2-chloroethylethylsulfide) exposure using high-resolution optical coherence tomography

    PubMed Central

    Kreuter, Kelly A.; Mahon, Sari B.; Mukai, David S.; Su, Jianping; Jung, Woong-Gyu; Narula, Navneet; Guo, Shuguang; Wakida, Nicole; Raub, Chris; Berns, Michael W.; George, Steven C.; Chen, Zhongping; Brenner, Matthew

    2009-01-01

    Optical coherence tomography (OCT) is a non-invasive, high-resolution imaging technology capable of delivering real-time, near-histologic images of tissues. Mustard gas is a vesicant-blistering agent that can cause severe and lethal damage to airway and lungs. The ability to detect and assess airway injury in the clinical setting of mustard exposure is currently limited. The purpose of this study is to assess the ability to detect and monitor progression of half-mustard [2-chloroethylethylsulfide (CEES)] airway injuries with OCT techniques. A ventilated rabbit mustard exposure airway injury model is developed. A flexible fiber optic OCT probe is introduced into the distal trachea to image airway epithelium and mucosa in vivo. Progression of airway injury is observed over eight hours with OCT using a prototype time-domain superluminescent diode OCT system. OCT tracheal images from CEES exposed animals are compared to control rabbits for airway mucosal thickening and other changes. OCT detects the early occurrence and progression of dramatic changes in the experimental group after exposure to CEES. Histology and immunofluorescence staining confirms this finding. OCT has the potential to be a high resolution imaging modality capable of detecting, assessing, and monitoring treatment for airway injury following mustard vesicant agent exposures. PMID:19725748

  14. [Vesical endometriosis after cesarean section: diagnostico-therapeutic aspects].

    PubMed

    García González, J I; Extramiana Cameno, J; Esteban Calvo, J M; Díez Rodríguez, J M; Esteban Artiaga, R; Arrizabalaga Moreno, M; Paniagua Andrés, P

    1997-09-01

    Endometriosis is a benign condition with an aggressive behaviour defined by the presence of ectopic endometrial tissue, outside the uterus. It occurs in 15-20% women with child bearing potential. Most commonly it affects organs such as the ovaries, uterine ligaments, fallopian tubes, rectum and the cervico-vaginal region. Involvement of the urinary tract, however, is rare. It can be seen in just about 1% cases, vesical location being the most frequent of these presentations (84% cases). We describe one case of vesical endometriosis that developed after a cesarean section. The intra-operative findings confirmed the existence of infiltration of the detrusor muscle and the vesical mucosa by endometrial tissue from the area of the uterine incision. A discussion of the different diagnostic and therapeutic options is also included.

  15. Upregulation of gamma-2 laminin-332 in the mouse ear vesicant wound model.

    PubMed

    Chang, Yoke-Chen; Sabourin, Carol L K; Lu, Shou-En; Sasaki, Takako; Svoboda, Kathy K H; Gordon, Marion K; Riley, David J; Casillas, Robert P; Gerecke, Donald R

    2009-01-01

    Epithelial cell migration during wound healing is regulated in part by enzymatic processing of laminin-332 (formerly LN-5), a heterodimer formed from alpha, beta, and gamma polypeptide chains. Under static conditions, laminin-332 is secreted into the extracellular matrix as a proform and has two chains processed to smaller forms, allowing it to anchor epithelial cells to the basement membrane of the dermis. During incisional wounding, laminin gamma2 chains in particular are processed to smaller sizes and function to promote epithelial sheet migration over the wound bed. The present study examines whether this same function occurs following chemical injury. The mouse ear vesicant model (MEVM) was used to follow the pathology in the ear and test whether processed laminin-332 enhances epithelial cell migration. Skin biopsies of sulfur mustard (SM) exposed ears for several time points were analyzed by histology, immunohistochemistry, real-time PCR, and Western blot analysis. SM exposure greatly increased mRNA levels for laminin-gamma2 in comparison to the other two chains. Protein production of laminin-gamma2 was upregulated, and there was an increase in the processed forms. Protein production was in excess of the amount required to form heterotrimeric laminin-332 and was associated with the migrating epithelial sheet, suggesting a potential role in wound healing for monomeric laminin-gamma2.

  16. [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.

  17. Neurotoxicity after intracarotid 1,3-bis(2-chloroethyl)-1-nitrosourea administration in the rat: Hemodynamic changes studied by double-tracer autoradiography

    SciTech Connect

    Nagahiro, S.; Yamamoto, Y.L.; Diksic, M.; Mitsuka, S.; Sugimoto, S.; Feindel, W. )

    1991-07-01

    Changes in blood-brain (BBB) permeability and local cerebral blood flow after intracarotid administration of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were examined quantitatively in rats with double-tracer autoradiography using (14C)alpha-amino-isobutyric acid and (18F)fluoroantipyrine. Forty-eight female Wistar rats were divided into four groups. The control group (Group 1) received 1 ml of 5% dextrose. The other three groups received three different doses of BCNU dissolved in 5% dextrose: Group 2 rats received 1 mg, Group 3 3 mg, and Group 4 10 mg. The tracer study was performed on Day 1 or Days 4 to 12 after intracarotid administration of BCNU. In 11 rats in Group 2, there were no changes of BBB permeability. Transient BBB permeability changes were seen in the striatum or hippocampus in 3 of the 5 rats (60%) in Group 3 within 24 hours. In 8 of 9 rats (89%) in the same group, late BBB permeability changes were observed in the hypothalamus with or without histological changes. BBB permeability changes were seen in all rats of Group 4. Focal increase of local cerebral blood flow on the infused side compared with the non-infused side of the brain was observed, although not at a significant level, in 5 of 25 rats examined with (18F)fluoroantipyrine. The results of BBB permeability and histological examinations and study of heterogenous distribution by (18F)fluorodeoxyglucose indicated that the ipsilateral subcortical structures such as the hypothalamus, amygdala, internal capsule, and caudate putamen have the highest incidence of neurotoxicity, which are closely related to histopathological damage seen in human BCNU leucoencephalopathy.

  18. 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.

  19. Lipid peroxidation and oxidative stress responses in juvenile salmon exposed to waterborne levels of the organophosphate compounds tris(2-butoxyethyl)- and tris(2-chloroethyl) phosphates.

    PubMed

    Arukwe, Augustine; Carteny, Camilla Catarci; Eggen, Trine

    2016-01-01

    There is limited knowledge on the toxicological, physiological, and molecular effects attributed to organophosphate (OP) compounds currently used as flame retardants or additives in consumer products. This study investigated the effects on oxidative stress and lipid peroxidation in juvenile Atlantic salmon liver and brain samples after exposure to two OP compounds, tris(2-butoxyethyl) phosphate (TBOEP) and tris(2-chloroethyl) phosphate (TCEP). In this study, groups of juvenile Atlantic salmon were exposed using a semistatic experimental protocol over a 7-d period to 3 different concentrations (0.04, 0.2, or 1 mg/L) of TBOEP and TCEP. When toxicological factors such as bioaccumulation and bioconcentration, and chemical structural characteristics and behavior, including absorption to solid materials, are considered, these concentrations represent environmentally relevant concentrations. The concentrations of the contaminants were derived from levels of their environmental occurrence. The expression of genes related to oxidative stress-glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST)-and to lipid peroxidation-peroxisome proliferator-activated receptors (PPAR)-were determined using quantitative (real-time) polymerase chain reaction (PCR). The presence of PPAR proteins was also investigated using immunochemical methods. Levels of thiobarbituric acid-reactive substances (TBARS) in liver were used as a measure of lipid peroxidation. Overall, our data show an increase in lipid peroxidation, and this was associated with an augmented expression of genes from the glutathione family of responses. Interestingly, PPAR expression in liver after exposure to TBOEP and TCEP was consistently decreased compared to controls, while expression in brain did not show a similar trend. The results suggest that OP contaminants may induce oxidative stress and thus production of reactive oxygen substances (ROS), and modulate lipid peroxidation processes

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

    PubMed

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

    2011-04-15

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

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

    PubMed

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

    2011-04-15

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

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

    SciTech Connect

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

    1993-05-13

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

  3. 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.

  4. Response of 9L rat brain tumor multicellular spheroids to single and fractionated doses of 1,3-bis(2-chloroethyl)-1-nitrosourea.

    PubMed

    Sano, Y; Hoshino, T; Barker, M; Deen, D F

    1984-02-01

    This study was designed to examine the relative effect of each of four fractions of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) against 9L rat brain tumor multicellular spheroids and to compare the results of the cell survival and growth delay assays. Similar levels of cell kill resulted when BCNU was administered either as single fractions of 1.5, 3.0, 4.5, or 6.0 micrograms/ml for 1 hr or as one to four fractions of 1.5 micrograms/ml that were administered sequentially for 1 hr each. Survival was increased if the assay was delayed until 24 hr after drug treatment, which indicates that 9L cells in spheroids recover from BCNU-induced potentially lethal damage. When BCNU was administered in 1.5-micrograms/ml fractions, plating efficiencies depended markedly on the interval between the fractions. The 12-hr protocol produced an overall higher cell kill. Fractionation schedules of 24 and 36 hr produced less cell kill than did the other schedules. Survival plateaued for the last three treatments with BCNU in the 36-hr schedule. Cells in S phase at the time of administration of the initial 1.5-micrograms/ml fraction of BCNU moved into G1- and G2-M phases by 12 hr after treatment. For time periods longer than 12 hr, cells began to appear in the BCNU-resistant S phase. Thus, the movement of cells into the drug-sensitive and -resistant phases after the first fraction correlates well with the corresponding overall cytotoxic effect produced by treatment with the combined BCNU (1.5 micrograms/ml) fractions. For a higher concentration (3.0 micrograms/ml for 1 hr), maximum cell kill was reached within the 12- to 18-hr interval, after which cell kill plateaued. Cells were not found in the S-phase fraction 12 to 36 hr after the first treatment with 3.0 micrograms/ml; maximum cell kill for the fractionated protocols resulted at these times. Therefore, BCNU, which is classified as a cell cycle-nonspecific drug, can induce a partial synchrony in 9L spheroid cells, which determines

  5. Synthesis, SAR and biological evaluation of a novel series of 1-(2-chloroethyl)-1-nitroso-3-(2-(3-oxobenzoelenazol-2(3H)-yl)ethyl) urea: Organoselenium compounds for cancer therapy.

    PubMed

    Ye, S; Zheng, X; Hu, T; Zeng, H

    2016-06-30

    Thioredoxin reductase 1 (TrxR1) is an important potential anticancer drug target and closely related to both carcinogenesis and cancer progression. Ethaselen (BBSKE), a novel organoselenium compound inhibiting TrxR1 with selective antitumor effect, while its symmetrical structure results in poor solubility. Carmustine (BCNU), a DNA cross-link agent and also a deactivator of TrxR, is with high toxicity and low selectivity which limit its clinical application to some extents. Herein, a novel compound, 1-(2-chloroethyl)-1-nitroso-3-(2-(3-oxobenzoelenazol-2(3H)-yl)ethyl)urea(4a-1), which was designed through the combination of Ethaselen and Carmustine, showed good solubility, good tagetability, low toxicity and excellent antitumor activity by synergism. Using the structure of 4a-1 as a key active scaffold, a series of novel 1-(2-chloroethyl)-1-nitroso-3-(2-(3-oxobenzoelenazol-2(3H)-yl)ethyl)urea was designed, synthesized and evaluated to explore the structure-activity relationships (SARs) of these inhibitors and to improve their antitumor activities. Notably, 1-(2-chloroethyl)-3-(2-(6-fluoro-3-oxobenzoselenazol-2(3H)-yl)ethyl)-1-nitrosourea(4b-1) was found to exhibit more potent antitumor activities comparable to 4a-1 against all the four cancer cell lines, including Mia PaCa-2, PANC-1, RKO, LoVo. These results have highlighted compound 4b-1 as a new potential lead candidate for future development of novel potent broad-spectrum antitumor agents. In addition, a SAR model was established to conduct further structural modification.

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

    PubMed

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

    2015-01-01

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

  7. Adipose-derived stromal cells for the reconstruction of a human vesical equivalent.

    PubMed

    Rousseau, Alexandre; Fradette, Julie; Bernard, Geneviève; Gauvin, Robert; Laterreur, Véronique; Bolduc, Stéphane

    2015-11-01

    Despite a wide panel of tissue-engineering models available for vesical reconstruction, the lack of a differentiated urothelium remains their main common limitation. For the first time to our knowledge, an entirely human vesical equivalent, free of exogenous matrix, has been reconstructed using the self-assembly method. Moreover, we tested the contribution of adipose-derived stromal cells, an easily available source of mesenchymal cells featuring many potential advantages, by reconstructing three types of equivalent, named fibroblast vesical equivalent, adipose-derived stromal cell vesical equivalent and hybrid vesical equivalent--the latter containing both adipose-derived stromal cells and fibroblasts. The new substitutes have been compared and characterized for matrix composition and organization, functionality and mechanical behaviour. Although all three vesical equivalents displayed adequate collagen type I and III expression, only two of them, fibroblast vesical equivalent and hybrid vesical equivalent, sustained the development of a differentiated and functional urothelium. The presence of uroplakins Ib, II and III and the tight junction marker ZO-1 was detected and correlated with impermeability. The mechanical resistance of these tissues was sufficient for use by surgeons. We present here in vitro tissue-engineered vesical equivalents, built without the use of any exogenous matrix, able to sustain mechanical stress and to support the formation of a functional urothelium, i.e. able to display a barrier function similar to that of native tissue.

  8. A critical evaluation of the implications for risk based land management of the environmental chemistry of Sulphur Mustard.

    PubMed

    Ashmore, Matthew Howard; Nathanail, C Paul

    2008-11-01

    Sulphur Mustard, or "Mustard Gas" is in fact an oily liquid which was used as a chemical weapon primarily for its vesicant action which necessitates whole body protection. It is also now recognised as a carcinogenic agent upon chronic exposure. Soil contaminated with Sulphur Mustard continues to present both acute and chronic human health risks and risks to groundwater, surface water and the wider ecology at a number of sites globally and, in some cases, has done for many decades. This is at odds with the simple aqueous chemistry of the compound which would suggest that it should be short lived in the environment, especially in the presence of water. A number of studies have examined the possible factors for this longevity and, though the causes are generally assumed to be understood, the precise reasons have not yet been definitively determined and the evidence in support of the existing theories is at best circumstantial. At present, the prevailing view is that Sulphur Mustard is somehow protected by oligomeric or polymeric sulphonium species produced during incomplete hydrolysis reactions. The following review discusses the pertinent degradation mechanisms in the environment; hydrolysis and thermal degradation and the reasons put forward for the longevity of Sulphur Mustard in the literature. Other factors, such as the role of polymeric species in Sulphur Mustard droplets in modifying the mobility of the agent are also examined. Ultimately, without a thorough understanding of the abiotic fate of the Sulphur Mustard, uncertainties will remain in the application of risk assessment and remediation strategies to such sites, potentially compromising the validity or effectiveness of such actions.

  9. 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.

  10. 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.

  11. 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.

  12. Hyponatraemia and mental symptoms following vesical ultrasonic lithotripsy.

    PubMed

    Batra, Y K; Kapoor, R; Hemal, A K; Vaidyanathan, S

    1988-08-01

    A patient became confused and restless after vesical ultrasonic lithotripsy performed with distilled water as the irrigant. Serum sodium decreased to 120 mmol/litre from the pre-operative value of 138 mmol/litre. A cystogram revealed intraperitoneal extravasation of contrast. She recovered promptly after intravenous infusion of normal saline and emergency surgery for repair of the damaged bladder wall. This case illustrates that hyponatraemia and mental symptoms similar to those following transurethral resection syndrome also occur with ultrasonic lithotripsy when distilled water is used as the irrigant. PMID:3421461

  13. 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

  14. Influence of glutathione and glutathione S-transferases on DNA interstrand cross-link formation by 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine, the active anticancer moiety generated by laromustine.

    PubMed

    Penketh, Philip G; Patridge, Eric; Shyam, Krishnamurthy; Baumann, Raymond P; Zhu, Rui; Ishiguro, Kimiko; Sartorelli, Alan C

    2014-08-18

    Prodrugs of 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine (90CE) are promising anticancer agents. The 90CE moiety is a readily latentiated, short-lived (t1/2 ∼ 30 s) chloroethylating agent that can generate high yields of oxophilic electrophiles responsible for the chloroethylation of the O-6 position of guanine in DNA. These guanine O-6 alkylations are believed to be responsible for the therapeutic effects of 90CE and its prodrugs. Thus, 90CE demonstrates high selectivity toward tumors with diminished levels of O(6)-alkylguanine-DNA alkyltransferase (MGMT), the resistance protein responsible for O(6)-alkylguanine repair. The formation of O(6)-(2-chloroethyl)guanine lesions ultimately leads to the generation of highly cytotoxic 1-(N(3)-cytosinyl),-2-(N(1)-guaninyl)ethane DNA interstrand cross-links via N(1),O(6)-ethanoguanine intermediates. The anticancer activity arising from this sequence of reactions is thus identical to this component of the anticancer activity of the clinically used chloroethylnitrosoureas. Herein, we evaluate the ability of glutathione (GSH) and other low molecular weight thiols, as well as GSH coupled with various glutathione S-transferase enzymes (GSTs) to attenuate the final yields of cross-links generated by 90CE when added prior to or immediately following the initial chloroethylation step to determine the major point(s) of interaction. In contrast to studies utilizing BCNU as a chloroethylating agent by others, GSH (or GSH/GST) did not appreciably quench DNA interstrand cross-link precursors. While thiols alone offered little protection at either alkylation step, the GSH/GST couple was able to diminish the initial yields of cross-link precursors. 90CE exhibited a very different GST isoenzyme susceptibility to that reported for BCNU, this could have important implications in the relative resistance of tumor cells to these agents. The protection afforded by GSH/GST was compared to that produced by MGMT.

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

    PubMed

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

    2013-02-01

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

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

    PubMed

    Pohanka, Miroslav; Sobotka, Jakub; Stetina, Rudolf

    2011-03-01

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

  17. THE PENETRATION OF VESICANT VAPORS INTO HUMAN SKIN.

    PubMed

    Nagy, S M; Golumbic, C; Stein, W H; Fruton, J S; Bergmann, M

    1946-07-20

    Analytical methods which are accurate to about 1 per cent have been developed for the determination of small amounts (ca. 500 gamma) of bis(beta-chloroethyl)-sulfide (H), ethyl-bis(beta-chloroethyl)amine (EBA), tris(beta-chloroethyl)amine (TBA), beta-chloroethyl-benzylsulfide (benzyl-H), and beta-chloroethyl-ethylsulfide (ethyl-H). The determinations are made by micro titration of the HCl liberated upon complete hydrolysis of the vesicants. A description is given of an apparatus suitable for applying vapors of vesicants to unit areas of skin. A very precise and reproducible micropipetting technique is described for the introduction of the vesicants into the penetration apparatus. By means of this penetration apparatus studies have been made of several factors which may influence the rate at which vesicant vapors penetrate into skin. Model experiments have been performed in which H was allowed to vaporize and the vapor was absorbed on a surface such as that of diethylene glycol or vaseline. It has been found that if the surface of liquid H is increased by spreading the agent on filter paper, the rate of evaporation is markedly increased. Furthermore, if the vapor is agitated by means of a magnetically driven fan, the rate of absorption by diethylene glycol is greatly accelerated. With vaseline as the absorbing surface it has been found that the area of the absorbing surface has an effect on the rate of absorption of H vapor. More H is absorbed by vaseline spread on filter paper to give a rough surface than is absorbed by a smooth film of vaseline. Measurements of the rate of penetration into human skin of H, EBA, TBA, benzyl-H, and ethyl-H vapors have been performed at 21-23 degrees C. and 30-31 degrees C. by means of the penetration apparatus described in this paper. The measurements were carred out on human volunteers under conditions of controlled temperature and humidity. When human skin is exposed to air saturated with H vapor, the H penetrates the skin of the

  18. 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

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

    NASA Astrophysics Data System (ADS)

    Werrlein, Robert; Madren-Whalley, Janna S.

    2002-06-01

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

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

    SciTech Connect

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

    1993-05-13

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

  1. 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.

  2. Preclinical activity of 17 beta-[N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-L-alanyl]-5 alpha-dihydrotestosterone (E91) against tumour colony forming units and haematopoietic progenitor cells.

    PubMed

    Rank, P; Peter, R; Depenbrock, H; Eisenbrand, G; Schmid, P; Pitzl, H; Hanauske, A R

    1999-06-01

    E91 (17 beta-[N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-L-alanyl]-5 alpha-dihydrotestosterone) (CNC-ala-DHT) is a newly synthesised alkylating compound consisting of N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-L-alanine (CNC-ala) as the alkylating moiety and of 5 alpha-dihydrotestosterone (DHT) as a steroid carrier molecule. We studied the antitumour activity of E91 (final concentrations: 0.1, 1, 10 and 30 mumol/l) against freshly explanted human tumours, using an in vitro soft agar cloning system. A total of 54 tumour samples was evaluated using 1 h-exposure and 51 tumour specimens were studied using a continuous exposure for 21-28 days. In addition, the compound's activity was compared with other clinically used anticancer agents. After short-term exposure, 49 of 53 evaluable specimens (92%) had adequate colony formation, as compared with 49 of 50 (98%) after long-term exposure. After short-term exposure, E91 exhibited only marginal antitumour activity. However, in long-term exposure experiments, E91 had marked and concentration-dependent antitumour activity (P < 0.001). At concentrations of > 10 mumol/l, E91 was as active as the other clinically used antineoplastic agents and at 30 mumol/l, E91 was significantly more active than 5-fluorouracil (P = 0.041). E91 showed activity against a wide spectrum of tumour types. The highest activity was observed against colorectal carcinomas (3/4 tumour specimens inhibited at 30 mumol/l). Sensitivity was also high remarkable in breast cancer specimens with 3/6 specimens inhibited at 30 mumol/l. In vitro myelotoxicity was less than that of doxorubicin. At 30 mumol/l, E91 induced a reduction of colony forming units-granulocyte macrophage (CFU-GM) to only 53% of control and of CFU-GEMM to 20% of control. We conclude that because of broad activity and reduced myelotoxicity further clinical development of E91 appears warranted. PMID:10533486

  3. 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

  4. Bis(dialkyl)dithiocarbamato cobalt(III) complexes of bidentate nitrogen mustards: synthesis, reduction chemistry and biological evaluation as hypoxia-selective cytotoxins.

    PubMed

    Ware, D C; Palmer, H R; Pruijn, F B; Anderson, R F; Brothers, P J; Denny, W A; Wilson, W R

    1998-03-01

    Cobalt(III) complexes [Co(R2dtc)2(L)]+ containing two dithiocarbamate ligands (R = Me, Et, pyrrolidine) and a bidentate nitrogen mustard ligand (L) have been prepared as potential hypoxia-selective cytotoxins. The complexes were synthesized by treatment of the binuclear precursor [Co2(R2dtc)5]+ with the diamine mustards N,N'-bis(2-chloroethyl)ethylenediamine (BCE) and N,N-bis(2-chloroethyl)ethylenediamine (DCE), or their non-alkylating analogues [N,N-diethylethylenediamine (DEE) and N,N'-diethylethylenediamine (BEE)]. Cyclic voltammetry of the complexes in MeCN reveals quasi-reversible behaviour for the Co(III)/Co(II) couple, with E1/2 increasing in the order DCE < DEE approximately BCE < BEE. In MeCN/H2O electrochemical reduction is irreversible, indicating rapid substitution of H2O into the coordination sphere of the Co(II) intermediate. This fast ligand loss was confirmed by pulse radiolysis of [Co(Me2dtc)2(DEE)]+, while steady-state radiolysis showed that the initial intermediate disproportionates to [CoII(H2O)6]2+ + 2[CoII(Me2dtc)3]. The latter species reduces additional parent complex to give an overall stoichiometry of 3 mol parent complex/mol reductant. [Co(Me2dtc)2(DCE)]+ decays rapidly by an analogous mechanism in hypoxic culture medium. This reaction is not inhibited by O2, indicating that reoxidation of the Co(II) intermediate by O2 is not rapid enough to compete with ligand dissociation. The resulting free R2dtc-ligands, rather than the released mustards, are primarily responsible for growth inhibition by [Co(R2dtc)2(L)]+ complexes, although DCE release does contribute to clonogenic cell killing. Clonogenic cell killing is not appreciably enhanced under hypoxic conditions for any of the dithiocarbamato complexes. This finding, coupled with their instability in culture medium, suggests that [Co(R2dtc)2(L)]+ complexes are probably not suited for further development as bioreductive anticancer drugs.

  5. Bis(dialkyl)dithiocarbamato cobalt(III) complexes of bidentate nitrogen mustards: synthesis, reduction chemistry and biological evaluation as hypoxia-selective cytotoxins.

    PubMed

    Ware, D C; Palmer, H R; Pruijn, F B; Anderson, R F; Brothers, P J; Denny, W A; Wilson, W R

    1998-03-01

    Cobalt(III) complexes [Co(R2dtc)2(L)]+ containing two dithiocarbamate ligands (R = Me, Et, pyrrolidine) and a bidentate nitrogen mustard ligand (L) have been prepared as potential hypoxia-selective cytotoxins. The complexes were synthesized by treatment of the binuclear precursor [Co2(R2dtc)5]+ with the diamine mustards N,N'-bis(2-chloroethyl)ethylenediamine (BCE) and N,N-bis(2-chloroethyl)ethylenediamine (DCE), or their non-alkylating analogues [N,N-diethylethylenediamine (DEE) and N,N'-diethylethylenediamine (BEE)]. Cyclic voltammetry of the complexes in MeCN reveals quasi-reversible behaviour for the Co(III)/Co(II) couple, with E1/2 increasing in the order DCE < DEE approximately BCE < BEE. In MeCN/H2O electrochemical reduction is irreversible, indicating rapid substitution of H2O into the coordination sphere of the Co(II) intermediate. This fast ligand loss was confirmed by pulse radiolysis of [Co(Me2dtc)2(DEE)]+, while steady-state radiolysis showed that the initial intermediate disproportionates to [CoII(H2O)6]2+ + 2[CoII(Me2dtc)3]. The latter species reduces additional parent complex to give an overall stoichiometry of 3 mol parent complex/mol reductant. [Co(Me2dtc)2(DCE)]+ decays rapidly by an analogous mechanism in hypoxic culture medium. This reaction is not inhibited by O2, indicating that reoxidation of the Co(II) intermediate by O2 is not rapid enough to compete with ligand dissociation. The resulting free R2dtc-ligands, rather than the released mustards, are primarily responsible for growth inhibition by [Co(R2dtc)2(L)]+ complexes, although DCE release does contribute to clonogenic cell killing. Clonogenic cell killing is not appreciably enhanced under hypoxic conditions for any of the dithiocarbamato complexes. This finding, coupled with their instability in culture medium, suggests that [Co(R2dtc)2(L)]+ complexes are probably not suited for further development as bioreductive anticancer drugs. PMID:9524553

  6. 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.

  7. 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.

  8. 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.

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

    SciTech Connect

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

    1988-01-01

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

  10. 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.

  11. 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.

  12. Management of vesical calculi: comparison of lithotripsy devices.

    PubMed

    Razvi, H A; Song, T Y; Denstedt, J D

    1996-12-01

    Although endoscopic lithotripsy of bladder stones has been well described and is widely practiced, comparison of the main modalities of mechanical, electrohydraulic, and ultrasonic lithotripsy is lacking. The exact role of these and other modalities such as the Swiss Lithoclast and extracorporeal shockwave lithotripsy is not clearly defined. The safety and efficacy of the various lithotripsy modalities available to treat bladder calculi were reviewed retrospectively over an 18-year period. A total of 106 patients were treated with some form of intracorporeal lithotripsy. In general, all devices proved to be effective with a low rate of complications. The addition of transurethral resection of the prostate to bladder stone management under the same anesthetic was also found to be a safe procedure for moderate benign prostatic hyperplasia. In summary, transurethral endoscopic lithotripsy is a safe and effective method of bladder stone management both alone and in combination with transurethral prostatectomy. All modalities of intracorporeal lithotripsy are effective; however, devices such as ultrasound lithotripters or the Swiss Lithoclast that utilize larger, rigid probes may be more efficient for patients with large or particularly hard vesical calculi.

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

    PubMed

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

    2013-12-01

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

  14. Noninvasive methods for determining lesion depth from vesicant exposure.

    PubMed

    Braue, Ernest H; Graham, John S; Doxzon, Bryce F; Hanssen, Kelly A; Lumpkin, Horace L; Stevenson, Robert S; Deckert, Robin R; Dalal, Stephen J; Mitcheltree, Larry W

    2007-01-01

    Before sulfur mustard (HD) injuries can be effectively treated, assessment of lesion depth must occur. Accurate depth assessment is important because it dictates how aggressive treatment needs to be to minimize or prevent cosmetic and functional deficits. Depth of injury typically is assessed by physical examination. Diagnosing very superficial and very deep lesions is relatively easy for the experienced burn surgeon. Lesions of intermediate depth, however, are often problematic in determining the need for grafting. This study was a preliminary evaluation of two noninvasive bioengineering methodologies, laser Doppler perfusion imaging (LDPI) and indocyanine green fluorescence imaging (ICGFI), to determine their ability to accurately diagnose depth of sulfur mustard lesions in a weanling swine model. Histological evaluation was used to assess the accuracy of the imaging techniques in determining burn depth. Six female weanling swine (8-12 kg) were exposed to 400 microl of neat sulfur mustard on six ventral sites for 2, 8, 30, or 60 minutes. This exposure regimen produced lesions of varying depths from superficial to deep dermal. Evaluations of lesion depth using the bioengineering techniques were conducted at 24, 48, and 72 hours after exposure. After euthanasia at 72 hours after exposure, skin biopsies were taken from each site and processed for routine hematoxylin and eosin histological evaluation to determine the true depth of the lesion. Results demonstrated that LDPI and ICGFI were useful tools to characterize skin perfusion and provided a good estimate of HD lesion depth. Traditional LDPI and the novel prototype ICGFI instrumentation used in this study produced images of blood flow through skin lesions, which provided a useful assessment of burn depth. LDPI and ICGFI accurately predicted the need for aggressive treatment (30- and 60-minute HD lesions) and nonaggressive treatment (2- and 8-minute HD lesions) for the lesions generated in this study. Histological

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

    PubMed

    Graham, John S; Schoneboom, Bruce A

    2013-12-01

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

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

    PubMed

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

    2009-09-01

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

  18. 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.

  19. Inflammatory effects of inhaled sulfur mustard in rat lung

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-01-01

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

  1. Histiocytosis X: treatment with topical nitrogen mustard.

    PubMed

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

    1980-07-01

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

  2. NTP Toxicology and Carcinogenesis Studies of Tris(2-chloroethyl) Phosphate (CAS No. 115-96-8) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    PubMed

    1991-05-01

    Tris(2-chloroethyl) phosphate (TRCP), a flame-retardant plasticizer used in plastics, polymeric foams, and synthetic fibers, was studied as part of the National Toxicology Program's class study of trisalkyl phosphate flame retardants. Toxicology and carcinogenesis studies were conducted by administering TRCP (approximately 98% pure) in corn oil by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 16 days, 16 weeks, or 2 years. Genetic toxicology studies were performed in Salmonella typhimurium and Chinese hamster ovary (CHO) cells. 16-Day Studies: There were no chemical-related deaths, differences in final mean body weight, or histopathological lesions in rats receiving 22 to 350 mg/kg TRCP or in mice receiving 44 to 700 mg/kg TRCP for 12 doses over 16 days. Serum cholinesterase activity in female rats receiving 175 or 350 mg/kg TRCP was reduced slightly (80% of control levels), but enzyme activity in dosed male rats and in mice was similar to that in controls. 16-Week Studies: Rats received 22 to 350 mg/kg TRCP for 16 weeks (female) or 18 weeks (male). Several male and female rats in the 175 or 350 mg/kg dose groups died from chemical toxicity. Final mean body weights of female rats receiving 350 mg/kg were 20% greater than those of controls; final mean body weights of the remaining groups of dosed female rats and dosed male rats were similar. Chemical-related neuronal necrosis occurred in the hippocampus and thalamus of female rats and, to a lesser extent, of male rats. Serum cholinesterase activity was reduced in females receiving 175 or 350 mg/kg TRCP. There were no chemical-related deaths, differences in final mean body weight, or differences in cholinesterase activity in mice receiving 44 to 700 mg/kg TRCP for 16 weeks. Tubule epithelial cells with enlarged nuclei (cytomegaly and karyomegaly) were observed in the kidneys of high-dose (700 mg/kg) male and female mice. 2-Year Studies: The 2-year studies in rats were conducted by administering 0

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

    PubMed Central

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

    2015-01-01

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

  4. Disarming the mustard oil bomb.

    PubMed

    Ratzka, Andreas; Vogel, Heiko; Kliebenstein, Daniel J; Mitchell-Olds, Thomas; Kroymann, Juergen

    2002-08-20

    Plants are attacked by a broad array of herbivores and pathogens. In response, plants deploy an arsenal of defensive traits. In Brassicaceae, the glucosinolate-myrosinase complex is a sophisticated two-component system to ward off opponents. However, this so-called "mustard oil bomb" is disarmed by a glucosinolate sulfatase of a crucifer specialist insect, diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae). Sulfatase activity of this enzyme largely prevents the formation of toxic hydrolysis products arising from this plant defense system. Importantly, the enzyme acts on all major classes of glucosinolates, thus enabling diamondback moths to use a broad range of cruciferous host plants. PMID:12161563

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

    PubMed

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

    2013-12-01

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

  6. Natural occurrence of bisphenol F in mustard.

    PubMed

    Zoller, Otmar; Brüschweiler, Beat J; Magnin, Roxane; Reinhard, Hans; Rhyn, Peter; Rupp, Heinz; Zeltner, Silvia; Felleisen, Richard

    2016-01-01

    Bisphenol F (BPF) was found in mustard up to a concentration of around 8 mg kg(-1). Contamination of the raw products or caused by the packaging could be ruled out. Also, the fact that only the 4,4'-isomer of BPF was detected spoke against contamination from epoxy resin or other sources where technical BPF is used. Only mild mustard made of the seeds of Sinapis alba contained BPF. In all probability BPF is a reaction product from the breakdown of the glucosinolate glucosinalbin with 4-hydroxybenzyl alcohol as an important intermediate. Hot mustard made only from brown mustard seeds (Brassica juncea) or black mustard seeds (Brassica nigra) contained no BPF. BPF is structurally very similar to bisphenol A and has a similar weak estrogenic activity. The consumption of a portion of 20 g of mustard can lead to an intake of 100-200 µg of BPF. According to a preliminary risk assessment, the risk of BPF in mustard for the health of consumers is considered to be low, but available toxicological data are insufficient for a conclusive evaluation. It is a new and surprising finding that BPF is a natural food ingredient and that this is the main uptake route. This insight sheds new light on the risk linked to the family of bisphenols. PMID:26555822

  7. 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

  8. 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.

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

    SciTech Connect

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

    1993-05-13

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

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

    PubMed

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

    2010-12-01

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

  11. 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.

  12. Neutralization and biodegradation of sulfur mustard

    SciTech Connect

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

    1995-12-31

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

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

    PubMed

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

    2004-01-01

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

  14. 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. PMID:26451472

  15. 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.

  16. Skin decontamination of mustards and organophosphates: comparative efficiency of RSDL and Fuller's earth in domestic swine.

    PubMed

    Taysse, L; Daulon, S; Delamanche, S; Bellier, B; Breton, P

    2007-02-01

    Research in skin decontamination and therapy of chemical warfare agents has been a difficult problem due to the simultaneous requirement of rapid action and non-aggressive behaviour. The aim of this study was to compare the performance of two decontaminating systems: the Canadian Reactive Skin Decontaminant Lotion (RSDL) and the Fuller's Earth (FE). The experiment was conducted with domestic swine, as a good model for extrapolation to human skin. RSDL and FE were tested against sulphur mustard (SM), a powerful vesicant, and VX, a potent and persistent cholinesterase inhibitor. When used 5 min after contamination, the results clearly showed that both systems were active against SM (10.1 mg/cm(2)) and VX (0.06 mg/cm(2)). The potency of the RSDL/sponge was statistically better than FE against skin injury induced by SM, observed 3 days post-exposure. RSDL was rather more efficient than FE in reducing the formation of perinuclear vacuoles and inflammation processes in the epidermis and dermis. Against a severe inhibition (67%) of plasmatic cholinesterases induced by VX poisoning, the potencies of the RSDL/sponge and FE were similar. Both systems completely prevented cholinesterase inhibition, which indirectly indicates a prevention of toxic absorption through the skin. PMID:17370872

  17. Early indicators of survival following exposure to mustard gas: Protective role of 25(OH)D.

    PubMed

    Das, Lopa M; Binko, Amy M; Traylor, Zachary P; Duesler, Lori R; Dynda, Scott M; Debanne, Sara; Lu, Kurt Q

    2016-04-25

    The use of sulfur mustard (SM) as a chemical weapon for warfare has once again assumed center stage, endangering civilian and the military safety. SM causes rapid local skin vesication and late-onset systemic toxicity. Most studies on SM rely on obtaining tissue and blood for characterizing burn pathogenesis and assessment of systemic pathology, respectively. However the present study focuses on developing a non-invasive method to predict mortality from high dose skin SM exposure. We demonstrate that exposure to SM leads to a dose dependent increase in wound area size on the dorsal surface of mice that is accompanied by a progressive loss in body weight loss, blood cytopenia, bone marrow destruction, and death. Thus our model utilizes local skin destruction and systemic outcome measures as variables to predict mortality in a novel skin-based model of tissue injury. Based on our recent work using vitamin D (25(OH)D) as an intervention to treat toxicity from SM-related compounds, we explored the use of 25(OH)D in mitigating the toxic effects of SM. Here we show that 25(OH)D offers protection against SM and is the first known demonstration of an intervention that prevents SM-induced mortality. Furthermore, 25(OH)D represents a safe, novel, and readily translatable potential countermeasure following mass toxic exposure. PMID:26940683

  18. 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.

  19. 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.

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

    PubMed

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

    2014-03-01

    Sulfur mustard (SM) is a vesicant warfare agent which causes severe skin injuries. Currently, we lack effective antidotes against SM-induced skin injuries, in part due to lack of appropriate animal model(s) that can be used for efficacy studies in laboratory settings to identify effective therapies. Therefore, to develop a relevant mouse skin injury model, we examined the effects of nitrogen mustard (NM), a primary vesicant and a bifunctional alkylating agent that induces toxic effects comparable to SM. Specifically, we conducted histopathological and immunohistochemical evaluation of several applicable cutaneous pathological lesions following skin NM (3.2mg) exposure for 12-120h in SKH-1 and C57BL/6 mice. NM caused a significant increase in epidermal thickness, incidence of microvesication, cell proliferation, apoptotic cell death, inflammatory cells (neutrophils, macrophages and mast cells) and myleoperoxidase activity in the skin of both mouse strains. However, there was a more prominent NM-induced increase in epidermal thickness, and macrophages and mast cell infiltration, in SKH-1 mice relative to what was seen in C57BL/6 mice. NM also caused collagen degradation and edema at early time points (12-24h); however, at later time points (72 and 120h), dense collagen staining was observed, indicating either water loss or start of integument repair in both the mouse strains. This study provides quantitative measurement of NM-induced histopathological and immunohistochemical cutaneous lesions in both hairless and haired mouse strains that could serve as useful tools for screening and identification of effective therapies for treatment of skin injuries due to NM and SM. PMID:24373750

  1. Development of an enzyme-linked immunosorbent assay method to detect mustard protein in mustard seed oil.

    PubMed

    Koppelman, Stef J; Vlooswijk, Riek; Bottger, Gina; Van Duijn, Gert; Van der Schaft, Peter; Dekker, Jacco; Van Bergen, Hans

    2007-01-01

    An enzyme-linked immunosorbent assay for the detection of mustard protein was developed. The assay is based on a polyclonal antiserum directed against a mixture of mustard proteins raised in rabbits. The assay has a detection limit of 1.5 ppm (milligrams per kilogram) and is suitable for the detection of traces of mustard protein in mustard seed-derived flavoring ingredients. Limited cross-reactivity testing showed that no other plant proteins reacted significantly. From the animal proteins tested, only milk showed some cross-reactivity. With this sensitive assay, it was shown that refined mustard seed oil produced by steam distillation does not contain detectable amounts of mustard protein. Mustard seed oil is used as a flavoring in very low quantities, typically between 40 and 200 mg/kg. Thus, 100 g of a food product flavored with 200 mg of mustard seed oil per kg containing < 1.5 mg of protein per kg would represent an amount of mustard seed protein of <30 ng. Taking into account the published literature on allergic reactions to the unintended ingestion of mustard, this conservatively low calculated level indicates that it is unlikely that food products containing mustard seed oil as a flavoring ingredient will elicit an allergic reaction in mustard-allergic individuals. PMID:17265878

  2. Protective role of spleen-derived macrophages in lung inflammation, injury, and fibrosis induced by nitrogen mustard.

    PubMed

    Venosa, Alessandro; Malaviya, Rama; Gow, Andrew J; Hall, Leroy; Laskin, Jeffrey D; Laskin, Debra L

    2015-12-15

    Nitrogen mustard (NM) is a vesicant that causes lung injury and fibrosis, accompanied by a persistent macrophage inflammatory response. In these studies we analyzed the spleen as a source of these cells. Splenectomized (SPX) and sham control rats were treated intratracheally with NM (0.125 mg/kg) or PBS control. Macrophage responses were analyzed 1-7 days later. Splenectomy resulted in an increase in lung macrophages expressing CCR2, but a decrease in ATR-1α(+) cells, receptors important in bone marrow and spleen monocyte trafficking, respectively. Splenectomy was also associated with an increase in proinflammatory M1 (iNOS(+), CD11b(+)CD43(+)) macrophages in lungs of NM-treated rats, as well as greater upregulation of iNOS and COX-2 mRNA expression. Conversely, a decrease in CD11b(+)CD43(-) M2 macrophages was observed in SPX rats, with no changes in CD68(+), CD163(+), CD206(+), or YM-1(+) M2 macrophages, suggesting distinct origins of M2 subpopulations responding to NM. Macrophage expression of M2 genes including IL-10, ApoE, PTX-2, PTX-3, 5-HT2α, and 5-HT7 was also reduced in NM-treated SPX rats compared with shams, indicating impaired M2 activity. Changes in lung macrophages responding to NM as a consequence of splenectomy were correlated with exacerbated tissue injury and more rapid fibrogenesis. These data demonstrate that the spleen is a source of a subset of M2 macrophages with anti-inflammatory activity; moreover, in their absence, proinflammatory/cytotoxic M1 macrophages predominate in the lung, resulting in heightened pathology. Understanding the origin of macrophages and characterizing their phenotype after vesicant exposure may lead to more targeted therapeutics aimed at reducing toxicity and disease pathogenesis.

  3. MUSTARD GAS EXPOSURE AND CARCINOGENESIS OF LUNG

    PubMed Central

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

    2009-01-01

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

  4. Biodegradation of mustard. Final report, April-October 1993

    SciTech Connect

    Young, R.J.

    1994-07-01

    A literature search to identify microorganisms of potential value for the degradation of mustard was carried out. Selection of microorganisms was based on tolerance to low pH and chloride ions, conditions that retard mustard hydrolysis. Several bacteria able to degrade organic sulfides and/or sulfonium compounds under these conditions were identified. Fungi and yeasts are also of potential use, as are enzymes from halo- and thermophilic organisms. The major difficulty in the use of microorganisms and enzymes for mustard degradation is the low solubility of mustard in water. Fungi, Sulfide, Halophilic, Microorganism, Yeast, Mustard, Bacteria, Degradation, Sulfonium, Acidophilic.

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

    PubMed

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

    2001-10-01

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

  6. 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

  7. Synthesis, anti-proliferative and genotoxicity studies of 6-chloro-5-(2-substituted-ethyl)-1,3-dihydro-2H-indol-2-ones and 6-chloro-5-(2-chloroethyl)-3-(alkyl/ary-2-ylidene)indolin-2-ones.

    PubMed

    Meti, Gangadhar Y; Kamble, Atulkumar A; Kamble, Ravindra R; Somagond, Shilpa M; Devarajegowda, H C; Kumari, Sandhya; Kalthur, Guruprasad; Adiga, Satish K

    2016-10-01

    A series of 6-chloro-5-(2-substituted-ethyl)-1,3-dihydro-2H-indol-2-ones (3a-h) and 6-chloro-5-(2-chloroethyl)-3-(alkyl/aryl-2-ylidene)indolin-2-ones (5i-x) were synthesized. Compounds 3a-e, 5i-l and 5q-r were selected by NIH, USA for in vitro anti-proliferative screening. Based on the impressive growth inhibitory (GI %) effect by the compounds 3a-b and 3e which showed growth inhibition in the range 1.22-76.30%, 2.85-76.03% and 10.98-82.05% respectively at 10(-5) concentration, these compounds were further analyzed for anti-proliferative activity at 5 dose concentration and genotoxicity. PMID:27240276

  8. Mustard (Sinapis alba) Seed Meal Suppresses Weeds in Container Grown Ornamentals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mustard seed meal is a byproduct of mustard (Sinapis alba L.) grown and oil production. Developing new uses for mustard seed meal could increase the profitability of growing mustard. Seed meal of mustard, var. ‘IdaGold’ was applied to the soil surface to evaluate its effect on several common weeds...

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

    PubMed Central

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

    2008-01-01

    Background Sulphur mustard gas, 2, 2'-dichlorodiethyl sulphide (HD), is a chemical warfare agent. Both mustard gas and its monofunctional analogue, 2-chloroethyl ethyl sulphide (CEES), are alkylating agents that react with and diminish cellular thiols and are highly toxic. Previously, we reported that lipopolysaccharide (LPS) significantly enhances the cytotoxicity of CEES in murine RAW 264.7 macrophages and that CEES transiently inhibits nitric oxide (NO) production via suppression of inducible NO synthase (iNOS) protein expression. NO generation is an important factor in wound healing. In this paper, we explored the hypotheses that LPS increases CEES toxicity by increasing oxidative stress and that treatment with N-acetyl-L-cysteine (NAC) would block LPS induced oxidative stress and protect against loss of NO production. NAC stimulates glutathione (GSH) synthesis and also acts directly as a free radical scavenger. The potential therapeutic use of the antibiotic, polymyxin B, was also evaluated since it binds to LPS and could thereby block the enhancement of CEES toxicity by LPS and also inhibit the secondary infections characteristic of HD/CEES wounds. Results We found that 10 mM NAC, when administered simultaneously or prior to treatment with 500 μM CEES, increased the viability of LPS stimulated macrophages. Surprisingly, NAC failed to protect LPS stimulated macrophages from CEES induced loss of NO production. Macrophages treated with both LPS and CEES show increased oxidative stress parameters (cellular thiol depletion and increased protein carbonyl levels). NAC effectively protected RAW 264.7 cells simultaneously treated with CEES and LPS from GSH loss and oxidative stress. Polymyxin B was found to partially block nitric oxide production and diminish CEES toxicity in LPS-treated macrophages. Conclusion The present study shows that oxidative stress is an important mechanism contributing to CEES toxicity in LPS stimulated macrophages and supports the notion

  10. 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.

    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.

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

    PubMed

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

    2012-01-01

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

  12. Bladder erosion of tension-free vaginal tape presented as vesical stone; management and review of literature.

    PubMed

    Mustafa, Mahmoud; Wadie, Bassem S

    2007-01-01

    The vesical stone formation due to intravesical mesh erosion of tension-free vaginal tape (TVT) is rare. In this report, a case of 48-year-old patient who underwent (TVT) elsewhere is discussed. The patient was presented with vesical stone and persistent stress urinary incontinence. Intravesical stone was detected by non-contrast computed tomography and cystourethroscopy. Stone fragmentation was done by pneumatic lithotripsy and transurethral resection of the mesh was performed. The postoperative control cystoscopy demonstrated complete healing of bladder mucosa. PMID:17310310

  13. 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

  14. 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

  15. 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.

  16. Soil biotransformation of thiodiglycol, the hydrolysis product of mustard gas: understanding the factors governing remediation of mustard gas contaminated soil.

    PubMed

    Li, Hong; Muir, Robert; McFarlane, Neil R; Soilleux, Richard J; Yu, Xiaohong; Thompson, Ian P; Jackman, Simon A

    2013-02-01

    Thiodiglycol (TDG) is both the precursor for chemical synthesis of mustard gas and the product of mustard gas hydrolysis. TDG can also react with intermediates of mustard gas degradation to form more toxic and/or persistent aggregates, or reverse the pathway of mustard gas degradation. The persistence of TDG have been observed in soils and in the groundwater at sites contaminated by mustard gas 60 years ago. The biotransformation of TDG has been demonstrated in three soils not previously exposed to the chemical. TDG biotransformation occurred via the oxidative pathway with an optimum rate at pH 8.25. In contrast with bacteria isolated from historically contaminated soil, which could degrade TDG individually, a consortium of three bacterial strains isolated from the soil never contaminated by mustard gas was able to grow on TDG in minimal medium and in hydrolysate derived from an historical mustard gas bomb. Exposure to TDG had little impacts on the soil microbial physiology or on community structure. Therefore, the persistency of TDG in soils historically contaminated by mustard gas might be attributed to the toxicity of mustard gas to microorganisms and the impact to soil chemistry during the hydrolysis. TDG biodegradation may form part of a remediation strategy for mustard gas contaminated sites, and may be enhanced by pH adjustment and aeration. PMID:22752796

  17. 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.

  18. Effects of stimulation of vesical afferents on colonic motility in cats.

    PubMed

    Bouvier, M; Grimaud, J C; Abysique, A

    1990-05-01

    The effects of distension and isovolumetric contraction of urinary bladder on colonic motility were studied in anesthetized cats. Distension and contraction of the urinary bladder induced an inhibition of spontaneous colonic electromyographic activity and a decrease in the amplitudes of the excitatory junction potentials evoked in the colon by stimulation of the distal end of the parasympathetic nerve fibers. This inhibition was blocked by guanethidine and phentolamine. Reversely, vesical emptying resulted in an increase in colonic motility, abolished by atropine, and an increase in the amplitude of the excitatory junction potentials. Both excitatory and inhibitory reflexes disappeared after hexamethonium. The inhibitory effects of bladder distension were abolished by bilateral section of the lumbar ventral or dorsal spinal roots and after bilateral section of the lumbar colonic or hypogastric nerves. These results indicate (a) that the vesical afferents responsible for the inhibitory and excitatory reflexes run in the hypogastric and pelvic nerves respectively and (b) that the inhibitory and excitatory effects are caused by the activation of sympathetic and parasympathetic efferent nerve fibers, respectively. The supraspinal nervous structures were not implicated in these reflexes because they persisted in spinal cats.

  19. Modeling the spinal pudendo-vesical reflex for bladder control by pudendal afferent stimulation.

    PubMed

    McGee, Meredith J; Grill, Warren M

    2016-06-01

    Electrical stimulation of the pudendal nerve (PN) is a promising approach to restore continence and micturition following bladder dysfunction resulting from neurological disease or injury. Although the pudendo-vesical reflex and its physiological properties are well established, there is limited understanding of the specific neural mechanisms that mediate this reflex. We sought to develop a computational model of the spinal neural network that governs the reflex bladder response to PN stimulation. We implemented and validated a neural network architecture based on previous neuroanatomical and electrophysiological studies. Using synaptically-connected integrate and fire model neurons, we created a network model with realistic spiking behavior. The model produced expected sacral parasympathetic nucleus (SPN) neuron firing rates from prescribed neural inputs and predicted bladder activation and inhibition with different frequencies of pudendal afferent stimulation. In addition, the model matched experimental results from previous studies of temporal patterns of pudendal afferent stimulation and selective pharmacological blockade of inhibitory neurons. The frequency- and pattern-dependent effects of pudendal afferent stimulation were determined by changes in firing rate of spinal interneurons, suggesting that neural network interactions at the lumbosacral level can mediate the bladder response to different frequencies or temporal patterns of pudendal afferent stimulation. Further, the anatomical structure of excitatory and inhibitory interneurons in the network model was necessary and sufficient to reproduce the critical features of the pudendo-vesical reflex, and this model may prove useful to guide development of novel, more effective electrical stimulation techniques for bladder control. PMID:26968615

  20. 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....

  1. 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....

  2. 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....

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., Chinese cabbage, cauliflower, collards, garden cress, upland cress, water cress, kale, Chinese kale, Siberian kale, kohlrabi, mustard, pakchoi, radish, rape, rutabaga, and turnip. (a) General description....

  4. 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....

  5. Pentoxifylline Attenuates Nitrogen Mustard-induced Acute Lung Injury, Oxidative Stress and Inflammation

    PubMed Central

    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.

    2014-01-01

    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 (250 g; 8–10 weeks) to NM (0.125 mg/kg, i.t.) resulted in severe histolopathological changes in the lung within 3 d 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 3 d 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. PMID:24886962

  6. 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.

  7. 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

  8. 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.

  9. Mustard bran in lactating dairy cow diets.

    PubMed

    Maiga, H A; Bauer, M L; Dahlen, C R; Badaruddin, M; Scholljegerdes, E J

    2011-06-01

    Two trials using lactating Holstein cows were conducted to evaluate effects of a diet containing oriental mustard bran on dry matter intake (DMI), milk production, milk components, and organoleptic properties. In experiment 1, 34 lactating cows (24 multiparous and 10 primiparous; days in milk ≥ 50 d) were used in a switchback design to determine the lactational response and organoleptic quality of milk when the diet contained 8% oriental mustard bran (MB) versus a control diet (CON). Mustard bran replaced a portion of soybean meal and all the beet pulp in the CON diet. Milk yields were greater for cows fed the MB diet; however, no differences were found in DMI, 3.5% fat- (FCM) or solids-corrected milk. Milk components and components production were not affected by treatment. Milk organoleptic qualities were not affected by diet. In experiment 2, 22 lactating cows (16 multiparous and 6 primiparous; days in milk ≥ 21 d) were assigned randomly within parity to receive MB or CON from wk 4 to 19 postpartum in a randomized complete block design. Cows were fed CON wk 1 to 3 postpartum. The MB diet contained the same ingredients as the CON, except sunflower seed and a portion of soybean meal were replaced with mustard bran. Milk and components data were collected during wk 3 postpartum and used as covariates to adjust treatment means. Intake was greater for cows fed the MB diet; however, daily milk, 3.5% FCM, and solids-corrected milk yields were not different between diets. Milk components and component yields were not affected by treatment. Milk urea concentration was less for cows fed the MB diet. Although cows fed the MB diet had greater DMI, this was not translated into a higher milk 3.5% FCM/DMI production efficiency ratio. During experiment 2, many cows fed MB experienced minor to severe hemolysis with bloody urine. This hemolysis believed to be caused by the S-methyl-cysteine sulfoxide contained in mustard bran could have affected milk production efficiency

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

    PubMed Central

    2011-01-01

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

  11. 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

  12. 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

  13. Vesical clear cell adenocarcinoma arising from endometriosis: A mullerian tumor, indistinguishable from ovarian clear cell adenocarcinoma.

    PubMed

    Miller, Eirwen M; Sun, Ying; Richardson, Ingride; Frimer, Marina

    2016-11-01

    Endometriosis is associated with increased rates of ovarian, particularly clear cell, adenocarcinomas. Malignant transformation of ovarian endometriosis is most common but rare cases have been reported in the bladder, abdominal wall, diaphragm, and rectum. We present the case of a 44-year-old female with vesical clear cell adenocarcinoma arising in a background of endometriosis in the absence of other pelvic endometriosis. The malignancy was diagnosed on transurethral resection of bladder tumor and managed with radical surgery. Histology and immunohistochemical findings were consistent mullerian origin and indistinguishable from similar tumors arising in the female genital tract. Extrapolating from the gynecologic literature, the recommendation was made for adjuvant chemotherapy. Further studies are needed to clarify the optimal treatment paradigm for ovarian and bladder clear cell adenocarcinomas. PMID:27660815

  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. PMID:27413310

  15. Effects of Exposure to Sulfur Mustard on Speech Aerodynamics

    ERIC Educational Resources Information Center

    Heydari, Fatemeh; Ghanei, Mostafa

    2011-01-01

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

  16. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Mustard crop insurance provisions. 457.168 Section 457.168 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.168 Mustard crop...

  17. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Mustard crop insurance provisions. 457.168 Section 457.168 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.168 Mustard crop...

  18. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Mustard crop insurance provisions. 457.168 Section 457.168 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.168 Mustard crop...

  19. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Mustard crop insurance provisions. 457.168 Section 457.168 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.168 Mustard crop...

  20. Molecular orbital calculations on tumour-inhibitory aniline mustards: QSARs.

    PubMed

    Lewis, D F

    1989-02-01

    1. Molecular orbital calculations by the MINDO/3 method are reported for a series of 23 para-substituted aniline mustards. 2. Quantitative structure-activity relationships are presented which show that electronic structural parameters can be related to a number of features of aniline mustard reactivity.

  1. 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.

  2. Pityriasis rosea-like eruptions due to mustard oil application.

    PubMed

    Zawar, Vijay

    2005-01-01

    A young man employed in a construction company, presented with cutaneous lesions clinically simulating pityriasis rosea. Satisfactory and complete response to corticosteroids and antihistamines was followed by recurrence. Multiple recurrences within a short span of time arose a suspicion of alternative diagnosis. Site visit helped us to rule out occupational contact dermatitis. Further history taking revealed that he was recently using mustard oil for body massage. Subsequent patch testing confirmed contact hypersensitivity to mustard oil. Avoidance of the contact with mustard oil arrested appearance of further skin lesions. We stress the importance of taking a good history in clinical practice in disclosing a possible contactant. PMID:16394442

  3. Vesical calculi formation on the slit valves of a migrated distal end of ventriculoperitoneal shunt

    PubMed Central

    Gupta, Rahul; Dagla, Rajan; Agrawal, Lila Dhar; Sharma, Pramila

    2015-01-01

    Various complications of distal end of the ventriculoperitoneal (VP) shunt have been described in the literature. We present, here, an extremely rare and potentially severe complication of vesical calculi formation on the slit valves of distal end of VP shunt which erosively migrated into the urinary bladder. Suprapubic cystolithotomy performed, peritoneal end of the tube found to be eroding and entering into the bladder with two calculi firmly stuck to slit valves in the distal end of the tubing were removed. Shunt was functional, therefore, it was pulled out and repositioned on the superior aspect of the liver; the urinary bladder was repaired. Patient did well postoperatively. This complication was revealed 1.5 years after the shunt was implanted. Although there were symptoms of dysuria and dribbling of urine of short duration, the patient did not show obvious peritoneal signs; suggesting that, penetration of a VP shunt into the urinary bladder can remain asymptomatic for a long period of time, disclosed late and can lead to considerable morbidity. Careful follow-up is important and management should be individualized. PMID:26962346

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

    PubMed

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

    2002-07-01

    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.

  5. 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.

  6. A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration

    PubMed Central

    Winter, Benjamin J.; O'Connell, Helen E.; Bowden, Scott; Carey, Marcus; Eisen, Damon P.

    2015-01-01

    Objectives To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis. Subjects and Methods A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus) specific, real-time PCR. Results Case patients were reflective of interstitial cystitis epidemiology with age range from 26–88 years (median 58) and female predominance (41/50 F). There was a significant increase in the frequency of polyomavirus shedding between cases and controls (p<0.02). Polyomavirus shedding, in particular BK viruria, was associated with vesical ulceration, a marker of disease severity, among interstitial cystitis cases after adjustment for age and sex (OR 6.8, 95% CI 1.89–24.4). There was a significant association among cases between the presence of BK viruria and response to intravesical Clorpactin therapy (OR 4.50, 95% CI 1.17–17.4). Conclusion The presence of polyomaviruria was found to be associated with the ulcerative form of interstitial cystitis. Clorpactin, which has anti-DNA virus activity, was more likely to improve symptoms in the presence of BK viruria. These data from this pilot study suggest associations between polyomaviruria and interstitial cystitis warranting further investigation. PMID:26325074

  7. Pathways of the eye's response to topical nitrogen mustard.

    PubMed

    Jampol, L M; Axelrod, A; Tessler, H

    1976-06-01

    We studied the effect of prior corneal herpes simplex infection with its resultant corneal hypesthesia on the irritative response of the rabbit eye to topical nitrogen mustard. Both the miosis and the breakdown of the blood-aqueous barrier that follow the application of topical nitrogen mustard were diminished in eyes infected three weeks previously with herpes simplex virus. Nonspecific corneal scarring did not affect the response. This suggests again that an axon reflex requiring intact sensory innervation mediates the response to nitrogen mustard. Pretreatment of normal (noninfected) rabbits with systemic H1 and H2 antihistamines, topical scopolamine hydrobromide, or topical and systemic corticosteroids was ineffective in blocking the miosis or increased protein in the aqueous humor following topical nitrogen mustard. PMID:6401

  8. Development and validation of a real-time PCR method for the simultaneous detection of black mustard (Brassica nigra) and brown mustard (Brassica juncea) in food.

    PubMed

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

    2013-05-01

    The paper presents a real-time PCR method allowing the simultaneous detection of traces of black mustard (Brassica nigra) and brown mustard (Brassica juncea) in food. The primers and the probe target the B. nigra partial RT gene for reverse transcriptase from gypsy-like retroelement 13G42-26. The real-time PCR method does not show any cross-reactivity with other Brassicaceae species with the exception of white mustard. Low cross-reactivities with cinnamon, cumin, fenugreek, ginger, rye and turmeric can be ignored because in common mustard containing foodstuffs these biological species are present in very low amounts. By analysing serially diluted DNA extracts from black and brown mustard, the DNA of both mustard species could be detected down to 0.1 pg. With 10 ng DNA per PCR tube the real-time PCR method allows the detection of 5 ppm black and brown mustard in brewed sausages. PMID:23265498

  9. 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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  12. Laminin in the cutaneous basement membrane as a potential target in lewisite vesication.

    PubMed

    King, J R; Peters, B P; Monteiro-Riviere, N A

    1994-05-01

    The epidermal-dermal junction has a complex molecular architecture, with numerous components playing key roles in adhesion of the epidermis to the dermis. The purpose of this study was to examine structural components of the epidermal-dermal junction as potential targets for toxicity by lewisite (dichloro(2-chlorovinyl)arsine). This was accomplished by (1) immunocytochemical mapping of laminin, type IV collagen, and bullous pemphigoid antigen (BPA) in lewisite-treated isolated perfused porcine skin flaps (IPPSF), (2) evaluation of protease activity in IPPSF blister fluid against laminin substrate from murine EHS tumor and human keratinocytes, and (3) examination of human keratinocyte laminin for direct chemical modification by lewisite. Lewisite-induced epidermal-dermal separation was localized to the lamina lucida. Localization of the separation suggested that laminin, a cysteine-rich and highly protease-sensitive adhesive glycoprotein, is a potential target for lewisite action. It was hypothesized that chemical modification of laminin directly (via chemical alkylation of laminin thiols by the arsenical) or indirectly (due to lewisite-induced cytotoxic release of proteases) could result in blister formation. Employing sensitive methodology, no evidence of proteolytic activity against EHS tumor laminin or human keratinocyte laminin was identified in the blister fluid. In addition, no evidence for direct chemical modification of laminin by lewisite was demonstrated. However, up to 36% of the thiol groups in human keratinocyte laminin immunoprecipitates was potentially available for reaction with alkylating agents. While these studies did not demonstrate a lewisite-induced chemical modification of laminin, they do not rule out the possibility that other adhesive molecules of the basement membrane are targets for lewisite action. Further evaluation of the molecular role that these binding modalities play in vesicant-induced separation may provide new insights into

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

    PubMed

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

    2009-09-01

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

  14. [Mustard gas bombs found astray in the Faxaflói bay. Mustard gas: usage and poisonings].

    PubMed

    Kristinsson, Jakop; Jóhannesson, Thorkell

    2009-05-01

    The finding in 1972 of two World War II mustard gas artillery shells in crushed shell sediment dredged in the Faxaflói Bay and transported as raw material for cement production at Akranes (Western Iceland) is reported. One of the shells was wedged in a stone crusher in the raw material processing line and was ruptured. As a result dark fluid with a garlic like smell seeped out from the metal canister. The attending employees believed the metal object to be inert and tried to cut it out with a blow torch. This resulted in the explosion of the shell charge and in the exposure of four employees to mustard gas. All suffered burns on their hands and two of them in the eyes also. The second shell was detonated in the open at a distance from the factory. Emphasis is given to the fact that instant, or at least as soon as possible, cleansing and washing is the most efficient measure to be taken against the debilitating effects of mustard gas. It is also pointed out that the active principle in mustard gas (dichlorodiethyl sulphide) can easily be synthesized and none of the precursor substances are subjected to any restrictions of use. The authors conclude that mustard gas bombs may still be found in the arsenals of some military powers in spite of an international convention that prohibits the production, stockpiling and the use of chemical weapons. Terrorist groups have also seemingly tried to aquire mustard gas bombs and other chemical weapons. Therefore cases of mustard gas poisoning might still occur. PMID:19430031

  15. 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...

  16. 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.

  17. 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.

  18. 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

  19. Novel liquid chromatography-mass spectrometry method for sensitive determination of the mustard allergen Sin a 1 in food.

    PubMed

    Posada-Ayala, Maria; Alvarez-Llamas, Gloria; Maroto, Aroa S; Maes, Xavier; Muñoz-Garcia, Esther; Villalba, Mayte; Rodríguez, Rosalía; Perez-Gordo, Marina; Vivanco, Fernando; Pastor-Vargas, Carlos; Cuesta-Herranz, Javier

    2015-09-15

    Mustard is a condiment added to a variety of foodstuffs and a frequent cause of food allergy. A new strategy for the detection of mustard allergen in food products is presented. The methodology is based on liquid chromatography analysis coupled to mass spectrometry. Mustard allergen Sin a 1 was purified from yellow mustard seeds. Sin a 1 was detected with a total of five peptides showing a linear response (lowest LOD was 5ng). Sin a 1 was detected in mustard sauces and salty biscuit (19±3mg/kg) where mustard content is not specified. Sin a 1, used as an internal standard, allowed quantification of this mustard allergen in foods. A novel LC/MS/MS SRM-based method has been developed to detect and quantify the presence of mustard. This method could help to detect mustard allergen Sin a 1 in processed foods and protect mustard-allergic consumers. PMID:25863610

  20. Novel liquid chromatography-mass spectrometry method for sensitive determination of the mustard allergen Sin a 1 in food.

    PubMed

    Posada-Ayala, Maria; Alvarez-Llamas, Gloria; Maroto, Aroa S; Maes, Xavier; Muñoz-Garcia, Esther; Villalba, Mayte; Rodríguez, Rosalía; Perez-Gordo, Marina; Vivanco, Fernando; Pastor-Vargas, Carlos; Cuesta-Herranz, Javier

    2015-09-15

    Mustard is a condiment added to a variety of foodstuffs and a frequent cause of food allergy. A new strategy for the detection of mustard allergen in food products is presented. The methodology is based on liquid chromatography analysis coupled to mass spectrometry. Mustard allergen Sin a 1 was purified from yellow mustard seeds. Sin a 1 was detected with a total of five peptides showing a linear response (lowest LOD was 5ng). Sin a 1 was detected in mustard sauces and salty biscuit (19±3mg/kg) where mustard content is not specified. Sin a 1, used as an internal standard, allowed quantification of this mustard allergen in foods. A novel LC/MS/MS SRM-based method has been developed to detect and quantify the presence of mustard. This method could help to detect mustard allergen Sin a 1 in processed foods and protect mustard-allergic consumers.

  1. 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).

  2. Anticancer activity of a cis-dichloridoplatinum(ii) complex of a chelating nitrogen mustard: insight into unusual guanine binding mode and low deactivation by glutathione.

    PubMed

    Karmakar, Subhendu; Purkait, Kallol; Chatterjee, Saptarshi; Mukherjee, Arindam

    2016-02-28

    A pyridine ring containing a chelating nitrogen mustard ligand bis(2-chloroethyl)pyridylmethylamine hydrochloride (L2·HCl) was synthesized from bis(2-hydroxyethyl)pyridylmethylamine (L1) on reaction with thionyl chloride. Both the ligands upon reaction with cis-[PtCl2(DMSO)2] afforded square planar complexes cis-[PtCl2(L1)] (1) and cis-[PtCl2(L2)] (2) respectively. Both the complexes were characterized by NMR, IR, UV and elemental analysis. 2 crystallized in the P21/c space group. 2 shows greater solution stability than 1 in kinetic studies by 1H NMR. Both 1 and 2 bind the model nucleobase 9-ethylguanine (9-EtG) and form multiple mono-adducts. Existence of unusual N7,O6 chelated guanine bound 2 (2e) was traced. Binding studies of 2 with glutathione (GSH) show formation of a mono-adduct cis-[PtCl(L2)SG] (2c), which transformed within a day to give an aziridinium ion of L2 (2b) after loss of L2. In vitro cytotoxicity of ligands, complexes and the clinical anticancer drug cisplatin show that 2 is the most potent against MCF-7, A549 and MIA PaCa2 exhibiting IC50 values of 12.6 ± 0.8, 18.2 ± 1.8 and 4.2 ± 1.0 μM respectively. The in vitro cytotoxicity of 2 against MCF-7, A549 and MIA PaCa2 was also probed in hypoxia and in the presence and absence of added GSH. Even in the presence of excess GSH in hypoxia, 2 exhibits significant cytotoxicity against MIA PaCa2 and MCF-7 with IC50 of 4.4 ± 0.8 and 12.5 ± 1.1 μM respectively. Metal accumulation studies by ICP-MS display greater cellular internalization of 2, than 1 and cisplatin in MCF-7 cells. 2 arrests the cell cycle at sub G1 and G2/M phases in MCF-7 whereas cisplatin exhibits S phase arrest to be dominant with increase in concentration. Complex 2 exhibits a change in mitochondrial membrane potential, caspase activity and suggests apoptotic cell death through the intrinsic pathway. Moreover it is encouraging to find that 2 also restricts angiogenesis in chick embryo.

  3. Mugwort-Mustard Allergy Syndrome due to Broccoli Consumption.

    PubMed

    Sugita, Yuri; Makino, Teruhiko; Mizawa, Megumi; Shimizu, Tadamichi

    2016-01-01

    Pollen-food allergy syndrome (PFAS) is a relatively rare form of food allergy which develops in individuals who are sensitized to pollen. Tree pollens, especially birch pollen, frequently induce PFAS; however, the incidence of PFAS due to grass or weed pollens such as ragweed or mugwort is relatively rare. Mugwort-mustard allergy syndrome (MMAS) is an example of a PFAS in which individuals sensitized to mugwort may develop an allergy to mustard and experience severe reactions. We herein describe a case of MMAS due to broccoli consumption. PMID:27478657

  4. Ion chromatographic determination of chloride in mustard sauces.

    PubMed

    López Agüero, E; Bosch Bosch, N; Barrera Vázquez, C; López Ruiz, B

    1999-11-01

    A new, simple, precise, and rapid ion chromatography (IC) method has been developed to determine chloride in mustard sauces using a mixture of phthalic acid, acetone, and water adjusted to pH 5.0 as eluent. Conductometric detection was carried out. The retention time for chloride was 1.5 min. Linearity was obtained up to a concentration level of 100 mg/L NaCl. The method was statistically evaluated for accuracy and precision after being used to assay the chloride from mustard sauces. Within the same samples, the chloride levels obtained by IC were compared with the sodium concentrations quantified by atomic absorption spectrophotometry.

  5. Mugwort-Mustard Allergy Syndrome due to Broccoli Consumption

    PubMed Central

    2016-01-01

    Pollen-food allergy syndrome (PFAS) is a relatively rare form of food allergy which develops in individuals who are sensitized to pollen. Tree pollens, especially birch pollen, frequently induce PFAS; however, the incidence of PFAS due to grass or weed pollens such as ragweed or mugwort is relatively rare. Mugwort-mustard allergy syndrome (MMAS) is an example of a PFAS in which individuals sensitized to mugwort may develop an allergy to mustard and experience severe reactions. We herein describe a case of MMAS due to broccoli consumption. PMID:27478657

  6. Characterization of mustard seeds and paste by DART ionization with time-of-flight mass spectrometry.

    PubMed

    Prchalová, Jana; Kovařík, František; Ševčík, Rudolf; Čížková, Helena; Rajchl, Aleš

    2014-09-01

    Direct analysis in real time (DART) is a novel technique with great potential for rapid screening analysis. The DART ionization method coupled with high-resolution time-of-flight mass spectrometry (TOF-MS) has been used for characterization of mustard seeds and table mustard. The possibility to use DART to analyse glucosinolates was confirmed on determination of sinalbin (4-hydroxybenzyl glucosinolate). The DART-TOF-MS method was optimized and validated. A set of samples of mustard seeds and mustard products was analyzed. High-performance liquid chromatography and DART-TOF-MS were used to determine glucosinolates in mustard seeds and compared. The correlation equation between these methods was DART = 0.797*HPLC + 6.987, R(2)  = 0.972. The DART technique seems to be a suitable method for evaluation of the quality of mustard seeds and mustard products. PMID:25230177

  7. Phytotoxicity of mustard seed meals alone and in combinations

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. 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...

  9. Onion and weed response to mustard (Sinapis alba) seed meal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Onion and weed response to mustard seed meal (MSM) were tested in greenhouse and field trials in 2007-2009. MSM was applied to the soil surface at rates of 1.1, 2.2, and 4.4 MT/ha. In greenhouse trials, onions were severely injured and stands reduced with all rates of MSM applied prior to onion emer...

  10. Mustard Seed Meal suppresses Weeds in Potato and Peppermint

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seed meal is a co-product remaining after pressing mustard seed to remove the oil. Seed meals containing high glucosinolates have been reported to have herbicidal activity. Weed suppression with seed meal of Sinapis alba, variety Ida Gold was evaluated in field trials on potatoes and peppermint in ...

  11. Nucleophilic substitution by grignard reagents on sulfur mustards.

    PubMed

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

    2004-10-15

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

  12. β-Amylase from Mustard (Sinapis alba L.) Cotyledons 1

    PubMed Central

    Subbaramaiah, Kotha; Sharma, Rameshwar

    1989-01-01

    A polyclonal antiserum against mustard (Sinapis alba L.) β-amylase was obtained by injecting a homogeneously purified enzyme preparation in rabbits. The formation of β-amylase specific antibodies was confirmed by staining the precipitin line in double diffusion gel for β-amylase activity. The monospecificity of antiserum against mustard β-amylase was also ascertained by Western blotting. The antiserum efficiently recognised both the denatured and the native form of β-amylase, but it did not cross-react with other higher plant β-amylase. The mode of photoregulation of β-amylase activity in mustard cotyledons was investigated by a variety of immunochemical techniques. Immunotitration experiments ruled out the possible contribution of enzyme activation/inactivation in photoregulation of β-amylase activity. The use of single radial immunodiffusion, rocket immunoelectrophoresis, and immunotitration confirmed that the light mediated increase in β-amylase activity quantitatively corresponds with the increase in β-amylase protein level. The in vivo labeling with l-[35S] methionine and pulse chase studies of in vivo labeled β-amylase protein revealed that the photoregulated increase in β-amylase activity in mustard cotyledon exclusively results from an increase in the rate of de novo synthesis of β-amylase protein against a very low background rate of enzyme degradation. Images Figure 1 Figure 2 PMID:16666633

  13. 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

  14. 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

  15. 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.

  16. 23. SOUTH PLANT MUSTARD FILLING BUILDING (BUILDING 728) AND WAREHOUSE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    23. SOUTH PLANT MUSTARD FILLING BUILDING (BUILDING 728) AND WAREHOUSE (BUILDING 729) FROM ROOF OF TON CONTAINER RECONDITIONING BUILDING, SHOWING FACILITIES MAINTENANCE BUILDING AT FOREGROUND AND BUILDING 741, 742 AND 743 AT CENTER BACKGROUND. VIEW TO SOUTHEAST. - Rocky Mountain Arsenal, Bounded by Ninety-sixth Avenue & Fifty-sixth Avenue, Buckley Road, Quebec Street & Colorado Highway 2, Commerce City, Adams County, CO

  17. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., and marketing of the mustard; except, if the salvage price can be increased by conditioning, we may..., each will be considered a separate price election that will be multiplied by the number of insurable... production based processor contracts which specify a maximum number of acres, the lesser of: (i)......

  18. 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

  19. 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

  20. 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.

  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. Possible long-term health effects of short-term exposure to chemical agents. Volume 2. Cholinesterase reactivators, psychochemicals, and irritants and vesicants. Final report

    SciTech Connect

    Not Available

    1984-01-01

    The present report evaluates toxicologic and epidemiologic data relevant to the testing of approximately 750 subjects exposed to cholinesterase reactivators, about 260 exposed to psychochemicals, and 1,500 exposed to irritants or vesicants. A remaining group of subjects used largely in tests involving placebo or innocuous chemicals or conditions is available for comparison and will be discussed later. The report is the work of three panels of scientists--the Panel on Cholinesterase Reactivator Chemicals, the Panel on Psychochemicals, and the Panel on Irritants and Vesicants. The chairman of each panel was selected from the Committee on Toxicology, and the members were selected on the basis of their knowledge of the compounds in question or because they represented required disciplines.

  3. 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.

  4. Sulfur mustard medical countermeasures in a nuclear environment.

    PubMed

    Smith, William J; Gross, Clark L

    2002-02-01

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

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

    PubMed

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

    2011-05-01

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

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

    PubMed

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

    2016-02-26

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

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

    PubMed

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

    2016-02-26

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

  8. Cyanide in the chemical arsenal of garlic mustard, Alliaria petiolata.

    PubMed

    Cipollini, Don; Gruner, Bill

    2007-01-01

    Cyanide production has been reported from over 2500 plant species, including some members of the Brassicaceae. We report that the important invasive plant, Alliaria petiolata, produces levels of cyanide in its tissues that can reach 100 ppm fresh weight (FW), a level considered toxic to many vertebrates. In a comparative study, levels of cyanide in leaves of young first-year plants were 25 times higher than in leaves of young Arabidopsis thaliana plants and over 150 times higher than in leaves of young Brassica kaber, B. rapa, and B. napus. In first-year plants, cyanide levels were highest in young leaves of seedlings and declined with leaf age on individual plants. Leaves of young plants infested with green peach aphids (Myzus persicae) produced just over half as much cyanide as leaves of healthy plants, suggesting that aphid feeding led to loss of cyanide from intact tissues before analysis, or that aphid feeding inhibited cyanide precursor production. In a developmental study, levels of cyanide in the youngest and oldest leaf of young garlic mustard plants were four times lower than in the youngest and oldest leaf of young Sorghum sudanense (cv. Cadan 97) plants, but cyanide levels did not decline in these leaves with plant age as in S. sudanense. Different populations of garlic mustard varied moderately in the constitutive and inducible expression of cyanide in leaves, but no populations studied were acyanogenic. Although cyanide production could result from breakdown products of glucosinolates, no cyanide was detected in vitro from decomposition of sinigrin, the major glucosinolate of garlic mustard. These studies indicate that cyanide produced from an as yet unidentified cyanogenic compound is a part of the battery of chemical defenses expressed by garlic mustard.

  9. Effect of mustard seed meal on early weed emergence in peppermint and potato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seed meal is the by-product remaining after pressing/crushing mustard seed to remove the majority of the oil. Trials to evaluate weed suppression were conducted at several locations on peppermint and potatoes using seed meal obtained from Sinapis alba, variety Ida Gold. White mustard seed meal appl...

  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. 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.

  12. 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.

  13. Consumer acceptability and sensory profile of cooked broccoli with mustard seeds added to improve chemoprotective properties.

    PubMed

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

    2014-09-01

    Broccoli, a rich source of glucosinolates, is a commonly consumed vegetable of the Brassica family. Hydrolysis products of glucosinolates, isothiocyanates, have been associated with health benefits and contribute to the flavor of Brassica. However, boiling broccoli causes the myrosinase enzyme needed for hydrolysis to denature. In order to ensure hydrolysis, broccoli must either be mildly cooked or active sources of myrosinase, such as mustard seed powder, can be added postcooking. In this study, samples of broccoli were prepared in 6 different ways; standard boiling, standard boiling followed by the addition of mustard seeds, sous vide cooking at low temperature (70 °C) and sous vide cooking at higher temperature (100 °C) and sous vide cooking at higher temperature followed by the addition of mustard seeds at 2 different concentrations. The majority of consumers disliked the mildly cooked broccoli samples (70 °C, 12 min, sous vide) which had a hard and stringy texture. The highest mean consumer liking was for standard boiled samples (100 °C, 7 min). Addition of 1% mustard seed powder developed sensory attributes, such as pungency, burning sensation, mustard odor, and flavor. One cluster of consumers (32%) found mustard seeds to be a good complement to cooked broccoli; however, the majority disliked the mustard-derived sensory attributes. Where the mustard seeds were partially processed, doubling the addition to 2% led to only the same level of mustard and pungent flavors as 1% unprocessed seeds, and mean consumer liking remained unaltered. This suggests that optimization of the addition level of partially processed mustard seeds may be a route to enhance bioactivity of cooked broccoli without compromising consumer acceptability. PMID:25156799

  14. 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.

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

    PubMed

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

    2010-01-01

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

  16. 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

  17. Evaluation of cranial capacity by mustard seed technique.

    PubMed

    Howale, D S; Shah, J V; Iyer, K; Patel, V H; Patel, D C

    2011-12-01

    The volume of the cranium is used as a rough indicator of the size of the brain. In the present study Breitinger's mustard seeds technique was applied for the measurement of cranial capacity. Grossly normal 75 male skulls of Gujarat population were studied at Kesar SAL Medical College, Ahmedabad (Gujarat) in the year 2010. The mean cranial capacity among the study group was recorded to be 1256 cc with a minimum of 1110 cc and maximum of 1430 cc. The results were compared with the similar studies by different authors from different geographical areas. PMID:23469572

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

    PubMed

    Jafari, Mahvash; Nateghi, M; Rabbani, A

    2010-01-01

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

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

    PubMed

    Ahmad, Shama; Ahmad, Aftab

    2016-06-01

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

  20. Thermal and pressure stability of myrosinase enzymes from black mustard (Brassica nigra L. W.D.J. Koch. var. nigra), brown mustard (Brassica juncea L. Czern. var. juncea) and yellow mustard (Sinapsis alba L. subsp. maire) seeds.

    PubMed

    Okunade, Olukayode Adediran; Ghawi, Sameer Khalil; Methven, Lisa; Niranjan, Keshavan

    2015-11-15

    This study investigates the effects of temperature and pressure on inactivation of myrosinase extracted from black, brown and yellow mustard seeds. Brown mustard had higher myrosinase activity (2.75 un/mL) than black (1.50 un/mL) and yellow mustard (0.63 un/mL). The extent of enzyme inactivation increased with pressure (600-800 MPa) and temperature (30-70° C) for all the mustard seeds. However, at combinations of lower pressures (200-400 MPa) and high temperatures (60-80 °C), there was less inactivation. For example, application of 300 MPa and 70 °C for 10 min retained 20%, 80% and 65% activity in yellow, black and brown mustard, respectively, whereas the corresponding activity retentions when applying only heat (70° C, 10 min) were 0%, 59% and 35%. Thus, application of moderate pressures (200-400 MPa) can potentially be used to retain myrosinase activity needed for subsequent glucosinolate hydrolysis. PMID:25977054

  1. Suppression of Hyperactive Immune Responses Protects against Nitrogen Mustard Injury

    PubMed Central

    Au, Liemin; Meisch, Jeffrey P; Das, Lopa M; Binko, Amy M; Boxer, Rebecca S; Wen, Amy M; Steinmetz, Nicole F; Lu, Kurt Q

    2015-01-01

    DNA alkylating agents like nitrogen mustard (NM) are easily absorbed through the skin and exposure to such agents manifest not only in direct cellular death but also in triggering inflammation. We show that toxicity resulting from topical mustard exposure is mediated in part by initiating exaggerated host innate immune responses. Using an experimental model of skin exposure to NM we observe activation of inflammatory dermal macrophages that exacerbate local tissue damage in an inducible nitric oxide synthase (iNOS)-dependent manner. Subsequently these activated dermal macrophages reappear in the bone marrow to aid in disruption of hematopoiesis and contribute ultimately to mortality in an experimental mouse model of topical NM exposure. Intervention with a single dose of 25-hydroxyvitamin D3 (25(OH)D) is capable of suppressing macrophage-mediated iNOS production resulting in mitigation of local skin destruction, enhanced tissue repair, protection from marrow depletion, and rescue from severe precipitous wasting. These protective effects are recapitulated experimentally using pharmacological inhibitors of iNOS or by compounds that locally deplete skin macrophages. Taken together, these data highlight a critical unappreciated role of the host innate immune system in exacerbating injury following exposure to NM and support the translation of 25(OH)D in the therapeutic use against these chemical agents. PMID:26288355

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

    PubMed

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

    2010-10-01

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

  3. 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.

  4. Selenium Assimilation and Volatilization from Selenocyanate-Treated Indian Mustard and Muskgrass1

    PubMed Central

    de Souza, Mark P.; Pickering, Ingrid J.; Walla, Michael; Terry, Norman

    2002-01-01

    Selenocyanate (SeCN−) is a major contaminant in the effluents from some oil refineries, power plants, and in mine drainage water. In this study, we determined the potential of Indian mustard (Brassica juncea) and muskgrass (a macroalga, Chara canescens) for SeCN− phytoremediation in upland and wetland situations, respectively. The tolerance of Indian mustard to toxic levels of SeCN− was similar to or higher than other toxic forms of Se. Indian mustard treated with 20 μm SeCN− removed 30% (w/v) of the Se supplied in 5 d, accumulating 554 and 86 μg of Se g−1 dry weight in roots and shoots, respectively. Under similar conditions, muskgrass removed approximately 9% (w/v) of the Se supplied as SeCN− and accumulated 27 μg of Se g−1 dry weight. A biochemical pathway for SeCN− degradation was proposed for Indian mustard. Indian mustard and muskgrass efficiently degraded SeCN− as none of the Se accumulated by either organism remained in this form. Indian mustard accumulated predominantly organic Se, whereas muskgrass contained Se mainly as selenite and organic Se forms. Indian mustard produced volatile Se from SeCN− in the form of less toxic dimethylselenide. Se volatilization by Indian mustard accounted for only 0.7% (w/v) of the SeCN− removed, likely because the biochemical steps in the production of dimethylselenide from organic Se were rate limiting. Indian mustard is promising for the phytoremediation of SeCN−-contaminated soil and water because of its remarkable abilities to phytoextract SeCN− and degrade all the accumulated SeCN− to other Se forms. PMID:11842165

  5. 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.

  6. 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.

  7. The presence of Bt-transgenic oilseed rape in wild mustard populations affects plant growth.

    PubMed

    Liu, Yongbo; Stewart, C Neal; Li, Junsheng; Huang, Hai; Zhang, Xitao

    2015-12-01

    The adventitious presence of transgenic plants in wild plant populations is of ecological and regulatory concern, but the consequences of adventitious presence are not well understood. Here, we introduced Bacillus thuringiensis Cry1Ac (Bt)-transgenic oilseed rape (Bt OSR, Brassica napus) with various frequencies into wild mustard (Brassica juncea) populations. We sought to better understand the adventitious presence of this transgenic insecticidal crop in a wild-relative plant population. We assessed the factors of competition, resource availability and diamondback moth (Plutella xylostella) infestation on plant population dynamics. As expected, Bt OSR performed better than wild mustard in mixed populations under herbivore attack in habitats with enough resources, whereas wild mustard had higher fitness when Bt OSR was rarer in habitats with limited resources. Results suggest that the presence of insect-resistant transgenic plants could decrease the growth of wild mustard and Bt OSR plants and their populations, especially under high herbivore pressure.

  8. The presence of Bt-transgenic oilseed rape in wild mustard populations affects plant growth.

    PubMed

    Liu, Yongbo; Stewart, C Neal; Li, Junsheng; Huang, Hai; Zhang, Xitao

    2015-12-01

    The adventitious presence of transgenic plants in wild plant populations is of ecological and regulatory concern, but the consequences of adventitious presence are not well understood. Here, we introduced Bacillus thuringiensis Cry1Ac (Bt)-transgenic oilseed rape (Bt OSR, Brassica napus) with various frequencies into wild mustard (Brassica juncea) populations. We sought to better understand the adventitious presence of this transgenic insecticidal crop in a wild-relative plant population. We assessed the factors of competition, resource availability and diamondback moth (Plutella xylostella) infestation on plant population dynamics. As expected, Bt OSR performed better than wild mustard in mixed populations under herbivore attack in habitats with enough resources, whereas wild mustard had higher fitness when Bt OSR was rarer in habitats with limited resources. Results suggest that the presence of insect-resistant transgenic plants could decrease the growth of wild mustard and Bt OSR plants and their populations, especially under high herbivore pressure. PMID:26338267

  9. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1.

    PubMed

    Jordt, Sven-Eric; Bautista, Diana M; Chuang, Huai-Hu; McKemy, David D; Zygmunt, Peter M; Högestätt, Edward D; Meng, Ian D; Julius, David

    2004-01-15

    Wasabi, horseradish and mustard owe their pungency to isothiocyanate compounds. Topical application of mustard oil (allyl isothiocyanate) to the skin activates underlying sensory nerve endings, thereby producing pain, inflammation and robust hypersensitivity to thermal and mechanical stimuli. Despite their widespread use in both the kitchen and the laboratory, the molecular mechanism through which isothiocyanates mediate their effects remains unknown. Here we show that mustard oil depolarizes a subpopulation of primary sensory neurons that are also activated by capsaicin, the pungent ingredient in chilli peppers, and by Delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Both allyl isothiocyanate and THC mediate their excitatory effects by activating ANKTM1, a member of the TRP ion channel family recently implicated in the detection of noxious cold. These findings identify a cellular and molecular target for the pungent action of mustard oils and support an emerging role for TRP channels as ionotropic cannabinoid receptors. PMID:14712238

  10. Inhibition of Listeria monocytogenes on bologna sausages by an antimicrobial film containing mustard extract or sinigrin.

    PubMed

    Lara-Lledó, Marta; Olaimat, Amin; Holley, Richard A

    2012-05-01

    The ability of Listeria (L.) monocytogenes to convert glucosinolates into antimicrobial isothiocyanates was investigated. Mustard glucosinolates in pure (sinigrin) or extract forms (sinigrin, oriental; sinalbin, yellow mustard) were used in broth media and in a polyvinyl polyethylene glycol graft copolymer (PPG) packaging film with bologna to examine their value as antimicrobial precursors for the control of L. monocytogenes viability and extension of bologna shelf-life at 4 °C. During broth tests with deodorized (myrosinase-inactivated) mustard extracts (10 d at 20 °C) or with purified sinigrin (21 d at 20 °C) L. monocytogenes was only inhibited when exogenous myrosinase was added. None the less, the organism was able to hydrolyze almost half the pure sinigrin by 21 d in tests without added enzyme. Reductions in sinigrin levels were measured by reversed-phase liquid chromatography, and in the absence of L. monocytogenes or added myrosinase the glucosinolate was stable. When pure sinigrin, oriental or yellow mustard extracts were incorporated in PPG films containing 3, 5 and 6% (w/w) of the corresponding glucosinolate and used to package bologna inoculated with 4 log CFU/g L. monocytogenes, the pathogen became undetectable in bologna packed with the oriental mustard extract at 52 d storage and remained undetectable at 70 d. The yellow mustard extract was less inhibitory and the pure sinigrin was not antimicrobial. L. monocytogenes numbers reached >7 log CFU/g in the film and untreated controls at 17 d storage. At 35 d storage, samples packed with control film contained sufficient numbers of lactic acid bacteria (LAB) (>7 log CFU/g) to be considered spoiled, whereas treatments containing mustard or sinigrin remained <7 log CFU/g LAB for ≤ 70 d. L. monocytogenes played a key role in exerting control over its own viability in bologna by hydrolysis of the glucosinolate in the oriental mustard film, but other antimicrobials in treatments may have contributed.

  11. 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.

  12. 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

  13. Ultrastructural pathology and immunohistochemistry of mustard gas lesion

    SciTech Connect

    Petrali, J.P.; Oglesby, S.B.; Hamilton, T.A.; Mills, K.R.

    1993-05-13

    The ultrastructural pathology of sulfur mustard gas (HD) skin toxicity has been characterized for several in vivo and in vitro model systems. In animal models, the pathology involves the latent lethal targeting of skin basal cells, a disabling of hemidesmosomes and a progressive edema of the lamina lucida, all of which contribute to the formation of characteristic microblisters at the dermal-epidermal junction. However, the effects of HD toxicity on structural proteins of extracellular domains of the dermal-epidermal junction have not been elucidated. We are beginning an immunohistochemical study of these domains in the hairless guinea pig and summarize here the time course effects of HD of three structural proteins: bullous pemphigoid antigen, laminin and Type IV collagen. The results of this combined ultrastructural and immunohistochemical study indicate that proteins of extracellular matrices of the basement membrane are antigenically altered during the development of HD-induced skin pathology and may contribute to the formation of microblisters.

  14. Preventive measures against the mustard gas: a review

    PubMed Central

    Razavi, Seyed Mansour; Karbakhsh, Mojgan

    2013-01-01

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

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

    PubMed

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

    2008-10-01

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

  16. Pathogenesis of skin lesions caused by sulfur mustard.

    PubMed

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

    1984-04-01

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

  17. Evolution of mustard (Brassica juncea Coss) subspecies in China: evidence from the chalcone synthase gene.

    PubMed

    Chen, F B; Liu, H F; Yao, Q L; Fang, P

    2016-01-01

    To explore the phylogenetic relationship, genome donor, and evolutionary history of the polyploid mustard (Brassica juncea) from China, eighty-one sequences of the chalcone synthase gene (Chs) were analyzed in 43 individuals, including 34 B. juncea, 2 B. rapa, 1 B. nigra, 2 B. oleracea, 1 B. napus, 1 B. carinata, and 2 Raphanus sativus. A maximum likelihood analysis showed that sequences from B. juncea were separated into two well-supported groups in accordance with the A and B genomes, whereas the traditional phenotypic classification of B. juncea was not wholly supported by the molecular results. The SplitsTree analysis recognized four distinct groups of Brassicaceae, and the median-joining network analysis recognized four distinct haplotypes of Chs. The estimates of Tajima's D, Fu and Li's D, and Fu and Li's F statistic for the Chs gene in the B genome were negative, while those in the A genome were significant. The results indicated that 1) the Chs sequences revealed a high level of sequence variation in Chinese mustard, 2) both tree and reticulate evolutions existed, and artificial selection played an important role in the evolution of Chinese mustard, 3) the original parental species of Chinese mustard are B. rapa var. sinapis arvensis and B. nigra (derived from China), 4) nucleotide variation in the B genome was higher than that in the A genome, and 5) cultivated mustard evolved from wild mustard, and China is one of the primary origins of B. juncea.

  18. 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.

  19. Evolution of mustard (Brassica juncea Coss) subspecies in China: evidence from the chalcone synthase gene.

    PubMed

    Chen, F B; Liu, H F; Yao, Q L; Fang, P

    2016-01-01

    To explore the phylogenetic relationship, genome donor, and evolutionary history of the polyploid mustard (Brassica juncea) from China, eighty-one sequences of the chalcone synthase gene (Chs) were analyzed in 43 individuals, including 34 B. juncea, 2 B. rapa, 1 B. nigra, 2 B. oleracea, 1 B. napus, 1 B. carinata, and 2 Raphanus sativus. A maximum likelihood analysis showed that sequences from B. juncea were separated into two well-supported groups in accordance with the A and B genomes, whereas the traditional phenotypic classification of B. juncea was not wholly supported by the molecular results. The SplitsTree analysis recognized four distinct groups of Brassicaceae, and the median-joining network analysis recognized four distinct haplotypes of Chs. The estimates of Tajima's D, Fu and Li's D, and Fu and Li's F statistic for the Chs gene in the B genome were negative, while those in the A genome were significant. The results indicated that 1) the Chs sequences revealed a high level of sequence variation in Chinese mustard, 2) both tree and reticulate evolutions existed, and artificial selection played an important role in the evolution of Chinese mustard, 3) the original parental species of Chinese mustard are B. rapa var. sinapis arvensis and B. nigra (derived from China), 4) nucleotide variation in the B genome was higher than that in the A genome, and 5) cultivated mustard evolved from wild mustard, and China is one of the primary origins of B. juncea. PMID:27173323

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

    PubMed

    Ghanei, Mostafa; Harandi, Ali Amini

    2011-06-01

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

  1. 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

  2. Electrolyte and Plasma Responses After Pickle Juice, Mustard, and Deionized Water Ingestion in Dehydrated Humans

    PubMed Central

    Miller, Kevin C.

    2014-01-01

    Context: Some athletes ingest pickle juice (PJ) or mustard to treat exercise-associated muscle cramps (EAMCs). Clinicians warn against this because they are concerned it will exacerbate exercise-induced hypertonicity or cause hyperkalemia. Few researchers have examined plasma responses after PJ or mustard ingestion in dehydrated, exercised individuals. Objective: To determine if ingesting PJ, mustard, or deionized water (DIW) while hypohydrated affects plasma sodium (Na+) concentration ([Na+]p), plasma potassium (K+) concentration ([K+]p), plasma osmolality (OSMp), or percentage changes in plasma volume or Na+ content. Design: Crossover study. Setting: Laboratory. Patients or Other Participants: A total of 9 physically active, nonacclimated individuals (age = 25 ± 2 years, height = 175.5 ± 9.0 cm, mass = 78.6 ± 13.8 kg). Intervention(s): Participants exercised vigorously for 2 hours (temperature = 37°C ± 1°C, relative humidity = 24% ± 4%). After a 30-minute rest, a baseline blood sample was collected, and they ingested 1 mL/kg body mass of PJ or DIW. For the mustard trial, participants ingested a mass of mustard containing a similar amount of Na+ as for the PJ trial. Postingestion blood samples were collected at 5, 15, 30, and 60 minutes. Main Outcome Measure(s): The dependent variables were [Na+]p, [K+]p, OSMp, and percentage change in plasma Na+ content and plasma volume. Results: Participants became 2.9% ± 0.6% hypohydrated and lost 96.8 ± 27.1 mmol (conventional unit = 96.8 ± 27.1 mEq) of Na+, 8.4 ± 2 mmol (conventional unit = 8.4 ± 2 mEq) of K+, and 2.03 ± 0.44 L of fluid due to exercise-induced sweating. They ingested approximately 79 mL of PJ or DIW or 135.24 ± 22.8 g of mustard. Despite ingesting approximately 1.5 g of Na+ in the PJ and mustard trials, no changes occurred within 60 minutes postingestion for [Na+]p, [K+]p, OSMp, or percentage changes in plasma volume or Na+ content (P > .05). Conclusions: Ingesting a small bolus of PJ or large

  3. Electrolyte and Plasma Responses After Pickle Juice, Mustard, and Deionized Water Ingestion in Dehydrated Humans.

    PubMed

    Miller, Kevin C

    2014-02-12

    Context : Some athletes ingest pickle juice (PJ) or mustard to treat exercise-associated muscle cramps (EAMCs). Clinicians warn against this because they are concerned it will exacerbate exercise-induced hypertonicity or cause hyperkalemia. Few researchers have examined plasma responses after PJ or mustard ingestion in dehydrated, exercised individuals. Objective : To determine if ingesting PJ, mustard, or deionized water (DIW) while hypohydrated affects plasma sodium (Na(+)) concentration ([Na(+)]p), plasma potassium (K(+)) concentration ([K(+)]p), plasma osmolality (OSMp), or percentage changes in plasma volume or Na(+) content. Design : Crossover study. Setting : Laboratory. Patients or Other Participants : A total of 9 physically active, nonacclimated individuals (age = 25 ± 2 years, height = 175.5 ± 9.0 cm, mass = 78.6 ± 13.8 kg). Intervention(s) : Participants exercised vigorously for 2 hours (temperature = 37°C ± 1°C, relative humidity = 24% ± 4%). After a 30-minute rest, a baseline blood sample was collected, and they ingested 1 mL/kg body mass of PJ or DIW. For the mustard trial, participants ingested a mass of mustard containing a similar amount of Na(+) as for the PJ trial. Postingestion blood samples were collected at 5, 15, 30, and 60 minutes. Main Outcome Measure(s) : The dependent variables were [Na(+)]p, [K(+)]p, OSMp, and percentage change in plasma Na(+) content and plasma volume. Results : Participants became 2.9% ± 0.6% hypohydrated and lost 96.8 ± 27.1 mmol (conventional unit = 96.8 ± 27.1 mEq) of Na(+), 8.4 ± 2 mmol (conventional unit = 8.4 ± 2 mEq) of K(+), and 2.03 ± 0.44 L of fluid due to exercise-induced sweating. They ingested approximately 79 mL of PJ or DIW or 135.24 ± 22.8 g of mustard. Despite ingesting approximately 1.5 g of Na(+) in the PJ and mustard trials, no changes occurred within 60 minutes postingestion for [Na(+)]p, [K(+)]p, OSMp, or percentage changes in plasma volume or Na(+) content (P > .05). Conclusions

  4. 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

  5. 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. PMID:25912227

  6. 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

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

    PubMed

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

    2012-01-01

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

  8. 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.

  9. 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

  10. 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.

  11. [Physical and antioxidant characteristics of black (Brassica nigra) and yellow mustard (Brassica alba) seeds and their products].

    PubMed

    Mejia-Garibay, Beatriz; Guerrero-Beltrán, José Ángel; Palou, Enrique; López-Malo, Aurelio

    2015-06-01

    The composition, some physical properties (density, refraction index, and color), antioxidant capacity (DPPH), and fatty acid profile of seeds of black (Brassica nigra) or yellow mustard (Brassica alba) were evaluated, as well as for their oils and residues from oil extraction. Density of the black and yellow mustard oils were 0.912 ± 0.01 and 0.916 ± 0.01 g/mL, respectively; their refraction indexes were 1.4611 ± 0.01 and 1.4617 ± 0.01, respectively; being not significantly different (p > 0.05) between two mustards. Color parameters of the black and yellow mustard oils presented greenish-yellow tones and reddish-yellow tones, respectively; regarding antioxidant activities, these ranged from 25 mg equivalents of Trolox/100 gin the yellow mustard oil to 1,366 mg equivalents of Trolox/100 g in the residues from oil extraction of black seed mustard. The fatty acid profile of the black mustard seed revealed that its predomipant fatty acid is oleic (22.96%), followed by linoleic (6.63%) and linolenic (3.22%), whereas foryellow mustard seed the major fatty acid is erucic (6.87%), followed by oleic (5.08%) and linoleic (1.87%) acids. PMID:26817385

  12. 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...

  13. ‘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)...

  14. The treatment of sulphur mustard burns with laser debridement.

    PubMed

    Evison, D; Brown, R F R; Rice, P

    2006-01-01

    The chemical warfare agent, sulphur mustard (SM), is a potent blistering agent in man. Skin exposure can produce partial-thickness burns which take up to three months to heal. The aim of this study was to investigate the use of early laser ablation as a means of accelerating this exceptionally slow rate of healing. Four circular partial-thickness SM burns were induced on the dorsum of nine large white pigs (under general anaesthesia). At 72 h post-exposure, three burns per animal were ablated with a single pass of an UltraPulse 5000C CO(2) laser, at a fluence of 5-6 J cm(-2). All the burns were dressed with silver sulphadiazine and a semi-occlusive dressing. At one, two and three weeks post-surgery three animals were culled and all lesions excised for histological analysis. Burn depth was confirmed and measurements of the radii of regenerative epithelium were performed allowing the area of the zone of re-epithelialisation in each lesion to be calculated. Laser-treated lesions showed a significant increase (350%) in healing rates compared to controls (p<0.005). At two weeks, the laser-treated sites were 95% healed in comparison with control sites (28% healed). These data suggest that laser ablation may be effective in the treatment of partial-thickness SM-induced skin injury. PMID:16996434

  15. Mechanisms of sulfur mustard-induced metabolic injury

    SciTech Connect

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

    1993-05-13

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

  16. Reduction and coordination of arsenic in Indian mustard.

    PubMed

    Pickering, I J; Prince, R C; George, M J; Smith, R D; George, G N; Salt, D E

    2000-04-01

    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 As(III)-tris-thiolate complex. The majority of the arsenic remains in the roots as an As(III)-tris-thiolate complex, which is indistinguishable from that found in the shoots and from As(III)-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.

  17. 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.

  18. The treatment of sulphur mustard burns with laser debridement.

    PubMed

    Evison, D; Brown, R F R; Rice, P

    2006-01-01

    The chemical warfare agent, sulphur mustard (SM), is a potent blistering agent in man. Skin exposure can produce partial-thickness burns which take up to three months to heal. The aim of this study was to investigate the use of early laser ablation as a means of accelerating this exceptionally slow rate of healing. Four circular partial-thickness SM burns were induced on the dorsum of nine large white pigs (under general anaesthesia). At 72 h post-exposure, three burns per animal were ablated with a single pass of an UltraPulse 5000C CO(2) laser, at a fluence of 5-6 J cm(-2). All the burns were dressed with silver sulphadiazine and a semi-occlusive dressing. At one, two and three weeks post-surgery three animals were culled and all lesions excised for histological analysis. Burn depth was confirmed and measurements of the radii of regenerative epithelium were performed allowing the area of the zone of re-epithelialisation in each lesion to be calculated. Laser-treated lesions showed a significant increase (350%) in healing rates compared to controls (p<0.005). At two weeks, the laser-treated sites were 95% healed in comparison with control sites (28% healed). These data suggest that laser ablation may be effective in the treatment of partial-thickness SM-induced skin injury.

  19. 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%). PMID:25466117

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

    PubMed

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

    2009-03-01

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

  1. Cleft Palate induced by Sulfur Mustard in mice fetus

    PubMed Central

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

    2012-01-01

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

  2. Antioxidants from defatted Indian Mustard (Brassica Juncea) protect biomolecules against in vitro oxidation.

    PubMed

    Dua, Anita; Chander, Subhash; Agrawal, Sharad; Mahajan, Ritu

    2014-10-01

    Indian mustard seeds were defatted by distillation with hexane and the residue extracted with methanol was analyzed for potential antioxidants; ascorbate, riboflavin, and polyphenols. Gallic acid (129.796 μg), caffeic acid (753.455 μg), quercetin (478.352 μg) and kaempferol (48.060 μg)/g dry seeds were identified by HPLC analysis of the extract. DPPH free radical scavenging activity and protection of lipids, proteins and DNA against metal induced oxidation was examined. Defatted mustard seed remnant had excellent free radical scavenging activity and protects biomolecules with IC50 value 2.0-2.25 mg dry seed weight. Significant content of polyphenols in methanol extract of defatted seeds accounts for high antioxidant potential. We are the first to report the detailed analysis of antioxidant composition and protection of biomolecules against oxidative damage by methanol extract of mustard seed remnant after oil extraction. PMID:25320478

  3. 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.

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

    PubMed

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

    2016-08-15

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

  5. 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.

  6. 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.

  7. Assessing Natural Isothiocyanate Air Emissions after Field Incorporation of Mustard Cover Crop

    SciTech Connect

    Trott, Donna M.; LePage, Jane; Hebert, Vincent

    2012-01-01

    A regional air assessment was performed to characterize volatile natural isothiocyanate (NITC) compounds in air during soil incorporation of mustard cover crops in Washington State. Field air sampling and analytical methods were developed specific to three NITCs known to be present in air at appreciable concentrations during/after field incorporation. The maximum observed concentrations in air for the allyl, benzyl, and phenethyl isothiocyanates were respectively 188, 6.1, and 0.7 lg m-3 during mustard incorporation. Based on limited inhalation toxicity information, airborne NITC concentrations did not appear to pose an acute human inhalation exposure concern to field operators and bystanders.

  8. 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. PMID:25529654

  9. 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.

  10. 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.

  11. Quality characterization of pasta enriched with mustard protein isolate.

    PubMed

    Alireza Sadeghi, M; Bhagya, S

    2008-06-01

    Mustard protein isolate (MPI) prepared by steam injection heating for removal of antinutritional factors was used at different levels, including 0%, 2.5%, 5%, and 10%, for supplementation of pasta products. The effects of supplementation levels on rheological properties of pasta dough and chemical composition, and cooking, nutritional, and color characteristics of dried samples were evaluated. The results showed that as the supplementation level increased, the dough development time (DDT) increased from 3.5 min in the control to 13.8 min in 10% supplementation level. Maximum consistency (MC) increased from 351 farinograph units (FU) in the control to 371 and 386 FU in 2.5% and 5% supplementation levels, respectively, but decreased to 346 FU in 10% supplementation level. Mixing tolerance index (MTI) decreased as the supplementation increased. The most pronounced effect of enrichment on chemical composition was the increase in protein content; the increase was around 4.5% with supplementation of each 5% MPI in pasta formulation. Study of cooking characteristics of enriched pasta samples showed that cooked weight, cooking loss, protein loss, and stickiness decreased and firmness increased as the supplementation level increased. The nutritional properties of sample showed that enrichment of semolina with MPI had a pronounced effect on lysine, cysteine, arginine, and histidine contents. All computed nutritional indices were higher in enriched samples compared to the control. Color measurement of sample showed that a and b values increased and L value decreased as the supplementation level increased. The SEM of different samples shows that enrichment of pasta with MPI increases the matrix around starch granules. PMID:18577015

  12. 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

  13. A case of split notochord syndrome with congenital ileal atresia, the total absence of a colon, and a dorsal enteric cyst communicating to the retroperitoneal isolated ceca with a vesical fistula.

    PubMed

    Asagiri, Kimio; Yagi, Minoru; Tanaka, Yoshiaki; Akaiwa, Masao; Asakawa, Takahiro; Kaida, Akiko; Kobayashi, Hidefumi; Tanaka, Hiroaki

    2008-09-01

    Split notochord syndrome (SNS) is an extremely rare anomaly. This report presents the case of a male infant with SNS associated with congenital ileal atresia and a dorsal enteric cyst communicating to the retroperitoneal isolated ceca with a vesical fistula. Dorsal fistulography and vesicography were useful and essential for the detailed study of the topology in this patient. The embryological mechanism and etiologic theories are discussed with a review of 19 cases reported in the literature.

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

    PubMed

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

    2016-05-17

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

  15. 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.

  16. 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...

  17. Effect of fatty acids isolated from edible oils like mustard, linseed or coconut on astrocytes maturation.

    PubMed

    Joardar, Anindita; Das, Sumantra

    2007-12-01

    The omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA, 22:6n-3) has been previously shown to facilitate some of the vital functions of astrocytes. Since some dietary oils contain alpha-linolenic acid (ALA, 18:3n-3), which is a precursor of DHA, we examined their effect on astrocyte development. Fatty acids (FAs) were isolated from commonly used oils and their compositions were determined by GLC. FAs from three oils, viz. coconut, mustard and linseed were studied for their effect on astrocyte morphology. Parallel studies were conducted with FAs from the same oils after heating for 72 h. Unlike coconut oil, FAs from mustard and linseed, both heated and raw, caused significant morphogenesis of astrocytes in culture. ss-AR binding was also substantially increased in astrocytes treated with FAs from raw mustard and linseed oils as compared to astrocytes grown in normal medium. The expression profile of the isoforms of GFAP showed that astrocyte maturation by FAs of mustard and linseed oil was associated with appearance of acidic variants of GFAP and disappearance of some neutral isoforms similar to that observed in cultures grown in serum containing medium or in the presence of DHA. Taken together, the study highlights the contribution of specific dietary oils in facilitating astrocyte development that can have potential impact on human health.

  18. [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. PMID:23359937

  19. What makes those collard, turnip and mustard greens so good for you?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Collard, turnip, and mustard greens are economically important leafy-green vegetables grown throughout the United States that are especially important in the South. These cruciferous vegetables are known to be rich sources of numerous vitamins and other important nutritional components, but formal ...

  20. [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.

  1. 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...

  2. 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. PMID:18840244

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

    PubMed Central

    2012-01-01

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

  4. 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...

  5. 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.

  6. Use of acid whey and mustard seed to replace nitrites during cooked sausage production.

    PubMed

    Wójciak, Karolina M; Karwowska, Małgorzata; Dolatowski, Zbigniew J

    2014-02-01

    The aim was to determine the effects of sea salt, acid whey, native and autoclaved mustard seed on the physico-chemical properties, especially colour formation, microbial stability and sensory evaluation of non-nitrite cooked sausage during chilling storage. The cooked pork sausages were divided into 4 groups (group I--control sausages with curing salt (2.8%) and water (5%) added; group II--sausages with sea salt (2.8%) and acid whey (5%) added; group III--sausages with sea salt (2.8%), acid whey (5%) and mustard seed (1%) added; group IV--sausages with sea salt (2.8%), acid whey (5%) and autoclaved mustard seed (1%) added). Instrumental colour (L*, a*, b*), oxygenation index (ΔR), 650/570 nm ratio, heme iron, pH value and water activity (aw) were determined 1 day after production and after 10, 20 and 30 days of refrigerated storage (4 °C). Sensory analysis was conducted immediately after production (day 1). Microbial analysis (lactic acid bacteria, total viable count, Clostridium spp.) was determinated at the end of storage (30 days). The autoclaved mustard with acid whey can be used at 1.0% (w/w) of model cooked sausages with beneficial effect on physico-chemical and sensory qualities of no-nitrite sausage. This product can be stored at refrigeration temperature for up to 30 days, in vacuum, with good acceptability. The colour, visual appearance and overall quality of samples with autoclaved mustard seed and acid whey were similar to the control with curing agent. PMID:24200566

  7. 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.

  8. 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.

  9. Proteomic analysis of DNA-protein cross-linking by antitumor nitrogen mustards.

    PubMed

    Loeber, Rachel L; Michaelson-Richie, Erin D; Codreanu, Simona G; Liebler, Daniel C; Campbell, Colin R; Tretyakova, Natalia Y

    2009-06-01

    Nitrogen mustards are antitumor agents used clinically for the treatment of a variety of neoplastic conditions. The biological activity of these compounds is typically attributed to their ability to induce DNA-DNA cross-links. However, nitrogen mustards are able to produce a variety of other lesions, including DNA-protein cross-links (DPCs). DPCs induced by nitrogen mustards are not well-characterized because of their structural complexity and the insufficient specificity and sensitivity of previously available experimental methodologies. In the present work, affinity capture methodology in combination with mass spectrometry-based proteomics was employed to identify mammalian proteins that form covalent cross-links to DNA in the presence of a simple nitrogen mustard, mechlorethamine. Following incubation of 5'-biotinylated DNA duplexes with nuclear protein extracts, DPCs were isolated by affinity capture on streptavidin beads, and the cross-linked proteins were identified by high-performance liquid chromatography-electrospray tandem mass spectrometry of tryptic peptides. Mechlorethamine treatment resulted in the formation of DPCs with nuclear proteins involved in chromatin regulation, DNA replication and repair, cell cycle control, transcriptional regulation, and cell architecture. Western blot analysis was employed to confirm protein identification and to quantify the extent of drug-mediated cross-linking. Mass spectrometry of amino acid-nucleobase conjugates found in total proteolytic digests revealed that mechlorethamine-induced DPCs are formed via alkylation of the N7 position of guanine in duplex DNA and cysteine thiols within the proteins to give N-[2-[S-cysteinyl]ethyl]-N-[2-(guan-7-yl)ethyl]methylamine lesions. The results described herein suggest that cellular exposure to nitrogen mustards leads to cross-linking of a large spectrum of nuclear proteins to chromosomal DNA, potentially contributing to the cytotoxic and mutagenic effects of these drugs.

  10. '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.

  11. 'Dilute-and-shoot' RSLC-MS-MS method for fast detection of nerve and vesicant chemical warfare agent metabolites in urine.

    PubMed

    Rodin, Igor; Braun, Arcady; Stavrianidi, Andrey; Baygildiev, Timur; Shpigun, Oleg; Oreshkin, Dmitry; Rybalchenko, Igor

    2015-01-01

    A sensitive screening method based on fast liquid chromatography tandem mass-spectrometry (RSLC-MS-MS) has shown the feasibility of separation and detection of low concentration β-lyase metabolites of sulfur mustard and of nerve agent phosphonic acids in urine. The analysis of these compounds is of interest because they are specific metabolites of the chemical warfare agents (CWAs), sulfur mustard (HD), sarin (GB), soman (GD), VX and Russian VX (RVX). The 'dilute-and-shoot' RSLC-MS-MS method provides a sensitive and direct approach for determining CWA exposure in non-extracted non-derivatized samples from urine. Chromatographic separation of the metabolites was achieved using a reverse phase column with gradient mobile phases consisting of 0.5% formic acid in water and acetonitrile. Identification and quantification of species were achieved using electrospray ionization-tandem mass-spectrometry monitoring two precursor-to-product ion transitions for each compound. The method demonstrates linearity over at least two orders of magnitude and had detection limits of 0.5 ng/mL in urine. PMID:25326204

  12. 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...

  13. 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)...

  14. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

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

  17. Calmodulin mediates sulfur mustard toxicity in human keratinocytes.

    PubMed

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

    2006-10-01

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

  18. 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.

  19. Contribution of endogenous plant myrosinase to the antimicrobial activity of deodorized mustard against Escherichia coli O157:H7 in fermented dry sausage.

    PubMed

    Cordeiro, Roniele Peixoto; Wu, Chen; Holley, Richard Alan

    2014-10-17

    This work investigated the antimicrobial activity of residual endogenous plant myrosinase in Oriental and yellow mustard powders and a deoiled meal (which contained more glucosinolate than unextracted mustard powder of each type of mustard), against Escherichia coli O15:H7 during dry-fermented sausage ripening. When small amounts of "hot" mustard powder or meal containing endogenous plant myrosinase were added to fully-deodorized powders and a meal of the same type, pathogen reduction rates were enhanced. The higher glucosinolate level in the deoiled mustard meal enabled the use of 50% less mustard in dry sausage to achieve the mandatory ≥5logCFU/g reduction of E. coli O157:H7. The myrosinase-like activity present in E. coli O157:H7 contributed to glucosinolate hydrolysis in sausages with fully-deodorized, deoiled mustard meal, although the period necessary for a 5log pathogen reduction was 14d longer. Yellow mustard derivatives were more potently antimicrobial than Oriental mustard.

  20. EPR/spin-label technique as an analytical tool for determining the resistance of reactive topical skin protectants (rTSPs) to the breakthrough of vesicant agents.

    PubMed

    Arroyo, C M; Janny, S J

    1995-04-01

    Ointment formulations of reactive topical skin protectants (rTSPs) or topical skin protectants (TSPs) based on perfluorinated polyether material (PFPE, i.e., fomblin RT-15) were prepared and spin labeled. Four N-oxyl-4-4'-dimethyloxazolidine derivatives of stearic acid, 5-NS, 7-NS, 12-NS, and 16-NS, were used as spin probes. The spin-labeled vehicle, fomblin-RT-15, and vehicle containing chloroamide (S-330, an antivesicant) were exposed to various concentrations of half-mustard gas. The order parameter (S) was dependent on the depth of penetration of the paramagnetic group into the vehicle (fomblin) and on the chemical composition of the reactive antivesicant under investigation. The net change of the viscosity of the vehicle and the chemical composition were seen to affect the penetration profile. This will provide a useful in vitro screening technique to develop antivesicant TSPs.

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

    PubMed

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

    2014-04-21

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

  2. Laser effects on the growth and photosynthesis process in mustard plants (Sinapis Alba)

    NASA Astrophysics Data System (ADS)

    Anghel, Sorin; Stanescu, Constantin S.; Giosanu, Dana; Flenacu, Monica; Iorga-Siman, Ion

    2001-06-01

    In this paper we present the results of our experiments concerning the influence of the low energy laser (LEL) radiation on the germination, growth and photosyntheses processes in mustard plants (sinapis alba). We used a He-Ne laser ((lambda) equals 632.8 nm, P equals 6 mW) to irradiate the mustard seeds with different exposure times. The seeds were sowed and some determinations (the germination and growth intensity, chlorophyll quantity, and respiration intensity) were made on the plant culture. We ascertained that the germination and growth of the plants are influenced by the irradiation. Also, the chlorophyll quantity is the same for both plants from irradiated and non-irradiated seeds but the respiration and photosynthesis processes are influenced by the irradiation.

  3. 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.

  4. Novel hybrids of natural oridonin-bearing nitrogen mustards as potential anticancer drug candidates.

    PubMed

    Xu, Shengtao; Pei, Lingling; Wang, Chengqian; Zhang, Yun-Kai; Li, Dahong; Yao, Hequan; Wu, Xiaoming; Chen, Zhe-Sheng; Sun, Yijun; Xu, Jinyi

    2014-07-10

    A series of novel hybrids from natural product oridonin and nitrogen mustards were designed and synthesized to obtain more efficacious and less toxic antitumor agents. The antiproliferative evaluation showed that most conjugates were more potent than their parent compounds oridonin and clinically used nitrogen mustards against four human cancer cell lines (K562, MCF-7, Bel-7402, and MGC-803). Furthermore, the representative compounds 16a-c exhibited antiproliferative activities against the multidrug resistant cell lines (SW620/AD300 and NCI-H460/MX20). It was shown that the most effective compound 16b possesses a strong inhibitory activity with an IC50 value 21-fold lower than that of oridonin in MCF-7 cells and also exhibits selective cytotoxicity toward the cancer cells. Intriguingly, compound 16b has been demonstrated to significantly induce apoptosis and affect cell cycle progression in human hepatoma Bel-7402 cells. PMID:25050168

  5. 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

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

    PubMed

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

    2016-09-01

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

  7. Modification of the Mustardé and Hughes methods of reconstructing the lower lid.

    PubMed

    Cies, W A; Bartlett, R E

    1975-11-01

    Reconstruction of the lower lid often is a greater task than originally anticipated in preoperative evaluations. The Mustardé and Hughes methods are commonly used for extensive lower lid reconstruction. Certain difficulties encountered in these methods may be minimized by variations in the basic techniques. Structural support for a Mustardé flap may be provided by a free tarsal conjunctival graft rather than a nasal septal cartilage mucosa graft. Late complications following the Hughes procedure include upper lid retraction and entropion. These may be minimized by removing Mueller's muscle from the flap at the time of the original dissection. The Hughes flap may be lysed in 3 to 4 weeks. Lid margin abnormalities, which occur occasionally, are corrected with minor modifications.

  8. 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.

  9. Novel hybrids of natural oridonin-bearing nitrogen mustards as potential anticancer drug candidates.

    PubMed

    Xu, Shengtao; Pei, Lingling; Wang, Chengqian; Zhang, Yun-Kai; Li, Dahong; Yao, Hequan; Wu, Xiaoming; Chen, Zhe-Sheng; Sun, Yijun; Xu, Jinyi

    2014-07-10

    A series of novel hybrids from natural product oridonin and nitrogen mustards were designed and synthesized to obtain more efficacious and less toxic antitumor agents. The antiproliferative evaluation showed that most conjugates were more potent than their parent compounds oridonin and clinically used nitrogen mustards against four human cancer cell lines (K562, MCF-7, Bel-7402, and MGC-803). Furthermore, the representative compounds 16a-c exhibited antiproliferative activities against the multidrug resistant cell lines (SW620/AD300 and NCI-H460/MX20). It was shown that the most effective compound 16b possesses a strong inhibitory activity with an IC50 value 21-fold lower than that of oridonin in MCF-7 cells and also exhibits selective cytotoxicity toward the cancer cells. Intriguingly, compound 16b has been demonstrated to significantly induce apoptosis and affect cell cycle progression in human hepatoma Bel-7402 cells.

  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. Response of a high-glucuronidase human tumour xenograft to aniline mustard.

    PubMed

    Warenius, H M; Workman, P; Bleehen, N M

    1982-01-01

    The HT29R colonic adenocarcinoma xenograft has been shown to be rich in the enzyme beta-glucuronidase. Experiments in rodent systems have demonstrated a marked anti-tumour effect of the drug aniline mustard (AM) on tumours with high levels of this enzyme (e.g. the plasmacytomas PC5 and PC6). We have found that AM is no more effective than its analogue paramethyl aniline mustard (PMAM) or other alkylating agents against the HT29R xenograft. Amongst the possible explanations for this may be: (1) The wide shoulder on the cell-survival curve shown for exposure to alkylating agents of HT29R in vivo. (2) Lack of correlation between physiological availability of beta-glucuronidase and the high levels measured by the standard assay. (3) Increased beta-glucuronidase levels in host mouse marrow, making the latter potentially more susceptible to AM damage.

  12. The Effect of the Vesical Adaptation Response to Diuresis on Lower Urinary Tract Symptoms after Robot-Assisted Laparoscopic Radical Prostatectomy: A Pilot Proof of Concept Study

    PubMed Central

    Haga, Nobuhiro; Aikawa, Ken; Hoshi, Seiji; Yabe, Michihiro; Akaihata, Hidenori; Hata, Junya; Sato, Yuichi; Ogawa, Soichiro; Ishibashi, Kei; Kojima, Yoshiyuki

    2016-01-01

    Background When urine output increases, voided volume at each voiding also increases in normal subjects. This is generally understood as a vesical adaptation response to diuresis (VARD). Because lower urinary tract symptoms (LUTS) are supposed to be improved by the change in bladder function after robot-assisted laparoscopic radical prostatectomy (RARP), the aim of the present study was to investigate whether VARD is involved in the improvement of LUTS after RARP. Methods 100 consecutive patients who underwent RARP and had the International Prostate Symptom Score (IPSS), quality of life (QOL) index, a frequency-volume chart (FVC), uroflowmetry, and post-voided residual urine (PVR) available were evaluated before and after RARP. This cohort was divided into patients with and without preoperative LUTS according to the preoperative IPSS total score. VARD was defined as the presence of a significant correlation between the urine output rate and voided volume at each voiding (R2>0.2). Results In patients with preoperative LUTS, the IPSS total, storage, and voiding symptom scores were significantly improved after RARP (all P<0.001). The QOL index was also significantly improved after RARP (P<0.05). Although VARD was not seen before RARP (R2 = 0.05), it was seen after RARP (3 months R2 = 0.22, 12 months R2 = 0.23). PVR was significantly reduced after RARP (P = 0.004). Conclusions Improvement of LUTS was seen with acquisition of VARD after RARP. As a result, urinary QOL was also improved in patients with preoperative LUTS. RARP might be an effective procedure for amelioration of LUTS by the acquisition of VARD. PMID:27447829

  13. Potential in two types of collagen scaffolds for urological tissue engineering applications - Are there differences in growth behaviour of juvenile and adult vesical cells?

    PubMed

    Leonhäuser, D; Vogt, M; Tolba, R H; Grosse, J O

    2016-02-01

    The aging society has a deep impact on patient care in urology. The number of patients in need of partial or whole bladder wall replacement is increasing simultaneously with the number of cancer incidents. Therefore, urological research requires a model of bladder wall replacement in adult and elderly people. Two types of porcine collagen I/III scaffolds were used in vitro for comparison of cell growth of two different pig breeds at different growth stages. Scaffolds were characterised with scanning electron and laser scanning microscopy. Urothelial and detrusor smooth muscle cells were isolated from 15 adult Göttingen minipigs and 15 juvenile German Landrace pigs. Growth behaviour was examined in cell culture and seeded onto the collagen scaffolds via immunohistochemistry, two-photon laser scanning microscopy and a viability assay. The collagen scaffolds showed different structured surfaces which are appropriate for seeding of the two different cell types. Moisturisation of the scaffolds resulted in a change of the structure. Cell growth of German Landrace urothelial cells and smooth muscle cells was significantly higher than cell growth of the Göttingen minipig cells. Seeding of scaffolds with both cell types from both pig races was possible which could be shown by immunohistochemistry and two-photon laser scanning microscopy. Growth behaviour on the scaffolds was significantly increased for the German Landrace compared to Göttingen minipig. Nevertheless, seeding with the adult Göttingen minipig cells resulted in a closed layer on the surface and urothelial cells and smooth muscle cells showed increasing growth until day 14. The results show that these collagen scaffolds are adequate for the seeding with vesical cells. Moreover, they seem appropriate for the use as an in vitro model for the adult or elderly as the cells of the adult Göttingen minipig too, show good growth behaviour.

  14. Discrimination between ricin and sulphur mustard toxicity in vitro using Raman spectroscopy.

    PubMed Central

    Notingher, I.; Green, C.; Dyer, C.; Perkins, E.; Hopkins, N.; Lindsay, C.; Hench, L. L.

    2004-01-01

    A Raman spectroscopy cell-based biosensor has been proposed for rapid detection of toxic agents, identification of the type of toxin and prediction of the concentration used. This technology allows the monitoring of the biochemical properties of living cells over long periods of time by measuring the Raman spectra of the cells non-invasively, rapidly and without use of labels (Notingher et al. 2004 doi:10.1016/j.bios.2004.04.008). Here we show that this technology can be used to distinguish between changes induced in A549 lung cells by the toxin ricin and the chemical warfare agent sulphur mustard. A multivariate model based on principal component analysis (PCA) and linear discriminant analysis (LDA) was used for the analysis of the Raman spectra of the cells. The leave-one-out cross-validation of the PCA-LDA model showed that the damaged cells can be detected with high sensitivity (98.9%) and high specificity (87.7%). High accuracy in identifying the toxic agent was also found: 88.6% for sulphur mustard and 71.4% for ricin. The prediction errors were observed mostly for the ricin treated cells and the cells exposed to the lower concentration of sulphur mustard, as they induced similar biochemical changes, as indicated by cytotoxicity assays. The concentrations of sulphur mustard used were also identified with high accuracy: 93% for 200 microM and 500 microM, and 100% for 1,000 microM. Thus, biological Raman microspectroscopy and PCA-LDA analysis not only distinguishes between viable and damaged cells, but can also discriminate between toxic challenges based on the cellular biochemical and structural changes induced by these agents and the eventual mode of cell death. PMID:16849154

  15. Reaction of (3H)meproadifen mustard with membrane-bound Torpedo acetylcholine receptor

    SciTech Connect

    Dreyer, E.B.; Hasan, F.; Cohen, S.G.; Cohen, J.B.

    1986-10-15

    The Torpedo nicotinic acetylcholine receptor (AChR) contains a binding site for aromatic amine noncompetitive antagonists that is distinct from the binding site for agonists and competitive antagonists. To characterize the location and function of this allosteric antagonist site, an alkylating analog of meproadifen has been synthesized, 2-(chloroethylmethylamino)-ethyl-2, 2-diphenylpentanoate HCl (meproadifen mustard). Reaction of (/sup 3/H)meproadifen mustard with AChR-rich membrane suspensions resulted in specific incorporation of label predominantly into the AChR alpha-subunit with minor incorporation into the beta-subunit. Specific labeling required the presence of high concentration of agonist and was inhibited by reversible noncompetitive antagonists including proadifen, meproadifen, perhydrohistrionicotoxin (HTX), and tetracaine when present at concentrations consistent with the binding affinity of these compounds for the allosteric antagonist site. No specific alkylation of the AChR alpha-subunit was detected in the absence of agonist, or in the presence of the partial agonist phenyltrimethylammonium or the competitive antagonists, d-tubocurarine, gallamine triethiodide, or decamethonium. Reaction with 35 microM meproadifen mustard for 70 min in the presence of carbamylcholine produced no alteration in the concentration of (/sup 3/H)ACh-binding sites, but decreased by 38 +/- 4% the number of allosteric antagonist sites as measured by (/sup 3/H)HTX binding. This decrease was not observed when the alkylation reaction was blocked by the presence of HTX. These results lead us to conclude that meproadifen mustard alkylates the allosteric antagonist site in the Torpedo AChR and that part of that site is associated with the AChR alpha-subunit.

  16. 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

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

    PubMed

    Lee, Jin Young; Lee, Yong Han

    2016-01-01

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

  18. Effect of white mustard essential oil on inoculated Salmonella sp. in a sauce with particulates.

    PubMed

    David, Jairus R D; Ekanayake, Athula; Singh, Indarpal; Farina, Brian; Meyer, Michael

    2013-04-01

    White mustard essential oil (WMEO), from white mustard seed (Sinapis alba L.), is obtained by solvent extraction of defatted and wetted ground mustard; endogenous myrosinase catalyzes the hydrolysis of the glucosinolate sinalbin to yield 4-hydroxybenzyl isothiocyanate (4-HBITC), the antimicrobial component of WMEO. Sauce with particulates was made by mixing sauce, which served as the carrier for WMEO, with frozen vegetable and chicken particulates inoculated with Salmonella sp. WMEO (at 250 to 750 ppm of 4-HBITC) was able to reduce inoculated Salmonella counts by 0.8 to 2.7 log (CFU/g) in a frozen sauce with particulates in a dose-dependent manner, starting from the point of formulating the sauce through the microwave cooking step. High-pressure liquid chromatography-based analytical data confirmed that 4-HBITC was present in all of the samples in the expected concentrations and was completely hydrolyzed after the recommended cooking time in microwave ovens. In another experiment simulating unintentional abuse conditions, where the WMEO containing sauce with particulates was kept at room temperature for 5 h, WMEO (at 250 to 750 ppm of 4-HBITC) was able to reduce inoculated Salmonella counts from the point of first contact and up to 5 h by 0.7 to 2.4 log (CFU/g). Despite the known hydrolytic instability of the active component 4-HBITC, particularly at close to neutral pH values, WMEO was effective in controlling deliberately inoculated Salmonella sp. in a frozen sauce with particulates. PMID:23575118

  19. Chromium-induced modulation in the antioxidant defense system during phenological growth stages of Indian mustard.

    PubMed

    Diwan, Hema; Ahmad, Altaf; Iqbal, Muhammad

    2010-02-01

    Chromium-induced modulation in the enzymes and metabolites of antioxidants was investigated at various phenological stages of Indian mustard (Brassica juncea (L.) Czern. & Coss. cv Pusa Jai Kisan)], grown with various levels of chromium (Cr) in pots under natural environmental conditions. Chromium accumulation in the root, stem and leaves increased with the advancement in the age of the plants. Growth of Indian mustard was not affected significantly by the supply of Cr up to the levels of 400 mg kg(-1) soil. Activities of superoxide dismutase (SOD), ascorbate peroxide (APX), catalase (CAT), and glutathione reductase (GR) increased in the leaves of Cr-treated plants, when compared with control. High activities of antioxidant enzymes supported by high Cr concentrations in roots and aerial parts (except seeds) established the Indian mustard as a potential hyperaccumulator anda hypertolerant species to Cr stress. For this study, an edible crop was chosen intentionally so as to tap maximum benefit by remediating the contaminated site on one hand and getting uncontaminated seeds to raise the next generation, on the other. PMID:20734612

  20. 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.

  1. 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.

  2. Effect of white mustard essential oil on inoculated Salmonella sp. in a sauce with particulates.

    PubMed

    David, Jairus R D; Ekanayake, Athula; Singh, Indarpal; Farina, Brian; Meyer, Michael

    2013-04-01

    White mustard essential oil (WMEO), from white mustard seed (Sinapis alba L.), is obtained by solvent extraction of defatted and wetted ground mustard; endogenous myrosinase catalyzes the hydrolysis of the glucosinolate sinalbin to yield 4-hydroxybenzyl isothiocyanate (4-HBITC), the antimicrobial component of WMEO. Sauce with particulates was made by mixing sauce, which served as the carrier for WMEO, with frozen vegetable and chicken particulates inoculated with Salmonella sp. WMEO (at 250 to 750 ppm of 4-HBITC) was able to reduce inoculated Salmonella counts by 0.8 to 2.7 log (CFU/g) in a frozen sauce with particulates in a dose-dependent manner, starting from the point of formulating the sauce through the microwave cooking step. High-pressure liquid chromatography-based analytical data confirmed that 4-HBITC was present in all of the samples in the expected concentrations and was completely hydrolyzed after the recommended cooking time in microwave ovens. In another experiment simulating unintentional abuse conditions, where the WMEO containing sauce with particulates was kept at room temperature for 5 h, WMEO (at 250 to 750 ppm of 4-HBITC) was able to reduce inoculated Salmonella counts from the point of first contact and up to 5 h by 0.7 to 2.4 log (CFU/g). Despite the known hydrolytic instability of the active component 4-HBITC, particularly at close to neutral pH values, WMEO was effective in controlling deliberately inoculated Salmonella sp. in a frozen sauce with particulates.

  3. 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.

  4. Successful term pregnancy after Mustard operation for transposition of the great arteries.

    PubMed

    Rousseil, M P; Irion, O; Béguin, F; Jaques, O; Adamec, R; Lerch, R; Friedli, B; Rifat, K

    1995-03-01

    Transposition of the great arteries is a complex cardiac malformation with poor prognosis without surgical correction. Since the introduction of surgical procedures such as the intra-auricular reorientation of the venous return (Mustard procedure), an increasing number of patients may reach adulthood and experience pregnancy. Because long-term complications after the Mustard operation include systemic heart failure, arrhythmias, venous return stenosis and pulmonary edema, hemodynamic changes during pregnancy and delivery may potentially engender life-threatening complications in these patients. We report the case of a 24-year-old primigravida who underwent a Mustard procedure at the age of 2 years for transposition of the great vessels, and who carried out a full-term pregnancy. The pregnancy was uneventful until the 34th week, when the woman developed signs of moderate right ventricular failure and frequent episodes of accelerated junctional rhythm. Digitalisation improved symptoms and elicited return to normal sinus rhythm. The patient delivered at term by elective cesarean section, under close hemodynamic monitoring. PMID:7781853

  5. Changes of phenolic acids and antioxidant activities during potherb mustard (Brassica juncea, Coss.) pickling.

    PubMed

    Fang, Zhongxiang; Hu, Yuxia; Liu, Donghong; Chen, Jianchu; Ye, Xingqian

    2008-06-01

    Phenolic acids in potherb mustard (Brassica juncea, Coss.) were determined and the effects of pickling methods on the contents of total free phenolic acids, total phenolic acids, total phenolics, and antioxidant activities were investigated. Gallic acid, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, caffeic acid, p-coumaric acid, ferulic acid, and sinapic acid were identified in the present study. The contents of total free phenolic acids, total phenolic acids and total phenolics in fresh potherb mustard were 84.8±0.58μg/g dry weight (DW), 539±1.36μg/g DW, and 7.95±0.28mg/g DW, respectively. The total free phenolic acids increased during the pickling processes, but the total phenolic acids, total phenolics, and antioxidant activities decreased. However, after 5 weeks of fermentation, all the pickling methods retained over 70% of total phenolic contents and above 65% of antioxidant capacities. The results indicated that pickling processes were relatively good methods for the preservation of phenolic acids and antioxidants for potherb mustard. PMID:26065739

  6. Endogenous Phenolics in Hulls and Cotyledons of Mustard and Canola: A Comparative Study on Its Sinapates and Antioxidant Capacity

    PubMed Central

    Mayengbam, Shyamchand; Aachary, Ayyappan; Thiyam-Holländer, Usha

    2014-01-01

    Endogenous sinapic acid (SA), sinapine (SP), sinapoyl glucose (SG) and canolol (CAN) of canola and mustard seeds are the potent antioxidants in various lipid-containing systems. The study investigated these phenolic antioxidants using different fractions of canola and mustard seeds. Phenolic compounds were extracted from whole seeds and their fractions: hulls and cotyledons, using 70% methanol by the ultrasonication method and quantified using HPLC-DAD. The major phenolics from both hulls and cotyledons extracts were SP, with small amounts of SG, and SA with a significant difference of phenolic contents between the two seed fractions. Cotyledons showed relatively high content of SP, SA, SG and total phenolics in comparison to hulls (p < 0.001). The concentration of SP in different fractions ranged from 1.15 ± 0.07 to 12.20 ± 1.16 mg/g and followed a decreasing trend- canola cotyledons > mustard cotyledons > mustard seeds > canola seeds > mustard hulls > canola hulls. UPLC-tandem Mass Spectrometry confirmed the presence of sinapates and its fragmentation in these extracts. Further, a high degree of correlation (r = 0.93) was noted between DPPH scavenging activity and total phenolic content. PMID:26785070

  7. 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

  8. 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.

  9. 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%.

  10. 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%. PMID:25872425

  11. Determination of amino acid nitrogen in tuber mustard using near-infrared spectroscopy with waveband selection stability

    NASA Astrophysics Data System (ADS)

    Liu, Zhenyao; Liu, Bing; Pan, Tao; Yang, Jidong

    2013-02-01

    Near-infrared (NIR) spectroscopy was successfully applied to the rapid chemical-free determination of amino acid nitrogen (AAN) in tuber mustard. Moving window partial least squares, combined with Savitzky-Golay smoothing, was used for the waveband selection. Based on the various divisions in the calibration and prediction sets, an effective modeling approach with good stability was proposed. The results confirmed that the long-wave NIR region contains sufficient information for the quantification of AAN in tuber mustard. An appropriate waveband (5874-4258 cm-1) located in the combination region of NIR was selected. The validation root mean square error of prediction and the validation correlation coefficients of prediction were 0.380 mg/g and 0.962, respectively, both indicating good validation effect and stability. The results provided a reliable NIR model and can serve as valuable references for designing spectroscopic instruments for quality evaluation of tuber mustard.

  12. 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.

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

    PubMed

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

    2016-04-01

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

  14. 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. PMID:25242823

  15. Self-(in)compatibility inheritance and allele-specific marker development in yellow mustard (Sinapis alba).

    PubMed

    Zeng, Fangqin; Cheng, Bifang

    2014-01-01

    Yellow mustard (Sinapis alba) has a sporophytic self-incompatibility reproduction system. Genetically stable self-incompatible (SI) and self-compatible (SC) inbred lines have recently been developed in this crop. Understanding the S haplotype of different inbred lines and the inheritance of the self-(in)compatibility (SI/SC) trait is very important for breeding purposes. In this study, we used the S-locus gene-specific primers in Brassica rapa and Brassica oleracea to clone yellow mustard S-locus genes of SI lines Y514 and Y1130 and SC lines Y1499 and Y1501. The PCR amplification results and DNA sequences of the S-locus genes revealed that Y514 carried the class I S haplotype, while Y1130, Y1499, and Y1501 had the class II S haplotype. The results of our genetic studies indicated that self-incompatibility was dominant over self-compatibility and controlled by a one-gene locus in the two crosses of Y514 × Y1499 and Y1130 × Y1501. Of the five S-locus gene polymorphic primer pairs, Sal-SLGI and Sal-SRKI each generated one dominant marker for the SI phenotype of Y514; Sal-SLGII and Sal-SRKII produced dominant marker(s) for the SC phenotype of Y1501 and Y1499; Sal-SP11II generated one dominant marker for Y1130. These markers co-segregated with the SI/SC phenotype in the F2 populations of the two crosses. In addition, co-dominant markers were developed by mixing the two polymorphic primer pairs specific for each parent in the multiplex PCR, which allowed zygosity to be determined in the F2 populations. The SI/SC allele-specific markers have proven to be very useful for the selection of the desirable SC genotypes in our yellow mustard breeding program.

  16. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2009-11-01

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

  19. 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. PMID:24491701

  20. 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.

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

    PubMed

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

    1994-12-01

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

  2. 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. PMID:26186597

  3. 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. PMID:25038712

  4. Relation between soil temperature and biophysical parameters in Indian mustard seeds

    NASA Astrophysics Data System (ADS)

    Adak, T.; Chakravarty, N. V. K.

    2013-12-01

    Temporal changes in surface soil temperature were studied in winter crop. Significant changes in bare and cropped soil temperature were revealed. Air temperature showed a statistically positive and strong relationship (R2 = 0.79** to 0.92**) with the soil temperature both at morning and afternoon hours. Linear regression analysis indicated that each unit increase in ambient temperature would lead to increase in minimum and maximum soil temperatures by 1.04 and 1.02 degree, respectively. Statistically positive correlation was revealed among biophysical variables with the cumulative surface soil temperature. Linear and non-linear regression analysis indicated 62-69, 72-86 and 72-80% variation in Leaf area index, dry matter production and heat use efficiency in Indian mustard crop as a function of soil degree days. Below 60% variation in yield in Indian mustard was revealed as a function of soil temperature. In contrast, non-significant relationship between oil content and soil temperature was found, which suggests that oil accumulation in oilseed crops was not affected significantly by the soil temperature as an independent variable.

  5. Phytoextraction of potentially toxic elements by Indian mustard, rapeseed, and sunflower from a contaminated riparian soil.

    PubMed

    Shaheen, Sabry M; Rinklebe, Jörg

    2015-12-01

    The objective of this study was to quantify the phytoextraction of the potentially toxic elements Al, As, Cd, Co, Cr, Cu, Mo, Ni, Pb, Se, V, and Zn by Indian mustard, rapeseed, and sunflower from a contaminated riparian soil. To achieve this goal, a greenhouse pot experiment was established using a highly contaminated grassland soil collected at the Wupper River (Germany). The impact of ethylene-diamine-tetra-acetic acid (EDTA), humate (HK), and phosphate potassium (PK) on the mobility and uptake of the elements by rapeseed also was investigated. Indian mustard showed the highest efficiency for phytoextraction of Al, Cr, Mo, Se, and V; sunflower for Cd, Ni, Pb, and Zn, and rapeseed for Cu. The bioconcentration ratios were higher than 1 for the elements (except As and Cu), indicating the suitability of the studied plants for phytoextraction. Application of EDTA to the soil increased significantly the solubility of Cd, Co, Cr, Ni, and Pb and decreased the solubility of Al, As, Se, V, and Mo. Humate potassium decreased significantly the concentrations of Al and As in rapeseed but increased the concentrations of Cu, Se, and Zn. We may conclude that HK can be used for immobilization of Al and As, while it can be used for enhancing the phytoextraction of Cu, Se, and Zn by rapeseed. Phosphate potassium immobilized Al, Cd, Pb, and Zn, but enhanced phytoextraction of As, Cr, Mo, and Se by rapeseed.

  6. 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.

  7. 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. PMID:27295923

  8. Effect of electroplating factory effluent on the germination and growth of hyacinth bean and mustard.

    PubMed

    Ajmal, M; Khan, A U

    1985-12-01

    The effect of electroplating factory effluent in different concentrations (viz., 0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.5, 2.0, 2.5, 3.0, and 4.0%) on the germination and growth of hyacinth beans (Dolichos lablab) and mustard seeds (Brassica compestris) was studied. The germination of seeds was delayed with the increase of effluent concentration and the germination of mustard seeds was totally inhibited at 1.5% effluent concentration while hyacinth bean seeds tolerated the effluent up to 2.5% concentration. The metal content in the hyacinth bean plants increased with increasing effluent concentration but after 1.0% effluent concentration, the concentration of all the metals (Ca, Mg, Na, K, Cu, Zn, Fe) decreased in the plants except Cr, which increased throughout. Percentage germination, fresh weight, dry weight, root length, and shoot length of the plants were also analyzed. Cd, Ni, Co, Mn, and Pb were not detectable in the hyacinth bean plants. PMID:4065075

  9. 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.

  10. 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

  11. 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

  12. Phytoextraction of potentially toxic elements by Indian mustard, rapeseed, and sunflower from a contaminated riparian soil.

    PubMed

    Shaheen, Sabry M; Rinklebe, Jörg

    2015-12-01

    The objective of this study was to quantify the phytoextraction of the potentially toxic elements Al, As, Cd, Co, Cr, Cu, Mo, Ni, Pb, Se, V, and Zn by Indian mustard, rapeseed, and sunflower from a contaminated riparian soil. To achieve this goal, a greenhouse pot experiment was established using a highly contaminated grassland soil collected at the Wupper River (Germany). The impact of ethylene-diamine-tetra-acetic acid (EDTA), humate (HK), and phosphate potassium (PK) on the mobility and uptake of the elements by rapeseed also was investigated. Indian mustard showed the highest efficiency for phytoextraction of Al, Cr, Mo, Se, and V; sunflower for Cd, Ni, Pb, and Zn, and rapeseed for Cu. The bioconcentration ratios were higher than 1 for the elements (except As and Cu), indicating the suitability of the studied plants for phytoextraction. Application of EDTA to the soil increased significantly the solubility of Cd, Co, Cr, Ni, and Pb and decreased the solubility of Al, As, Se, V, and Mo. Humate potassium decreased significantly the concentrations of Al and As in rapeseed but increased the concentrations of Cu, Se, and Zn. We may conclude that HK can be used for immobilization of Al and As, while it can be used for enhancing the phytoextraction of Cu, Se, and Zn by rapeseed. Phosphate potassium immobilized Al, Cd, Pb, and Zn, but enhanced phytoextraction of As, Cr, Mo, and Se by rapeseed. PMID:26040974

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

    PubMed

    Lin, Long-Ze; Harnly, James M

    2010-06-01

    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.

  14. 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

  15. 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

  16. 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.

  17. 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.

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

    PubMed

    Lin, Long-Ze; Harnly, James M

    2010-06-01

    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

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

    PubMed

    Schmidt, Annette; Steinritz, Dirk; Thiermann, Horst

    2016-02-26

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

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

    PubMed Central

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

    2013-01-01

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

  2. 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. PMID:26208541

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

    SciTech Connect

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

    1995-12-31

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

  4. 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.

  5. 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...

  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. 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...

  8. 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...

  9. 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

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Allyl isothiocyanate as a component of food grade oil of mustard; exemption from the requirement of a tolerance. 180.1167 Section 180.1167 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES...

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

    PubMed Central

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

    2006-01-01

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

  11. Inhibition of Listeria monocytogenes on cooked cured chicken breasts by acidified coating containing allyl isothiocyanate or deodorized Oriental mustard extract.

    PubMed

    Olaimat, Amin N; Holley, Richard A

    2016-08-01

    Ready-to-eat meats are considered foods at high risk to cause life-threatening Listeria monocytogenes infections. This study screened 5 L. monocytogenes strains for their ability to hydrolyze sinigrin (a glucosinolate in Oriental mustard), which formed allyl isothiocyanate (AITC) and reduced L. monocytogenes viability on inoculated vacuum-packed, cooked, cured roast chicken slices at 4 °C. Tests involved incorporation of 25-50 μl/g AITC directly or 100-250 mg/g Oriental mustard extract in 0.5% (w/v) κ-carrageenan/2% (w/v) chitosan-based coatings prepared using 1.5% malic or acetic acid. L. monocytogenes strains hydrolyzed 33.6%-48.4% pure sinigrin in MH broth by 21 d at 25 °C. Acidified κ-carrageenan/chitosan coatings containing 25-50 μl/g AITC or 100-250 mg/g mustard reduced the viability of L. monocytogenes and aerobic bacteria on cooked, cured roast chicken slices by 4.1 to >7.0 log10 CFU/g compared to uncoated chicken stored at 4 °C for 70 d. Coatings containing malic acid were significantly more antimicrobial than those with acetic acid. During storage for 70 d, acidified κ-carrageenan/chitosan coatings containing 25-50 μl/g AITC or 250 mg/g mustard extract reduced lactic acid bacteria (LAB) numbers 3.8 to 5.4 log10 CFU/g on chicken slices compared to uncoated samples. Acidified κ-carrageenan/chitosan-based coatings containing either AITC or Oriental mustard extract at the concentrations tested had the ability to control L. monocytogenes viability and delay growth of potential spoilage bacteria on refrigerated, vacuum-packed cured roast chicken. PMID:27052706

  12. Microbial mutagenic effects of the DNA minor groove binder pibenzimol (Hoechst 33258) and a series of mustard analogues.

    PubMed

    Ferguson, L R; Denny, W A

    1995-06-01

    A series of aniline mustards and half-mustards targeted to DNA by linkage (through a polymethylene chain) to the bisbenzimidazole chromophore of pibenzimol (Hoechst 33258) have been evaluated for their mutagenic properties, as estimated in three strains of Salmonella typhimurium, and for their mitotic crossing-over and petite mutagenesis activities in Saccharomyces cerevisiae strain D5. Agarose gel electrophoresis studies showed that only the derivative with the longest linker chain cross-linked DNA, with the remaining compounds being monoalkylators. The parent (non-alkylator) minor groove binding ligand (Hoechst 33258) was inactive in the bacterial strains TA98 or TA100 but weakly mutagenic in TA102, and caused neither mitotic crossing-over nor 'petite' mutagenesis in yeast. Aniline half-mustard itself (monoalkylator) was an effective base-pair substitution mutagen (events in S. typhimurium strain TA100) with some frameshift mutagenesis activity in TA98, but showed only weak effects in the yeast assays, whereas aniline mustard (cross-linker) was inactive in these bacterial systems but caused substantial amounts of mitotic crossing-over in yeast. The composite molecules studied here showed effects more characteristic of the minor groove binding chromophore than of alkylating moieties. All showed weak mutagenic activity in TA102 and none in TA98. The only compound to show significant mitotic crossing-over ability was the long-chain derivative which cross-linked DNA. For most of the compounds, the mutagenicity data provided no supportive evidence for DNA alkylation. Since other evidence suggests this does occur readily, it is likely to have a different target to that seen with untargeted aniline mustards. The significant antitumor activity and low mutagenic potential shown by these compounds make them worthy of further study.

  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. PMID:25986970

  15. 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.

  16. Stigmatic receptivity determines the seed set in Indian mustard, rice and wheat crops.

    PubMed

    Gupta, Ramwant; Sutradhar, Hrishikesh; Chakrabarty, S K; Ansari, Mohhammed Wahid; Singh, Yogendra

    2015-01-01

    Stigmatic receptivity restricts the successful pollination in cereal crops. The present study deals with the biochemical test for enzymes producing in stigma of field crops such as Indian mustard, rice and wheat. The alcohol dehydrogenase and hydrogen peroxide assays revealed stigmatic receptivity as a violet color and oxygen bubbles released by the chemical reaction. Therefore, the 2 quick tests are in conformity to each other and supported the seed set data, which was utmost at blooming stage of flower ranged between 2-4 d All the 3 crops showed variation in stigmatic receptivity with respect to different time periods of blooming stages and hence, it may affects simultaneous pollen germination and tube growth, fertilization and seed set. The present finding suggests that the growth of pollen tube and stigma receptivity could be influenced by specific enzymes on stigma surface after 2-4 d of blooming stage, which contributes to proper seed set. PMID:27066163

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

    PubMed

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

    2013-12-01

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

  19. Combined effects of diphenyliodonium chloride, pine oils, and mustard oil soaps on certain microorganisms.

    PubMed

    Ahmed, Z; Siddiqui, M A; Khan, I

    1969-06-01

    Bactericidal and bacteriostatic activities of an emulsion containing 10.0% (v/v) terpineol, 0.5% (w/v) diphenyliodonium chloride, 11.0% (v/v) ethyl alcohol, and 5.62% saponified mustard oil were tested against a number of different types of organisms. The bactericidal concentration for Salmonella typhosa was 1:400. In the presence of 5.0% horse serum, it increased to 1:250. The bacteriostatic concentration varied from organism to organism; Escherichia coli and Staphylococcus aureus required 4,000 mug/ml for complete bacteriostasis, whereas Corynebacterium diphtheriae, Salmonella paratyphi-A, and Shigella required only 2,000 mug/ml for complete inhibition. A 4.0% concentration of the emulsion killed the spores of Bacillus subtilis within 6 hr.

  20. Clastogenic effects of transplacental exposure of mouse embryos to nitrogen mustard of cyclophosphamide

    SciTech Connect

    Meyne, J.; Legator, M.S.

    1983-01-01

    Embryos from day 12 pregnant Swiss mice given intraperitoneal injections of nitrogen mustard (HN/sub 2/) or cyclophosphamide (CP) were evaluated for chromosomal aberrations. Both agents induced dose-dependent increases in the frequency of cells with aberrations observed in embryos from females treated 6 hr before sacrifice. The highest frequencies of cells with aberrations were observed when females were injected 15 or 18 hr before sacrifice on day 12. A teratogenic dose of HN/sub 2/ (1.0 mg/kg) induced significantly higher frequencies of damaged cells than a teratogenic dose of CP (20 mg/kg). Cytogenetic analysis of rodent embryos from pregnant females exposed to xenobiotic agents may be an effective screening test for evaluation of genetic effects induced by transplacental exposure.

  1. The effect of 1-phenylalanine mustard on anti-globulin antibodies in multiple myeloma

    PubMed Central

    Waller, Marion; Moon, J. H.; Irby, R.; Toone, E. C.

    1971-01-01

    An immunochemical and serological study of a patient with rheumatoid arthritis who developed multiple myeloma and was treated with 1-phenylalanine mustard showed a striking difference in the effect of this drug on the rapidly dividing cells, as opposed to the resting plasma cells. The titres of anti-globulin antibodies such as the IgG serum agglutinators and the IgM rheumatoid factors were little altered although the IgG myeloma spike has disappeared following therapy. Fractionation of two different serum samples from 1966 and 1970 showed the IgG paraprotein to be serologically inactive for anti-globulin activity. This paraprotein was also characterized by producing only a single IgG precipitin line with horse anti-human whole serum antibody while the normal IgG globulins always showed a double line. ImagesFIG. 1FIG. 2FIG. 3FIG. 5 PMID:4993198

  2. 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).

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

    PubMed

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

    2013-09-01

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

  4. 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.

  5. 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.

  6. Determination of nitrogen mustard degradation products in water samples using a portable capillary electrophoresis instrument.

    PubMed

    Sáiz, Jorge; Mai, Thanh Duc; Hauser, Peter C; García-Ruiz, Carmen

    2013-07-01

    In this work, a new purpose-made portable CE instrument with a contactless conductivity detector was used for the determination of degradation products of nitrogen mustards in different water samples. The capillary was coated with poly(1-vinylpyrrolidone-co-2-dimethylaminoethyl methacrylate) to avoid analyte-wall interactions. The coating procedure was studied to obtain the best repeatability of the migration time of the analytes. Four different coating procedures were compared; flushing the capillary with the copolymer at 100 psi for 2 min at 60°C provided the best RSD values (<4%). The analytical method was also optimized. The use of 20 mM of MES adjusted to pH 6.0 with His as running buffer allowed a good baseline separation of the three analytes in different water samples without matrix interferences. The method permitted the detection of the three degradation products down to 5 μM. PMID:23686627

  7. 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. PMID:25895272

  8. Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard essential oil).

    PubMed

    Sávio, André Luiz Ventura; da Silva, Glenda Nicioli; Salvadori, Daisy Maria Fávero

    2015-01-01

    Natural compounds hold great promise for combating antibiotic resistance, the failure to control some diseases, the emergence of new diseases and the toxicity of some contemporary medical products. Allyl isothiocyanate (AITC), which is abundant in cruciferous vegetables and mustard seeds and is commonly referred to as mustard essential oil, exhibits promising antineoplastic activity against bladder cancer, although its mechanism of action is not fully understood. Therefore, the aim of this study was to investigate the effects of AITC activity on bladder cancer cell lines carrying a wild type (wt; RT4) or mutated (T24) TP53 gene. Morphological changes, cell cycle kinetics and CDK1, SMAD4, BAX, BCL2, ANLN and S100P gene expression were evaluated. In both cell lines, treatment with AITC inhibited cell proliferation (at 62.5, 72.5, 82.5 and 92.5μM AITC) and induced morphological changes, including scattered and elongated cells and cellular debris. Gene expression profiles revealed increased S100P and BAX and decreased BCL2 expression in RT4 cells following AITC treatment. T24 cells displayed increased BCL2, BAX and ANLN and decreased S100P expression. No changes in SMAD4 and CDK1 expression were observed in either cell line. In conclusion, AITC inhibits cell proliferation independent of TP53 status. However, the mechanism of action of AITC differed in the two cell lines; in RT4 cells, it mainly acted via the classical BAX/BCL2 pathway, while in T24 cells, AITC modulated the activities of ANLN (related to cytokinesis) and S100P. These data confirm the role of AITC as a potential antiproliferative compound that modulates gene expression according to the tumor cell TP53 genotype. PMID:25771977

  9. 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

  10. Nutritional evaluation of low glucosinolate mustard meals (Brassica juncea) in broiler diets.

    PubMed

    Newkirk, R W; Classen, H L; Tyler, R T

    1997-09-01

    Experiments were conducted to evaluate the nutritional value of meal derived from low glucosinolate cultivars of mustard (Brassica juncea) in comparison to samples of canola meal (Brassica napus, Brassica rapa). Samples of Brassica seed (four B. juncea, one B. napus, and one B. rapa) were processed using laboratory procedures to produce oil-extracted meals, which were examined for composition (DM basis), and nutritional value for broiler chickens as judged by nutrient retention (AMEn, ileal protein digestibility) and performance. Meals derived from B. juncea contained more CP and less total dietary fiber (TDF) on a dry basis than either B. napus or B. rapa, 45.9 vs 44.6 and 43.1% CP and 27.22 vs 29.47 and 29.67% TDF, respectively. Acid detergent fiber (ADF) and neutral detergent fiber (NDF) levels for B. juncea and B. rapa meals were similar to each other, but lower than those of B. napus, 12.79 and 13.20 vs 20.6% ADF, and 21.15 and 19.58 vs 29.47% NDF, respectively. Brassica juncea meals contained more glucosinolates than B. napus and B. rapa, 34.3 vs 21.8 and 25.5 mumol/g total glucosinolates, respectively. Brassica juncea meals were equal or superior to B. napus and B. rapa meals for AMEn and apparent ileal protein digestibility. Similarly, broilers fed B. juncea meals grew as quickly and converted feed to BW gain as efficiently to 21 d of age as those birds fed B. napus and B. rapa meals. Feeding meal from B. rapa reduced growth rate and gain to feed ratio. In conclusion, the nutritional value of meal from low glucosinolate mustard was equal or superior to that of canola meal samples derived from B. napus and B. rapa cultivars.

  11. Inverse relationship between splenomegaly and stem cell compartment size in mice treated with nitrogen mustard.

    PubMed

    Jensen, R H; Sharp, J G; Zajic, G H; Anderson, R W

    1977-04-01

    Following the administration of similar doses of nitrogen mustard (4 mg/kg) to different strains of mice, wide variations in the subsequent degree of splenomegaly were observed, implying strain differences in the role of the spleen in the compensatory erythropoietic response to haematopoietic stress. This investigation was undertaken to determine whether or not these differences were related to the size of the haematopoietic stem cell compartment size in the various strains of mice. Groups of 4 different strains of mice (Swiss Webster, A/J, C57BL/6J and CS1/ASH) were injected i.v. with nitrogen mustard (4 mg/kg body weight) and autopsied at regular intervals up to 20 d post-injection. At autopsy, the wet weight of the spleen was determined. Subsequently, groups of the same 4 strains of mice were exposed to single doses of wholebody gamma-irradiation in the range of 500-900 rads. 9 d after gamma-irradiation the mice were autopsied, their spleens removed, and the number of endogenous spleen colonies determined. The greatest degree of splenomegaly was observed in the C57BL/6J mice. The Swiss Webster mice showed no splenomegaly during the time period studied. There existed a linear inverse relationship between the maximum degree of splenomegaly observed and the dose of wholebody gamma-irradiation required to completely eliminate endogenous spleen colonies. This data is in accord with the hypothesis that there exists an inverse relationship between the extent of splenomegaly observed following haematopoietic stress and the haematopoietic stem cell compartment size.

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

    PubMed Central

    McNutt, Patrick; Lyman, Megan; Swartz, Adam; Tuznik, Kaylie; Kniffin, Denise; Whitten, Kim; Milhorn, Denise; Hamilton, Tracey

    2012-01-01

    A subset of victims of ocular sulfur mustard (SM) exposure develops an irreversible, idiotypic keratitis with associated secondary pathologies, collectively referred to as mustard gas keratopathy (MGK). MGK involves a progressive corneal degeneration resulting in chronic ocular discomfort and impaired vision for which clinical interventions have typically had poor outcomes. Using a rabbit corneal vapor exposure model, we previously demonstrated a clinical progression with acute and chronic sequelae similar to that observed in human casualties. However, a better understanding of the temporal changes that occur during the biphasic SM injury is crucial to mechanistic understanding and therapeutic development. Here we evaluate the histopathologic, biochemical and ultrastructural expressions of pathogenesis of the chronic SM injury over eight weeks. We confirm that MGK onset exhibits a biphasic trajectory involving corneal surface regeneration over the first two weeks, followed by the rapid development and progressive degeneration of corneal structure. Preclinical markers of corneal dysfunction were identified, including destabilization of the basal corneal epithelium, basement membrane zone abnormalities and stromal deformation. Clinical sequelae of MGK appeared abruptly three weeks after exposure, and included profound anterior edema, recurring corneal erosions, basement membrane disorganization, basal cell necrosis and stromal degeneration. Unlike resolved corneas, MGK corneas exhibited frustrated corneal wound repair, with significantly elevated histopathology scores. Increased lacrimation, disruption of the basement membrane and accumulation of pro-inflammatory mediators in the aqueous humor provide several mechanisms for corneal degeneration. These data suggest that the chronic injury is fundamentally distinct from the acute lesion, involving injury mechanisms that operate on different time scales and in different corneal tissues. Corneal edema appears to be the

  13. Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard essential oil).

    PubMed

    Sávio, André Luiz Ventura; da Silva, Glenda Nicioli; Salvadori, Daisy Maria Fávero

    2015-01-01

    Natural compounds hold great promise for combating antibiotic resistance, the failure to control some diseases, the emergence of new diseases and the toxicity of some contemporary medical products. Allyl isothiocyanate (AITC), which is abundant in cruciferous vegetables and mustard seeds and is commonly referred to as mustard essential oil, exhibits promising antineoplastic activity against bladder cancer, although its mechanism of action is not fully understood. Therefore, the aim of this study was to investigate the effects of AITC activity on bladder cancer cell lines carrying a wild type (wt; RT4) or mutated (T24) TP53 gene. Morphological changes, cell cycle kinetics and CDK1, SMAD4, BAX, BCL2, ANLN and S100P gene expression were evaluated. In both cell lines, treatment with AITC inhibited cell proliferation (at 62.5, 72.5, 82.5 and 92.5μM AITC) and induced morphological changes, including scattered and elongated cells and cellular debris. Gene expression profiles revealed increased S100P and BAX and decreased BCL2 expression in RT4 cells following AITC treatment. T24 cells displayed increased BCL2, BAX and ANLN and decreased S100P expression. No changes in SMAD4 and CDK1 expression were observed in either cell line. In conclusion, AITC inhibits cell proliferation independent of TP53 status. However, the mechanism of action of AITC differed in the two cell lines; in RT4 cells, it mainly acted via the classical BAX/BCL2 pathway, while in T24 cells, AITC modulated the activities of ANLN (related to cytokinesis) and S100P. These data confirm the role of AITC as a potential antiproliferative compound that modulates gene expression according to the tumor cell TP53 genotype.

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

    PubMed

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

    2015-01-01

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

  15. Accumulation, detoxification, and genotoxicity of heavy metals in Indian mustard (Brassica juncea L.).

    PubMed

    Seth, C S; Misra, V; Chauhan, L K S

    2012-01-01

    Plants of Indian mustard (Brassica juncea L.) were exposed to different concentrations (15, 30, 60, 120 microM) of (Cd, Cr, Cu, Pb) for 28 and 56 d for accumulation and detoxification studies. Metal accumulation in roots and shoots were analyzed and it was observed that roots accumulated a significant amount of Cd (1980 microg g(-1) dry weight), Cr (1540 microg g(-1) dry weight), Cu (1995 microg g(-1) dry weight), and Pb (2040 microg g(-1) dry weight) after 56 d of exposure, though in shoot this was 1110, 618, 795, and 409 microg g(-1) dry weight of Cd, Cr, Cu, and Pb, respectively. In order to assess detoxification mechanisms, non-protein thiols (NP-SH), glutathione (GSH) and phytochelatins (PCs) were analyzed in plants. An increase in the quantity of NP-SH (9.55), GSH (8.30), and PCs (1.25) micromol g(-1) FW were found at 15 microM of Cd, however, a gradual decline in quantity was observed from 15 microM of Cd onwards, after 56 d of exposure. For genotoxicity in plants, cytogenetic end-points such as mitotic index (MI), micronucleus formation (MN), mitotic aberrations (MA) and chromosome aberrations (CA) were examined in root meristem cells of B. juncea. Exposure of Cd revealed a significant (P < 0.05) inhibition of MI, induction of MA, CA, and MN in the root tips for 24 h. However, cells examined at 24 h post-exposure showed concentration-wise recovery in all the endpoints. The data revealed that Indian mustard could be used as a potential accumulator of Cd, Cr, Cu, and Pb due to a good tolerance mechanisms provided by combined/concerted action of NP-SH, GSH, and PCs. Also, exposure of Cd can cause genotoxic effects in B. juncea L. through chromosomal mutations, MA, and MN formation.

  16. 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

  17. Chronic alteration in phosphatidylinositol 4,5-bisphosphate levels regulates capsaicin and mustard oil responses

    PubMed Central

    Patil, Mayur J.; Belugin, Sergei; Akopian, Armen N.

    2011-01-01

    There is an agreement that acute (in minutes) hydrolysis and accumulation of phosphatidylinositol 4,5-bisphosphate (PIP2) modulate TRPV1 and TRPA1 activities. Since inflammation results in PIP2 depletion, persisting for long periods (hours-to-days) in pain models and in clinic, we examined whether chronic depletion and accumulation of PIP2 affects capsaicin and mustard oil responses. In addition we also wanted to evaluate whether the effects of PIP2 depend on TRPV1 and TRPA1 co-expression, and whether the PIP2 actions vary in expression cells versus sensory neurons. Chronic PIP2 production was stimulated by over-expression of phosphatidylinositol-4-phosphate-5-kinase, while PIP2-specific phospholipid 5′-phosphatase was selected to reduce plasma membrane levels of PIP2. Our results demonstrate that capsaicin (100 nM; CAP) responses and receptor tachyphylaxis are not significantly influenced by chronic changes in PIP2 levels in wild-type (WT) or TRPA1 null-mutant sensory neurons, as well as CHO cells expressing TRPV1 alone or with TRPA1. However, low concentrations of CAP (20 nM) produced a higher response after PIP2 depletion in cells containing TRPV1 alone, but not TRPV1 together with TRPA1. Mustard oil (25 μM; MO) responses were also not affected by PIP2 in WT sensory neurons and cells co-expressing TRPA1 and TRPV1. In contrast, PIP2 reduction leads to pronounced tachyphylaxis to MO in cells with both channels. Chronic effect of PIP2 on TRPA1 activity depends on presence of the TRPV1 channel and cell type (CHO vs. sensory neurons). In summary, chronic alterations in PIP2 levels regulate magnitude of CAP and MO responses, as well as MO-tachyphylaxis. This regulation depends on co-expression profile of TRPA1 and TRPV1 and cell type. PMID:21337373

  18. 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.

  19. Impacts of mustard gas exposure on veterans mental health: A study on the role of education

    PubMed Central

    Karami, Gholam-Reza; Ameli, Javad; Roeintan, Rahim; Jonaidi-Jafari, Nematollah; Saburi, Amin

    2013-01-01

    Background: The mustard gas (MG) exposure can impair physical health and therefore increase the probability of the posttraumatic stress disorder (PTSD) and psychological disorders. Aim: The aim of this study was to investigate long-term effects of MG exposure on veterans’ mental health. Materials and Methods: This was a cross-sectional study. In order to assess prevalence of mental health and PTSD of 100 MG victims 25 years after the exposure to MG in Iran-Iraq conflict, the general health questionnaire (GHQ-28) and Impact of Event Scale-Revised, respectively was administered. Results: The mean (±standard deviation (SD)) age of participants was 40.63 (±5.86) years. The mean GHQ-28 (47.34) of the study group was higher compared to standardized cutoff point (23) of the Iranian community. Also, it was found that 38 participants (38%) suffer from PTSD. The results of this study showed that academic education in the PTSD group was less than that in the non-PTSD group (P=0.03). In addition, in multivariate analysis it was found that only education level of the veterans and their wives were effective on the mental health score (adjusted P=0.036 and 0.041, respectively). The mean score of depression and psychosocial activity subscale in patients at higher education level was lower than patients at lower education level (P<0.05). Conclusion: This study found that sulfur mustard (SM) exposure can be effect on mental health even 25 years after exposure. Therefore, the psychological state should be more considered in chemical injured veterans and it is important that providing more mental health centers for this community. PMID:24459369

  20. Enhanced cytostatic effectiveness of aniline mustard against 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors during regression in response to ovariectomy.

    PubMed

    Benckhuysen, C; Ter Hart, H G; Van Dijk, P J

    1981-01-01

    Sprague-Dawley rats bearing 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors were treated with either of two aromatic alkylating agents, aniline mustard or melphalan, alone or combined with ovariectomy. Both drugs were applied once a week for 8 weeks. Eight-four percent of the tumors responded to ovariectomy, 38% regressing completely and 46% regressing partially. Aniline mustard, though virtually ineffective as a single agent, appeared synergistic with ovariectomy: a 100% regression rate (72% complete, 28% partial) was observed for this combination. Treatment with melphalan was as effective as ovariectomy, but the combination of melphalan with ovariectomy was no more effective than either treatment alone. The end product of aniline mustard metabolism, p-hydroxyaniline mustard O-glucuronide, may be more extensively activated by beta-glucuronidase in hormonally regressing than in growing or stationary tumors. Intratumoral levels of beta-glucoronidase occurring in DMBA-induced tumors 4 days after ovariectomy were found to be similar to those in the aniline mustard-sensitive mouse plasma cell tumor ADJ/PC6. It remains to be more extensively studied whether an effect of endocrine treatment on tumor beta-glucuronidase levels, and possibly on intracellular distribution of enzyme, could be used therapeutically. An effectively scheduled cytostatic treatment (with a drug conjugate such as that formed metabolically from aniline mustard) in conjunction with ovariectomy might be effective in the treatment of hormone-responsive breast cancer.

  1. 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. PMID:24516460

  2. 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

  3. [Photocatalytic removing of a mustard gas analogue 2-CEES vapor over SO4(2-)/TiO2].

    PubMed

    Han, Shi-tong; Xi, Hai-ling; Wang, Xu-xu; Fu, Xian-zhi

    2005-05-01

    Disinfection with photocatalysis, compared to with the conventional cleanout, is both high efficient and non contaminative, but the simple TiO2 photocatalyst is showing to be of low activity and low active stability so to be hardly practical application. In the paper, SO4(2-)/TiO2 were papered by surface modification of TiO2 with dilute H2SO4, and the photocatalytic degradation of 2-chloroethyl ethyl sulfide (2-CEES) on the samples was examined in a fixed-bed microreactor. The examination show that the acidic modification enhanced both the activity and the active stability of TiO2, and the sample ST200 prepared by calcination at 200 degrees C was better than ST400 by calcination at 400 degrees C. The effect of water vapor content and reaction temperature on the photocatalytic degradation of 2-CEES was also tested, showing that the sample ST200 had high activity and stability at 90 degrees C, and kept a constant activity when adding 30.5 mL/L water vapor into the reactive system in which 2-CEES initial concentration was low to < 61 microL x L(-1). In addition, it was found that supporting SO4(2-)/TiO2 on gamma-Al2O3, SiO2 and active carbon could improve on the activity and stability of SO4(2-)/TiO2, and on supports SiO2 is the best one.

  4. Effects of mercury on visible/near-infrared reflectance spectra of mustard spinach plants (Brassica rapa P.).

    PubMed

    Dunagan, Sarah C; Gilmore, Martha S; Varekamp, Johan C

    2007-07-01

    Mustard spinach plants were grown in mercury-spiked and contaminated soils collected in the field under controlled laboratory conditions over a full growth cycle to test if vegetation grown in these soils has discernible characteristics in visible/near-infrared (VNIR) spectra. Foliar Hg concentrations (0.174-3.993ppm) of the Mustard spinach plants were positively correlated with Hg concentration of soils and varied throughout the growing season. Equations relating foliar Hg concentration to spectral reflectance, its first derivative, and selected vegetation indices were generated using stepwise multiple linear regression. Significant correlations are found for limited wavelengths for specific treatments and dates. Ratio Vegetation Index (RVI) and Red Edge Position (REP) values of plants in Hg-spiked and field-contaminated soils are significantly lower relative to control plants during the early and middle portions of the growth cycle which may be related to lower chlorophyll abundance or functioning in Hg-contaminated plants.

  5. 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.

  6. 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.

  7. 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.

  8. Urinary and cutaneous complications of sulphur mustard poisoning preceding pulmonary and ocular involvement: an unusual sequence of symptoms.

    PubMed

    Emadi, S N; Moeineddin, F; Sorush, M R

    2009-07-01

    Sulphur mustard was used as a disabling chemical warfare agent during World War I, and, in more recent times, the Iran-Iraq conflict. Various chronic and acute complications have been documented in almost 100,000 Iranian victims to date. Several individual and environmental factors affect the severity and persistency of the complications. The most common adverse effects occur in the respiratory system, skin and eyes, with ocular and respiratory features usually preceding cutaneous lesions. In this paper, we present the unusual case of a chemical victim presenting with characteristic mustard scar leading to stenosis of the external meatus. In this case, initial cutaneous involvement of the injured external genitalia and thighs preceded the ocular and respiratory symptoms. We discuss the possible aetiologies.

  9. Synergistic action of tropospheric ozone and carbon dioxide on yield and nutritional quality of Indian mustard (Brassica juncea (L.) Czern.).

    PubMed

    Singh, Satyavan; Bhatia, Arti; Tomer, Ritu; Kumar, Vinod; Singh, B; Singh, S D

    2013-08-01

    Field experiments were conducted in open top chamber during rabi seasons of 2009-10 and 2010-11 at the research farm of the Indian Agricultural Research Institute, New Delhi to study the effect of tropospheric ozone (O3) and carbon dioxide (CO2) interaction on yield and nutritional quality of Indian mustard (Brassica juncea (L.) Czern.). Mustard plants were grown from emergence to maturity under different treatments: charcoal-filtered air (CF, 80-85 % less O3 than ambient O3 and ambient CO2), nonfiltered air (NF, 5-10 % less O3 than ambient O3 and ambient CO2 ), nonfiltered air with elevated carbon dioxide (NF + CO2, NF air and 550 ± 50 ppm CO2), elevated ozone (EO, NF air and 25-35 ppb elevated O3), elevated ozone along with elevated carbon dioxide (EO + CO2, NF air, 25-35 ppb O3 and 550 ± 50 ppm CO2), and ambient chamber less control (AC, ambient O3 and CO2). Elevated O3 exposure led to reduced photosynthesis and leaf area index resulting in decreased seed yield of mustard. Elevated ozone significantly decreased the oil and micronutrient content in mustard. Thirteen to 17 ppm hour O3 exposure (accumulated over threshold of 40 ppm, AOT 40) reduced the oil content by 18-20 %. Elevated CO2 (500 ± 50 ppm) along with EO was able to counter the decline in oil content in the seed, and it increased by 11 to 13 % over EO alone. Elevated CO2, however, decreased protein, calcium, zinc, iron, magnesium, and sulfur content in seed as compared to the nonfiltered control, whereas removal of O3 from air in the charcoal-filtered treatment resulted in a significant increase in the same.

  10. 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. PMID:25765856

  11. Transvenous cardiac resynchronization therapy in complex congenital heart diseases: dextrocardia with transposition of the great arteries after Mustard operation.

    PubMed

    Zartner, Peter A; Wiebe, Walter; Volkmer, Marius; Thomas, Daniel; Schneider, Martin

    2009-04-01

    Cardiac resynchronization therapy revealed first promising results in patients with a congenital heart disease and a systemic right ventricle. Contrast-enhanced magnetic resonance imaging showed accessibility of the coronary sinus in an 18-year-old male patient with mirror dextrocardia, d-transposition of the great arteries and ventricular septal defect (VSD) after Mustard operation and VSD patch closure. In literatures, transvenous lead placement is discussed in this anatomical setting, with opposed position of the ventricular leads and reliable lead characteristics.

  12. 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.

  13. Elicitation of jasmonate-mediated host defense in Brassica juncea (L.) attenuates population growth of mustard aphid Lipaphis erysimi (Kalt.).

    PubMed

    Koramutla, Murali Krishna; Kaur, Amandeep; Negi, Manisha; Venkatachalam, Perumal; Bhattacharya, Ramcharan

    2014-07-01

    The productivity of Brassica oilseeds is severely affected by its major pest: aphids. Unavailability of resistance source within the crossable germplasms has stalled the breeding efforts to derive aphid resistant cultivars. In this study, jasmonate-mediated host defense in Indian mustard Brassica juncea (L.) Czern. was evaluated and compared with regard to its elicitation in response to mustard aphid Lipaphis erysimi (Kalt.) and the defense elicitor methyl jasmonate (MeJ). Identification of jasmonate-induced unigenes in B. juncea revealed that most are orthologous to aphid-responsive genes, identified in taxonomically diverse plant-aphid interactions. The unigenes largely represented genes related to signal transduction, response to biotic and abiotic stimuli and homeostasis of reactive oxygen species (ROS), in addition to genes related to cellular and metabolic processes involved in cell organization, biogenesis, and development. Gene expression studies revealed induction of the key jasmonate biosynthetic genes (LOX, AOC, 12-OPDR), redox genes (CAT3 and GST6), and other downstream defense genes (PAL, ELI3, MYR, and TPI) by several folds, both in response to MeJ and plant-wounding. However, interestingly aphid infestation even after 24 h did not elicit any activation of these genes. In contrast, when the jasmonate-mediated host defense was elicited by exogenous application of MeJ the treated B. juncea plants showed a strong antibiosis effect on the infesting aphids and reduced the growth of aphid populations. The level of redox enzymes CAT, APX, and SOD, involved in ROS homeostasis in defense signaling, and several defense enzymes viz. POD, PPO, and PAL, remained high in treated plants. We conclude that in B. juncea, the jasmonate activated endogenous-defense, which is not effectively activated in response to mustard aphids, has the potential to reduce population growth of mustard aphids. PMID:24771023

  14. 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.

  15. Long-term effects of mustard gas on respiratory system of Iranian veterans after Iraq-Iran war: a review.

    PubMed

    Razavi, Seyed-Mansour; Ghanei, Mostafa; Salamati, Payman; Safiabadi, Mehdi

    2013-01-01

    To review long-term respiratory effects of mustard gas on Iranian veterans having undergone Iraq-Iran war. Electronic databases of Scopus, Medline, ISI, IranMedex, and Irandoc sites were searched. We accepted articles published in scientific journals as a quality criterion.The main pathogenic factors are free radical mediators. Prevalence of pulmonary involvement is approximately 42.5%. The most common complaints are cough and dyspnea. Major respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, and asthma. Spirometry results can reveal restrictive and obstructive pulmonary disease. Plain chest X-ray does not help in about 50% of lung diseases. High-resolution CT of the lung is the best modality for diagnostic assessment of parenchymal lung and bronchi. There is no definite curative treatment for mustard lung. The effective treatment regimens consist of oxygen administration, use of vaporized moist air, respiratory physiotherapy, administration of mucolytic agents, bronchodilators, corticosteroids, and long-acting beta-2 agonists, antioxidants, surfactant, magnesium ions, therapeutic bronchoscopy, laser therapy, placement of respiratory stents, early tracheostomy in laryngospasm, and ultimately lung transplantation. High-resolution CT of the lung is the most accurate modality for the evaluation of the lung parenchyma and bronchi. The treatment efficacy of patients exposed to mustard gas depends on patient conditions (acute or chronic, upper or lower respiratory tract involvement). There are various treatment protocols, but unfortunately none of them is definitely curable. PMID:23735551

  16. 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. PMID:23411305

  17. 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.

  18. 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.

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

    PubMed

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

    2013-10-01

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

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

    PubMed

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

    1989-08-01

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

  1. 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.

  2. Role of Trichoderma harzianum in mitigating NaCl stress in Indian mustard (Brassica juncea L) through antioxidative defense system.

    PubMed

    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

  3. Role of Trichoderma harzianum in mitigating NaCl stress in Indian mustard (Brassica juncea L) through antioxidative defense system.

    PubMed

    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

  4. 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

  5. Survival and Transfer of Murine Norovirus within a Hydroponic System during Kale and Mustard Microgreen Harvesting.

    PubMed

    Wang, Qing; Kniel, Kalmia E

    2016-01-01

    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

  6. 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

  7. 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

  8. 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. PMID:27275005

  9. Mustard seeds (Sinapis Alba Linn) attenuate azoxymethane-induced colon carcinogenesis.

    PubMed

    Yuan, Haifeng; Zhu, Minggu; Guo, Wen; Jin, Ling; Chen, Weihong; Brunk, Ulf T; Zhao, Ming

    2011-01-01

    Mustard seeds (MS), which are consumed in considerable amounts by the Japanese people that, interestingly, have the longest life expectancy in the world, are known to contain a number of yet not fully defined but quite powerful anti-oxidants. A suspension of extracted MS was found to suppress oxidized-LDL-induced macrophage respiratory burst in vitro, to prevent growth, and to induce apoptotic death of SW480 cells (a human colon cancer cell line), while no such effects were found for normal 3T3 cells. A diet enriched with MS decreased plasma levels of the lipid peroxidation product malonaldehyde in mice exposed to the colon cancer-inducer azoxymethane (AOM). Such a diet also dose-dependently enhanced the activity of several anti-oxidant enzymes, such as superoxide dismutase (SOD), catalase, and GSH-peroxidase and, moreover, reduced AOM-mediated formation of colon adenomas by about 50%. Further studies are required to detail and explore the beneficial effects of MS and their rich content of powerful anti-oxidants. PMID:21605497

  10. Inorganic materials as ameliorants for soil remediation of metal toxicity to wild mustard (Sinapis arvensis L.).

    PubMed

    Ribeiro Filho, Mateus Rosas; Siqueira, José Oswaldo; Vangronsveld, Jaco; Soares, Cláudio Roberto Fonsêca Sousa; Curi, Nilton

    2011-01-01

    The ameliorating effects of different inorganic materials were investigated on a soil originating from a zinc smelter dumping site contaminated by toxic metals. Wild mustard (Sinapis arvensis L.) was used as a test plant. The soil was amended with different doses of mining sludge, Perferric Red Latosol (LVj), steel shots, cyclonic ash, silifertil, and superphosphate. The most effective amendments improved plant growth with 45% and reduced metal uptake by over 70% in comparison to untreated soil. Reductions in availability as estimated by BaCl2-extractable metals reached up to 90% for Zn and 65% for Cd as compared to unamended soil. These reductions were associated with lower shoot and root metal contents. Shoot Zn content was reduced from 1,369 microg g(-1) in plants grown on untreated soil to 377 microg g(-1) when grown on cyclonic ash amended soil while Cd decreased from 267 to 44 microg g(-1) in steel shots amended soil. Superphosphate addition had no ameliorating effect. On the contrary, it increased BaCl2-extractable amounts of Zn. Considering all parameters we determined, steel shots, cyclonic ash and silifertil are the most promising for remediating metal contaminated soil in the tropics. Further studies evaluating impacts, cost-effectiveness and durability of effects will be conducted. PMID:21598779

  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. Biorefinery process for protein extraction from oriental mustard (Brassica juncea (L.) Czern.) using ethanol stillage.

    PubMed

    Ratanapariyanuch, Kornsulee; Tyler, Robert T; Shim, Youn Young; Reaney, Martin Jt

    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

  13. 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. PMID:21622327

  14. 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

  15. 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

  16. Impregnated silica nanoparticles for the reactive removal of sulphur mustard from solutions.

    PubMed

    Singh, Beer; Saxena, Amit; Nigam, Anil Kumar; Ganesan, Kumaran; Pandey, Pratibha

    2009-01-30

    High surface area (887.3m(2)/g) silica nanoparticles were synthesized using aerogel route and thereafter, characterized by N(2)-Brunauer-Emmet-Teller (BET), SEM and TEM techniques. The data indicated the formation of nanoparticles of silica in the size range of 24-75 nm with mesoporous characteristics. Later, these were impregnated with reactive chemicals such as N-chloro compounds, oxaziridines, polyoxometalates, etc., which have already been proven to be effective against sulphur mustard (HD). Thus, developed novel mesoporous reactive sorbents were tested for their self-decontaminating feature by conducting studies on kinetics of adsorptive removal of HD from solution. Trichloroisocyanuric acid impregnated silica nanoparticles (10%, w/w)-based system was found to be the best with least half-life value (t(1/2)=2.8 min) among prepared systems to remove and detoxify HD into nontoxic degradation products. Hydrolysis, dehydrohalogenation and oxidation reactions were found to be the route of degradation of HD over prepared sorbents. The study also inferred that 10% loading of impregnants over high surface area and low density silica nanoparticles enhances the rate of reaction kinetics and seems to be useful in the field of heterogeneous reaction kinetics.

  17. 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

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

    PubMed

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

    2010-04-01

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

  19. 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.

  20. 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.