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Sample records for model sulfur mustard

  1. Sulfur Mustard

    Science.gov (United States)

    ... Poisoning Methyl isocyanate Case Definition: Methyl Isocyanate Poisoning Mustard gas (H) (sulfur mustard) Facts About Sulfur Mustard Case ... About Strychnine Case Definition: Strychnine Sulfur mustard (H) (mustard gas) Facts About Sulfur Mustard Case Definition: Vesicant (Mustards, ...

  2. Toxicokinetics of sulfur mustard

    NARCIS (Netherlands)

    Langenberg, J.P.; Schans, M.J. van der; Noort, D.

    2016-01-01

    In this chapter an overview is presented on the state of knowledge concerning the toxicokinetics of sulfur mustard. The procedures to analyze intact sulfur mustard in the blood and tissues of laboratory animals at toxicologically relevant levels are discussed. In view of the fact that the reviewed

  3. Quantum molecular modeling of the interaction between guanine and alkylating agents--1--sulfur mustard.

    Science.gov (United States)

    Broch, H; Hamza, A; Vasilescu, D

    1996-06-01

    Interaction between Guanine and the episulfonium form of Sulfur mustard (HD) was studied using the ab initio LCAO-MO method at the HF/6-31G level. The alkylation mechanism on guanine-N7 was analyzed by using a supermolecular modeling. Our stereostructural results associated with the molecular electrostatic potentials and HOMO-LUMO properties, show that in vacuum the alkylation of the N7 of guanine by HD in the aggressive episulfonium form is a direct process without transition state and of which the pathway is determined.

  4. Ocular Effects of Sulfur Mustard

    Directory of Open Access Journals (Sweden)

    Yunes Panahi

    2013-06-01

    Full Text Available Purpose: To review current knowledge about ocular effects of sulfur mustard (SM and the associated histopathologic findings and clinical manifestationsMethods: Literature review of medical articles (human and animal studies was accomplished using PubMed, Scopus and ISI databases. A total of 274 relevant articles in English were retrieved and reviewed thoroughly.Results: Eyes are the most sensitive organs to local toxic effects of mustard gas. Ocular injuries are mediated through different toxic mechanisms including: biochemical damages, biomolecular and gene expression modification, induction of immunologic and inflammatory reactions, disturbing ultrastructural architecture of the cornea, and long-lasting corneal denervation. The resulting ocular injuries can roughly be categorized into acute or chronic complications. Most of the patients recover from acute injuries, but a minority of victims will suffer from chronic ocular complications. Mustard gas keratopathy (MGK is a devastating late complication of SM intoxication that proceeds from limbal stem cell deficiency (LSCD.Conclusion: SM induces several different damaging changes in case of ocular exposure; hence leading to a broad spectrum of ocular manifestations in terms of severity, timing and form. Unfortunately, no effective strategy has been introduced yet to inhibit or restore these damaging changes.

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

    Science.gov (United States)

    2010-01-01

    8923 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Issue: Thymosins in Health and Disease Progression of ocular sulfur mustard injury: development of a...suggesting either inmigration of CE cells or an expansion of the erosion. Changes in the size and shape of the margins between 24 and 48 h suggest a...dynamic interplay between ex- pansion and inmigration . The lesion is either sig- nificantly reduced in size or gone by 72 h, and is completely resolved

  6. Sulfur Mustard Damage to Cornea: Preventive Studies

    National Research Council Canada - National Science Library

    Varma, Shambhu

    2004-01-01

    .... A preventive effect has been observed at the level of tissue morphology. Studies are in progress at the level of cellular metabolism, Here, CEES has been used as a representative compound simulating the action of sulfur mustard (HD...

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yoke-Chen; Wang, James D. [Rutgers University, Pharmacology and Toxicology, 170 Frelinghuysen Rd, Piscataway, NJ 08854 (United States); Svoboda, Kathy K. [Texas A and M University, Baylor College of Dentistry, Center for Craniofacial Research 3302 Gaston Ave, Dallas, Texas 75246 (United States); Casillas, Robert P. [MRIGlobal, 425 Volker Boulevard, Kansas City, MO 64110 (United States); Laskin, Jeffrey D. [UMDNJ-Robert Wood Johnson Medical School, Environmental and Occupational Medicine, 170 Frelinghuysen Rd, Piscataway, NJ 08854 (United States); Gordon, Marion K. [Rutgers University, Pharmacology and Toxicology, 170 Frelinghuysen Rd, Piscataway, NJ 08854 (United States); Gerecke, Donald R., E-mail: gerecke@eohsi.rutgers.edu [Rutgers University, Pharmacology and Toxicology, 170 Frelinghuysen Rd, Piscataway, NJ 08854 (United States)

    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.

  9. Nitrogen Mustards

    Science.gov (United States)

    ... Poisoning Methyl isocyanate Case Definition: Methyl Isocyanate Poisoning Mustard gas (H) (sulfur mustard) Facts About Sulfur Mustard Case ... About Strychnine Case Definition: Strychnine Sulfur mustard (H) (mustard gas) Facts About Sulfur Mustard Case Definition: Vesicant (Mustards, ...

  10. Wound Healing of Cutaneous Sulfur Mustard Injuries

    Science.gov (United States)

    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

  11. Accidental sulfur mustard exposure: A case report.

    Science.gov (United States)

    Schmidt, Annette; Steinritz, Dirk; Rudolf, Klaus-Dieter; Thiermann, Horst; Striepling, Enno

    2017-11-28

    The clinical progression following a sulfur mustard-induced skin exposure is well documented in the literature. Upon skin contact and a characteristic latency period, sulfur mustard (SM) causes erythema, blister formation and ulceration, which is associated with wound healing disorders that may require surgical treatment. Here, we present a case report of accidental exposure to SM in a laboratory setting which required surgical treatment of the skin. The case was illustrated at close intervals over a period of two years and underlines that exposure to SM has to be taken into account when typical clinical symptoms occur. Moreover skin grafts appear to be effective in SM-induced non healing skin ulcerations. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Novel Molecular Strategies Against Sulfur Mustard Toxicity

    Directory of Open Access Journals (Sweden)

    Zeki Ilker Kunak

    2012-04-01

    Full Text Available Among the available chemical warfare agents, sulfur mustard (SM, also known as mustard gas, has been widely used chemical weapon. In our laboratory, we have shown that, acute toxicity of SM is related to reactive oxygen and nitrogen species, DNA damage, poly(ADP-ribose polymerase activation and energy depletion within the affected cell. In spite of the knowledge about acute SM-induced cellular toxicity, unfortunately, it is not clear how mustard gas causes severe multi-organ damage years after even a single exposure. A variety of treatment modalities including antioxidants, anti-inflammatory drugs and others have resulted no promising results. We, therefore, made an attempt whether epigenetic aberrations may contribute to pathogenesis of mustard poisoning. The term epigenetic describes the study of inheritable alterations in gene expression that occur in the absence of changes in genome sequence. Therefore, epigenetic gene regulation requires molecular mechanisms that encode information in addition to the DNA base sequence and can be propagated through mitosis and meiosis. Our current understanding of epigenetic regulation of gene expression involves basically two classes of molecular mechanisms: histone modifications and DNA methylation. Preliminary evidence obtained from our laboratory reveals that exposure to mustards may not only cause nitro-oxidative stress and DNA (genetic damage, but epigenetic perturbations as well. Epigenetic therapy is a new and rapidly developing field in pharmacology. Epigenetic drugs alone or in combination with conventional drugs may prove to be a significant advance over the conventional drugs used to treat both acute and delayed SM toxicity. Future studies are urgently needed to clarify the mechanism of delayed SM-induced toxicity and novel treatment modalities. [TAF Prev Med Bull 2012; 11(2.000: 231-236

  13. Time course of lesion development in the hairless guinea-pig model of sulfur mustard-induced dermal injury

    Science.gov (United States)

    Benson, Janet M.; Seagrave, JeanClare; Weber, Waylon M.; Santistevan, Colleen D.; Grotendorst, Gary R.; Schultz, Gregory S.; March, Thomas H.

    2013-01-01

    The objective of these studies was to provide detailed analyses of the time course of sulfur mustard (SM) vapor-induced clinical, histological, and biochemical changes following cutaneous exposure in hairless guinea-pigs. Three 6cm2 sites on the backs of each guinea-pig were exposed to SM vapor (314 mg3) for 6 minutes (low dose) or 12 minutes (high dose). Animals were killed at 6, 24, and 48 hours, or 2 weeks postexposure. Erythema, edema, histopathology, and analysis of matrix metalloproteinase (MMP)-2 and -9 content were evaluated. Erythema was observed by 6 hours, and edema by 24 hours postexposure. Vapor exposure caused epidermal necrosis with varying degrees of dermatitis, ulceration, hemorrhage, and separation of the dermis from the epidermis. Later changes included epidermal regeneration with hyperplasia and formation of granulation tissue in the dermis with loss of hair follicles and glandular structures. Relative amounts of pro and active MMP-2 and MMP-9 were significantly increased in the high-dose SM group at 2 weeks. Erythema, edema, and histologic changes are consistent with findings among human victims of SM attack. This model, with observations to 2 weeks, will be useful in assessing the efficacy of countermeasures against SM. PMID:21410818

  14. 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

    International Nuclear Information System (INIS)

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

    2010-01-01

    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 TM , a commercially available full-thickness human skin equivalent. CEES (100-1000 μM) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300-1000 μM), 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 2 synthases, leukotriene (LT) A 4 hydrolase and LTC 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.

  15. Effects of Exposure to Sulfur Mustard on Speech Aerodynamics

    Science.gov (United States)

    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. Protection Against the Acute and Delayed Toxicities of Sulfur Mustard

    National Research Council Canada - National Science Library

    Matijasevic, Zdenka

    2002-01-01

    Our investigations of the mechanisms of sulfur mustard (SM) toxicity and conditions that can improve cell survival after exposure have previously demonstrated that cells with compromised nucleotide excision repair (NER...

  17. Protection Against the Acute and Delayed Toxicities of Sulfur Mustard

    National Research Council Canada - National Science Library

    Matijasevic, Zdenka

    2003-01-01

    .... In order to identify targets for therapeutic intervention and conditions that can modulate the outcome of exposure to sulfur mustard we sought to investigate pathways and early events involved...

  18. N-acetyl-L-cysteine protects against inhaled sulfur mustard poisoning in the large swine.

    Science.gov (United States)

    Jugg, B; Fairhall, S; Smith, A; Rutter, S; Mann, T; Perrott, R; Jenner, J; Salguero, J; Shute, J; Sciuto, A M

    2013-05-01

    Sulfur mustard is a blister agent that can cause death by pulmonary damage. There is currently no effective treatment. N-acetyl-L-cysteine (NAC) has mucolytic and antioxidant actions and is an important pre-cursor of cellular glutathione synthesis. These actions may have potential to reduce mustard-induced lung injury. Evaluate the effect of nebulised NAC as a post-exposure treatment for inhaled sulfur mustard in a large animal model. Fourteen anesthetized, surgically prepared pigs were exposed to sulfur mustard vapor (100 μg.kg⁻¹), 10 min) and monitored, spontaneously breathing, to 12 h. Control animals had no further intervention (n = 6). Animals in the treatment group were administered multiple inhaled doses of NAC (1 ml of 200 mg.ml⁻¹ Mucomyst™ at + 30 min, 2, 4, 6, 8, and 10 h post-exposure, n = 8). Cardiovascular and respiratory parameters were recorded. Arterial blood was collected for blood gas analysis while blood and bronchoalveolar lavage fluid were collected for hematology and inflammatory cell analysis. Urine was collected to detect a sulfur mustard breakdown product. Lung tissue samples were taken for histopathological and post-experimental analyses. Five of six sulfur mustard-exposed animals survived to 12 h. Arterial blood oxygenation (PaO₂) and saturation levels were significantly decreased at 12 h. Arterial blood carbon dioxide (PaCO₂) significantly increased, and arterial blood pH and bicarbonate (HCO₃⁻) significantly decreased at 12 h. Shunt fraction was significantly increased at 12 h. In the NAC-treated group all animals survived to 12 h (n = 8). There was significantly improved arterial blood oxygen saturation, HCO₃⁻ levels, and shunt fraction compared to those of the sulfur mustard controls. There were significantly fewer neutrophils and lower concentrations of protein in lavage compared to sulfur mustard controls. NAC's mucolytic and antioxidant properties may be responsible for the beneficial effects seen, improving

  19. Cytometric analysis of DNA changes induced by sulfur mustard

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Respiratory Complications Due to Sulfur Mustard Exposure.

    Science.gov (United States)

    Rahmani, Hossein; Javadi, Iraj; Shirali, Saeed

    2016-06-01

    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.

  1. Mechanism and treatment of sulfur mustard-induced cutaneous injury

    Directory of Open Access Journals (Sweden)

    Gu Tianyi

    2014-12-01

    Full Text Available Skin is the fi rst organ exposed to sulfur mustard (SM. The mechanism of SM-induced cutaneous injury has not been fully clarifi ed so far, which is a major obstacle to the development of effective treatments for SM-induced injury. So far, there is no satisfactory therapy for acute symptoms and long-term complications. This review summarized recent researches on the mechanisms of SM-induced cutaneous injuries and the therapies for acute symptoms and long-term complications. Key words: Sulfur mustard; Injury mechanism; Therapy

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  3. Quantum molecular study of S-methylated forms of sulfur mustard

    Science.gov (United States)

    Hamza, A.; Broch, H.; Vasilescu, D.

    1996-04-01

    An ab initio quantum molecular modeling of sulfur mustard and various S-methylated forms is presented in this work. The geometries, conformations and Mulliken charge distributions were obtained at the level HF/6-31G ∗ computations for: neutral sulfur mustard (HD); the HD + episulfonium; the 2-chloroethyl ethyl methyl sulfonium; the bis(2-chloroethyl)methyl (MeHD +) sulfonium and the bicationic form MeHD ++ obtained by loosing a chloride in the chloroethyl branch of MeHD +. The conformational and the electrostatic situations are discussed with the aim to explain a possible rationale for detoxification of sulfur mustard proposed by Mozier and Hoffman. A theoretical reaction pathway of MeHD ++ involving a closure way and a fragmentation way is proposed.

  4. Sulfur Mustard Damage to Cornea: Preventive Studies

    National Research Council Canada - National Science Library

    Varma, Shambhu

    2004-01-01

    Studies are in progress to determine the efficacy and mechanism of a formulation containing anti-alkylating, antioxidants and metabolic accelerators present in VM against mustard induced skin toxicity...

  5. 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

    International Nuclear Information System (INIS)

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

    2010-01-01

    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 β-naphthoflavone-treated rats, and cytochrome P450 reductase from type II lung epithelial cells. Using rat liver microsomes from β-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.

  6. Alterations in Inflammatory Cytokine Gene Expression in Sulfur Mustard-Exposed Mouse Skin

    Science.gov (United States)

    2000-01-01

    vivo hairless guinea pig model, systemically ad- ministered niacinamide (NAM) and a systemic com- bination pretreatment with niacinamide , prometha... niacinamide [50]. Similarly, in an ex vivo isolated pig flap model, no protection against subepidermal blisters was observed following perfusion with... Niacinamide pre- treatment reduces microvesicle formation in hairless guinea pigs cutaneously exposed to sulfur mustard. Fund Appl Toxicol 1991;17

  7. Sulfur mustard causes caspase-mediated cleavage of cytoskeletal keratins

    NARCIS (Netherlands)

    Mol, M.A.E.; Berg, R.M. van den; Dijk, C. van; Jong, A.L. de

    2004-01-01

    In order to study the toxic mechanism of action of sulfur mustard (HD), we examined protein expression in control and HD-treated cultured human epidermal keratinocytes (HEK) at 24 h after exposure to 100 μM HD. Protein patterns of cell lysates were prepared using two-dimensional gel electrophoresis

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

    International Nuclear Information System (INIS)

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

    2011-01-01

    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 TNFα (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 TNFα 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 TNFα signaling may be useful in mitigating lung injury, inflammation and functional alterations induced by vesicants.

  9. Sulfur mustard-stimulated proteases and their inhibitors in a cultured normal human epidermal keratinocytes model: A potential approach for anti-vesicant drug development

    Directory of Open Access Journals (Sweden)

    Xiannu Jin

    Full Text Available Protease stimulation in cultured normal human epidermal keratinocytes (NHEK due to sulfur mustard (SM exposure is well documented. However, the specific protease(s stimulated by SM and the protease substrates remain to be determined. In this study, we observed that SM stimulates several proteases and the epidermal-dermal attachment protein laminin-5 is one of the substrates. We propose that following SM exposure of the skin, laminin-5 degradation causes the detachment of the epidermis from the dermis and, therefore, vesication. We utilized gelatin zymography, Western blotting, immuno-fluorescence staining, and real-time polymerase chain reaction (RT-PCR analyses to study the SM-stimulated proteases and laminin-5 degradation in NHEK. Two major protease bands (64 kDa and 72 kDa were observed by zymography in SM-exposed cells. Addition of serine protease inhibitor (aprotinin, 100 μM, or the metalloprotease inhibitor (amastatin, 100 μM to NHEK cultures prior to SM exposure decreased the SM-stimulated protease bands seen by zymography. These inhibitors completely or partially prevented SM-induced laminin-5 γ2 degradation as seen by Western blotting as well as immuno-fluorescence staining. Our results from Western blotting and RT-PCR studies also indicated that the membrane-type matrix metalloproteinase-1 (MT-MM-1 may be involved in SM-induced skin blistering.To summarize, our results in the NHEK model indicate the following: (a SM stimulates multiple proteases including serine protease(s, and metalloproteases; (b SM decreases the level of laminin-5 γ2, which is prevented by either a serine protease inhibitor or a metalloprotease inhibitor and (c MT-MMP-1 maybe one of the proteases that is involved in skin blistering due to SM exposure. Keywords: Sulfur mustard, Serine protease, Metalloprotease, Protease inhibiter, Zymography, Laminin-5 γ2

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. A comparison of sulfur mustard and heptane penetrating a dipalmitoylphosphatidylcholine bilayer membrane

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Thomas J., E-mail: t.mueller@theo.chemie.tu-darmstadt.de [Theoretische Physikalische Chemie, Eduard-Zintl-Institut fuer Anorganische und Physikalische Chemie, Technische Universitaet Darmstadt, Petersenstrasse 20, 64287 Darmstadt (Germany); Mueller-Plathe, Florian [Theoretische Physikalische Chemie, Eduard-Zintl-Institut fuer Anorganische und Physikalische Chemie, Technische Universitaet Darmstadt, Petersenstrasse 20, 64287 Darmstadt (Germany)

    2009-08-30

    In the present molecular dynamics simulations we study the chemical warfare agent sulfur mustard (bis(2-chloroethyl) sulfide) and the alkane heptane inserted into a dipalmitoylphosphatidylcholine (DPPC) bilayer, a generic model for a biological membrane. We investigate the diffusion, the orientation, the preferred positioning, and the end-to-end distance of the solutes within the membrane as well as the corresponding coupling times. We compare results of equilibrium simulations and simulation at different external forces, which drag the solutes through the membrane. These properties lead to a general comparison of the rotational and translational behaviors of the two solutes during the penetration of the membrane. We show that sulfur mustard, due to its atomic charge polarization, its bigger flexibility and its smaller molecular volume, is the faster moving molecule within the membrane. In last consequence, we show that this leads to different limits for the transport mechanism as observed in these simulations. For heptane the hindrance to penetrate into the membrane is significantly higher than for sulfur mustard. In contrast to heptane molecules, which spend the most of the time penetrating the tail groups, sulfur mustard needs more time to escape the tail group-head group interface of the membrane.

  12. A comparison of sulfur mustard and heptane penetrating a dipalmitoylphosphatidylcholine bilayer membrane

    International Nuclear Information System (INIS)

    Mueller, Thomas J.; Mueller-Plathe, Florian

    2009-01-01

    In the present molecular dynamics simulations we study the chemical warfare agent sulfur mustard (bis(2-chloroethyl) sulfide) and the alkane heptane inserted into a dipalmitoylphosphatidylcholine (DPPC) bilayer, a generic model for a biological membrane. We investigate the diffusion, the orientation, the preferred positioning, and the end-to-end distance of the solutes within the membrane as well as the corresponding coupling times. We compare results of equilibrium simulations and simulation at different external forces, which drag the solutes through the membrane. These properties lead to a general comparison of the rotational and translational behaviors of the two solutes during the penetration of the membrane. We show that sulfur mustard, due to its atomic charge polarization, its bigger flexibility and its smaller molecular volume, is the faster moving molecule within the membrane. In last consequence, we show that this leads to different limits for the transport mechanism as observed in these simulations. For heptane the hindrance to penetrate into the membrane is significantly higher than for sulfur mustard. In contrast to heptane molecules, which spend the most of the time penetrating the tail groups, sulfur mustard needs more time to escape the tail group-head group interface of the membrane.

  13. Advanced biotherapy for the treatment of sulfur mustard poisoning.

    Science.gov (United States)

    Sun, Mingxue; Yang, Yuyan; Meng, Wenqi; Xu, Qingqiang; Lin, Fengwu; Chen, Yongchun; Zhao, Jie; Xiao, Kai

    2018-04-25

    Sulfur mustard (SM), a bifunctional alkylating agent, can react with a variety of biochemical molecules (DNA, RNA, proteins and other cell components) to cause a series of serious health issues or even death. Although a plethora of research has been done, the pathogenesis of SM poisoning has yet to be fully understood due to its high complexity. As a consequence, a specific antidote has not yet been developed and the treatment of SM poisoning remains a medical challenge. In recent years, various biological products and cell transplantation in the treatment of SM poisoning offered a significant clinical treatment progress. By highlighting these and other research studies, we hereby summarize the progress in this field in an effort to provide useful information on the clinical treatment of SM poisoning. This review summarizes the major advances of SM poisoning therapy by means of biological products (peptide and protein drugs, polysaccharides drugs, nucleic acid drugs, etc.), and cell transplantation (e.g., bone marrow, limbal stem cells, mesenchymal stem cells), as well as other relevant biotherapeutic approaches. We searched the database PubMed for published domestic and international articles using web based resources for information on histological, immunochemical, ultrastructural, and treatment features of SM-induced manifestations in both animal models and human tissues. To this end, we applied keywords containing mustard gas, chemical warfare, SM, eye, lung and skin. Our review provides a comprehensive understanding of the advances of available biotherapies in SM poisoning, and its potential for the treatment of SM-induced injuries. Potentially, our review will provide new insights for future research studies in this field. Copyright © 2018. Published by Elsevier B.V.

  14. Nitric Oxide Synthase Gene Transfer Overcomes the Inhibition of Wound Healing by Sulfur Mustard in a Human Keratinocyte In Vitro Model

    Science.gov (United States)

    Ishida, Hiroshi; Ray, Radharaman; Amnuaysirikul, Jack; Ishida, Keiko; Ray, Prabhati

    2012-01-01

    Sulfur mustard (SM) is a chemical warfare agent that causes extensive skin injury. Previously we reported that SM exposure resulted in suppression of inducible nitric oxide synthase (iNOS) expression to inhibit the healing of scratch wounds in a cultured normal human epidermal keratinocyte (NHEK) model. Based on this finding, the present study was to use adenovirus-mediated gene transfer of iNOS to restore the nitric oxide (NO) supply depleted by exposure to SM and to evaluate the effect of NO on wound healing inhibited by SM in NHEKs. The effect of the iNOS gene transfer on iNOS protein expression and NO generation were monitored by Western blot and flow cytometry, respectively. Wound healing with or without the iNOS gene transfer after SM exposure was assessed by light and confocal microscopy. The iNOS gene transfer via adenovirus resulted in overexpression of the iNOS and an increase in NO production regardless of SM exposure in the NHEK model. The gene transfer was also effective in overcoming the inhibition of wound healing due to SM exposure leading to the promotion of wound closure. The findings in this study suggest that the iNOS gene transfer is a promising therapeutic strategy for SM-induced skin injury. PMID:23762631

  15. Thiodiglycol, the Hydrolysis Product of Sulfur Mustard: Analysis of In Vitro Biotransformation by Mammalian Alcohol Dehydrogenases using Nuclear Magnetic Resonance

    National Research Council Canada - National Science Library

    Brimfield, A. A; Novak, Mark J; Hodgson, Ernest

    2006-01-01

    Thiodiglycol (2,2'-bis-hydroxyethylsulfide, TDG), the hydrolysis product of the chemical warfare agent sulfur mustard, has been implicated in toxicity of sulfur mustard through the inhibition of protein phosphatases in mouse liver cytosol...

  16. 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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  17. Acute and chronic pathological effects of sulfur mustard on genitourinary system and male fertility.

    Science.gov (United States)

    Panahi, Yunes; Ghanei, Mostafa; Ghabili, Kamyar; Ansarin, Khalil; Aslanabadi, Saeid; Poursaleh, Zohreh; Golzari, Samad Eslam Jamal; Etemadi, Jalal; Khalili, Majid; Shoja, Mohammadali Mohajel

    2013-01-01

    To review the acute and chronic pathological effects of sulfur mustard on the genitourinary system and male fertility. We searched PubMed and Google Scholar to find studies related to the sulfur mustard-induced genitourinary effects and male infertility. Information in the abstracts of non-English related papers as well as those in the proceedings of congresses on sulfur mustard were reviewed as well. In acute phase after sulfur mustard exposure, evidences are in favor of microscopic and macroscopic renal lesions, very low androgen levels, and impaired spermatogenesis. Several years following sulfur mustard exposure, the long-term pathological effects vary from the renal function impairment to the gonadal damage, in particular the spermatogenesis. Nevertheless, carcinogenic effect of sulfur mustard on the genitourinary system as well as the prevalence of male infertility among sulfur mustard-exposed veterans in the chronic post-exposure phase is still unclear. Sulfur mustard causes both acute and chronic injuries to different parts of the genitourinary system.

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

    Science.gov (United States)

    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

  19. Mesenchymal stem cells are highly resistant to sulfur mustard.

    Science.gov (United States)

    Schmidt, Annette; Scherer, Michael; Thiermann, Horst; Steinritz, Dirk

    2013-12-05

    The effect of sulfur mustard (SM) to the direct injured tissues of the skin, eyes and airways is well investigated. Little is known about the effect of SM to mesenchymal stem cells (MSC). However, this is an interesting aspect. Comparing the clinical picture of SM it is known today that MSC play an important role e.g. in chronic impaired wound healing. Therefore we wanted to get an understanding about how SM affects MSC and if these findings might become useful to get a better understanding of the effect of sulfur mustard gas with respect to skin wounds. We used mesenchymal stem cells, isolated from femoral heads from healthy donors and treated them with a wide range of SM to ascertain the dose-response-curve. With the determined inhibitory concentrations IC1 (1μM), IC5 (10μM), IC10 (20μM) and IC25 (40μM) we did further investigations. We analyzed the migratory ability and the differentiation capacity under influence of SM. Already very low concentrations of SM demonstrated a strong effect to the migratory activity whereas the differentiation capacity seemed not to be affected. Putting these findings together it seems to be likely that a link between MSC and the impaired wound healing after SM exposure might exist. Same as in patients with chronic impaired wound healing MSC had shown a reduced migratory activity. The fact that MSC are able to tolerate very high concentrations of SM and still do not lose their differentiation capacity may reveal new ways of treating wounds caused by sulfur mustard. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Capsaicinoids, chloropicrin and sulfur mustard: Possibilities for exposure biomarkers

    Directory of Open Access Journals (Sweden)

    Maija Pesonen

    2010-12-01

    Full Text Available 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.

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

    Science.gov (United States)

    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. © 2016 New York Academy of Sciences.

  2. Signaling Molecules in Sulfur Mustard-Induced Cutaneous Injury

    Science.gov (United States)

    Ruff, Albert L.; Dillman, James F.

    2008-01-01

    Objective: Sulfur mustard (SM) is a potent alkylating agent that can induce severe cutaneous injury. Though much is known regarding the gross pathology of SM injury, the molecular and cellular basis for this pathology is not well understood. General cellular processes such as inflammation, DNA damage response, and apoptosis have been hypothesized to be involved in SM injury. However, the specific molecules, signaling pathways, and gene products involved in the pathogenesis of SM injury have not been elucidated. This review discusses the molecular mechanisms observed in in vivo and in vitro models of cutaneous SM injury. Methods: The historical literature on the clinical pathology of SM-induced cutaneous injury is summarized, and recent work elucidating molecular signaling pathways involved in SM toxicity is extensively reviewed. In addition, this review focuses the discussion of SM-induced molecular mechanisms on those that have been experimentally validated in models of SM injury. Results: Recent work has uncovered potential roles for a number of signaling molecules. In particular, molecules in inflammatory signaling, DNA damage response, apoptosis signaling, and calcium signaling have been implicated in SM injury. These include signaling molecules involved in inflammation (e.g. p38 MAP kinase), apoptosis (e.g. p53, NF-κ B, caspases, Fas), and cell stress responses (e.g. calcium, calmodulin). Conclusions: Many of the molecules and mechanisms implicated in SM injury are now being experimentally validated. Critical questions are proposed that remain to be answered to increase our understanding of SM toxicity and accelerate the development of vesicant therapeutics. PMID:18213398

  3. Whole body exposure of rats to sulfur mustard vapor.

    Science.gov (United States)

    Dachir, Shlomit; Rabinovitz, Ishai; Yaacov, Guy; Gutman, Hila; Cohen, Liat; Horwitz, Vered; Cohen, Maayan; Kadar, Tamar

    2017-11-24

    Sulfur mustard (SM) is an incapacitating chemical warfare agent used in numerous conflicts around the world and it is still a major threat for both, army troops and civilians. To evaluate its multiple targets effects in experimental setup, a model of whole body exposure (WBE) to SM vapor was established in rats and its simultaneous effects on lungs and eyes as well as on general wellbeing were examined. Rats were exposed to SM vapor. Evaluation (up to 10 weeks post-exposure) included body weight, general observation, blood counts and histological analysis. Results showed that following a latency-period of several hours, rats typical symptoms developed over a period of more than one week. The initial symptoms, characterized by swollen and erythematic nose, deteriorated into extensive rhinorrhea, eye closure, excessive lacrimation as well as rhonchi, wheezing and breathing difficulties. Alopecia and behavioral abnormality were also recorded. A weight loss of up to 40% was measured within one week with spontaneous recovery to baseline level within three weeks after exposure. Blood counts revealed leukopenia during the first three days post-exposure. Histological evaluation revealed a long lasting damage to the trachea, lungs and eyes. Thus, WBE to SM, was found to closely mimic the deleterious effects of SM on the sensitive tissues previously described in human victims during WWI and the Iran-Iraq war. The use of this animal model will enable comprehensive characterization of changes in biological processes that may lead to the development of therapeutic measures to ameliorate SM induced multi-system injuries.

  4. Sulfur mustard-stimulated proteases and their inhibitors in a cultured normal human epidermal keratinocytes model: A potential approach for anti-vesicant drug development.

    Science.gov (United States)

    Jin, Xiannu; Ray, Radharaman; Ray, Prabhati

    2016-01-01

    Protease stimulation in cultured normal human epidermal keratinocytes (NHEK) due to sulfur mustard (SM) exposure is well documented. However, the specific protease(s) stimulated by SM and the protease substrates remain to be determined. In this study, we observed that SM stimulates several proteases and the epidermal-dermal attachment protein laminin-5 is one of the substrates. We propose that following SM exposure of the skin, laminin-5 degradation causes the detachment of the epidermis from the dermis and, therefore, vesication. We utilized gelatin zymography, Western blotting, immuno-fluorescence staining, and real-time polymerase chain reaction (RT-PCR) analyses to study the SM-stimulated proteases and laminin-5 degradation in NHEK. Two major protease bands (64 kDa and 72 kDa) were observed by zymography in SM-exposed cells. Addition of serine protease inhibitor (aprotinin, 100 μM), or the metalloprotease inhibitor (amastatin, 100 μM) to NHEK cultures prior to SM exposure decreased the SM-stimulated protease bands seen by zymography. These inhibitors completely or partially prevented SM-induced laminin-5 γ2 degradation as seen by Western blotting as well as immuno-fluorescence staining. Our results from Western blotting and RT-PCR studies also indicated that the membrane-type matrix metalloproteinase-1 (MT-MM-1) may be involved in SM-induced skin blistering. To summarize, our results in the NHEK model indicate the following: (a) SM stimulates multiple proteases including serine protease(s), and metalloproteases; (b) SM decreases the level of laminin-5 γ2, which is prevented by either a serine protease inhibitor or a metalloprotease inhibitor and (c) MT-MMP-1 maybe one of the proteases that is involved in skin blistering due to SM exposure.

  5. Skin manifestations in sulfur mustard exposed victims with ophthalmologic complications: Association between early and late phase.

    Science.gov (United States)

    Hejazi, Somayeh; Soroush, Mohammadreza; Moradi, Ahmad; Khalilazar, Sara; Mousavi, Batool; Firooz, Alireza; Younespour, Shima

    2016-01-01

    Sulfur mustard (SM) was used during the Iraq-Iran war (1980-1988). Exposed veterans continue to suffer from its ocular, skin, and respiratory complications. We aimed to evaluate associations between early (at the time of acute exposure) and decades later skin manifestations in individuals with severe ophthalmologic complications secondary to sulfur mustard exposure. One hundred forty-nine veterans with severe ocular injuries were evaluated for acute and chronic skin complications. Logistic regression models were used to examine the associations between early and late skin manifestations. Late skin complaints were observed in nearly all survivors who had early skin lesions (131 out of 137; 95.62%). Seven out of 12 patients (58.33%) who did not have early skin lesions ultimately developed late skin complications. There was a significant relationship between the presence of lesions at the time of exposure and developing late skin complaints (two-sided Fisher's exact test, OR = 15.59, p sulfur mustard exposure.

  6. Prophylactic ophthalmic bethametazone for sulfur mustard-induced ocular Injury

    Directory of Open Access Journals (Sweden)

    Mostafa Naderi

    2009-09-01

    Full Text Available

    • BACKGROUND: The present study sought to evaluate the prophylactic effect of bethametazone on sulfur mustard (SM- induced ocular morphometric damage in the rabbit eye.
    • METHODS: Twenty five healthy New Zealand white rabbits were divided into 4 groups of normal (not exposed to SM or solution, solution (exposed to solution, SM (exposed to SM, and prophylactic bethametazone (received eye solution of bethametazone then exposed to SM solution; then treated for 2 weeks. On the day 14 after exposure, five-micron sections were stained with haematoxylin and eosin for light microscopy valuation. The ocular morphometric characteristics in the study groups were compared to determine the prophylactic effects of the   ethametazone.
    • RESULTS: Bethamethazone could protect eyes from SM effect by means of decrease in changes in number of Keratocyte in 10000 μm2, thickness of cornea (μm, thickness of corneal epithelium (μm, number of meibomian gland's cells in 2500 μm2, thickness of palpebral conjuctival epithelium (μm, thickness of epithelial of palpebral skin (μm, number of epithelial layers of palpebral skin, and number of goblet cells in conjunctival sac in 1000 μm.
    • CONCLUSIONS: Bethametazone may have a prophylactic effect on the early lesions of the eye of the rabbit due to SM exposure.
    • KEYWORDS: Betamethasone, Sulfur Mustard, Ocular Lesions.

  7. Multiphoton imaging the disruptive nature of sulfur mustard lesions

    Science.gov (United States)

    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.

  8. Sulfur mustard destruction using ozone, UV, hydrogen peroxide and their combination

    International Nuclear Information System (INIS)

    Popiel, Stanislaw; Witkiewicz, Zygfryd; Chrzanowski, Michal

    2008-01-01

    Numerous methods are used for destruction of sulfur mustard. Oxidation is one of those methods. There have been only limited data concerning application of the advanced oxidation technologies (AOTs) for mustard destruction available before. In this study sulfur mustard oxidation rate depending on kind of the oxidative system and process parameters used was assessed using selected AOT. The following were selected for mustard oxidation: ozone (O 3 ), UV light (UV), hydrogen peroxide (H 2 O 2 ); double systems: UV/O 3 , UV/H 2 O 2 , and O 3 /H 2 O 2 ; a triple system: O 3 /H 2 O 2 /UV and Fenton reaction. Effectiveness of the selected AOT methods has been evaluated and the most suitable one for mustard destruction was chosen. Using ozone in various combinations with hydrogen peroxide and UV radiation mustard can be destroyed much quicker comparing to the classical oxidizers. Fast mustard oxidation (a few minutes) occurred in those systems where ozone alone was used, or in the following combinations: O 3 /H 2 O 2 , O 3 /UV and O 3 /H 2 O 2 /UV. When those advanced oxidation technologies are used, mustard becomes destroyed mainly in course of the direct oxidation with ozone, and reactions of mustard with radicals formed due to ozone action play a secondary role. Rate of sulfur mustard oxidation in the above mentioned ozone-containing oxidative systems decreases with pH value increasing from 2 to 12. Only when pH value of reaction solutions is close to pH 5, mustard oxidation rate is minimal, probably due to 'disappearance' of radicals participating in oxidation in this pH. Sulfur mustard can be most effectively destroyed using just ozone in pH 7. In that case mustard destruction rate is only slightly lower than the rate achieved in optimal conditions, and the system is the simplest

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Sulfur Mustard Exposure from Dredged Artillery Shell in a Commercial Clammer

    Directory of Open Access Journals (Sweden)

    Jenna Otter

    2017-09-01

    Full Text Available A 40-year-old commercial fisherman presented with a blistering second degree burn to the right arm after handling a dredged and undetonated World War I-era sulfur mustard artillery shell. He sustained isolated second degree cutaneous injury requiring wound care and skin grafting. Sulfur mustard, or dichlorethylsulphide, is a vesicant chemical warfare agent that causes significant cutaneous chemical burn and is managed with burn wound care. Long-term effects include cosmetic disfigurement and increased risk of developing cancer. Sulfur mustard exposure is a rare but devastating injury when discarded artillery shells are encountered in coastal waters.

  11. Protein Changes in Sulfur Mustard Exposure: Diagnostic and Therapeutic Implications

    International Nuclear Information System (INIS)

    Ray, P.; Jin, X.; Ray, R.

    2007-01-01

    Laminin-5, a heterotrimer of laminin α3, β3, and γ2 subunits, is a component of the skin basal epithelium. Laminin-5 functions as a ligand of the α3β1 and α6β4 integrins in epidermal keratinocytes to regulate cell adhesion, migration, morphogenesis, and assembly of basement membranes; thus it is essential for a stable attachment of the epidermis to the dermis and recovery of damaged skin. Sulfur mustard (SM), also known as mustard gas, is a vesicant chemical warfare and terrorism agent. Skin exposure to SM results in fluid-filled blisters; proposed mechanisms are inflammation, protease stimulation, basal cell death, and separation of the epidermis from the dermis apparently due to the degradation of attachment proteins like laminin-5. Therefore, we investigated the effects of SM exposure on the degradation of laminin-5 by exposing normal human epidermal keratinocytes (NHEK) to SM (0-300 μM, 1-24 hours). We found that SM degraded laminin-5 and its two subunits β3 and γ2, but not α3. Preincubation of cells with a serine protease inhibitor (PMSF), or a metalloprotease inhibitor (1, 10-phenanthroline) prior to SM exposure partially prevented SM-induced degradation of laminin-5 subunits, β3 and γ2. Regarding specificity, laminin-5 γ2 was degraded due to a bifunctional mustard compound like SM, but not due to the other alkylating agents tested. Our results support that laminin-5 degradation is an important mechanism of SM injury as well as a useful biomarker of SM exposure. This knowledge of the mechanism of laminin-5 degradation due to SM has potential application in developing cutaneous therapeutics against SM.(author)

  12. Dermatotoxicology of sulfur mustard: Historical perspectives from World War I.

    Science.gov (United States)

    Jiang, Austin; Maibach, Howard

    2018-01-01

    Sulfur mustard has been used as a chemical warfare agent for the past century. After its introduction by the Germans in World War I, investigators quickly began studying its impact on the human body including its deleterious effects on skin. This review focuses on two groups in particular who conducted experiments from 1917 to 1918: the United States Army at the American University Experiment Station Laboratories and Torald Sollmann at Western Reserve University. Through this work, these researchers proved far ahead of their time by anticipating dermatologic phenomena not described in the literature until later in the twentieth century. These include regional variation of percutaneous penetration, effect of vehicle on penetration and predicting immunologic contact urticaria. The work conducted by these researchers set the groundwork for much of twentieth century dermatotoxicology. Copyright © 2017 John Wiley & Sons, Ltd.

  13. A review on symptoms, treatments protocols, and proteomic profile in sulfur mustard-exposed victims.

    Science.gov (United States)

    Panahi, Yunes; Abdolghaffari, Amir H; Sahebkar, Amirhossein

    2018-01-01

    Sulfur mustard (SM) as an alkylating and vesicating agent was used for 100 years as a chemical weapon. SM as bi-functional mustard can attacks and alkylates lots of biomolecules. Different cellular mechanism and molecular pathways are responsible for damages to body tissues. Such as DNA damages, oxidative stress, Apoptosis, and inflammation. Sulfur mustard penetrated body organs and induces long term eye, skin, lung, gastrointestinal, urogenital damages and can cause carcinogenic and mutagenic consequences. Currently there is no definitive treatment protocol for SM exposed patients. The goal of treatment is relieving the symptoms with fast healing rate and retrieval of damaged tissues to normal function and appearance in short period of time. Evaluation of proteomics profile in SM-exposed victims has been performed in animal model and human patients. These studies revealed that different protein were involved in the patients with SM damages to skin and lungs. Apolipoprotein A1, type I cytokeratins K14, K16 and K17, S100 calcium-binding protein A8, α1 haptoglobin isoforms, Amyloid A1, albumin, haptoglobin, and keratin isoforms, immunoglobulin kappa chain are defined expressed proteins in the damaged tissues. © 2017 Wiley Periodicals, Inc.

  14. Ocular Effects of Sulfur Mustard and Therapeutic Approaches.

    Science.gov (United States)

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

    2017-11-01

    Sulfur mustard (SM) is a strong blistering, highly reactive, lipophilic chemical war agent that causes injury in different organs including the skin, eyes, and respiratory tract. The Eyes are especially susceptible to the consequences of SM poisoning because of the aqueous and mucosal nature of conjunctiva and cornea. DNA alkylation and depletion of glutathione, are the most important mechanisms of SM action in the eye injuries. Acute clinical symptoms are including decrease in visual acuity, dryness, photophobia, blepharospasm, conjunctivitis, and complaints of foreign body sensation and soreness that gradually progress to severe ocular pain. Corneal abrasions, ulcerations, vesication, and perforations are common corneal consequences in SM injured victims. Appearance of chronic symptoms has been reported as chronic inflammation of the corneal and conjunctival vasculature, ischemia, lipid and cholesterol deposition, scarring in cornea, corneal thinning, opacification and perforation of the cornea, limbal stem cell deficiency (LSCD), and neovascularization. Different medical and surgical protocols have been documented in the management of SM-induced ocular injuries, including preservative-free artificial tears, topical steroids and antibiotic, mydriatic, antiglaucoma drops, therapeutic contact lenses, dark glasses and punctal plugs/cauterization, N-acetylcysteine, tarsorrhaphy, amniotic membrane transplantation, stem cell transplantation, and corneal transplantation. New drugs such as resolvin E1, topical form of essential fatty acids, thymosin β4, 43 amino-acid polypeptides, topical form of curcumin, newly formulated artificial tears, diquafosol, rebamipide, tretinoin, and oral uridineseems to be beneficial in the management of ocular lesion associated with sulfur mustard poisoning. Further studies are needed to approve these drugs in SM victims. J. Cell. Biochem. 118: 3549-3560, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. The Cytoskeleton and ATP in Sulfur Mustard-Medicated Injury to Endothelial Cells and Keratinocytes

    National Research Council Canada - National Science Library

    Hinshaw, Daniel

    1998-01-01

    The major goal of this project is to test the hypothesis that sulfur mustard (SM)-mediated cell death in keratinocytes and endothelial cells is primarily apoptotic in nature, and that several factors...

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

    International Nuclear Information System (INIS)

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

    2003-01-01

    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 ∼100 and ∼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

  17. Skin manifestations in sulfur mustard exposed victims with ophthalmologic complications: Association between early and late phase

    Directory of Open Access Journals (Sweden)

    Somayeh Hejazi, MD

    Full Text Available Context: Sulfur mustard (SM was used during the Iraq-Iran war (1980–1988. Exposed veterans continue to suffer from its ocular, skin, and respiratory complications. Objective: We aimed to evaluate associations between early (at the time of acute exposure and decades later skin manifestations in individuals with severe ophthalmologic complications secondary to sulfur mustard exposure. Materials and methods: One hundred forty-nine veterans with severe ocular injuries were evaluated for acute and chronic skin complications. Logistic regression models were used to examine the associations between early and late skin manifestations. Results: Late skin complaints were observed in nearly all survivors who had early skin lesions (131 out of 137; 95.62%. Seven out of 12 patients (58.33% who did not have early skin lesions ultimately developed late skin complications. There was a significant relationship between the presence of lesions at the time of exposure and developing late skin complaints (two-sided Fisher's exact test, OR = 15.59, p < 0.001. There was an association between having at least one early skin lesion and occurrence of late skin complications. Survivors with blisters at the time of chemical exposure were more likely to complain of itching (95% CI: 3.63–25.97, p < 0.001, burning (OR = 11.16; 95% CI: 2.97–41.89, p < 0.001, pigmentation changes (OR = 10.17; 95% CI: 2.54–40.75, p = 0.001, dryness (OR = 6.71, 95% CI: 1.22–37.01, p = 0.03 or cherry angioma (OR = 2.59; 95% CI:1.21–5.55, p = 0.01 during the late phase. Using multivariate logistic models, early blisters remained significantly associated with latent skin complaints. Of note, the genitalia and great flexure areas were the most involved anatomical sites for both early and late skin lesions in SM exposed survivors. Conclusion: According to this study, the presence of blisters at the time of exposure to SM is the most important predictor of developing

  18. Mesoporous binary metal oxide nanocomposites: Synthesis, characterization and decontamination of sulfur mustard

    Energy Technology Data Exchange (ETDEWEB)

    Praveen Kumar, J., E-mail: praveenjella10@gmail.com; Prasad, G.K.; Ramacharyulu, P.V.R.K.; Singh, Beer; Gopi, T.; Krishna, R.

    2016-04-15

    Mesoporous MnO{sub 2}–ZnO, Fe{sub 2}O{sub 3}–ZnO, NiO–ZnO, and CeO{sub 2}–ZnO binary metal oxide nanocomposites were studied as sorbent decontaminants against sulfur mustard. They were synthesized by precipitation pyrolysis method and characterized by means of transmission electron microscopy, scanning electron microscopy coupled with energy dispersive analysis of X rays, X ray diffraction, and nitrogen adsorption techniques. The transmission electron microscopy and nitrogen adsorption data indicated the presence of pores with diameter ranging from 10 to 70 nm in the binary metal oxide nanocomposites and these materials exhibited surface area values in the range of 76–134 m{sup 2}/g. These binary metal oxide nanocomposites demonstrated large decontamination efficiencies against sulfur mustard when compared to their single component metal oxide nanoparticles. The binary metal oxide nanocomposites effectively decontaminated sulfur mustard into relatively non toxic products such as chloro ethyl vinyl sulfide, divinyl sulfide, 1,4-oxathiane, etc. The promising decontamination properties of binary metal oxide nanocomposites against sulfur mustard were attributed to the basic sites, Lewis acid sites, and the presence of these sites was confirmed by CO{sub 2} and NH{sub 3} temperature programmed desorption. - Graphical abstract: Mesoporous MnO{sub 2}–ZnO, Fe{sub 2}O{sub 3}–ZnO, NiO–ZnO, and CeO{sub 2}–ZnO binary metal oxide nanocomposites were studied as sorbent decontaminants against sulfur mustard. - Highlights: • Binary metal oxide nanocomposites were synthesized by co-precipitation method. • They were studied as sorbent decontaminants against sulfur mustard. • They decontaminated sulfur mustard into non toxic products. • MnO{sub 2}–ZnO and CeO{sub 2}–ZnO nanocomposites showed greater decontamination efficiency.

  19. Mesoporous binary metal oxide nanocomposites: Synthesis, characterization and decontamination of sulfur mustard

    International Nuclear Information System (INIS)

    Praveen Kumar, J.; Prasad, G.K.; Ramacharyulu, P.V.R.K.; Singh, Beer; Gopi, T.; Krishna, R.

    2016-01-01

    Mesoporous MnO 2 –ZnO, Fe 2 O 3 –ZnO, NiO–ZnO, and CeO 2 –ZnO binary metal oxide nanocomposites were studied as sorbent decontaminants against sulfur mustard. They were synthesized by precipitation pyrolysis method and characterized by means of transmission electron microscopy, scanning electron microscopy coupled with energy dispersive analysis of X rays, X ray diffraction, and nitrogen adsorption techniques. The transmission electron microscopy and nitrogen adsorption data indicated the presence of pores with diameter ranging from 10 to 70 nm in the binary metal oxide nanocomposites and these materials exhibited surface area values in the range of 76–134 m 2 /g. These binary metal oxide nanocomposites demonstrated large decontamination efficiencies against sulfur mustard when compared to their single component metal oxide nanoparticles. The binary metal oxide nanocomposites effectively decontaminated sulfur mustard into relatively non toxic products such as chloro ethyl vinyl sulfide, divinyl sulfide, 1,4-oxathiane, etc. The promising decontamination properties of binary metal oxide nanocomposites against sulfur mustard were attributed to the basic sites, Lewis acid sites, and the presence of these sites was confirmed by CO 2 and NH 3 temperature programmed desorption. - Graphical abstract: Mesoporous MnO 2 –ZnO, Fe 2 O 3 –ZnO, NiO–ZnO, and CeO 2 –ZnO binary metal oxide nanocomposites were studied as sorbent decontaminants against sulfur mustard. - Highlights: • Binary metal oxide nanocomposites were synthesized by co-precipitation method. • They were studied as sorbent decontaminants against sulfur mustard. • They decontaminated sulfur mustard into non toxic products. • MnO 2 –ZnO and CeO 2 –ZnO nanocomposites showed greater decontamination efficiency.

  20. Sulfur mustard induces expression of metallothionein-1A in human airway epithelial cells.

    Science.gov (United States)

    Nourani, Mohammad Reza; Ebrahimi, Majid; Roudkenar, Mehryar Habibi; Vahedi, Ensieh; Ghanei, Mostafa; Imani Fooladi, Abbas Ali

    2011-01-01

    Sulfur mustard can cause several long-term complications in the organs of individuals exposed to this toxic gas, and among these, pulmonary sequelae are the most important. More than 25 years after the Iran-Iraq war, thousands of Iranians are suffering from the chronic respiratory complications of sulfur mustard. Currently, based on several clinical findings, bronchiolitis obliterans is confirmed as the major diagnosis in these patients. Numerous studies have revealed that this disorder is strongly associated with oxidative stress due to excessive production of harmful reactive substances and decreased levels of endogenous antioxidants. Metallothioneins (MTs) are a group of low molecular weight sulfhydryl-rich intra-cellular proteins, and several isoforms have been identified in humans. MT-1A is an inducible and important MT isoform, which is transcriptionally activated by a variety of stress stimuli, such as free radicals. MT-1 mRNA expression and protein levels in endobronchial biopsy samples from 24 sulfur mustard-exposed patients and 15 unexposed control cases were evaluated by semi-quantitative reverse transcriptase polymerase chain reaction, real-time reverse transcriptase polymerase chain reaction, and immunohistochemistry. mRNA- MT-1A expression levels in sulfur mustard-exposed patients were upregulated compared with normal samples. Protein expression was also markedly higher in controls than in sulfur mustard-exposed patients. Upregulation of MT-1A mRNA in patients who have been exposed to sulfur mustard seems to be due to oxidative stress, which is induced in an attempt to ameliorate this harmful situation by reestablishment of homeostasis, but depletion of its protein might be due to secondary consequences of sulfur mustard toxicity, which are as yet not understood.

  1. Retrospective detection of exposure to sulfur mustard: Improvements on an assay for liquid chromatography-tandem mass spectrometry analysis of albumin/sulfur mustard adducts

    NARCIS (Netherlands)

    Noort, D.; Fidder, A.; Hulst, A.G.; Woolfitt, A.R.; Ash, D.; Barr, J.R.

    2004-01-01

    We here report on the further development of the method comprising the pronase digestion of albumin alkylated by sulfur mustard and the subsequent mass spectrometric analysis of an adducted tripeptide. This includes significant improvements in both the albumin isolation procedure and the automation

  2. Mesoporous CuO–ZnO binary metal oxide nanocomposite for decontamination of sulfur mustard

    Energy Technology Data Exchange (ETDEWEB)

    Praveen Kumar, J.; Prasad, G.K., E-mail: gkprasad2001@yahoo.com; Ramacharyulu, P.V.R.K.; Garg, P.; Ganesan, K.

    2013-11-01

    Mesoporous CuO–ZnO binary metal oxide nanocomposites were studied as sorbent decontaminants against sulfur mustard, a well known chemical warfare agent. They were prepared by precipitation pyrolysis method and characterized by means of X-ray diffraction, transmission electron microscopy, nitrogen adsorption, Fourier transform infrared spectroscopy techniques. Obtained data indicated the presence of mesopores with diameter ranging from 2 to 80 nm and the materials exhibited relatively high surface area 86 m{sup 2} g{sup −1} when compared to the individual metal oxide nanoparticles. Reactive sites of mesoporous CuO–ZnO binary metal oxide nanocomposites were studied by infrared spectroscopy technique using pyridine as a probe molecule. These materials demonstrated superior decontamination properties against sulfur mustard when compared to single component metal oxides and decontaminated it to divinyl sulfide, chloroethyl vinyl sulfide, hemisulfur mustard, etc. - Graphical abstract: Mesoporous CuO–ZnO binary metal oxide nanocomposites were studied as sorbent decontaminants against sulfur mustard, a well known chemical warfare agent. These materials demonstrated superior decontamination properties against sulfur mustard and decontaminated it to divinyl sulfide, chloroethyl vinyl sulfide, hemisulfur mustard, etc. - Highlights: • Preparation of mesoporous CuO–ZnO binary metal oxide nanocomposite. • CuO–ZnO with better surface area was synthesized by precipitation pyrolysis. • Decontamination of HD using mesoporous CuO–ZnO binary metal oxide nanocomposite. • HD decontaminated by elimination and hydrolysis reactions.

  3. Mesoporous CuO–ZnO binary metal oxide nanocomposite for decontamination of sulfur mustard

    International Nuclear Information System (INIS)

    Praveen Kumar, J.; Prasad, G.K.; Ramacharyulu, P.V.R.K.; Garg, P.; Ganesan, K.

    2013-01-01

    Mesoporous CuO–ZnO binary metal oxide nanocomposites were studied as sorbent decontaminants against sulfur mustard, a well known chemical warfare agent. They were prepared by precipitation pyrolysis method and characterized by means of X-ray diffraction, transmission electron microscopy, nitrogen adsorption, Fourier transform infrared spectroscopy techniques. Obtained data indicated the presence of mesopores with diameter ranging from 2 to 80 nm and the materials exhibited relatively high surface area 86 m 2 g −1 when compared to the individual metal oxide nanoparticles. Reactive sites of mesoporous CuO–ZnO binary metal oxide nanocomposites were studied by infrared spectroscopy technique using pyridine as a probe molecule. These materials demonstrated superior decontamination properties against sulfur mustard when compared to single component metal oxides and decontaminated it to divinyl sulfide, chloroethyl vinyl sulfide, hemisulfur mustard, etc. - Graphical abstract: Mesoporous CuO–ZnO binary metal oxide nanocomposites were studied as sorbent decontaminants against sulfur mustard, a well known chemical warfare agent. These materials demonstrated superior decontamination properties against sulfur mustard and decontaminated it to divinyl sulfide, chloroethyl vinyl sulfide, hemisulfur mustard, etc. - Highlights: • Preparation of mesoporous CuO–ZnO binary metal oxide nanocomposite. • CuO–ZnO with better surface area was synthesized by precipitation pyrolysis. • Decontamination of HD using mesoporous CuO–ZnO binary metal oxide nanocomposite. • HD decontaminated by elimination and hydrolysis reactions

  4. Sulfur Mustard Induces Immune Sensitization in Hairless Guinea Pigs

    Science.gov (United States)

    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

  5. Sulfur mustard vapor effects on differentiated human lung cells

    Science.gov (United States)

    Seagrave, JeanClare; Weber, Waylon M.; Grotendorst, Gary R.

    2011-01-01

    Context sulfur mustard (SM) causes skin blistering and long-term pulmonary dysfunction. Its adverse effects have been studied in battlefield-exposed humans, but lack of knowledge regarding confounding factors makes interpretation challenging. Animal studies are critical to understanding mechanisms, but differences between animals and humans must be addressed. Studies of cultured human cells can bridge animal studies and humans. Objective Evaluate effects of SM vapor on airway cells. Materials and methods We examined responses of differentiated human tracheal/bronchial epithelial cells, cultured at an air-liquid interface, to SM vapors. SM effects on metabolic activity (Water Soluble Tetrazolium (WST) assay), cytokine and metalloproteinase secretion, and cellular heme oxygenase 1 (HO-1), an oxidative stress indicator, were measured after 24 h. Results At noncytotoxic levels of exposure, interleukin 8 and matrix metalloproteinase-13 were significantly increased in these cultures, but HO-1 was not significantly affected. Discussion and conclusion Exposure of differentiated airway epithelial cells to sub-cytotoxic levels of SM vapor induced inflammatory and degradative responses that could contribute to the adverse health effects of inhaled SM. PMID:20569120

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

    Science.gov (United States)

    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.

  7. Mechanisms of sulfur mustard-induced metabolic injury

    Energy Technology Data Exchange (ETDEWEB)

    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).

  8. Sulfur mustard destruction using ozone, UV, hydrogen peroxide and their combination

    Energy Technology Data Exchange (ETDEWEB)

    Popiel, Stanislaw [Institute of Chemistry, Military University of Technology, 2, Kaliskiego-Street, 00-908 Warsaw (Poland)], E-mail: spopiel@wat.edu.pl; Witkiewicz, Zygfryd [Institute of Chemistry, Military University of Technology, 2, Kaliskiego-Street, 00-908 Warsaw (Poland); ' Jan Kochanowski' Swietokrzyska Academy, Institute of Chemistry, 5, Checinska-Street, 25-020 Kielce (Poland); Chrzanowski, Michal [Institute of Chemistry, Military University of Technology, 2, Kaliskiego-Street, 00-908 Warsaw (Poland)

    2008-05-01

    Numerous methods are used for destruction of sulfur mustard. Oxidation is one of those methods. There have been only limited data concerning application of the advanced oxidation technologies (AOTs) for mustard destruction available before. In this study sulfur mustard oxidation rate depending on kind of the oxidative system and process parameters used was assessed using selected AOT. The following were selected for mustard oxidation: ozone (O{sub 3}), UV light (UV), hydrogen peroxide (H{sub 2}O{sub 2}); double systems: UV/O{sub 3}, UV/H{sub 2}O{sub 2}, and O{sub 3}/H{sub 2}O{sub 2}; a triple system: O{sub 3}/H{sub 2}O{sub 2}/UV and Fenton reaction. Effectiveness of the selected AOT methods has been evaluated and the most suitable one for mustard destruction was chosen. Using ozone in various combinations with hydrogen peroxide and UV radiation mustard can be destroyed much quicker comparing to the classical oxidizers. Fast mustard oxidation (a few minutes) occurred in those systems where ozone alone was used, or in the following combinations: O{sub 3}/H{sub 2}O{sub 2}, O{sub 3}/UV and O{sub 3}/H{sub 2}O{sub 2}/UV. When those advanced oxidation technologies are used, mustard becomes destroyed mainly in course of the direct oxidation with ozone, and reactions of mustard with radicals formed due to ozone action play a secondary role. Rate of sulfur mustard oxidation in the above mentioned ozone-containing oxidative systems decreases with pH value increasing from 2 to 12. Only when pH value of reaction solutions is close to pH 5, mustard oxidation rate is minimal, probably due to 'disappearance' of radicals participating in oxidation in this pH. Sulfur mustard can be most effectively destroyed using just ozone in pH 7. In that case mustard destruction rate is only slightly lower than the rate achieved in optimal conditions, and the system is the simplest.

  9. Low Level Exposure to Sulfur Mustard: Development of a SOP for Analysis of Albumin Adducts and of a System for Non-Invasive Diagnosis on Skin

    National Research Council Canada - National Science Library

    Noort, Dann

    2007-01-01

    .... In Volume I, the development of a Standard Operating Procedure (SOP) for diagnosis of exposure to sulfur mustard is described, based on mass spectrometric analysis of the sulfur mustard-adducted tripeptide...

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

    Directory of Open Access Journals (Sweden)

    mansour Razavi Seyed

    2012-10-01

    Full Text Available Abstract 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2012-10-09

    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.

  13. Enzyme-Based Test Strips for Visual or Photographic Detection and Quantitation of Gaseous Sulfur Mustard.

    Science.gov (United States)

    Bidmanova, Sarka; Steiner, Mark-Steven; Stepan, Martin; Vymazalova, Kamila; Gruber, Michael A; Duerkop, Axel; Damborsky, Jiri; Prokop, Zbynek; Wolfbeis, Otto S

    2016-06-07

    Sulfur mustard is a chemical agent of high military and terroristic significance. No effective antidote exists, and sulfur mustard can be fairly easily produced in large quantity. Rapid field testing of sulfur mustard is highly desirable. Existing analytical devices for its detection are available but can suffer from low selectivity, laborious sample preparation, and/or the need for complex instrumentation. We describe a new kind of test strip for rapid detection of gaseous sulfur mustard that is based on its degradation by the enzyme haloalkane dehalogenase that is accompanied by a change of local pH. This change can be detected using pH indicators contained in the strips whose color changes from blue-green to yellow within 10 min. In addition to visual read-out, we also demonstrate quantitative reflectometric readout by using a conventional digital camera based on red-green-blue data acquisition. Organic haloalkanes, such as 1,2-dichloroethane, have a negligible interfering effect. The visual limit of detection is 20 μg/L, and the one for red-green-blue read-out is as low as 3 μg/L. The assays have good reproducibility ±6% and ±2% for interday assays and intraday assays, respectively. The strips can be stored for at least 6 months without loss of function. They are disposable and can be produced fairly rapidly and at low costs. Hence, they represent a promising tool for in-field detection of sulfur mustard.

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

    Directory of Open Access Journals (Sweden)

    Mohammad Abdollahi

    2012-10-01

    Full Text Available 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.

  15. Cognitive and emotional impairments after cutaneous intoxication by CEES (a sulfur mustard analog) in mice.

    Science.gov (United States)

    Gros-Désormeaux, Fanny; Béracochéa, Daniel; Dorandeu, Frédéric; Piérard, Christophe

    2017-07-22

    Cognitive and emotional disorders have been reported in veterans intoxicated with sulfur mustard (SM) a chemical weapon belonging to the category of vesicating agents. However, the intense stress associated with the SM intoxication may render difficult determining the exact role played by SM intoxication itself on the emergence and maintaining of cognitive disorders. Animal's model would allow overcoming this issue. So far, we presently investigated the cognitive and emotional impact of an acute cutaneous intoxication with CEES (2-chloroethyl ethyl sulfide), a SM analog in C57/Bl6 mice. Our study evidenced that up to 5days after a single acute neat CEES skin exposure, compared to controls, mice exhibited i) a significant increase in anxiety-like reactivity in an elevated plus-maze and in an open-field tasks and ii) an alteration of working memory in a sequential alternation task. In contrast, mice submitted to intoxication with a diluted CEES solution or hydrochloric acid (HCl) did not show any memory or emotional impairments. Given that, Our data shows that a single local cutaneous intoxication with neat CEES induced long-lasting cognitive and emotional pejorative effects, in accordance with the epidemiological observations in veterans. Thus, the single acute neat CEES cutaneous intoxication in mice could allow studying the sulfur mustard-induced cognitive and emotional disorders and their further counter-measures. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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. Published by Elsevier B.V.

  18. Characterization of sulfur mustard induced structural modifications in human hemoglobin by liquid chromatography-tandem mass spectrometry

    NARCIS (Netherlands)

    Noort, D.; Verheij, E.R.; Hulst, A.G.; Jong, L.P.A. de; Benschop, H.P.

    1996-01-01

    In this paper we describe the use of tandem mass spectrometry to identify modified sites in human hemoglobin after in vitro exposure to bis(2- chloroethyl) sulfide (sulfur mustard). Globin isolated from human whole blood which had been exposed to sulfur mustard was degraded with trypsin, and the

  19. Cytokine Pattern In Sera and Broncho-Alveolar Lavage Six Months After Single Exposure to Sulfur Mustard

    Directory of Open Access Journals (Sweden)

    GHASEM SOLGUE

    2006-07-01

    Full Text Available Background:Cytokines play a major role in both acute and chronic inflammatory processes,including those produced by Sulfur Mustard.This study describes the cytokine level six months after exposure to a single dose of sulfur mustard,defined by IL-1

  20. Retrospective detection of sulfur mustard exposure by mass spectrometric analysis of adducts to albumin and hemoglobin: An in vivo study

    NARCIS (Netherlands)

    Noort, D.; Fidder, A.; Degenhardt-Langelaan, C.E.A.M.; Hulst, A.G.

    2008-01-01

    The persistence in rats of sulfur mustard adducts to albumin and hemoglobin was studied in vivo after exposure (intravenously; 0.3 mg/kg; approximately 0.1 LD50) of rats to sulfur mustard. The albumin adduct (S-HETE)Cys-Pro-Tyr was detectable up to 7 days after the exposure, while the adduct to the

  1. Immunochemical detection of sulfur mustard-adducts with DNA and proteins: Exploratory research on adducts with proteins

    NARCIS (Netherlands)

    Schans, G.P. van der; Noort, D.; Mars-Groenendijk, R.H.; Dijk-Knijnenburg, H.C.M. van; Fidder, A.; Jong, L.P.A. de; Benschop, H.P.

    2000-01-01

    We have developed two modes of a standard operating procedure (SOP) for immunochemical detection of sulfur mustard adducts to DNA in human blood and skin. In the shortened mode data could be generated within 9 h after in vitro exposure of human blood to > 1 μM sulfur mustard. The sensitive mode

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Teratogenic Effects of Sulfur Mustard on Mice Fetuses

    Science.gov (United States)

    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

  4. Inflammatory effects of inhaled sulfur mustard in rat lung

    International Nuclear Information System (INIS)

    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.

    2010-01-01

    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.

  5. SELECTED YIELD COMPONENTS IN WHITE MUSTARD (SINAPIS ALBA VERSUS SULFUR FERTILIZATION

    Directory of Open Access Journals (Sweden)

    Bożena BARCZAK

    2011-10-01

    Full Text Available As shown by the research made based on the four-year field experiment, sulfur fertilization, in general, significantly differentiated the white mustard yield components. Of all the factors (sulfur application method, its form and dose, the greatest effect on the yield structure components was demonstrated for the sulfur dose. The use of 40 kg S·ha-1, regardless of the form applied and the sulfur application method, resulted in significant increases in most of the characters, as compared with the control. The application of sulfur into soil showed a significantly more favorable effect on the seed weigh and number per silique and on the weight of seeds of the entire plant than the foliar application of this nutrient. The white mustard seed yield size was most correlated with the number of siliques per plant, and successively less with the thousand seed weight.

  6. Sulfur mustard induces expression of metallothionein-1A in human airway epithelial cells

    Directory of Open Access Journals (Sweden)

    Nourani MR

    2011-05-01

    Full Text Available Mohammad Reza Nourani1, Majid Ebrahimi1, Mehryar Habibi Roudkenar3, Ensieh Vahedi1, Mostafa Ghanei1, Abbas Ali Imani Fooladi21Chemical Injury Research Center; 2Microbial Product Research Center, Baqiyatallah University of Medical Sciences; 3Research Center, Iranian Blood Transfusion Organization, Tehran, IranBackground: Sulfur mustard can cause several long-term complications in the organs of individuals exposed to this toxic gas, and among these, pulmonary sequelae are the most important. More than 25 years after the Iran–Iraq war, thousands of Iranians are suffering from the chronic respiratory complications of sulfur mustard. Currently, based on several clinical findings, bronchiolitis obliterans is confirmed as the major diagnosis in these patients. Numerous studies have revealed that this disorder is strongly associated with oxidative stress due to excessive production of harmful reactive substances and decreased levels of endogenous antioxidants. Metallothioneins (MTs are a group of low molecular weight sulfhydryl-rich intracellular proteins, and several isoforms have been identified in humans. MT-1A is an inducible and important MT isoform, which is transcriptionally activated by a variety of stress stimuli, such as free radicals.Methods: MT-1 mRNA expression and protein levels in endobronchial biopsy samples from 24 sulfur mustard-exposed patients and 15 unexposed control cases were evaluated by semiquantitative reverse transcriptase polymerase chain reaction, real-time reverse transcriptase polymerase chain reaction, and immunohistochemistry.Results: mRNA- MT-1A expression levels in sulfur mustard-exposed patients were upregulated compared with normal samples. Protein expression was also markedly higher in controls than in sulfur mustard-exposed patients.Conclusion: Upregulation of MT-1A mRNA in patients who have been exposed to sulfur mustard seems to be due to oxidative stress, which is induced in an attempt to ameliorate this

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

    Energy Technology Data Exchange (ETDEWEB)

    Brevett, Carol A.S. [SAIC, Gunpowder Branch, P.O. Box 68, APG, MD 21010-0068 (United States)], E-mail: carol.brevett@us.army.mil; Sumpter, Kenneth B. [U.S. Army Edgewood Chemical Biological Center, 5183 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5424 (United States); Nickol, Robert G. [SAIC, Gunpowder Branch, P.O. Box 68, APG, MD 21010-0068 (United States)

    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 {sup 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{sub 2}CH{sub 2}){sub 2}S{sup +}CH{sub 2}CH{sub 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{sub 2}CH{sub 2}){sub 2}S{sup +}CH{sub 2}CH{sub 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{sub 2}CH{sub 2}){sub 2}S{sup +}CH{sub 2}CH{sub 2}OH, thus demonstrating the reversibility of sulfur mustard degradation pathways. The sulfur mustard degradation half-lives on ambient concrete at 22 deg. C ranged from 3.5 to 54 weeks. When the substrates were moistened, the degradation half-lives at 22 deg. C ranged from 75 to 350 h. 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 deg. C and weeks to months on concrete at 35 deg. C, before decomposing to the relatively non-toxic compounds thiodiglycol and 1,4-oxathiane.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    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 deg. C ranged from 3.5 to 54 weeks. When the substrates were moistened, the degradation half-lives at 22 deg. C ranged from 75 to 350 h. 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 deg. C and weeks to months on concrete at 35 deg. C, before decomposing to the relatively non-toxic compounds thiodiglycol and 1,4-oxathiane

  9. Quantum molecular modeling of the interaction between guanine and alkylating agents--2--nitrogen mustard.

    Science.gov (United States)

    Hamza, A; Broch, H; Vasilescu, D

    1996-06-01

    The alkylation mechanism of guanine by nitrogen mustard (HN2) was studied by using a supermolecular modeling at the ab initio 6-31G level. Our computations show that interaction of guanine with the aziridinium form of HN2 necessitates a transition state for the N7 alkylation route. The pathway of N7-guanine alkylation by nitrogen and sulfur mustards is discussed on the basis of the Molecular Electrostatic Potential and HOMO-LUMO properties of these molecules.

  10. Effects of sulfur mustard on mesenchymal stem cells.

    Science.gov (United States)

    Schmidt, Annette; Steinritz, Dirk; Rothmiller, Simone; Thiermann, Horst; Scherer, A Michael

    2017-08-14

    Chronic wound healing disorders that occur as a result of a sulfur mustard (SM) exposure present a particular challenge. These chronic wounds are similar to other chronic wounds. In the past, it has been shown that mesenchymal stem cells (MSC) play an important role in the healing of chronic wounds. An important property to support wound healing is their ability to migrate. However, we were able to show that SM leads to a reduction in MSC migration even at low concentrations. Currently, exposed MSCs are still able to differentiate. Further alterations are not known. The current investigation therefore focused onto the question how SM affects MSC. The effect of SM on MSC was investigated. Here, the alkylation of DNA was considered, and DNA adducts were quantified over a period of 48h. The modification of the nuclei under the influence of SM was analyzed as well as proliferation of the cells by immunohistochemical staining with Ki-67 and quantification. For the quantification of the apoptosis rate, antibodies against cleaved Caspase-3, 8, and apoptosis inducing factor (AIF) were used. The senescence analysis was performed after histological staining against β-galactosidase. Quantifications were carried out by using the TissueQuest System and the software TissueFAX. SM exposure of MSC results in a dose dependent formation of nuclear DNA adducts. 4h after exposure the cells display a decreasing concentration of DNA adducts. This process is accompanied by a change of nuclei shape but without an increase of apoptosis induction. In parallel the number of cells undergoing senescence increases as a function of the SM concentration. SM exposure of MSC leads to adduct formation on chromosomal DNA. These DNA adducts can be reduced without MSC are undergoing apoptosis. This indicates an active DNA damage response (DDR) pathway in combination with the formation of persistent nuclear DNA damage foci. This process is accompanied by a reduced capability of proliferation and a

  11. Delayed effects of sulfur mustard poisoning on CD4+ and CD8+ lymphocytes in Iranian veterans 25 years after exposure.

    Science.gov (United States)

    Mohammadhoseiniakbari, Hassan; Ghanei, Mostafa; Eajazi, Alireza; Mohammadi, Zahra; Daftari Besheli, Laleh

    2008-11-01

    Sulfur mustard is a chemical warfare agent that produces cellular damage via alkylation and protein cross-linking. Sulfur mustard affects the skin, lungs, and eyes, as well as the gastrointestinal, endocrinal, and hematologic systems. We studied the potential delayed toxic effects of sulfur mustard on white blood cells and some of its derivatives including polymorphonuclear lymphocytes and lymphocytes (CD4+ and CD8+) among Iranian veterans, approximately 25 years after exposure. One hundred thirteen sulfur mustard-poisoned veterans registered for this prospective study. Hematologic, immunophenotyping, and flow cytometric evaluations were done to samples from patients as well as 20 healthy age- and sex-matched control volunteers. Hematologic and immunologic variables were compared between both groups of subjects. Values for P less than.05 were considered statistically significant. Total white blood cell count and percentage of polymorphonuclear lymphocytes were significantly higher in sulfur-mustard-exposed veterans than in control subjects (P=0.008 and sulfur mustard may cause long-term damage to the immune system in humans. CD4+ T cells were significantly lower in persons exposed to sulfur mustard. However, there was no statistically significant between-group difference regarding CD8+ T cells. Impaired immunity may be responsible for the increased risk of infections in these patients.

  12. Skin hydration and transepidermal water loss in patients with a history of sulfur mustard contact: a case-control study.

    Science.gov (United States)

    Davoudi, Seyyed Masoud; Keshavarz, Saeed; Sadr, Bardia; Shohrati, Majid; Naghizadeh, Mohammad Mehdi; Farsinejad, Khalil; Rashighi-Firouzabadi, Mehdi; Zartab, Hamed; Firooz, Alireza

    2009-08-01

    Skin lesions are among the most common complications of contact with sulfur mustard. This study was aimed to measure skin water content and transepidermal water loss (TEWL) in patients with a history of sulfur mustard contact. Three hundred ten male participants were included in this study: 87 (28.1%) sulfur mustard-exposed patients with current skin lesions (group 1), 71 (22.9%) sulfur mustard-exposed patients without skin lesions (group 2), 78 (25.2%) patients with dermatitis (group 3) and 74 (23.8%) normal controls (group 4) The water content and TEWL of skin was measured at four different locations of the body: forehead, suprasternal, palm and dorsum of hand. Nonparametric statistical tests (Kruskal-Wallis) were used to compare the four groups, and P sulfur mustard-exposed participants or non-exposed participants with dermatitis (P sulfur mustard contact than in non-injured participants (P sulfur mustard agent can alter biophysical properties of the skin--especially the function of stratum corneum as a barrier to water loss-several years after exposure.

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

    International Nuclear Information System (INIS)

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

    2007-01-01

    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 24 h. 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

  14. A Large-Scale Quantitative Proteomic Approach to Identifying Sulfur Mustard-Induced Protein Phosphorylation Cascades

    Science.gov (United States)

    2010-01-01

    Maryland 21010 ReceiVed July 31, 2009 Probing the Dynamic Effect of Cys- CdTe Quantum Dots toward Cancer Cells in Vitro. See article on pp 82–88... modulating the effects of sulfur mustard. J. Appl. Toxicol. 20 (Suppl. 1), S43–49. (23) Xia, Z., Morales, J. C., Dunphy, W. G., and Carpenter, P. B. (2001

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

    Energy Technology Data Exchange (ETDEWEB)

    Brevett, Carol A.S. [GEO-CENTERS Operations, SAIC, Gunpowder Branch, P.O. Box 68, APG, MD 21010-0068 (United States)]. E-mail: carol.brevett@us.army.mil; Sumpter, Kenneth B. [CDR USA RDECOM, ATTN: AMSRD-ECB-RT-PD, 5183 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5424 (United States)]. E-mail: kenneth.sumpter@us.army.mil; Wagner, George W. [CDR USA RDECOM, ATTN: AMSRD-ECB-RT-PD, 5183 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5424 (United States)]. E-mail: george.wagner@us.army.mil; Rice, Jeffrey S. [CDR USA RDECOM, ATTN: AMSRD-ECB-RT-PD, 5183 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5424 (United States)]. E-mail: jeffrey.rice@us.army.mil

    2007-02-09

    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), {sup 1}H NMR, 2D {sup 1}H-{sup 13}C NMR and {sup 13}C solid state magic angle spinning (SSMAS) NMR. In situ and extraction experiments were performed. Sulfur mustard was detected in the in situ {sup 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 24 h. 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.

  16. Immunochemical detection of sulfur mustard adducts with keratins in the stratum corneum of human skin

    NARCIS (Netherlands)

    Schans, G.P. van der; Noort, D.; Mars-Groenendijk, R.H.; Fidder, A.; Chau, L.F.; Jong, L.P.A. de; Benschop, H.P.

    2002-01-01

    As part of a program to develop methods for diagnosis of exposure to chemical warfare agents, we developed immunochemical methods for detection of adducts of sulfur mustard to keratin in human skin. Three partial sequences of keratins containing glutamine or asparagine adducted with a

  17. Detection of sulfur mustard adducts in human callus by phage antibodies

    NARCIS (Netherlands)

    Bikker, F.J.; Mars-Groenendijk, R.H.; Noort, D.; Fidder, A.; Schans, G.P. van der

    2007-01-01

    As part of a research program to develop novel methods for diagnosis of sulfur mustard exposure in the human skin the suitability of phage display was explored. Phage display is a relative new method that enables researchers to quickly evaluate a huge range of potentially useful antibodies, thereby

  18. Early oxidative stress, DNA damage and inflammation resulting from subcutaneous injection of sulfur mustard into mice.

    Science.gov (United States)

    Zhang, Xiaorui; Mei, Yizhou; Wang, Tongxing; Liu, Feng; Jiang, Ning; Zhou, Wenxia; Zhang, Yongxiang

    2017-10-01

    Oxidative stress, DNA damage repair, and inflammation are three important reactions of sulfur mustard (SM) exposure. But molecular related chronological events in the earlier stage of SM exposure model are still unclear. In the research, reactive oxygen species (ROS) was measured by using flow cytometry. Cytokines were tested in Luminex method. Myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG) and glutathione (GSH) activity or levels in serum were determined by commercially available kits. Western blot was used to determination of phosphorylated histone 2A.X (γ-H2A.X). Results showed that the oxidative stress biomarker of ROS and 8-OHdG were significantly increased early at 0.5h of SM exposure, but GSH level was decreased at 0.5h. Similarly, SM increased γ-H2A.X level early at 2h, which reached to peak at 8h and recovered to normal at 24h. MPO and iNOS activity were also increased early at 2h and 0.5h respectively. However, all selected inflammation biomarkers, including IL-6, TNF-α, IL-1β, MCP-1, GM-CSF and IL-10 concentrations are all unchangeable in 2h. The results indicated that oxidative stress and DNA damage had happened more quickly than inflammation reaction. These chronological events may be due to uncovered generation of reactive oxygen species, DNA alkylation and oxidative DNA damage. In conclusion, this research showed that both oxidative stress and DNA damage are earlier events than inflammation in sulfur mustard toxic mouse model. Copyright © 2017. Published by Elsevier B.V.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  20. Calmodulin mediates sulfur mustard toxicity in human keratinocytes

    International Nuclear Information System (INIS)

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

    2006-01-01

    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 48 h 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

  1. Kinetic Modeling of the Thermal Destruction of Nitrogen Mustard Gas.

    Science.gov (United States)

    Lizardo-Huerta, Juan-Carlos; Sirjean, Baptiste; Verdier, Laurent; Fournet, René; Glaude, Pierre-Alexandre

    2017-05-04

    The destruction of stockpiles or unexploded ammunitions of nitrogen mustard (tris(2-chloroethyl)amine, HN-3) requires the development of safe processes. The thermal destruction of this kind of compound is one of the most efficient method of destruction. Because of the high-level of toxicity of this chemical, there is a considerable lack of knowledge on the chemical kinetics at high temperatures. In this study, a detailed chemical kinetic model for the pyrolysis of nitrogen mustard gas is developed based on a large number of thermokinetic parameters calculated with theoretical chemistry. The thermal decomposition of HN-3 is shown to mainly proceed through stepwise dechlorination with Cl-atom being the principal chain carrier. The successive losses of chlorine atom mainly lead to unsaturated amines without chlorine groups. Theoretical calculations demonstrated that the thermal decomposition of these compounds ultimately lead to the formation of pyrrole, which can accumulate at low temperature. At higher temperatures, pyrrole yields HCN and acetylene. Simulations also predict that about 52% of the total flux of decomposition of HN-3 leads to the formation of N,N-diethenyl-2-chloroethylamine (P29), which acts as a chain branching agent because its unimolecular decomposition is preponderant and produces one chlorine and one hydrogen atoms. Comparisons with the simulated reactivity of sulfur mustard gas are also performed and show that HN-3 is more reactive that the former toxic. The higher number of chlorine atoms in HN-3 compared to sulfur mustard (3 vs 2) and the formation of the chain branching intermediate P29 during its decomposition explain this behavior.

  2. Diagnosis and Dosimetry of Exposure to Sulfur Mustard: Development of Standard Operating Procedures; Further Exploratory Research on Protein Adducts

    National Research Council Canada - National Science Library

    Benschop, H

    1999-01-01

    .... Both procedures could be substantially shortened, while their sensitivities were improved. Furthermore, exploratory research is performed aiming at the development of a fieldable immunochemical assay for sulfur mustard adducts with proteins, i.e...

  3. The GC/AED studies on the reactions of sulfur mustard with oxidants

    International Nuclear Information System (INIS)

    Popiel, StanisIaw; Witkiewicz, Zygfryd; Szewczuk, Aleksander

    2005-01-01

    A gas chromatograph coupled with an atomic emission detector was used to identify and to determine the products formed on oxidation of sulfur mustard. The oxidation rate and the resulting oxidates were studied in relation to oxidant type and reaction medium parameters. Hydrogen peroxide, sodium hypochlorite, sodium perborate, potassium monopercarbonate, ammonium peroxydisulfate, potassium peroxymonosulfate (oxone), and tert-butyl peroxide were used as oxidants. Oxidations were run in aqueous media or in solvents of varying polarities. The oxidation rate was found to be strongly related to oxidant type: potassium peroxymonosulfate (oxone) and sodium hypochlorite were fast-acting oxidants; sodium perborate, hydrogen peroxide, ammonium peroxydisulfate, and sodium monopercarbonate were moderate oxidants; tert-butyl peroxide was the slowest-acting oxidant. In non-aqueous solvents, the oxidation rate was strongly related to solvent polarity. The higher the solvent polarity, the faster the oxidation rate. In the acid and neutral media, the mustard oxidation rates were comparable. In the alkaline medium, oxidation was evidently slower. A suitable choice of the initial oxidant-to-mustard concentration ratio allowed to control the type of the resulting mustard oxidates. As the pH of the reaction medium was increased, the reaction of elimination of hydrogen chloride from mustard oxidates becomes more and more intensive

  4. The GC/AED studies on the reactions of sulfur mustard with oxidants

    Energy Technology Data Exchange (ETDEWEB)

    Popiel, StanisIaw [Institute of Chemistry, Military University of Technology, 2, Kaliskiego-Street, 00-908 Warsaw (Poland); Witkiewicz, Zygfryd [Institute of Chemistry, Military University of Technology, 2, Kaliskiego-Street, 00-908 Warsaw (Poland) and Jan Kochanowski Swietokrzyska Academy, Institute of Chemistry, 5, Checinska-Street, 25-020 Kielce (Poland)]. E-mail: witkiew@wp.pl; Szewczuk, Aleksander [Institute of Chemistry, Military University of Technology, 2, Kaliskiego-Street, 00-908 Warsaw (Poland)

    2005-08-31

    A gas chromatograph coupled with an atomic emission detector was used to identify and to determine the products formed on oxidation of sulfur mustard. The oxidation rate and the resulting oxidates were studied in relation to oxidant type and reaction medium parameters. Hydrogen peroxide, sodium hypochlorite, sodium perborate, potassium monopercarbonate, ammonium peroxydisulfate, potassium peroxymonosulfate (oxone), and tert-butyl peroxide were used as oxidants. Oxidations were run in aqueous media or in solvents of varying polarities. The oxidation rate was found to be strongly related to oxidant type: potassium peroxymonosulfate (oxone) and sodium hypochlorite were fast-acting oxidants; sodium perborate, hydrogen peroxide, ammonium peroxydisulfate, and sodium monopercarbonate were moderate oxidants; tert-butyl peroxide was the slowest-acting oxidant. In non-aqueous solvents, the oxidation rate was strongly related to solvent polarity. The higher the solvent polarity, the faster the oxidation rate. In the acid and neutral media, the mustard oxidation rates were comparable. In the alkaline medium, oxidation was evidently slower. A suitable choice of the initial oxidant-to-mustard concentration ratio allowed to control the type of the resulting mustard oxidates. As the pH of the reaction medium was increased, the reaction of elimination of hydrogen chloride from mustard oxidates becomes more and more intensive.

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

    Directory of Open Access Journals (Sweden)

    Nasser Shoeibi

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    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.

  8. Cell Death Mechanisms in Sulfur Mustard Injury: Basis for Therapeutics Development

    International Nuclear Information System (INIS)

    Ray, R.; Keyser, B.; Benton, B.; Rosenthal, D. S.

    2007-01-01

    Sulfur mustard (SM, bis-(2-chloroethyl) sulfide), commonly called mustard gas, is a vesicant chemical warfare agent and a potential terrorism agent. SM is relatively easy to make and to deploy, which makes this chemical most likely to be used. SM exposure causes debilitating skin blisters (vesication) and injury to the eyes and the respiratory tract. Therefore, developing an effective medical countermeasure to protect against the dermal, ocular and airway injuries due to this dreaded chemical agent is an urgent priority of the US Army. SM pathophysiology is consistent with epithelial cell damage, particularly basal cell apoptosis. SM-induced apoptosis may occur via multiple pathways dependent on one or more of the following: (a) abnormal Ca2plus homeostasis, (b) disturbed cellular bioenergetics, and (c) Fas (death receptor) response. Apoptosis pathways are characterized by the involvement of the pathway-specific caspases (cysteine aspartase). We determined caspase activity by assay of fluorogenic caspase type-specific peptide substrate hydrolysis. We studied caspase processing, i.e., proteolytic conversion of procaspase to active caspase by immunoblot analyses utilizing caspase type-specific antibodies. Our results in cell culture models of both human epidermal keratinocytes and human airway epithelial cells indicated that SM activates (a) caspase-9, an indicator of the Ca2plus/CaM-mediated mitochondrial pathway, (b) caspase-8, a marker for the Fas-mediated pathway, and (c) caspase-3, the executioner caspase involved in both pathways. A peptide caspase inhibitor, specific for caspase-3 (AC-DEVD-CHO), added to cells prior to SM decreased apoptosis. These observations suggest apoptosis as a mechanism of SM toxicity and caspase inhibitors as prospective medical countermeasures.(author)

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

    Science.gov (United States)

    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

  10. The Role of NAD+ Depletion in the Mechanisms of Sulfur Mustard-Induced Metabolic Injury

    Science.gov (United States)

    2008-01-01

    reprint. 15. SUBJECT TERMS Cell cultures, glycolysis, HD, keratinocytes, NAD+, niacinamide , sulfur mustard, toxicology 16. SECURITY CLASSIFICATION...NAD+ depletion. To define tl,e role of NAD+ in mu.~tUl·d-induced metabolic injury, we examined the effects ofmustard ± niacinamide on energy metabolism...not earlier, and time- and concentration-dependent glycolytic inhibition and NAD+ depletion as early as 4 hours. Niacinamide partially protected NAD

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

    International Nuclear Information System (INIS)

    Batal, Mohamed; Boudry, Isabelle; Mouret, Stéphane; Wartelle, Julien; Emorine, Sandy; Bertoni, Marine; Bérard, Izabel; Cléry-Barraud, Cécile

    2013-01-01

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

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

    Science.gov (United States)

    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. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Detoxification of sulfur mustard by enzyme-catalyzed oxidation using chloroperoxidase.

    Science.gov (United States)

    Popiel, S; Nawała, J

    2013-10-10

    One of the most interesting methods for the detoxification of sulfur mustard is enzyme-catalyzed oxidation. This study examined the oxidative destruction of a sulfur mustard by the enzyme chloroperoxidase (EC 1.11.1.10). Chloroperoxidase (CPO) belongs to a group of enzymes that catalyze the oxidation of various organic compounds by peroxide in the presence of a halide ion. The enzymatic oxidation reaction is affected by several factors: pH, presence or absence of chloride ion, temperature, the concentrations of hydrogen peroxide and enzyme and aqueous solubility of the substrate. The optimum reaction conditions were determined by analyzing the effects of all factors, and the following conditions were selected: solvent, Britton-Robinson buffer (pH=3) with tert-butanol (70:30 v/v); CPO concentration, 16U/mL; hydrogen peroxide concentration, 40mmol/L; sodium chloride concentration, 20mmol/L. Under these reaction conditions, the rate constant for the reaction is 0.006s(-1). The Michaelis constant, a measure of the affinity of an enzyme for a particular substrate, is 1.87×10(-3)M for this system. The Michaelis constant for enzymes with a high affinity for their substrate is in the range of 10(-5) to 10(-4)M, so this value indicates that CPO does not have a very high affinity for sulfur mustard. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Batal, Mohamed [Laboratoire «Lésions des Acides Nucléiques», Université Joseph Fourier – Grenoble 1, CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble (France); Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche (France); Boudry, Isabelle; Mouret, Stéphane; Wartelle, Julien; Emorine, Sandy; Bertoni, Marine [Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche (France); Bérard, Izabel [Laboratoire «Lésions des Acides Nucléiques», Université Joseph Fourier – Grenoble 1, CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble (France); Cléry-Barraud, Cécile [Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche (France); 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.

  15. Changes in the oxidative stress/anti-oxidant system after exposure to sulfur mustard and antioxidant strategies in the therapy, a review.

    Science.gov (United States)

    Pohanka, Miroslav; Martinkova, Pavla; Brtnicky, Martin; Kynicky, Jindrich

    2017-07-01

    Sulfur mustard, in a chemical name bis(2-chloroethyl) sulfide, is a chemical warfare agent. It is cytotoxic and blister forming once spread over the skin. Though exact molecular mechanism of sulfur mustard toxic action remains unknown, inflammation and oxidative stress development are considered as the most relevant pathological consequences. Applications of either low-molecular weight antioxidants or cofactors for enzymatic antioxidants are considered as suitable ways how to ameliorate the poisoning. In this article, survey of literature on countermeasures against sulfur mustard poisoning are given and evidence of oxidative stress role during sulfur mustard poisoning and availability of antioxidants for the therapy are discussed.

  16. Vascular Endothelial Growth Factor in Bronchoalveolar Lavage Fluid in SulfurMustard Exposed Lung Patients

    Directory of Open Access Journals (Sweden)

    Mobin Yassini

    2011-03-01

    Full Text Available Objectives: To determine the levels of vascular endothelial growth factor isoform consisting of 165 amino acids (VEGF165 in Bronchoalveolar Lavage Fluid from Mustard Exposed Patients.Methods: Bronchoscopy with Bronchoalveolar Lavage was performed on sulphur mustard exposed patients. A total of 39 patients with documented exposure to Sulfur Mustard during the Iran-Iraq war participated in this study, of which 38 patients were males and one patient was female.Results: The mean±SD age of patients was 41 ± 6.6 years. The mean time after exposure to sulfur mustard was 19 ±1.7 years. Eighteen patients had concomitant war injuries but they were not related to the respiratory system. While Twenty-two patients had a history of submassive persistent hemoptysis. There was no case with massive hemoptysis. Most of the patients had small airway obstruction (FEV1/FVC�0= 78.14 ± 9.76 and FEV1�0=82.79±18.23. Twenty-three patients had significant air trapping in the chest. High Resolution Computed Tomography was compatible with BOS. VEGF165 concentrations in BALF were 36.87 ± 34.68 pg/ml. When corrected to total protein of Bronchoalveolar Lavage Fluid (BALF it was 0.76 ± 0.70 pg/mg. BALF of VEGF did not correlate with hemoptysis or air trapping in chest HRCT. Thus, there was also no correlation between level of VEGF165 in BALF and any of PFT indexes (FVC, FEV1, MMEF or PEF.Conclusions: Although VEGF is one of the cytokines which has an important role in chronic pulmonary disorders, it seems that it has no essential role in the severity of Mustard Lung Disease.

  17. A Histological Assessment of Lung Injury in Rats Exposed to Inhaled Sulfur Mustard across Dose and Time

    Science.gov (United States)

    2015-06-01

    Institute of Chemical Defense. June, p 177. Laskin J D, Black A T, Jan Y-H, Sinko P J, Heindel N D, et al. (2010) Oxidants and antioxidants in sulfur...intratracheal exposure of guinea pigs to sulfur mustard aerosol: Therapeutic efficacy of exogenous lung surfactant curosurf and salbutamol

  18. Sulfur mustard gas adsorption on ZnO fullerene-like nanocage: Quantum chemical calculations

    Science.gov (United States)

    Kazemi, Mohammad; Rad, Ali Shokuhi

    2017-06-01

    In the present study, we used density functional theory calculations (at B3LYP and ωB97XD Levels) to search on the adsorption of Sulfur mustard gas (defined as mustard gas) on the surface of fullerene-like ZnO nanocage as a semiconductor. We found three different configurations of adsorbed gas on the surface of this nanostructure semiconductor. The values of adsorption energy of mustard gas are calculated in the range of -144∼ -200 kJ/mol with enthalpies in the range of -132∼-195 kJ/mol and Gibbs free energies in the range of -88∼-144 kJ/mol (T = 298 K, based on ωB97XD level), which indicate exothermic and spontaneous chemisorption. For all geometries, we calculated geometry parameters by taking into account the charge analysis and frontier molecular orbital study. The result of this study can be a support for next studies to develop new nanomaterials as adsorbent/sensor for mustard gas.

  19. Sulfur mustard inhalation: mechanisms of injury, alteration of coagulation, and fibrinolytic therapy.

    Science.gov (United States)

    White, Carl W; Rancourt, Raymond C; Veress, Livia A

    2016-08-01

    Acute lung injury due to sulfur mustard (SM) inhalation causes the formation of airway fibrin casts that obstruct airways at multiple levels, leading to acute respiratory failure and death. These pathophysiological effects are seen in rodent models of acute SM vapor inhalation, as well as in human victims of acute SM inhalation. In rat models, the initial steps in activation of the coagulation system at extravascular sites depend on tissue factor (TF) expression by airway cells, especially in the microparticle fraction, and these effects can be inhibited by TF pathway inhibitor protein. Not only does the procoagulant environment of the acutely injured lung contribute to airway cast formation, but these lesions persist in airways because of the activation of multiple antifibrinolytic pathways, including plasminogen activator inhibitor-1, thrombin-activatable fibrinolysis inhibitor, and α2-antiplasmin. Airway administration of tissue plasminogen activator can overwhelm these effects and save lives by preventing fibrin-dependent airway obstruction, gas-exchange abnormalities, and respiratory failure. In human survivors of SM inhalation, fibrotic processes, including bronchiolitis obliterans and interstitial fibrosis of the lung, are among the most disabling chronic lesions. Antifibrotic therapies may prove useful in preventing either or both of these forms of chronic lung damage. © 2016 New York Academy of Sciences.

  20. Gas chromatographic-tandem mass spectrometric analysis of β-lyase metabolites of sulfur mustard adducts with glutathione in urine and its use in a rabbit cutaneous exposure model.

    Science.gov (United States)

    Lin, Ying; Dong, Yuan; Chen, Jia; Li, Chun-Zheng; Nie, Zhi-Yong; Guo, Lei; Liu, Qin; Xie, Jian-Wei

    2014-01-15

    A method for quantitation of β-lyase metabolites of sulfur mustard (SM) adducts with glutathione has been developed and validated using gas chromatography-tandem mass spectrometry (GC-MS/MS). The linear range of quantitation was 0.1-1000ng/mL in urine with a method detection limit of 0.02ng/mL. The method was applied in a rabbit exposure model. Domestic rabbits were cutaneously exposed to neat liquid SM in three dosage levels, and the β-lyase metabolites in urine were determined as 1,1'-sulfonylbis[2-(methylthio)ethane] (SBMTE). The study showed that even though more than 99% of the total amount of β-lyase metabolites was excreted in the first week after exposure, the β-lyase metabolites of SM adducts with glutathione could be detected in urine from rabbits for up to 3 or 4 weeks after the SM cutaneous exposure. For high dosage group (15mg/kg, 0.15 LD50), the mean concentration of SBMTE detected was 0.32ng/mL on day 28. For middle (5mg/kg, 0.05 LD50) and low (2mg/kg, 0.02 LD50) dosage groups, the mean concentrations of SBMTE were 0.07ng/mL and 0.02ng/mL on day 21, respectively. The data from this study indicate that the method is sensitive and provides a relatively long time frame for the retrospective detection of SM exposure. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Sulfur mustard inhalation induced respiratory lesions in guinea pigs: Physiological, biochemical, and histological study

    Energy Technology Data Exchange (ETDEWEB)

    Allon, N.; Gilat, E.; Amir, A.; Fishbine, E.; Liani, H.

    1993-05-13

    Inhalation exposure to sulfur mustard (SM) vapor causes long term damage to the respiratory system. The lesions were characterized by specific physiological, biochemical and histopathological methods. Awake 128 guinea-pigs (GP) were exposed for 10 min to SM (1200-1700 microns x min/1). Respiratory parameters were monitored per animal before, during and after the exposure using plethysmography. Biochemical and histological evaluations were performed at different time intervals for up to 7 days post exposure. SM inhalation resulted in a decrease in both respiratory rate and minute volume, and in an increase in tidal volume. These changes occurred immediately after the onset of exposure and lasted for up to 7 days. The changes in the respiratory parameters were accompanied by a massive reduction in O2 diffusion capacity. Evaluation of bronchoalveolar lavage (BAL) fluid indicated neutrophil infiltration, an increase in the protein content, and in the activity of both lysosomal enzymes and lactic dehydrogenase (LDH) in the alveolar space. In addition, a decrease in glutathione content was observed one day post exposure in the BAL fluid and the lung whereas an increase in lung glutathione content was observed 6 days later. Histological evaluation of the lungs and trachea revealed severe lesions in both tissues. Recovery was incomplete 7 days post exposure. The detailed characterization of the effect of SM inhalation offers a reliable model for the evaluation of potential therapies against SM exposure.

  2. Bronchiolitis Obliterans and Pulmonary Fibrosis After Sulfur Mustard Inhalation in Rats.

    Science.gov (United States)

    McGraw, Matthew D; Dysart, Marilyn M; Hendry-Hofer, Tara B; Houin, Paul R; Rioux, Jacqueline S; Garlick, Rhonda B; Loader, Joan E; Smith, Russell; Paradiso, Danielle C; Holmes, Wesley W; Anderson, Dana R; White, Carl W; Veress, Livia A

    2018-01-09

    Inhalation of powerful chemical agents, such as sulfur mustard (SM), can have debilitating pulmonary consequences, such as bronchiolitis obliterans (BO) and parenchymal fibrosis (PF). The underlying pathogenesis of disorders after SM inhalation is not clearly understood, resulting in a paucity of effective therapies. To evaluate the role of pro-fibrotic pathways involving TGF-β and PDGF in the development of BO and PF after inhalation injury sustained by SM, using a rat model. Adult Sprague-Dawley rats were intubated and exposed to SM (1.0 mg/kg), then monitored daily for respiratory distress, oxygen saturation changes, and weight loss. Rats were euthanized at 7, 14, 21 or 28 days, and markers of injury were determined by histopathology, pulmonary function testing, and assessment for TGF- β, PDGF and PAI-1 levels. Respiratory distress developed over time after SM inhalation, with progressive hypoxemia, respiratory distress, and weight loss. Histopathology confirmed the presence of both BO and PF, gradually worsening with time. Pulmonary function testing demonstrated a time-dependent increase in lung resistance, and a decrease in lung compliance. Levels of TGF-β, PDGF, and PAI-1 were elevated at 28 days, in lung, bronchoalveolar lavage fluid (BALF), and/or plasma. Time-dependent development of BO and PF occurs in lungs of rats exposed to SM inhalation, and the elevated levels of TGF-β, PDGF and PAI-1 suggest involvement of these pro-fibrotic pathways in the aberrant remodeling after injury.

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

    Science.gov (United States)

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

    2010-01-01

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

  4. Histopathologic features seen in sulfur mustard induced cutaneous lesions in hairless guinea pigs.

    Science.gov (United States)

    Smith, K J; Graham, J S; Moeller, R B; Okerberg, C V; Skelton, H; Hurst, C G

    1995-06-01

    Sulfur mustard (SM), a chemical warfare agent first used early in the 20th century, has re-emerged in the past decade as a major threat around the world. At present, there are no effective therapeutic measures for SM exposure. Because the skin as well as other interface epithelial surfaces are the first tissues effected as this agent is absorbed, reactions within the skin are an area of active research into the mechanism of action of this alkylating agent. The euthymic hairless guinea pig has been used as the animal model for the study of SM induced injuries because of morphologic similarity of its skin to human skin, with a multiple layer epidermis, and because this animal has a normal immune system. We reviewed 102 biopsy specimens from 51 animals exposed to three different dose times of saturated SM vapor. Histopathologic evidence exists for increased programmed cell death as well as cellular necrosis, subepidermal blister formation, and delayed re-epithelialization secondary to problems with adhesion. Information obtained from this study adds to the body of information important in the investigation of the mechanisms of action of SM.

  5. Prevalence of Skin Cancers Among Iranian Veterans, 18-23 Years Following Exposure to Sulfur Mustard

    International Nuclear Information System (INIS)

    Emadi, S. N.; Soroush, R.; Khateri, S.

    2007-01-01

    In this historical Cohort, in a population of 800 veterans with documented history of exposure to Sulfur Mustard during the period of 1984-88 (all have been under the close health monitoring program) 25 cases are found to have developed skin cancer over the past years. The most common cancer among these cases has been Basal Cell Carcinoma -BCC- with 9 cases and then Squamous Cell Carcinoma -SCC- , mycosis fungoides-MF-, Bowen disease and Dermatofibrosarcoma protuberans-DFSP- (5, 5, 4 and 2 cases respectively). Considering the number of diagnosed skin cancers among the subjects of this study and new cases even 2 decades after exposure, more in depth studies are necessary to investigate the possible casual relationship between the exposure to mustard gas and the skin cancers. (author)

  6. Novel treatment opportunities for sulfur mustard-related cancers: genetic and epigenetic perspectives.

    Science.gov (United States)

    Rahmani, Soheila; Abdollahi, Mohammad

    2017-12-01

    Sulfur mustard (SM), also known as mustard gas, is a chemical weapon which by now has been used in many wars. The most concerning SM toxic effect is probable carcinogenicity. In this study, the genetic and epigenetic mechanisms of SM carcinogenicity, by focusing on treatment of SM-associated malignancies, particularly gene therapeutics, cancer vaccines, and epigenetic medications, have been criticized. The required data were collected through an organized search on valid scientific databases. For SM carcinogenicity due to acute or chronic exposure, the entire original and review articles were evaluated. In addition, studies on the therapeutic effects of available genetic and epigenetic medications were included. Currently, four gene therapeutics, two cancer vaccines with genetic bases, and seven epigenetic medications are available for cancer treatment. Genetic and epigenetic cancer treatments including Gendicine, Imlygic, Provenge, Cimavax-EGF, Azacitidine, Vorinostat, Romidepsin, and Belinostat will yield outstanding benefits for SM-exposed patients who suffer from cancer.

  7. Treatment for Sulfur Mustard Lung Injuries; New Therapeutic Approaches from Acute to Chronic Phase

    Directory of Open Access Journals (Sweden)

    Zohreh Poursaleh

    2012-09-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Poursaleh Zohreh

    2012-09-01

    Full Text Available Abstract 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.

  9. Diagnosis and dosimetry of exposure to sulfur mustard: Development of a standard operating procedure for hemoglobin adducts: Exploratory research on albumin and keratin adducts

    NARCIS (Netherlands)

    Noort, D.; Fidder, A.; Jong, L.P.A. de; Schans, G.P. van der; Benschop, H.P.

    2000-01-01

    A standard operating procedure (SOP) for determination of the sulfur mustard adduct to the N-terminal valine in hemoglobin was developed. By using this SOP, it was found that the Nterminal valine adduct in globin of hairless guinea pigs and marmosets which had been exposed to sulfur mustard (0.5

  10. Alkylation of human serum albumin by sulfur mustard in vitro and in vivo : Mass spectrometric analysis of a cysteine adduct as a sensitive biomarker of exposure

    NARCIS (Netherlands)

    Noort, D.; Hulst, A.G.; Jong, L.P.A. de; Benschop, H.P.

    1999-01-01

    To develop a mass spectrometric assay for the detection of sulfur mustard adducts with human serum albumin, the following steps were performed: quantitation of the binding of the agent to the protein by using [14C] sulfur mustard and analysis of acidic and tryptic digests of albumin from blood after

  11. Efficient and selective oxidation of sulfur mustard using singlet oxygen generated by a pyrene-based metal-organic framework.

    Science.gov (United States)

    Liu, Yangyang; Buru, Cassandra T; Howarth, Ashlee J; Mahle, John J; Buchanan, James H; DeCoste, Jared B; Hupp, Joseph T; Farha, Omar K

    2016-01-01

    A pyrene-based metal-organic framework (MOF) NU-1000 was used as a heterogeneous photocatalyst for the degradation of a sulfur mustard simulant, 2-chloroethyl ethyl sulfide (CEES). Using irradiation from a commercially available and inexpensive ultraviolet (UV) light-emitting diode (LED), singlet oxygen ( 1 O 2 ) is generated by NU-1000 and selectively oxidizes CEES to the nontoxic product 2-chloroethyl ethyl sulfoxide (CEESO). More importantly, this method was tested on the warfare agent sulfur mustard (HD) for the first time using 1 O 2 and a MOF catalyst, and this method proved to be effective in oxidizing sulfur mustard to nontoxic products without forming the toxic sulfone by-product.

  12. Reduced sulfur mustard-induced skin toxicity in cyclooxygenase-2 knockout and celecoxib-treated mice

    International Nuclear Information System (INIS)

    Wormser, Uri; Langenbach, Robert; Peddada, Shyamal; Sintov, Amnon; Brodsky, Berta; Nyska, Abraham

    2004-01-01

    Sulfur mustard (SM), a potent vesicant and chemical warfare agent, induces tissue damage involving an inflammatory response, including vasodilatation, polymorphonuclear infiltration, production of inflammatory mediators, and cyclooxygenase activity. To evaluate the role of cyclooxygenase-1 and -2 (COX-1, COX-2) in sulfur mustard-induced skin toxicity, we applied the agent to the ears of wildtype (WT) and COX-1- and COX-2-deficient mice. In the latter, ear swelling 24 and 48 h after exposure was significantly reduced (P < 0.05) by 55% and 30%, respectively, compared to WT. Quantitative histopathology revealed no epidermal ulceration in COX-2-deficient mice but some degree of severity in WT. COX-2-deficient mice showed significant reductions (P < 0.05) in severity of epidermal necrosis (29%), acute inflammation (42%), and hemorrhage (25%), compared to the WT mice. COX-1 deficiency resulted in significant exacerbation (P < 0.05) in severity of some parameters, including increases of 4.6- and 1.2-fold in epidermal ulceration and epidermal necrosis, respectively, compared to WT. Postexposure treatment of normal male ICR mice with the selective COX-2 inhibitor celecoxib resulted in significant reductions of 27% (P < 0.05) and 28% (P < 0.01) in ear swelling at intervals of 40 and 60 min between exposure and treatment, respectively. Histopathological evaluation revealed significant reductions (P < 0.05) in subepidermal microblister formation (73%) and dermal necrosis (32%), compared to the control group. These findings may indicate that COX-2 participates in the early stages of sulfur mustard-induced acute skin toxicity and that COX-1 might exert some protective function against this chemical insult

  13. Epoxy Resin Modified Quartz Crystal Microbalance Sensor for Chemical Warfare Agent Sulfur Mustard Vapor Detection

    Directory of Open Access Journals (Sweden)

    Rajendra BUNKAR

    2010-02-01

    Full Text Available An epoxy resin polymer coated quartz crystal microbalance (PC-QCM is used for detection of sulfur mustard vapor (SM. When SM vapor is exposed to PC-QCM sensor frequency shift is observed. The response of the sensor in ambient condition is 554 Hz with ±10 % variation upon exposure of 155 ppm of the SM concentration. The observed response loss is nearly 40 % over the period of 15 months. The response of the sensor is higher for SM than compare to structurally similar chloroethyl ether (CEE and other interferences.

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

    Science.gov (United States)

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

    2013-12-05

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

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

    Science.gov (United States)

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

    2009-11-06

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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Khafaei Mostafa

    2015-12-01

    Full Text Available 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 32 healthy 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.

  18. Tissue Plasminogen Activator Prevents Mortality from Sulfur Mustard Analog–Induced Airway Obstruction

    Science.gov (United States)

    Hendry-Hofer, Tara B.; Loader, Joan E.; Rioux, Jacqueline S.; Garlick, Rhonda B.; White, Carl W.

    2013-01-01

    Sulfur mustard (SM) inhalation causes the rare but life-threatening disorder of plastic bronchitis, characterized by bronchial cast formation, resulting in severe airway obstruction that can lead to respiratory failure and death. Mortality in those requiring intubation is greater than 80%. To date, no antidote exists for SM toxicity. In addition, therapies for plastic bronchitis are solely anecdotal, due to lack of systematic research available to assess drug efficacy in improving mortality and/or morbidity. Adult rats exposed to SM analog were treated with intratracheal tissue plasminogen activator (tPA) (0.15–0.7 mg/kg, 5.5 and 6.5 h), compared with controls (no treatment, isoflurane, and placebo). Respiratory distress and pulse oximetry were assessed (for 12 or 48 h), and arterial blood gases were obtained at study termination (12 h). Microdissection of fixed lungs was done to assess airway obstruction by casts. Optimal intratracheal tPA treatment (0.7 mg/kg) completely eliminated mortality (0% at 48 h), and greatly improved morbidity in this nearly uniformly fatal disease model (90–100% mortality at 48 h). tPA normalized plastic bronchitis–associated hypoxemia, hypercarbia, and lactic acidosis, and improved respiratory distress (i.e., clinical scores) while decreasing airway fibrin casts. Intratracheal tPA diminished airway-obstructive fibrin–containing casts while improving clinical respiratory distress, pulmonary gas exchange, tissue oxygenation, and oxygen utilization in our model of severe chemically induced plastic bronchitis. Most importantly, mortality, which was associated with hypoxemia and clinical respiratory distress, was eliminated. PMID:23258228

  19. Prevention and treatment of respiratory consequences induced by sulfur mustard in Iranian casualties.

    Science.gov (United States)

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

    2013-04-01

    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. 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. 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. Most treatments are symptomatic but using preventive points immediately after exposure could improve following outcomes.

  20. Long Term Follow-Up of Sulfur Mustard Related Bronchiolitis Obliterans Treatment.

    Science.gov (United States)

    Abtahi, Hamidreza; Peiman, Soheil; Foroumandi, Morteza; Safavi, Enayat

    2016-09-01

    Bronchiolitis obliterans (BO) is the most remarkable pulmonary sequels of war-related sulfur mustard inhalation. There is little if any data about long-term efficacy of associated BO treatment. Five years spirometric records of three groups of patients with obstructive pulmonary diseases (asthma, COPD, BO) and documented sulfur mustard inhalation were evaluated. The BO patients were treated with inhaled Seretide 125-250/25 (2 puffs BID), azithromycin (250 mg, three times/week) and N-acetylcysteine (1200-1800/day). Asthma and COPD patients were treated according to existing guidelines. Seventy-three (38 asthma, 16 COPD and 19 BO) patients completed the 5 years follow-up. Basal and final FEV1 in BO patients (2.69±0.81 and 2.39±0.65 respectively) were not significantly different from COPD patients (2.46±0.56 and 1.96±0.76 respectively). There was also no significant difference between the yearly FEV1 decline in BO patients compared to COPD patients (60±84 cc vs. 99±79 cc respectively, P=0.163). The non-significant difference of FEV1 decline in BO compared to COPD patients suggests the effectiveness of azithromycin, inhaled steroid and N-acetyl cysteine in BO patients. Considering safety and possible effectiveness, this treatment is recommended until more data is available from controlled clinical studies.

  1. Characterization of sulfur mustard resistant keratinocyte cell line HaCaT/SM.

    Science.gov (United States)

    Wolf, Markus; Siegert, Markus; Rothmiller, Simone; Scheithauer, Nina; Strobelt, Romano; Steinritz, Dirk; Worek, Franz; Thiermann, Horst; Schmidt, Annette

    2016-02-26

    The cell line HaCaT/SM was derived from the human keratinocyte cell line HaCaT. HaCaT/SM cells display a high resistance against sulfur mustard (SM). Intention of the presented study was to determine the cellular and molecular differences between HaCaT/SM and HaCaT so as to evaluate which changes might be responsible for being resistant against SM. Both cell lines HaCaT and HaCaT/SM were analyzed with respect to their cell growth, nuclei perimeter, clonogenicity and secretion profile. Moreover DNA alkylation pattern under presence of SM was investigated. In comparison to HaCaT, the HaCaT/SM showed a significant smaller nuclei perimeter. For DNA alkylation a significant difference was observed over time. The clonogenicity of HaCaT/SM was increased to 150%. The secretion profile of these cells demonstrated a strong increase of ANG, PDGF-AA, TIMP1, TIMP2, and a decrease of AREG, CCL5, CXC1, CXC2/3, CXCL6, CXCL7, CXCL8, CXCL10, MIF, Trappin-1. The sulfur mustard (SM) resistant cell line HaCaT/SM demonstrates a wide range of significant differences to their origin cell line HaCaT. These differences might be responsible to provide resistance against SM and might also be useful to establish treatment concepts for humans after SM exposure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Prevention and treatment of respiratory consequences induced by sulfur mustard in Iranian casualties

    Directory of Open Access Journals (Sweden)

    Seyed M Razavi

    2013-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Long Term Follow-Up of Sulfur Mustard Related Bronchiolitis Obliterans Treatment

    Directory of Open Access Journals (Sweden)

    Hamidreza Abtahi

    2016-10-01

    Full Text Available Bronchiolitis obliterans (BO is the most remarkable pulmonary sequels of war-related sulfur mustard inhalation. There is little if any data about long-term efficacy of associated BO treatment. Five years spirometric records of three groups of patients with obstructive pulmonary diseases (asthma, COPD, BO and documented sulfur mustard inhalation were evaluated. The BO patients were treated with inhaled Seretide 125-250/25 (2 puffs BID, azithromycin (250 mg, three times/week and N-acetylcysteine (1200-1800/day. Asthma and COPD patients were treated according to existing guidelines. Seventy-three (38 asthma, 16 COPD and 19 BO patients completed the 5 years follow-up. Basal and final FEV1 in BO patients (2.69±0.81 and 2.39±0.65 respectively were not significantly different from COPD patients (2.46±0.56 and 1.96±0.76 respectively. There was also no significant difference between the yearly FEV1 decline in BO patients compared to COPD patients (60±84 cc vs. 99±79 cc respectively, P=0.163. The non-significant difference of FEV1 decline in BO compared to COPD patients suggests the effectiveness of azithromycin, inhaled steroid and N-acetyl cysteine in BO patients. Considering safety and possible effectiveness, this treatment is recommended until more data is available from controlled clinical studies.

  5. TGF-β and Th17 cells related injuries in patients with sulfur mustard exposure.

    Science.gov (United States)

    Panahi, Yunes; Ghanei, Mostafa; Hassani, Saeed; Sahebkar, Amirhossein

    2018-04-01

    Sulfur mustard (SM) is a vesicating agent that has been employed as a chemical warfare agent. High-dose exposure to sulfur mustard may lead to the damage of rapidly proliferating cells of bone marrow and, therefore, suppression of the immune system. This may be continued as dysfunction of the immune system, and ultimately result in secondary immune disorders. Studies have suggested a role for T cells in SM-induced lung injury. Moreover, observations from animal studies indicate a delayed-type hypersensitivity (DTH) response after skin exposure to SM, providing an understanding that SM can stimulate specific T cell-mediated immune responses. On the other hand, T helper (Th) 17 cells, which are a subset of CD4+ T cells, have recently been reported to be involved in a number of inflammatory, autoimmune, and chronic fibrotic lung diseases. Furthermore, a strong association has been established between the overproduction of profibrotic cytokines like transforming growth factor (TGF)-β and Th17 cell number. In this review, we aimed to go through the new findings about the involvement and interactions of TGF-β and Th17 in SM-related injuries. © 2017 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2009-07-22

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

  7. Mechanism underlying acute lung injury due to sulfur mustard exposure in rats.

    Science.gov (United States)

    Xiaoji, Zhu; Xiao, Meng; Rui, Xu; Haibo, Chu; Chao, Zhao; Chengjin, Lian; Tao, Wang; Wenjun, Guo; Shengming, Zhang

    2016-08-01

    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 the cytotoxic effects of SM are unknown and were investigated in this study. The purpose of this study was to establish a rat model of SM-induced lung injury to observe the resulting changes in the lungs. Male rats (Sprague Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM by intratracheal instillation. Animals were euthanized 6, 24, 48, and 72 h post-exposure, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including partial bronchiolar epithelium cell shedding, focal ulceration, and an increased amount of inflammatory exudate and number of cells in the alveoli. There was also evidence that the protein content and cell count of BALF peaked at 48 h, and the alveolar septum was widened and filled with lymphocytes. SM exposure also resulted in partial loss of type I alveolar epithelial cell membranes, fuzzy mitochondrial cristae, detachment and dissociation of ribosomes attached to the surface of rough endoplasmic reticulum, cracked, missing, and disorganized microvilli of type II alveolar epithelial cells, and increased apoptotic cells in the alveolar septum. The propylene glycol control group, however, was the same as the normal group. These data demonstrate that the mechanism of a high concentration of SM (2 mg/kg) induced acute lung injury include histologic changes, inflammatory reactions, apoptosis, oxidative stress, and nuclear DNA damage; the degree of injury is time dependent. © The Author(s) 2014.

  8. Immediate responses of the cockroach Blaptica dubia after the exposure to sulfur mustard.

    Science.gov (United States)

    Popp, Tanja; Lüling, Robin; Boekhoff, Ingrid; Seeger, Thomas; Branoner, Francisco; Gudermann, Thomas; Thiermann, Horst; Worek, Franz; Steinritz, Dirk

    2018-01-01

    The chemical agent sulfur mustard (SM) causes erythema, skin blisters, ulcerations, and delayed wound healing. It is accepted that the underlying molecular toxicology is based on DNA alkylation. With an expected delay, DNA damage causes impairment of protein biosynthesis and disturbance of cell division. However, using the cockroach model Blaptica dubia, the presented results show that alkylating compounds provoke immediate behavior responses along with fast changes in the electrical field potential (EFP) of neurons, suggesting that lesions of DNA are probably not the only effect of alkylating compounds. Blaptica dubia was challenged with SM or 2-chloroethyl-ethyl sulfide (CEES). Acute toxicity was objectified by a disability score. Physiological behavior responses (antennae pullback reflex, escape attempts, and grooming) were monitored after exposure. To estimate the impact of alkylating agents on neuronal activity, EFP recordings of the antennae and the thoracic ganglion were performed. After contact to neat SM, a pullback reflex of the antennae was the first observation. Subsequently, a striking escape behavior occured which was characterized by persistent movement of the legs. In addition, an instantaneous processing of the electrical firing pattern from the antennae to the descending ganglia was detectable. Remarkably, comparing the toxicity of the applied alkylating agents, effects induced by CEES were much more pronounced compared to SM. In summary, our findings document immediate effects of B. dubia after exposure to alkylating substances. These fast responses cannot be interpreted as a consequence of DNA alkylation. Therefore, the dogma that DNA alkylation is the exclusive cause for SM toxicity has to be questioned.

  9. Determination of the sulfur mustard hydrolysis product thiodiglycol by microcolumn liquid chromatography coupled on-line with sulfur flame photometric detection using large-volume injections and peak

    NARCIS (Netherlands)

    Hooijschuur, E.W.J.; Kientz, C.E.; Brinkman, U.A.T.

    1999-01-01

    A selective, direct and relatively rapid method has been developed for the determination of thiodiglycol (TDG) in aqueous samples. TDG is the main hydrolysis product of the chemical warfare agent sulfur mustard. The method of analysis is based on the on-line coupling of reversed-phase microcolumn

  10. Intravenous toxicokinetics of sulfur mustard and its DNA-adducts in the hairless guinea pig and marmoset

    NARCIS (Netherlands)

    Langenberg, J.P.; Spruit, W.E.T.; Kuijpers, W.C.; Mars, R.H.; Helden, H.P.M. van; Schans, G.P. van der; Benschop, H.P.

    2009-01-01

    ln order to provide a quantitative basis for pretreatment and therapy of intoxications with sulfur mustard the toxicokinetics of this agent as well as its major DNA-adducts are being studied in male hairless guinea pigs for the intravenous, respiratory and percutaneous routes. A highly sensitive

  11. An enhanced throughput method for quantification of sulfur mustard adducts to human serum albumin via isotope dilution tandem mass spectrometry

    NARCIS (Netherlands)

    Andacht, T.M.; Pantazides, B.G.; Crow, B.S.; Fidder, A.; Noort, D.; Thomas, J.D.; Blake, T.A.; Johnson, R.C.

    2014-01-01

    Here, we report an enhanced throughput method for the diagnosis of human exposure to sulfur mustard. A hydroxyethylthioethyl (HETE) ester-adducted tripeptide, produced by pronase digestion of human serum albumin, was selected as the quantitative exposure biomarker. Cibacron Blue enrichment was

  12. Inhalation and Percutaneous Toxicokinetics of Sulfur Mustard and Its adducts in Hairless Guinea Pigs and Marmosets. Efficacy of Nasal Scavengers

    National Research Council Canada - National Science Library

    Langenberg, Jan P

    2004-01-01

    As a follow-up to DAMDl7-94-V-4OO9, the inhalation toxicokinetics of sulfur mustard are studied in more detail in the hairless guinea pig as well as in a species more relevant for man, i.e., the marmoset...

  13. Diagnosing human exposure to sulfur mustard by measuring human serum albumin adducts via isotope dilution tandem mass spectrometry (Poster)

    NARCIS (Netherlands)

    Andacht, T.M.; Blake, T.A.; Noort, D.; Johnson, R.C.

    2012-01-01

    Sulfur mustard agent (HD) (2,2’-dichloroethyl sulfide) is a reactive electrophile that readily alkylates aromatic nitrogen atoms, carboxyl groups, sulfides, and sulfhydryl groups on DNA and protein. Adducts to both DNA and specific proteins have been used to assess human exposure to HD. Human serum

  14. MicroRNA expression in serum samples of sulfur mustard veterans as a diagnostic gateway to improve care.

    Science.gov (United States)

    Gharbi, Sedigheh; Khateri, Shahriar; Soroush, Mohammad Reza; Shamsara, Mehdi; Naeli, Parisa; Najafi, Ali; Korsching, Eberhard; Mowla, Seyed Javad

    2018-01-01

    Sulfur mustard is a vesicant chemical warfare agent, which has been used during Iraq-Iran-war. Many veterans and civilians still suffer from long-term complications of sulfur mustard exposure, especially in their lung. Although the lung lesions of these patients are similar to Chronic Obstructive Pulmonary Disease (COPD), there are some differences due to different etiology and clinical care. Less is known on the molecular mechanism of sulfur mustard patients and specific treatment options. microRNAs are master regulators of many biological pathways and proofed to be stable surrogate markers in body fluids. Based on that microRNA expression for serum samples of sulfur mustard patients were examined, to establish specific microRNA patterns as a basis for diagnostic use and insight into affected molecular pathways. Patients were categorized based on their long-term complications into three groups and microRNA serum levels were measured. The differentially regulated microRNAs and their corresponding gene targets were identified. Cell cycle arrest, ageing and TGF-beta signaling pathways showed up to be the most deregulated pathways. The candidate microRNA miR-143-3p could be validated on all individual patients. In a ROC analysis miR-143-3p turned out to be a suitable diagnostic biomarker in the mild and severe categories of patients. Further microRNAs which might own a link to the biology of the sulfur mustard patients are miR-365a-3p, miR-200a-3p, miR-663a. miR-148a-3p, which showed up only in a validation study, might be linked to the airway complications of the sulfur mustard patients. All the other candidate microRNAs do not directly link to COPD phenotype or lung complications. In summary the microRNA screening study characterizes several molecular differences in-between the clinical categories of the sulfur mustard exposure groups and established some useful microRNA biomarkers. qPCR raw data is available via the Gene Expression Omnibus https://www.ncbi

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

    Science.gov (United States)

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

    2016-01-01

    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. 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. 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. SM is a proven carcinogen in chronic situations although data are not enough to strongly conclude in acute exposure.

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

    International Nuclear Information System (INIS)

    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 [ 3 H]thymidine incorporation, although complete recovery occurs by 24 h. Significant inhibition of [ 3 H]uridine and [ 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

  17. Sulfur Mustard-Induced Ocular Injuries: Update on Mechanisms and Management.

    Science.gov (United States)

    Panahi, Yunes; Roshandel, Danial; Sadoughi, Mohammad Mehdi; Ghanei, Mostafa; Sahebkar, Amirhossein

    2017-01-01

    Sulfur mustard (SM; mustard gas) is a classic chemical warfare agent that has been used in several wars and is still a potential threat especially in the Middle-East region. Victims experience acute symptoms in airexposed organs including skin, respiratory tract and the eyes. Survivors of the acute stage might develop chronic or delayed-onset complications in the exposed organs. The exact mechanism(s) of SM-induced tissue damage is still unknown, however DNA alkylation and oxidative damage are the most relevant mechanisms. Eye is the most sensitive organ to the SM vapor and ocular symptoms usually precede other manifestations. Ocular findings including blepharitis, dry eye disease, corneal vascularization, persistent epithelial defects, limbal ischemia, limbal stem cell deficiency, corneal thinning, corneal opacity and corneal innervation abnormalities have been reported several years after SM exposure. In this review, mechanisms of acute and chronic/delayed ocular manifestations of SM and their current management and potential future therapies have been discussed. We have also included recent advances in amniotic membrane transplantation, cultivated stem cell transplantation and anti-angiogenic therapies which might be considered as therapeutic options in SM-induced ocular damage in the future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Ethylene potentiates sulfur-mediated reversal of cadmium inhibited photosynthetic responses in mustard

    Directory of Open Access Journals (Sweden)

    Nafees A Khan

    2016-11-01

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

  19. In vitro oxidation of the hydrolysis product of sulfur mustard, 2,2'-thiobis-ethanol, by mammalian alcohol dehydrogenase.

    Science.gov (United States)

    Brimfield, A A; Zweig, L M; Novak, M J; Maxwell, D M

    1998-01-01

    The mechanism of vesication from sulfur mustard remains unknown in spite of 80 years of investigation. We recently reported sulfur mustard-related inhibition of one or more protein (serine/threonine) phosphatases in tissue cytosol in vitro, suggesting a mechanism common to other vesicants such as cantharidin and Lewisite. Our investigation showed that this inhibition was related to the concentration of 2,2'-thiobis-ethanol (thiodiglycol), the hydrolysis product of sulfur mustard, rather than to the concentration of mustard itself. Related work showed an increase in the rate of NAD (but not NADP) reduction upon the addition of thiodiglycol to mouse liver cytosol. This result provided evidence that metabolism beyond thiodiglycol may be contributing to protein phosphatase inhibition. This observation indicated that metabolism involving one or more dehydrogenases may be necessary to produce the ultimate inhibitor of the protein phosphatases. We report here that thiodiglycol is a substrate for horse liver alcohol dehydrogenase (Km = 3.68+/-0.45 mM and Vmax = 0.22 +/-0.01 micromol min(-1) mg protein(-1)) and for pyridine nucleotide-linked enzymes in mouse liver and human skin cytosol. The alcohol dehydrogenase-specific inhibitor 4-methylpyrazole inhibited the oxidation of thiodiglycol by the pure horse liver enzyme as well as by the enzymes in human skin and mouse liver cytosol, indicating that the activity in the tissue preparations is also alcohol dehydrogenase.

  20. Coronary angiography findings in lung injured patients with sulfur mustard compared to a control group

    Directory of Open Access Journals (Sweden)

    Reza Karbasi-Afshar

    2013-01-01

    Full Text Available Aims and Objectives: We evaluated the incidence of coronary artery disease (CAD in Sulfur mustard (SM exposed veterans. We also evaluated the relationship between exposure to SM and angiography findings and compared angiography findings of SM exposed individuals with unexposed ones after two decades from the time of exposure to SM. Materials and Methods: A case-control study was conducted on 200 consecutive patients (100 SM exposed vs. 100 unexposed undergoing angiographic assessments due to CAD. Results: The coronary angiography findings between two groups were significantly different ( P < 0.001. Ninety two (92% patients in SM exposed group and 82 (82% in unexposed group had abnormal findings in their coronary arteries ( P = 0.031. Conclusions: The incidence of CAD and angiographic changes were significantly increased with exposure to SM. Further studies on cardiovascular effects of SM are needed.

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

    Science.gov (United States)

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

    1992-03-01

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

  2. Models of invasion and establishment of African Mustard (Brassica tournefortii)

    Science.gov (United States)

    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.

  3. Acute Gene Expression Profile of Lung Tissue Following Sulfur Mustard Inhalation Exposure in Large Anesthetized Swine.

    Science.gov (United States)

    Jugg, Bronwen J A; Hoard-Fruchey, Heidi; Rothwell, Cristin; Dillman, James F; David, Jonathan; Jenner, John; Sciuto, Alfred M

    2016-10-17

    Sulfur mustard (HD) is a vesicating and alkylating agent widely used on the battlefield during World War I and more recently in the Iran-Iraq War. It targets the eyes, skin, and lungs, producing skin burns, conjunctivitis, and compromised respiratory function; early acute effects lead to long-term consequences. However, it is the effects on the lungs that drive morbidity and eventual mortality. The temporal postexposure response to HD within lung tissue raises the question of whether toxicity is driven by the alkylating properties of HD on critical homeostatic pathways. We have established an anesthetized swine model of inhaled HD vapor exposure to investigate the toxic effects of HD 12 h postexposure. Large white female swine were anesthetized and instrumented prior to exposure to air, 60 (sublethal) or 100 μg·kg -1 (∼LD 40 ) doses of HD (10 min). Physiological parameters were continuously assessed. Data indicate that exposure to 100 μg·kg -1 HD lowered arterial blood oxygenation and increased shunt fraction and lavage protein compared with those of air-exposed controls and the 60 μg·kg -1 dose of HD. Histopathology showed an increased total pathology score between the 100 μg·kg -1 HD group and air-exposed controls. Principal component analysis of differentially expressed genes demonstrated a distinct and separable response of inhaled HD between air-exposed controls and the 60 and 100 μg·kg -1 doses of HD. Canonical pathway analysis demonstrated changes in acute phase response signaling, aryl hydrocarbon receptor signaling, NRF-2 mediated oxidative stress, and zymosterol biosynthesis in the 60 and 100 μg·kg -1 HD dose group. Transcriptional changes also indicated alterations in immune response, cancer, and cell signaling and metabolism canonical pathways. The 100 μg·kg -1 dose group also showed significant changes in cholesterol biosynthesis. Taken together, exposure to inhaled HD had a significant effect on physiological responses coinciding with

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Sulfur mustard causes oxidants/antioxidants imbalance through the overexpression of free radical producing-related genes in human mustard lungs.

    Science.gov (United States)

    Tahmasbpour Marzony, Eisa; Nejad-Moghadam, Amir; Ghanei, Mostafa; Panahi, Yunes

    2016-07-01

    The aim of this study is to analyze oxidative stress (OS) and changes in expression of reactive oxygen species (ROS) producing-related genes in mustard lungs. Human lung biopsies provided from controls (n=5) and sulfur mustard (SM)-exposed patients (n=6). Changes in expression of dual oxidases (DUOXs), aldehyde oxidase 1 (AOX1), thyroid peroxidase (TPO), myeloperoxidase (MPO) and eosinophil Peroxidase (EPO) were measured using RT(2) Profiler(™) PCR Array. OS was evaluated by determining bronchoalveolar lavage fluids (BALF) levels of total antioxidant capacity (TAC) and malondialdehyde (MDA). Higher TAC value was observed in BALF of controls compared with patients (0.138±0.02683μmol/l vs 0.0942±0.01793μmol/l), whereas a significant increase in MDA concentration was found in patients (0.486±0.04615 nmol/l vs 0.6467±0.05922 nmol/l). All ROS producing-related genes were overexpressed in the order AOX1>MPO>DUOX2>DUOX1>TPO>EPO. Upregulation of these genes may be a reason for overproduction of ROS, oxidants/antioxidants imbalance, OS and respiratory failures in mustard lungs. Copyright © 2016. Published by Elsevier B.V.

  6. Mobilization of human mesenchymal stem cells through different cytokines and growth factors after their immobilization by sulfur mustard.

    Science.gov (United States)

    Schreier, Cassandra; Rothmiller, Simone; Scherer, Michael A; Rummel, Christoph; Steinritz, Dirk; Thiermann, Horst; Schmidt, Annette

    2018-02-06

    The chemical warfare agent sulfur mustard (SM), also known as mustard gas, was first used in World War I. Although prohibited by the chemical warfare convention, significant amounts of SM still exist and have still to be regarded as a threat for military personnel and civilians. After SM exposure, the most prominent clinical symptom is the development of extensive non-healing skin wounds. This chronic wound healing dysfunction is persisting over long time. Mesenchymal stem cells (MSC) are known to play an important role in wound healing. Moreover, it is also known that patients with chronic wound healing diseases have compromised mesenchymal stem cell functionality. Based on these observations and the known relationship between wound healing dysfunction and MSC function we investigated the impact of sulfur mustard on human MSC. Mesenchymal stem cells (MSC) were isolated from femoral heads of healthy donors. They were cultured for less than four passages. MSC were exposed towards different sulfur mustard concentrations. After exposure we analyzed the secretome and the migration capacity. The migration capacity under influence of SM was analyzed after treatment with various cytokines. SM exposure (even at very low concentrations) showed negative effects on the migration capability. Many cytokines that are necessary for MSC migration were secreted in a reduced manner. The reduced migratory capacity can be compensated in part by the addition of cytokines. Here especially IL-8 (e and m) and IL-6 significantly compensated the SM induced migration reduction. The effect of sulfur mustard on MSC might play an important role in the persistence of long-term adverse effects; here the reduced migration could particularly be important. The compensation of the SM-induced migration reduction by addition of cytokines could possibly solve this problem. Moreover, our current results will help to understand the relationship between alkylating agents and MSC and thus will also give

  7. Catalytic Antioxidant Aeol 10150 Treatment Ameliorates Sulfur Mustard Analog 2-Chloroethyl Ethyl Sulfide Associated Cutaneous Toxic Effects

    Science.gov (United States)

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

    2014-01-01

    Our previous studies and other published reports with the chemical warfare agent sulfur mustard (SM) and its analog 2-chloroethyl ethyl sulfide (CEES) have indicated a role of oxidative stress in skin injuries caused by these vesicating agents. We examined the effects of the catalytic antioxidant AEOL 10150 in attenuation of CEES-induced toxicity in our established skin injury models (skin epidermal cells and SKH-1 hairless mice) to validate the role of oxidative stress in the pathophysiology of mustard vesicating agents. Treatment of mouse epidermal JB6 and human HaCaT cells with AEOL 10150 (50 μM) 1 h post CEES exposure resulted in significant (p<0.05) reversal of CEES-induced decreases in both cell viability and DNA synthesis. Similarly, AEOL 10150 treatment 1 h after CEES exposure attenuated CEES-induced DNA damage in these cells. Similar AEOL 10150 treatments also caused significant (p<0.05) reversal of CEES-induced decreases in cell viability in normal human epidermal keratinocytes. Cytoplasmic and mitochondrial reactive oxygen species measurements showed that AEOL 10150 treatment drastically ameliorated the CEES-induced oxidative stress in both JB6 and HaCaT cells. Based on AEOL 10150 pharmacokinetic studies in SKH-1 mouse skin, mice were treated with topical formulation plus subcutaneous (injection; 5 mg/kg) AEOL 10150, 1 h after CEES (4 mg/mouse) exposure and every 4 h thereafter for 12 h. This AEOL 10150 treatment regimen resulted in over 50% (p<0.05) reversal in CEES-induced skin bi-fold and epidermal thickness, myeloperoxidase activity, and DNA oxidation in mouse skin. Results from this study demonstrate potential therapeutic efficacy of AEOL 10150 against CEES-mediated cutaneous lesions supporting AEOL 10150 as a medical countermeasure against SM-induced skin injuries. PMID:24815113

  8. Bicarbonate-activated hydrogen peroxide and efficient decontamination of toxic sulfur mustard and nerve gas simulants.

    Science.gov (United States)

    Zhao, Sanping; Xi, Hailing; Zuo, Yanjun; Wang, Qi; Wang, Zhicheng; Yan, Zengyuan

    2018-02-15

    13 C NMR spectra showed that peroxymonocarbonate (HCO 4 - ) was generated in the NaHCO 3 -activated H 2 O 2 solution and pH was a key factor in its production. A cycle for the bicarbonate anion was proposed as HCO 3 - →HCO 3 → (CO 2 ) 2 *→CO 2 (aq)→HCO 4 - (H 2 CO 4 )→HCO 3 - (HCO 3 ) basing on the results of NMR, electron paramagnetic resonance, chemiluminescence analysis. In this cycle, (CO 2 ) 2 * was the key intermediate and (CO 2 ) 2 *→2CO 2 +hv was the rate controlling step. Thioanisole and paraoxon, the simulants of sulfur mustard gas and nerve gas, respectively, were efficiently decontaminated by the NaHCO 3 -activated H 2 O 2 solution. While HCO 4 - was the primary oxidant for the oxidation of thioanisole, O 2 - generated during the decomposition of HCO 4 - or H 2 O 2 led to the secondary oxidation of the sulfide. Paraoxon was degraded in the NaHCO 3 -activated H 2 O 2 solution via nucleophilic substitution by OOH - and OH - , and the degradation rate increased exponentially with increasing pH. Alkali metal ions had a catalytic effect on the degradation of paraoxon. Mustard gas and soman degraded efficiently into nontoxic products in NaHCO 3 -activated H 2 O 2 . A pH range of 9-10 was found to be optimum for the broad-spectrum decontamination of chemical warfare agents and other eco-toxicants using NaHCO 3 -activated H 2 O 2 . Copyright © 2017. Published by Elsevier B.V.

  9. Quality of Life of Chemically-Disabled War Veterans Involved in Pulmonary Complications of Sulfur Mustard Gas in Sardasht

    Directory of Open Access Journals (Sweden)

    Abbasi M

    2012-01-01

    Full Text Available Background and Objectives: Chemical gasses, particularly Sulfur Mustard, have a negative impact on physical, psychological, social and spiritual aspects of quality of life of those suffering from this gas. It is so serious that even 20 years after being exposed to Sulfur Mustard, we can witness people who are still suffering from various damages of organs particularly the pulmonary system. This research aimed at determining the quality of life of chemically-disabled war veterans with pulmonary complications of Sulfur Mustard from physical, social, psychological, and spiritual aspects.Methods: This was a descriptive study in which 260 chemically-disabled war veterans living in Sardasht, Iran then, were randomly selected for the study. It should be mentioned that all these people are now treated as chemically-disabled war veterans suffering from the pulmonary complications of Sulfur Mustard Gas and were living in Sardasht at the time of bombardment of that city. Having been acquainted with the procedure, they were then asked to fill in the questionnaires.Results: The results showed that quality of life in 71.5% of the samples was moderate, only in 5.8%, it was considered as good. 11.9% of them in physical domain, 8.1% in psychological domain, 1.9% in social domain, and 22.8% in spiritual domain had a good quality of life. Conclusion: Based on the findings, the quality of life in the social, physical and psychological domains was 1.9%, 11.9% and 8.1% poor, therefore; responsible organizations can help these people in various ways by, for example, providing them with low price drugs, which are usually costly in the market, public transportation designed especially for chemically-disabled war veterans, improving insurance services and developing public services in Sardasht. The researchers, finally suggests a qualitative study be performed on each domain of quality of life of chemically-disabled war veterans.

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

    NARCIS (Netherlands)

    Wormser, U; Izrael, M; Van der Zee, EA; Brodsky, B; Yanai, J

    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

  11. Alteration of miRNA expression in a sulfur mustard resistant cell line.

    Science.gov (United States)

    Rothmiller, Simone; Wolf, Markus; Worek, Franz; Steinritz, Dirk; Thiermann, Horst; Schmidt, Annette

    2017-08-18

    MicroRNAs (miRNAs) are responsible for post-transcriptional control of protein expression. Numerous miRNAs have been identified to be responsible for the resistance of tumor cells to cytostatic drugs. Possibly, the same miRNAs also play a role in the sulfur mustard (SM)-resistance of the keratinocyte cell line HaCaT/SM as alkylating cytostatics exhibit similar cytotoxic effects as SM. Basal expression levels of 1920 miRNAs in total were analyzed in HaCaT/SM compared to the origin human keratinocyte cell line HaCaT. The effect for selected miRNAs on cell survival was analyzed using antagomirs for ectopic miRNA level decrease or miRNA mimics for increase. Cell survival was calculated as SM dose-dependent-curves. Out of 1920 miRNAs analyzed, 49 were significantly up- and 29 were significantly downregulated in HaCaT/SM when compared to HaCaT controls. Out of these, 36 could be grouped in miRNA families. Most of the 15 miRNA family members showed either a common increase or decrease. Only the members of miR-10, miR-154, miR-430 and miR-548 family showed an inconsistent picture. The ectopic increase of miR-181 in HaCaT/SM had a positive effect on cell survival in the presence of SM. In summary, the extensive differences in miRNA expression pattern between these cell lines indicate that specific miRNAs may play a role in the resistance mechanism against sulfur mustard. The miR-125b-2 and miR-181b alone are not responsible for the resistance development against SM, but an ectopic increase of miR-181 even enhances the SM resistance of HaCaT/SM. Improving the resistance in normal keratinocytes by treatment with either both miRNAs together or a different combination might be used as an initial step in development of an innovative new drug or prophylactic agent against SM. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Airway tissue plasminogen activator prevents acute mortality due to lethal sulfur mustard inhalation.

    Science.gov (United States)

    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

    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. 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. 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. 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-saving rescue therapy after a significant SM

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

    Science.gov (United States)

    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. Copyright © 2016. Published by Elsevier B.V.

  14. The role of N-acetylcysteine in the management of acute and chronic pulmonary complications of sulfur mustard: a literature review.

    Science.gov (United States)

    Shohrati, Majid; Karimzadeh, Iman; Saburi, Amin; Khalili, Hossein; Ghanei, Mostafa

    2014-08-01

    Sulfur mustard exposure, as the most widely used chemical weapon, can lead to acute and long-term pulmonary complications via various pathways, such as triggering an imbalance between the oxidant and antioxidant system. Currently, there is no validated antidote, chemoprophylaxis and curative modality for pulmonary toxicities secondary to sulfur mustard exposure. The aim of this literature review is to collect available experimental and clinical data on the efficacy of N-acetylcysteine (NAC), as a prominent antioxidant agent, in the prevention and/or treatment of sulfur mustard-induced acute and chronic pulmonary toxicities. A literature search was performed by the relevant keywords like "N-acetyl cysteine", "Sulfur mustard" and "Lung injury" in databases such as Scopus, Medline, Embase and ISI Web of Knowledge. No time limitation was considered. Nineteen articles were selected for review. A number of in vitro and experimental studies concluded that oral, intravenous, intraperitoneal and intra-tracheal administration of NAC is effective in the management of sulfur mustard-induced acute lung injury, in a time-dependent manner, via direct scavenging, inhibition of oxidative stress, inflammatory responses and apoptosis. In addition, oral NAC alone (1200 or 1800 mg/day for 4 months) or at a dose 600 mg/day for 6 months in combination with clarithromycin (500 mg/day) have led to improvements of clinical and paraclinical pulmonary parameters of patients with bronchiolitis obliterans due to sulfur mustard, through undetermined mechanisms. Despite limitations of relevant experimental and clinical studies, NAC can be considered as a candidate agent for prevention and/or treatment of sulfur mustard-induced acute lung injuries, as well as its long-term pulmonary toxicities, especially bronchiolitis obliterans.

  15. Th17/Treg immunoregulation and implications in treatment of sulfur mustard gas-induced lung diseases.

    Science.gov (United States)

    Iman, Maryam; Rezaei, Ramazan; Azimzadeh Jamalkandi, Sadegh; Shariati, Parvin; Kheradmand, Farrah; Salimian, Jafar

    2017-12-01

    Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, some develop obstructive airway diseases referred to as SM-lung syndrome. Pathophysiologically, SM-lung shares many characteristics with smoking-induced chronic obstructive pulmonary disease (COPD), including airway remodeling, goblet cell metaplasia, and obstructive ventilation defect. Some of the hallmarks of COPD pathogenesis, which include dysregulated lung inflammation, neutrophilia, recruitment of interleukin 17A (IL -17A) expressing CD4 + T cells (Th17), and the paucity of lung regulatory T cells (Tregs), have also been described in SM-lung. Areas covered: A literature search was performed using the MEDLINE, EMBASE, and Web of Science databases inclusive of all literature prior to and including May 2017. Expert commentary: Here we review some of the recent findings that suggest a role for Th17 cell-mediated inflammatory changes associated with pulmonary complications in SM-lung and suggest new therapeutic approaches that could potentially alter disease progression with immune modulating biologics that can restore the lung Th17/Treg balance.

  16. Paraclinical findings in Iranian veterans exposed to sulfur mustard gas: A literature review.

    Science.gov (United States)

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

    2017-04-01

    Sulfur mustard (SM) causes various systemic disturbances in human beings. This study aimed to assess paraclinical changes caused by exposure to SM gas in Iranian veterans during the war between Iraq and Iran. A literature review was carried out in international and national medical databases including ISI, Medline, Scopus, Iranmedex and Irandoc. Both Farsi and English literature were searched. Search of the literature yielded 422 medical articles related to SM poisoning. Among them, 30 relevant articles were thoroughly reviewed. The most important reported complications were leukopenia, neutropenia, lymphopenia, eosinophilia, thrombocytopenia, increased bleeding time, positive C-reactive protein (CRP), rheumatoid factor (RF), antinuclear antibody (ANA), decreased T helper cells, natural killer cells, IL6, and IL8 levels, elevation of serum immunoglobulins, decreased levels of T3, T4 and cortisol, increased level of adrenocorticotropic hormone (ACTH), proteinuria, hematuria, and elevated liver enzymes. Also, there were some changes in chest assessments. SM causes profound systemic complications in victims, even years after exposure. The paraclinical changes can be observed in hematology, immune system, biochemistry, hormonal profile and some imaging studies. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-05-13

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

  18. Fate of sulfur mustard on soil: Evaporation, degradation, and vapor emission.

    Science.gov (United States)

    Jung, Hyunsook; Kah, Dongha; Chan Lim, Kyoung; Lee, Jin Young

    2017-01-01

    After application of sulfur mustard to the soil surface, its possible fate via evaporation, degradation following absorption, and vapor emission after decontamination was studied. We used a laboratory-sized wind tunnel, thermal desorber, gas chromatograph-mass spectrometry (GC-MS), and 13 C nuclear magnetic resonance ( 13 C NMR) for systematic analysis. When a drop of neat HD was deposited on the soil surface, it evaporated slowly while being absorbed immediately into the matrix. The initial evaporation or drying rates of the HD drop were found to be power-dependent on temperature and initial drop volume. Moreover, drops of neat HD, ranging in size from 1 to 6 μL, applied to soil, evaporated at different rates, with the smaller drops evaporating relatively quicker. HD absorbed into soil remained for a month, degrading eventually to nontoxic thiodiglycol via hydrolysis through the formation of sulfonium ions. Finally, a vapor emission test was performed for HD contaminant after a decontamination process, the results of which suggest potential risk from the release of trace chemical quantities of HD into the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Behavior of sulfur mustard in sand, concrete, and asphalt matrices: Evaporation, degradation, and decontamination.

    Science.gov (United States)

    Jung, Hyunsook; Choi, Seungki

    2017-10-15

    The evaporation, degradation, and decontamination of sulfur mustard on environmental matrices including sand, concrete, and asphalt are described. A specially designed wind tunnel and thermal desorber in combination with gas chromatograph (GC) produced profiles of vapor concentration obtained from samples of the chemical agent deposited as a drop on the surfaces of the matrices. The matrices were exposed to the chemical agent at room temperature, and the degradation reactions were monitored and characterized. A vapor emission test was also performed after a decontamination process. The results showed that on sand, the drop of agent spread laterally while evaporating. On concrete, the drop of the agent was absorbed immediately into the matrix while spreading and evaporating. However, the asphalt surface conserved the agent and slowly released parts of the agent over an extended period of time. The degradation reactions of the agent followed pseudo first order behavior on the matrices. Trace amounts of the residual agent present at the surface were also released as vapor after decontamination, posing a threat to the exposed individual and environment.

  20. Progressive delayed respiratory complications of sulfur mustard poisoning in 43 Iranian veterans, three decades after exposure.

    Science.gov (United States)

    Darchini-Maragheh, E; Balali-Mood, M; Malaknezhad, M; Mousavi, S R

    2018-02-01

    The most common delayed complication of sulfur mustard (SM) poisoning has been observed in the respiratory tracts. It was thus aimed to investigate the delayed respiratory complications in SM-exposed patients around 25 years before the study. Forty-three veterans with more than 25% disability of due to SM poisoning were investigated. Clinical examinations as well as pulmonary function test (PFT) were performed. High-resolution computed tomography (HRCT) of the lungs was done as clinically indicated. Triad of chronic cough, dyspnea, and expectoration were the most common symptoms that were recorded in 88.2%, 88.2%, and 64.7% of the patients, respectively. PFT abnormalities were detected in 44.18% of the patients. Restrictive pattern was the most common (41.86%), while pure obstructive pattern did not detect at all. Mixed pattern was significantly correlated with higher disability percentages among the veterans ( p < 0.001). Significant reverse correlation between the disability percentages and forced expiratory volume in 1 s/forced vital capacity ratio was obtained ( p = 0.010, r = -0.389). Air trapping was the most common abnormality in HRCTs (50%). Bronchiectasis (25%), pulmonary fibrosis (25%), and ground-glass attenuation (16.66%) were other common HRCT findings. Comparing with the previous studies on these patients, more restrictive and mixed pattern were observed. Moreover, bronchiolitis, bronchiectasis, and lung fibrosis were the main pathological findings in these patients.

  1. DNA repair mechanisms in response to genotoxicity of warfare agent sulfur mustard.

    Science.gov (United States)

    Panahi, Yunes; Fattahi, Amir; Nejabati, Hamid Reza; Abroon, Sina; Latifi, Zeinab; Akbarzadeh, Abolfazl; Ghasemnejad, Tohid

    2018-03-01

    Sulfur mustard (SM) is an alkylating agent that causes severe damages to the skin, eyes, and the respiratory system. DNA alkylation is one of the most critical lesions that could lead to monoadducts and cross-links, as well as DNA strand breaks. In response to these adducts, cells initiate a series of reactions to recruit specific DNA repair pathways. The main DNA repair pathways in human cells, which could be involved in the DNA SM-induced DNA damages, are base excision repair (BER), nucleotide excision repair (NER), homologous recombination (HR) and non-homologous end joining (NHEJ). There is, thus, a need for a short review to clarify which damage caused by SM is repaired by which repair pathway. Increasing our knowledge about different DNA repair mechanisms following SM exposure would lay the first step for developing new therapeutic agents to treat people exposed to SM. In this review, we describe the major DNA repair pathways, according to the DNA adducts that can be caused by SM. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hossein Ayatollahi

    2015-09-01

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

  4. Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2-dimensional gel electrophoresis

    Directory of Open Access Journals (Sweden)

    Mehrani Hossein

    2011-01-01

    Full Text Available Abstract Introduction Sulfur mustard "bis (2-chlroethyl sulphide" (SM is a chemical warfare agent that remains a threat to human health. The aim of this study was to identify protein expression signature or biomarkers that reflect chronic lung damages induced by SM exposure. Methods Prior to analysis, plasma was fractionated using ethanol precipitation. Using two dimensional SDS-PAGE; fractionated protein profiles of 20 healthy and 20 exposed patients with lung diseases were established. Selected protein spots were successfully identified with MALDI TOF MS/MS. Results The results show that α1 haptoglobin isoforms were detected in plasma of the all lung disease patients but none of the healthy controls. Amyloid A1 isoforms was also detected in plasma of the lung disease patients but none of the healthy controls. Moreover, low molecular weight proteins were enriched in ethanol supernatant compared to ethanol precipitate. Conclusion Our present results and previous studies suggest that ongoing tissue remodeling is involved in SM exposed lung damage patients. These finding might improve patient care and suitable therapies.

  5. Evaluation of Apoptosis in the Lung Tissue of Sulfur Mustard-exposed Individuals.

    Science.gov (United States)

    Mosayebzadeh, Marjan; Ghazanfari, Tooba; Delshad, Alireza; Akbari, Hassan

    2016-08-01

    Lung exposure to sulfur mustard (SM) results in pulmonary complications, which is the main cause of long-term disability and morbidity. Up to now, the precise mechanisms of SM-induced lung complications has not been identified. The aim of this study was to evaluate apoptosis in the lung tissue of SM-exposed individuals. The study was performed on archived lung paraffin-embedded tissue specimens of21 patients suffering from pulmonary complications due to previous SM exposure and 9 unexposed patients who had undergone lung resections for another lung disease. Evaluation of apoptosis in paraffin-embedded lung tissue sections was performed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay and the cleaved caspase-3 immunohistochemistry assays. TUNEL-positive apoptotic features and caspase-3 expression of specimens were significantly higher in the SM-exposed group compared with the control group. This result demonstrates higher apoptosis rate in the SM-exposed group. Furthermore, the majority of positive cells consisted of alveolar epithelial cells in both methods. In conclusion,it seems that exposure to SM may result in increased apoptosis in respiratory epithelium. More studies are needed to evaluate the role of apoptosis in SM-induced lung complications in order to design new and effective therapeutic protocols.

  6. Tissue injury and repair following cutaneous exposure of mice to sulfur mustard.

    Science.gov (United States)

    Joseph, Laurie B; Composto, Gabriella M; Heck, Diane E

    2016-08-01

    In mouse skin, sulfur mustard (SM) is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of SM and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and pro-growth/pro-wound healing mediators, including cyclooxygenase-2, which generates prostanoids, inducible nitric oxide synthase, which generates nitric oxide, fibroblast growth factor receptor 2, and galectin-3. Characterization of the mediators regulating structural changes in the skin during SM-induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes. © 2016 New York Academy of Sciences.

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

    Science.gov (United States)

    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.

  8. Bronchiolitis obliterans following exposure to sulfur mustard: chest high resolution computed tomography

    International Nuclear Information System (INIS)

    Ghanei, Mostafa; Mokhtari, Majid; Mohammad, Mehdi Mir; Aslani, Jafar

    2004-01-01

    Background: Pulmonary complications are known to occur in over half of the patients exposed to sulfur mustard (SM). Chemical weapons of mass destruction (WMD) including SM were used by Iraq during Iran-Iraq war between 1983 and 1989. We undertook this study to evaluate the chest high resolution computerized tomography (HRCT) as a diagnostic tool in patients with documented exposure to SM and chronic respiratory symptoms. Method: The medical records of 155 patients exposed to SM during Iran-Iraq war and suffered respiratory complications were reviewed. Chest HRCTs of these patients were examined. Ten healthy controls with no history of exposure to HD were matched for age, gender, and chest HRCT protocol applied. Results: Fifty chest HRCTs of these patients were randomly selected for this study. The most frequent findings were; air trapping 38 (76%), bronchiectasis 37 (74%), mosaic parenchymal attenuation (MPA) 36 (72%), irregular and dilated major airways 33 (66%) bronchial wall thickening (BWT) 45 (90%), and interlobular septal wall thickening (SWT) 13 (26%), respectively. Air trapping in one patient (10%) was the only positive finding in the control group. Conclusions: Chest HRCT findings of bronchiectasis, air trapping, MPA, SWT, and BWT were seen in our patients 15 years after exposure to HD. These findings suggest the diagnosis of bronchiolitis obliterans (BO). We did not encounter chest HRCT features consistent with pulmonary fibrosis

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

    Science.gov (United States)

    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.

  10. Relationship of oxidative stress with male infertility in sulfur mustard-exposed injuries

    Directory of Open Access Journals (Sweden)

    Eisa Tahmasbpour Marzony

    2016-03-01

    Full Text Available Sulfur mustard (SM is a cytotoxic and chemical agent that targets different tissues such as reproductive system. SM causes a wide variety of pathological effects on reproductive system such as disturbance in reproductive hormones, testis atrophy, spermatogenesis deficiency, low quality of sperm and fertility problem. However, molecular and cellular mechanisms of its adverse effects are still not well known. General events such as tissue damage, inflammation, DNA alkylation, cell membrane defects, apoptosis and cell death are observed frequently in SM-exposed subjects. Oxidative stress (OS and antioxidants depletion induced by SM seem to be one of the main factors that lead to low sperm quality and male infertility among exposed patients. It is believed that SM can trigger several molecular and cellular pathways linked to OS and inflammation in reproductive system that can cause impaired spermatogenesis, sperm apoptosis and poor sperm quality as well as loss of tissue structure and function. Identification of these signaling pathways and molecules gives us valuable information regarding the mechanisms of SM effect on reproductive dysfunction and the way for developing a better clinical treatment. Therefore, in this review we aimed to discuss the proposed cellular and molecular mechanisms of SM effect on reproductive system, the significance of oxidative stress and the mechanisms by which SM induces OS and antioxidants depletion in SM exposed men.

  11. The effect of vitamin E on lung pathology in sulfur mustard-exposed guinea pigs.

    Science.gov (United States)

    Gholamnezhad, Zahra; Boskabady, Mohammad Hossein; Amery, Sediqa; Vahedi, Nassim; Tabatabaei, Abass; Boskabady, Morteza; Shahriary, Alireza

    2016-12-01

    Pulmonary complications of exposure to sulfur mustard (SM) gas range from no effect or mild symptoms to severe bronchial stenosis. In the present study, the protective effect of vitamin E on the lung inflammation of SM-exposed guinea pigs was examined. Guinea pigs (n = 5 for each group) were exposed to ethanol (control group), 40 mg/m 3 inhaled SM (SME group), SME treated with vitamin E (SME + E), SME treated with dexamethasone (SME + D), and SME treated with both treatments (SME + E + D). Pathological evaluation of the lung was done 14 days postexposure. The epithelial desquamation of trachea and other pathologic changes in the lung of the SME group were significantly higher than those in the control group. Furthermore, the pathological changes of trachea and lung in the SME + E and SME + E + D groups were significantly improved compared with those of SME group. In addition, the pathological changes of trachea and lung of SME + E and SME + E + D animals were significantly less than those of SME + D group. © The Author(s) 2015.

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

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

    2008-01-01

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

  13. Bronchiolitis obliterans following exposure to sulfur mustard: chest high resolution computed tomography

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    Ghanei, Mostafa E-mail: m.ghanei@bmsu.ac.ir; Mokhtari, Majid; Mohammad, Mehdi Mir; Aslani, Jafar

    2004-11-01

    Background: Pulmonary complications are known to occur in over half of the patients exposed to sulfur mustard (SM). Chemical weapons of mass destruction (WMD) including SM were used by Iraq during Iran-Iraq war between 1983 and 1989. We undertook this study to evaluate the chest high resolution computerized tomography (HRCT) as a diagnostic tool in patients with documented exposure to SM and chronic respiratory symptoms. Method: The medical records of 155 patients exposed to SM during Iran-Iraq war and suffered respiratory complications were reviewed. Chest HRCTs of these patients were examined. Ten healthy controls with no history of exposure to HD were matched for age, gender, and chest HRCT protocol applied. Results: Fifty chest HRCTs of these patients were randomly selected for this study. The most frequent findings were; air trapping 38 (76%), bronchiectasis 37 (74%), mosaic parenchymal attenuation (MPA) 36 (72%), irregular and dilated major airways 33 (66%) bronchial wall thickening (BWT) 45 (90%), and interlobular septal wall thickening (SWT) 13 (26%), respectively. Air trapping in one patient (10%) was the only positive finding in the control group. Conclusions: Chest HRCT findings of bronchiectasis, air trapping, MPA, SWT, and BWT were seen in our patients 15 years after exposure to HD. These findings suggest the diagnosis of bronchiolitis obliterans (BO). We did not encounter chest HRCT features consistent with pulmonary fibrosis.

  14. Mass spectrometric analysis of sulfur mustard-induced biomolecular adducts: Are DNA adducts suitable biomarkers of exposure?

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    Zubel, Tabea; Bürkle, Alexander; Mangerich, Aswin

    2017-12-23

    The bi-functional chemical warfare agent sulfur mustard (SM), whose release in asymmetric conflicts or terrorist attacks represents a realistic threat, induces several kinds of biomolecular adducts, including highly toxic DNA adducts. Isotope dilution liquid chromatographic tandem mass spectrometry (ID-LC-MS/MS) is considered the gold standard for highly accurate, precise, specific and sensitive quantification of DNA adducts in general. Recently, a number of LC-MS/MS approaches have been established to analyze SM-induced protein and DNA adducts in cell culture and rodent animal models. As DNA adducts are mechanism-based biomarkers for SM exposure, results from such studies provide a deeper understanding of the etiology of SM-induced pathologies, especially of long-term effects such as cancer formation. As a result, medical treatment of SM-exposed individuals might be improved. Yet, despite the progress that has been made during the last years, there is still a need for advanced methods of ID-LC-MS/MS for the detection and quantitation of SM adducts. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Silibinin attenuates sulfur mustard analog-induced skin injury by targeting multiple pathways connecting oxidative stress and inflammation.

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    Neera Tewari-Singh

    Full Text Available Chemical warfare agent sulfur mustard (HD inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p90%, and activation of transcription factors NF-κB and AP-1 (complete reversal. Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants.

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

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    Saber Imani

    2015-08-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  18. Nocturnal serum melatonin levels in sulfur mustard exposed patients with sleep disorders.

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    Mousavi, Seyyedeh Soghra; Vahedi, E; Shohrati, M; Panahi, Y; Parvin, S

    2017-12-01

    Sulfur mustard (SM) exposure causes respiratory disorders, progressive deterioration in lung function and mortality in injured victims and poor sleep quality is one of the most common problems among SM-exposed patients. Since melatonin has a critical role in regulation of sleep and awareness, this study aimed to evaluate the serum melatonin levels in SM-injured subjects. A total of 30 SM-exposed male patients and 10 controls was evaluated. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI); daytime sleepiness was measured by the Epworth Sleepiness Scale (ESS), and the risk of obstructive sleep apnoea was determined by the STOP-Bang questionnaire. Polysomnography (PSG) and pulmonary function tests (PFTs) were also available. Nocturnal serum melatonin levels were measured using an ELISA kit. The mean of PSQI, ESS and STOP-Bang scores in patients (11.76±3.56, 12.6±3.03 and 5.03±1.09, respectively) were significantly (pmelatonin levels in patients (29.78±19.31 pg/mL) was significantly (p=0.005) lower than that in the controls (78.53±34.41 pg/mL). Reduced nocturnal serum melatonin and respiratory disorders can be the reasons for poor sleep quality among these patients. IRCT2015092924267N1, Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. Differential toxicity of sulfur mustard administered through percutaneous, subcutaneous, and oral routes

    International Nuclear Information System (INIS)

    Vijayaraghavan, R.; Kulkarni, Abhay; Pant, S.C.; Kumar, Pravin; Lakshmana Rao, P.V.; Gupta, Nidhi; Gautam, Anshoo; Ganesan, K.

    2005-01-01

    Sulfur mustard (SM), chemically 2,2'-dichloro diethyl sulphide, is an incapacitating and extremely toxic chemical warfare agent. It causes serious blisters on contact with human skin. While screening various antidotes against its toxicity, we observed that SM was more toxic through percutaneous (p.c.) route compared to oral (p.o.) and subcutaneous (s.c.) routes. The LD 50 of SM in female mice was found to be 5.7, 8.1 and 23.0 mg/kg through p.c., p.o., and s.c. routes, respectively. The body weight of the animals was monitored and it was found that percentage body weight loss was more in the p.c. route. There was significant DNA fragmentation in liver in all the three routes evaluated at 19.3 mg/kg dose of SM. The depletion of hepatic GSH content was found to be more in the p.c. route of exposure compared to s.c. route. There was significant reduction in WBC count in all the three routes of exposure. Histopathological evaluation of lung, liver, and spleen also showed that the damage was more in the p.c. route and severity of lesions was dependent on the dose of exposure. The most affected organ was liver by all the three routes. LD 50 was also determined in male rats and it was found to be 2.4, 2.4, and 3.4 mg/kg through p.c., p.o. and s.c. routes respectively. Since skin contains maximum number of metabolically active and rapidly dividing cells, differential metabolism of SM cannot be ruled out. Probably, this is the first report of a chemical showing more toxicity through p.c. route compared to s.c. route

  20. Late-onset Radiologic Findings of Respiratory System Following Sulfur Mustard Exposure

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    Mahnaz Amini

    2013-06-01

    Full Text Available Background: Sulfur mustard (SM as a chemical warfare agent, increases permeability of bronchial vessels and damages airway epithelium. SM exposure causes debilitating respiratory complications. This study was designed to evaluate clinical respiratory manifestations, and to compare chest X ray (CXR and high resolution computed tomography (HRCT scan of chest in SM exposed patients with respiratory complaints. Methods:All patients with history of SM exposure who visited Imam Reza Specialized Clinic of Respiratory Diseases from September 2001 to March 2011 were included. Patients with other comorbidities which affect respiratory system were excluded. CXR and chest HRCT scan were performed on the same day and were repeated after 5 years. Clinical and radiologic findings were collected and were compared with each other. Results: In total, 62 male patients with mean age of 53 (6.9, 41-65 were studied. Dyspnea (61 cases; 100%, dry cough (40 cases; 66%, hemoptysis (21 cases; 35% and productive cough (20 cases; 33% were the most common respiratory manifestations. Pulmonary infiltration (51; 83%, pleural thickening (25; 40% and emphysema (16; 26% were the most common findings on CXR. According to HRCT scan, pulmonary infiltration (53; 85%, bronchiolitis obliterans (38; 61% and pleural thickening (36; 58% were the most common findings (Table 2. Repeated radiologic assessments after 5 years showed a few additional findings in HRCT scan, while in about one fifth of CXRs, new pathologic findings were found. Conclusion: Patients with SM exposure experience debilitating respiratory disorders in long term. Repeating CXR in patients who present with subjective symptoms may show new findings; however, repeating HRCT scan is probably not necessary.

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

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

    2017-05-01

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

  2. N-Acetylcysteine as a chemical scavenger for sulfur mustard: New insights by mass spectrometry.

    Science.gov (United States)

    Siegert, Markus; Kranawetvogl, Andreas; Thiermann, Horst; John, Harald

    2018-02-01

    The vesicant sulfur mustard (SM) is a banned chemical warfare agent. Although, SM has been used in combat since WWI, there is no causal therapy currently available. Accordingly, development and investigation of antidotes and scavengers targeting SM are of high clinical relevance. N-acetylcysteine (NAC) was shown to mitigate symptoms of SM intoxications in vitro and in vivo. However, it is still unclear whether the beneficial effects of NAC are only due to physiological processes or also due to chemical scavenging of SM. Therefore, in this study, we examined the scavenging potential of NAC toward SM. Co-incubations of SM and different NAC concentrations in human serum were performed to monitor diverse adducts (covalent reaction products) of human serum albumin (HSA), NAC, and SM. After proteolytic cleavage of HSA with proteinase K the alkylated tripeptide hydroxyethylthioethyl-CysProPhe (HETE-CPF) and the disulfide bridged tripeptide NAC-CPF were detected. Samples were analyzed by microbore liquid chromatography-electrospray ionization-high-resolution tandem-mass spectrometry (μLC-ESI MS/HR MS). Furthermore, degradation kinetics of SM in phosphate buffered saline were measured in the presence and absence of NAC. Although NAC-CPF was identified and characterized for the first time by mass spectrometry and reaction products of NAC and SM were detected and identified by MS/HR MS, analyses clearly documented minor reactivity not significantly contributing to reduction of SM concentrations. Therefore, we conclude that chemical scavenging of SM by NAC does not play the key role in NAC therapy of SM poisoning. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Biochemical and hematological findings of Khorasan veterans 23 years after sulfur mustard exposure

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    Mohammad Reza Keramati

    2013-01-01

    Full Text Available Background: Sulfur mustard (SM is an incapacitating chemical warfare agent, which has been widely employed in particular regions including Iran. We investigated and reported delayed biochemical and hematological complications of SM in severely toxic Iranian veterans 23 years after exposure. Materials and Methods : Forty-two Iranian veterans, residents of Khorasan Razavi, poisoned by SM, and suffering from clinical complications were investigated. A total of 30 healthy male volunteers were also selected as a control group. Biochemical and hematological variables were measured for the case and control groups. Data were analyzed using a Student′s t-test by InStat software (GraphPad Inc., San Diego, CA to determine significant differences between the data from the two groups. Results: The percentages of reticulocytes were significantly higher in patients (0.82 ± 0.04, P < 0.05. Total protein and albumin levels were significantly lower in veterans (total protein: 7.58 ± 0.07 g/dL, albumin: 4.97 ± 0.04 g/dL, P < 0.01. In addition, we observed a significant increase in serum cholesterol (226.74 ± 5.23 mg/dL, P < 0.01, triglyceride (173.53 ± 17.05 mg/dL, P < 0.05, and gamma-glutamyl transferase (GTT activity of the patients (44.04 ± 3.35 IU/L, P < 0.05. Conclusion: Results showed that SM can cause long-term effects on some biochemical factors of veterans. As many of the functional tests of liver and kidney between two groups were statistically unchanged, it seems that the observed biochemical changes may be secondary to delayed respiratory complications of the patients.

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

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    Sadeghi, Meysam; Yekta, Sina; Ghaedi, Hamed

    2016-07-01

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

  5. An evidence-based review of the genotoxic and reproductive effects of sulfur mustard.

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    Khan, Fazlullah; Niaz, Kamal; Ismail Hassan, Fatima; Abdollahi, Mohammad

    2017-03-01

    Sulfur mustard (SM) is a chemical warfare agent which is cytotoxic in nature, and at the molecular level, SM acts as DNA alkylating agent leading to genotoxic and reproductive effects. Mostly, the exposed areas of the body are the main targets for SM; however, it also adversely affects various tissues of the body and ultimately exhibits long-term complications including genotoxic and reproductive effects, even in the next generations. The effect of SM on reproductive system is the reason behind male infertility. The chronic genotoxic and reproductive complications of SM have been observed in the next generation, such as reproductive hormones disturbances, testicular atrophy, deficiency of sperm cells, retarded growth of sperm and male infertility. SM exerts toxic effects through various mechanisms causing reproductive dysfunction. The key mechanisms include DNA alkylation, production of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide (NAD) depletion. However, the exact molecular mechanism of such long-term effects of SM is still unclear. In general, DNA damage, cell death and defects in the cell membrane are frequently observed in SM-exposed individuals. SM can activate various cellular and molecular mechanisms related to oxidative stress (OS) and inflammatory responses throughout the reproductive system, which can cause decreased spermatogenesis and impaired sperm quality via damage to tissue function and structure. Moreover, the toxic effects of SM on the reproductive system as well as the occurrence of male infertility among exposed war troopers in the late exposure phase is still uncertain. The chronic effects of SM exposure in parents can cause congenital defects in their children. In this review, we aimed to investigate chronic genotoxic and reproductive effects of SM and their molecular mechanisms in the next generations.

  6. Editor's Highlight: Pulmonary Vascular Thrombosis in Rats Exposed to Inhaled Sulfur Mustard.

    Science.gov (United States)

    McGraw, Matthew D; Osborne, Christopher M; Mastej, Emily J; Di Paola, Jorge A; Anderson, Dana R; Holmes, Wesley W; Paradiso, Danielle C; Garlick, Rhonda B; Hendry-Hofer, Tara B; Rancourt, Raymond C; Smith, Russell W; Burns, Carol; Roe, Gates B; Rioux, Jacqueline S; White, Carl W; Veress, Livia A

    2017-10-01

    Sulfur mustard (SM) is a chemical warfare agent. When inhaled, SM causes significant injury to the respiratory tract. Although the mechanism involved in acute airway injury after SM inhalation has been well described previously, the mechanism of SM's contribution to distal lung vascular injury is not well understood. We hypothesized that acute inhalation of vaporized SM causes activated systemic coagulation with subsequent pulmonary vascular thrombi formation after SM inhalation exposure. Sprague Dawley rats inhaled SM ethanolic vapor (3.8 mg/kg). Barium/gelatin CT pulmonary angiograms were performed to assess for pulmonary vascular thrombi burden. Lung immunohistochemistry was performed for common procoagulant markers including fibrin(ogen), von Willebrand factor, and CD42d in control and SM-exposed lungs. Additionally, systemic levels of d-dimer and platelet aggregometry after adenosine diphosphate- and thrombin-stimulation were measured in plasma after SM exposure. In SM-exposed lungs, chest CT angiography demonstrated a significant decrease in the distal pulmonary vessel density assessed at 6 h postexposure. Immunohistochemistry also demonstrated increased intravascular fibrin(ogen), vascular von Willebrand factor, and platelet CD42d in the distal pulmonary vessels (<200 µm diameter). Circulating d-dimer levels were significantly increased (p < .001) at 6, 9, and 12 h after SM inhalation versus controls. Platelet aggregation was also increased in both adenosine diphosphate - (p < .01) and thrombin- (p < .001) stimulated platelet-rich plasma after SM inhalation. Significant pulmonary vascular thrombi formation was evident in distal pulmonary arterioles following SM inhalation in rats assessed by CT angiography and immunohistochemistry. Enhanced systemic platelet aggregation and activated systemic coagulation with subsequent thrombi formation likely contributed to pulmonary vessel occlusion. © The Author 2017. Published by Oxford University Press on

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

    Science.gov (United States)

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

    2016-02-26

    Sulfur mustard (SM) is a chemical warfare agent (CWA) that was first used in World War I and in several military conflicts afterwards. The threat by SM is still present even today due to remaining stockpiles, old and abandoned remainders all over the world as well as to its ease of synthesis. CWA are banned by the Chemical Weapons Convention (CWC) interdicting their development, production, transport, stockpiling and use and are subjected to controlled destruction. The present case report describes an accidental exposure of three workers that occurred during the destruction of SM. All exposed workers presented a characteristic SM-related clinical picture that started about 4h after exposure with erythema and feeling of tension of the skin at the upper part of the body. Later on, superficial blister and a burning phenomenon of the affected skin areas developed. Similar symptoms occurred in all three patients differing severity. One patient presented sustained skin affections at the gluteal region while another patient came up with affections of the axilla and genital region. Fortunately, full recovery was observed on day 56 after exposure except some little pigmentation changes that were evident even on day 154 in two of the patients. SM-exposure was verified for all three patients using bioanalytical GC MS and LC MS/MS based methods applied to urine and plasma. Urinary biotransformation products of the β-lyase pathway were detected until 5 days after poisoning whereas albumin-SM adducts could be found until day 29 underlining the beneficial role of adduct detection for post-exposure verification. In addition, we provide general recommendations for management and therapy in case of SM poisoning. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Cytostatic resistance profile of the sulfur mustard resistant keratinocyte cell line HaCaT/SM.

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    Schmidt, Annette; Wolf, Markus; Rothmiller, Simone; Worek, Franz; Steinritz, Dirk; Thiermann, Horst

    2018-03-15

    The cell line HaCaT/SM was developed as a sulfur mustard (SM) resistant cell line from the human keratinocyte cell line HaCaT. This cell line was established to learn more about the effect of SM and possible therapeutic approaches to counteract the cytotoxic effects of SM. The aim of this study was to clarify whether the SM-resistant cell line HaCaT/SM exhibit also resistance to other alkylating agents or cytotoxic drugs with different mechanism of action. The chemosensitivity of SM-resistant human keratinocyte cell line HaCaT/SM and the original cell line HaCaT were tested using the XTT assay. Nine cytotoxic drugs from five different substance groups were investigated. HaCaT/SM showed a significant increase in resistance against all tested drugs. From the substance class of the alkylating agents, HaCaT/SM showed the strongest resistance increase against chlorambucil (1.7 fold increase). Whereas over all substances strongest increase was observed against cisplatin (5.1 fold increase). The highest resistance was observed for cisplatin. The SM resistant cells revealed changes in the miRNA profile as described before. The resistance to cisplatin is also connected to a specific miRNA profile. Interestingly, changes of miRNA-203 and miRNA-21 levels were found in HaCaT/SM as well as in cisplatin resistant cells. It is therefore conceivable that the same resistance pathways are involved for both substances. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Skin decontamination efficacy of potassium ketoxime on rabbits exposed to sulfur mustard.

    Science.gov (United States)

    Sun, Jing-Hai; Sun, Pei-Pei; Zheng, Wei; Han, Song; Ying, Ying; Liu, Hong-Yan; Zhang, Cheng; Zhao, Bao-Quan; Zuo, Guo-Min; Lu, Hong; Zhong, Yu-Xu

    2015-03-01

    The chemical weapon sulfur mustard (SM) is a blister agent, and currently, there is no effective antidote. To evaluate the decontamination efficacy of potassium ketoxime against SM and preliminarily elucidate its decontamination mechanism. Potassium ketoxime reacted with SM, and SM residues were tested at different time intervals by T-135 colorimetry after the reaction. Rabbit skin was topically exposed to 2 mg/cm(2) SM, treated with potassium ketoxime 1 min later, and observed after 6, 12, and 24 h. Gas chromatography-mass spectroscopy was employed to screen and identify the main products of potassium ketoxime decontamination of SM. Potassium ketoxime had a great effect against SM contamination. With a mass ratio of decontaminant: SM of 50:1, decontamination rates against SM were 87.5% after 30 s, 95.9% after 1 min, and 99.0% after 5 min. Fifteen minutes after exposure to SM, the untreated group showed clear erythema lesions, whereas the experimental group showed no clear erythema lesions within 6 h. After 12 and 24 h, the areas of damaged skin in the experimental group were 0.038 and 0.125 cm(2), respectively, compared with 2.21 and 2.65 cm(2) in the control group. Histopathological analysis revealed that treatment with potassium ketoxime also reduced inflammation-induced damage. The results of this study indicate that potassium ketoxime reacted rapidly and completely with SM, and thus, it was found to be a suitable and effective skin decontaminant against SM. The decontamination reaction mechanism is mainly related to nucleophilic substitution.

  10. Molecular toxicology of sulfur mustard-induced cutaneous inflammation and blistering

    International Nuclear Information System (INIS)

    Kehe, K.; Balszuweit, F.; Steinritz, D.; Thiermann, H.

    2009-01-01

    Sulfur mustard (SM) is a strong alkylating agent, which produces subepidermal blisters, erythema and inflammation after skin contact. Despite the well-described SM-induced gross and histopathological changes, the exact underlying molecular mechanisms of these events are still a matter of research. As part of an international effort to elucidate the components of cellular signal transduction pathways, a large body of data has been accumulated in the last decade of SM research, revealing deeper insight into SM-induced inflammation, DNA damage response, cell death signaling, and wound healing. SM potentially alkylates nearly every constituent of the cell, leading to impaired cellular functions. However, SM-induced DNA alkylation has been identified as a major trigger of apoptosis. This includes monofunctional SM-DNA adducts as well as DNA crosslinks. As a consequence, DNA replication is blocked, which leads to cell cycle arrest and DNA single and double strand breaks. The SM-induced DNA damage results in poly(ADP-ribose) polymerase (PARP) activation. High SM concentrations induce PARP overactivation, thus depleting cellular NAD + and ATP levels, which in consequence results in necrotic cell death. Mild PARP activation does not disturb cellular energy levels and allows apoptotic cell death or recovery to occur. SM-induced apoptosis has been linked both to the extrinsic (death receptor, Fas) and intrinsic (mitochondrial) pathway. Additionally, SM upregulates many inflammatory mediators including interleukin (IL)-1α, IL-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α) and others. Recently, several investigators linked NF-κB activation to this inflammatory response. This review briefly summarizes the skin toxicity of SM, its proposed toxicodynamic actions and strategies for the development of improved medical therapy.

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

    Directory of Open Access Journals (Sweden)

    Khademolhosseini Seyyed M

    2010-07-01

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

  12. Applying human and pig hepatic in vitro experiments for sulfur mustard study: screening and identification of metabolites by liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Halme, Mia; Pesonen, Maija; Hakala, Ullastiina; Pasanen, Markku; Vähäkangas, Kirsi; Vanninen, Paula

    2015-07-30

    Sulfur mustard is a chemical warfare agent (CWA) with high toxicity and complex metabolism. This study aimed at identification of new metabolic biomarkers for sulfur mustard using in in vitro exposures and various mass spectrometric techniques. Human and pig liver subcellular fractions were used as biocatalysts. Metabolites were screened by liquid chromatography and tandem mass spectrometry (LC/MS/MS) using positive electrospray ionization (ESI). For structural identification, product ion scans (MS/MS, MS(3) ) and accurate mass measurements using liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) were acquired. Sulfur mustard is metabolized in vitro by S-oxidation and glutathione (GSH) conjugations. One S-oxidized metabolite, bis(2-chloroethyl) sulfoxide (m/z 175), was formed in both species only when liver microsomes were present in incubations, and it was the main metabolite if GSH was not added into the reaction mixture. However, conjugation with GSH was found to be a spontaneous reaction in physiological pH and buffered solution. Three GSH conjugates of sulfur mustard were detected and identified, among which two were novel; 2-((2-(S-glutathionyl)ethyl)thio)ethanol (m/z 412) and 2-((2-(S-glutathionyl)ethyl)thio)ethyl phosphate (m/z 492). To our knowledge, this was the first time that S-oxidized metabolites and GSH conjugates of sulfur mustard have been detected and identified from human samples in vitro by LC/MS/MS. The usefulness of the GSH conjugates to serve as biomarkers for sulfur mustard exposure in human samples requires further studies. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Alteration of miRNA expression in early endothelial cells after exposure with sub-lethal sulfur mustard concentrations.

    Science.gov (United States)

    Schmidt, Annette; Steinritz, Dirk; Thiermann, Horst; Meineke, Viktor; Abend, Michael

    2016-02-26

    Sulfur mustard (SM) is known to induce chronic wound healing disorders as well as disturbed endothelial regeneration. It is known that wound healing as well as endothelial regeneration are controlled by micro-RNA (miRNA). As nothing is known today about the effect of SM onto miRNA expression we wanted to investigate whether there is an effect of sub-lethal concentrations of SM onto the miRNA expression of endothelial cells. Early endothelial cells (EEC) were incubated with different sub-lethal concentrations of sulfur mustard (SM) in-vitro. Cells were subsequently analyzed with respect to survival and colony-forming capacity. In addition, the nuclear structure was investigated with respect to apoptosis, micronuclei or abnormal forming using the MAA assay. Six hundred sixty-seven different miRNA species from both, treated and untreated EEC were quantified. The sub-lethal concentrations IC1, IC5 or IC10 were used. While performing the MAA assay the cells showed a time dependent change in nucleus structure from normal to abnormal, without significant changes in apoptosis being observed. In the colony-forming assay a weak cell proliferation capacity was revealed. Under all conditions they lost their capacity to form colonies. Out of 667 investigated miRNAs in total 66 showed a significant change in expression upon incubation with SM. 19 miRNAs were up-regulated and 47 down-regulated. The strongest correlation between SM concentration and up-regulation was found for mmu-miR-92a-3p* (hsa-miR-92a). Seven miRNAs showed a change in expression similar to endothelial cells from younger or older mice. The presented work demonstrates that sulfur mustard (SM) has an effect on miRNA expression in general. The observed changes in expression in early endothelial cells correlates to the known effects of SM. Further studies have to investigate if these findings are in direct dependence and if these relationships can be used to alleviate the sulfur mustard induced clinical damage

  14. Quality of Life of Chemically-Disabled War Veterans Involved in Pulmonary Complications of Sulfur Mustard Gas in Sardasht

    Directory of Open Access Journals (Sweden)

    M Abbasi

    2012-05-01

    Full Text Available

    Background and Objectives: Chemical gasses, particularly Sulfur Mustard, have a negative impact on physical, psychological, social and spiritual aspects of quality of life of those suffering from this gas. It is so serious that even 20 years after being exposed to Sulfur Mustard, we can witness people who are still suffering from various damages of organs particularly the pulmonary system. This research aimed at determining the quality of life of chemically-disabled war veterans with pulmonary complications of Sulfur Mustard from physical, social, psychological, and spiritual aspects.

     

    Methods: This was a descriptive study in which 260 chemically-disabled war veterans living in Sardasht, Iran then, were randomly selected for the study. It should be mentioned that all these people are now treated as chemically-disabled war veterans suffering from the pulmonary complications of Sulfur Mustard Gas and were living in Sardasht at the time of bombardment of that city. Having been acquainted with the procedure, they were then asked to fill in the questionnaires.

     

    Results: The results showed that quality of life in 71.5% of the samples was moderate, only in 5.8%, it was considered as good. 11.9% of them in physical domain, 8.1% in psychological domain, 1.9% in social domain, and 22.8% in spiritual domain had a good quality of life.

     

    Conclusion: Based on the findings, the quality of life in the social, physical and psychological domains was 1.9%, 11.9% and 8.1% poor, therefore; responsible organizations can help these people in various ways by, for example, providing them with low price drugs, which are usually costly in the market, public transportation designed especially for chemically-disabled war veterans, improving insurance services and developing public services in Sardasht. The researchers, finally

  15. Detoxification of a Sulfur Mustard Simulant Using a BODIPY-Functionalized Zirconium-Based Metal-Organic Framework.

    Science.gov (United States)

    Atilgan, Ahmet; Islamoglu, Timur; Howarth, Ashlee J; Hupp, Joseph T; Farha, Omar K

    2017-07-26

    Effective detoxification of chemical warfare agents is a global necessity. As a powerful photosensitizer, a halogenated BODIPY ligand is postsynthetically appended to the Zr 6 nodes of the metal-organic framework (MOF), NU-1000, to enhance singlet oxygen generation from the MOF. The BODIPY/MOF material is then used as a heterogeneous photocatalyst to produce singlet oxygen under green LED irradiation. The singlet oxygen selectively detoxifies the sulfur mustard simulant, 2-chloroethyl ethyl sulfide (CEES), to the less toxic sulfoxide derivative (2-chloroethyl ethyl sulfoxide, CEESO) with a half-life of approximately 2 min.

  16. Simplified Method for Quantifying Sulfur Mustard Adducts to Blood Proteins by Ultrahigh Pressure Liquid Chromatography−Isotope Dilution Tandem Mass Spectrometry.

    Science.gov (United States)

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

    2015-02-16

    Sulfur mustard binds to reactive cysteine residues, forming a stable sulfur-hydroxyethylthioethyl [SHETE]adduct that can be used as a long-term biomarker of sulfur mustard exposure in humans. The digestion of sulfur mustard-exposed blood samples with proteinase K following total protein precipitation with acetone produces the tripeptide biomarker [S-HETE]-Cys-Pro-Phe. The adducted tripeptide is purified by solid phase extraction, separated by ultra high pressure liquid chromatography, and detected by isotope dilution tandem mass spectrometry. This approach was thoroughly validated and characterized in our laboratory. The average interday relative standard deviation was ≤ 9.49%, and the range of accuracy was between 96.1 and 109% over a concentration range of 3.00 to 250. ng/mL with a calculated limit of detection of1.74 ng/mL. A full 96-well plate can be processed and analyzed in 8 h, which is 5 times faster than our previous 96-well plate method and only requires 50 μL of serum, plasma, or whole blood. Extensive ruggedness and stability studies and matrix comparisons were conducted to create a robust, easily transferrable method. As a result, a simple and high-throughput method has been developed and validated for the quantitation of sulfur mustard blood protein adducts in low volume blood specimens which should be readily adaptable for quantifying human exposures to other alkylating agents.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Rancourt, Raymond C., E-mail: raymond.rancourt@ucdenver.edu; Veress, Livia A., E-mail: livia.veress@ucdenver.edu; Ahmad, Aftab, E-mail: aftab.ahmad@ucdenver.edu; Hendry-Hofer, Tara B., E-mail: tara.hendry-hofer@ucdenver.edu; Rioux, Jacqueline S., E-mail: jacqueline.rioux@ucdenver.edu; Garlick, Rhonda B., E-mail: rhonda.garlick@ucdenver.edu; White, Carl W., E-mail: carl.w.white@ucdenver.edu

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    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 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 had

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-31

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

  1. Structural flexibility of the sulfur mustard molecule at finite temperature from Car-Parrinello molecular dynamics simulations.

    Science.gov (United States)

    Lach, Joanna; Goclon, Jakub; Rodziewicz, Pawel

    2016-04-05

    Sulfur mustard (SM) is one of the most dangerous chemical compounds used against humans, mostly at war conditions but also in terrorist attacks. Even though the sulfur mustard has been synthesized over a hundred years ago, some of its molecular properties are not yet resolved. We investigate the structural flexibility of the SM molecule in the gas phase by Car-Parrinello molecular dynamics simulations. Thorough conformation analysis of 81 different SM configurations using density functional theory is performed to analyze the behavior of the system at finite temperature. The conformational diversity is analyzed with respect to the formation of intramolecular blue-shifting CH⋯S and CH⋯Cl hydrogen bonds. Molecular dynamics simulations indicate that all structural rearrangements between SM local minima are realized either in direct or non-direct way, including the intermediate structure in the last case. We study the lifetime of the SM conformers and perform the population analysis. Additionally, we provide the anharmonic dynamical finite temperature IR spectrum from the Fourier Transform of the dipole moment autocorrelation function to mimic the missing experimental IR spectrum. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Brimfield, A.A.; Novak, Mark J.; Hodgson, Ernest

    2006-01-01

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

  3. Prediction of Acute Mammalian Toxicity Using QSAR Methods: A Case Study of Sulfur Mustard and Its Breakdown Products

    Directory of Open Access Journals (Sweden)

    John Wheeler

    2012-07-01

    Full Text Available Predicting toxicity quantitatively, using Quantitative Structure Activity Relationships (QSAR, has matured over recent years to the point that the predictions can be used to help identify missing comparison values in a substance’s database. In this manuscript we investigate using the lethal dose that kills fifty percent of a test population (the LD50 for determining relative toxicity of a number of substances. In general, the smaller the LD50 value, the more toxic the chemical, and the larger the LD50 value, the lower the toxicity. When systemic toxicity and other specific toxicity data are unavailable for the chemical(s of interest, during emergency responses, LD50 values may be employed to determine the relative toxicity of a series of chemicals. In the present study, a group of chemical warfare agents and their breakdown products have been evaluated using four available rat oral QSAR LD50 models. The QSAR analysis shows that the breakdown products of Sulfur Mustard (HD are predicted to be less toxic than the parent compound as well as other known breakdown products that have known toxicities. The QSAR estimated break down products LD50 values ranged from 299 mg/kg to 5,764 mg/kg. This evaluation allows for the ranking and toxicity estimation of compounds for which little toxicity information existed; thus leading to better risk decision making in the field.

  4. Deoxyribonucleic acid damage in Iranian veterans 25 years after wartime exposure to sulfur mustard

    Directory of Open Access Journals (Sweden)

    Effat Behravan

    2013-01-01

    Full Text Available Background : More than 100,000 Iranian veterans and civilians still suffer from various long-term complications due to their exposure to sulfur mustard (SM during the Iran-Iraq war in 1983-88. The aim of the study was to investigate DNA damage of SM in veterans who were exposed to SM, 23-27 years prior to this study. Materials and Methods: Blood samples were obtained from the veterans and healthy volunteers as negative controls. Lymphocytes were isolated from blood samples and DNA breaks were measured using single-cell microgel electrophoresis technique under alkaline conditions (comet assay. Single cells were analyzed with "Tri Tek Comet Score version 1.5" software and DNA break was measured based on the percentage of tail DNA alone, or in the presence of H 2 O 2 (25 μM as a positive control. Results: A total of 25 SM exposed male veterans and 25 male healthy volunteers with similar ages (44.66 ± 6.2 and 42.12 ± 5.75 years, respectively were studied. Percentage of the lymphocyte DNA damage was significantly (P < 0.01 higher in the SM-exposed individuals than in the controls (6.47 ± 0.52 and 1.31 ± 0.35, respectively. Percentages of DNA damage in the different age groups of 35-39, 40-44, 45-49, and 50-54 years in SM-exposed veterans (5.48 ± 0.17, 6.7 3 ± 1.58, 6.42 ± 0.22, and 7.27 ± 0.38, respectively were all significantly (P < 0.05 higher than the controls (1.18 ± 0.25, 1.53 ± 0.22, 1.27 ± 0.20, and 1.42 ± 0.10, respectively. The lymphocytes incubated with H 2 O 2 had much higher DNA damage as expected. The average of tail DNA is 42.12 ± 2.75% for control cells + H 2 O 2 and 18.48 ± 2.14% for patients cells + H 2 O 2 ; P < 0.001. Conclusion: SM exposure of the veterans revealed DNA damage as judged by the comet assay.

  5. From the Cover: Catalytic Antioxidant Rescue of Inhaled Sulfur Mustard Toxicity.

    Science.gov (United States)

    McElroy, Cameron S; Min, Elysia; Huang, Jie; Loader, Joan E; Hendry-Hofer, Tara B; Garlick, Rhonda B; Rioux, Jackie S; Veress, Livia A; Smith, Russell; Osborne, Chris; Anderson, Dana R; Holmes, Wesley W; Paradiso, Danielle C; White, Carl W; Day, Brian J

    2016-12-01

    Sulfur mustard (bis 2-chloroethyl ethyl sulfide, SM) is a powerful bi-functional vesicating chemical warfare agent. SM tissue injury is partially mediated by the overproduction of reactive oxygen species resulting in oxidative stress. We hypothesized that using a catalytic antioxidant (AEOL 10150) to alleviate oxidative stress and secondary inflammation following exposure to SM would attenuate the toxic effects of SM inhalation. Adult male rats were intubated and exposed to SM (1.4 mg/kg), a dose that produces an LD 50 at approximately 24 h. Rats were randomized and treated via subcutaneous injection with either sterile PBS or AEOL 10150 (5 mg/kg, sc, every 4 h) beginning 1 h post-SM exposure. Rats were euthanized between 6 and 48 h after exposure to SM and survival and markers of injury were determined. Catalytic antioxidant treatment improved survival after SM inhalation in a dose-dependent manner, up to 52% over SM PBS at 48 h post-exposure. This improvement was sustained for at least 72 h after SM exposure when treatments were stopped after 48 h. Non-invasive monitoring throughout the duration of the studies also revealed blood oxygen saturations were improved by 10% and clinical scores were reduced by 57% after SM exposure in the catalytic antioxidant treatment group. Tissue analysis showed catalytic antioxidant therapy was able to decrease airway cast formation by 69% at 48 h post-exposure. To investigate antioxidant induced changes at the peak of injury, several biomarkers of oxidative stress and inflammation were evaluated at 24 h post-exposure. AEOL 10150 attenuated SM-mediated lung lipid oxidation, nitrosative stress and many proinflammatory cytokines. The findings indicate that catalytic antioxidants may be useful medical countermeasure against inhaled SM exposure. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Sulfur mustard resistant keratinocytes obtained elevated glutathione levels and other changes in the antioxidative defense mechanism.

    Science.gov (United States)

    Rothmiller, Simone; Schröder, Sarah; Strobelt, Romano; Wolf, Markus; Wang, Jin; Jiang, Xiqian; Worek, Franz; Steinritz, Dirk; Thiermann, Horst; Schmidt, Annette

    2017-11-26

    Sulfur mustard (SM) is a potent blistering chemical warfare agent, which was first used in 1917. Despite the Chemical Weapons Convention, a use was recently reported in Syria in 2015. This emphasizes the importance to develop countermeasures against chemical warfare agents. Despite intensive research, there is still no antidote or prophylaxis available against SM. The newly developed SM-resistant keratinocyte cell line HaCaT/SM was used to identify new target structures for drug development, particularly the adaptations in protective measures against oxidative stress. For this purpose, glutathione (GSH) and NAD(P)H levels, the effect of glutathione S-transferase (GST) inhibition as well as activation and expression of Nrf2, GST, glutamate cysteine ligase (GCL) and glutathione-disulfide reductase (GSR) as well as multi-drug resistance (MDR) proteins 1, 3 and 5 were investigated. The HaCaT/SM cells showed not only a better survival after treatment with SM or cytostatic drugs, but also hydrogen peroxide (H 2 O 2 ). They exhibit more GSH even after SM treatment. Nrf2 levels were significantly lower. Inhibition of GST led to significantly decreased, activation to slightly higher IC 50 values after SM treatment and a lower expression of GST was observed. The cells also expressed less GCLC and GSR. Expression of MDR1, MDR3 and MDR5 was higher under control conditions, but less stimulated by SM treatment. An increased NADP + /NADPH ratio as well as higher NAD + levels were shown. In summary, an improved response of the resistant cell line to oxidative stress was observed. The underlying mechanisms are elevated GSH levels as well as lower expression of Nrf2 and its targets GCLC and GST as well as GSR and MDR1, MDR3 and MDR5. GST is an especially interesting target because its inhibition already induced a significant SM sensitivity. SM resistance also caused redox equivalent level differences. Taken together, these findings provide further insight into the mechanism of SM

  7. Diagnosis and dosimetry of exposure to sulfur mustard: Development of a standard operating procedure for mass spectrometric analysis of haemoglobin adducts - Exploratory research on albumin and keratin adducts

    NARCIS (Netherlands)

    Noort, D.; Fidder, A.; Hulst, A.G.; Jong, L.P.A. de; Benschop, H.P.

    2000-01-01

    Experiments were carried out to develop a standard operating procedure for analysis of sulfur mustard adducts to the N-terminal valine in haemoglobin and to explore adduct formation with albumin and keratin. In the first approach, gas chromatography-negative chemical ionization/mass spectrometry

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

    Science.gov (United States)

    Roshan, Rasoul; Rahnama, Parvin; Ghazanfari, Zeinab; Montazeri, Ali; Soroush, Mohammad Reza; Naghizadeh, Mohammad Mehdi; Melyani, Mahdiyeh; Tavoli, Azadeh; Ghazanfari, Tooba

    2013-04-24

    Sulfur mustard (SM) is an alkylating agent that induces short and long term toxicity on various organs. The aim of this study was to assess the long-term psychological symptoms among samples of exposed to sulfur mustard gas compared with unexposed civilians 20 years after exposure. This historical cohort study was conducted on 495 civilians of Sardasht and Rabat in two age matched groups, including 367 sulfur mustard exposed participants from Sardasht and 128 unexposed subjects from Rabat. Psychological symptoms was assessed using the Symptom Check List-90 Revised (SCL-90-R) including measures of somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism providing three global distress indices namely: Global Severity Index (GSI), Positive Symptom Total (PST) and Positive Symptom Distress Index (PSDI). Comparison was made between exposed and unexposed civilians. There were significant differences in somatization (P = 0.002), obsessive-compulsive (P = 0.031), depression (P = 0.007), anxiety (P = 0.042), and hostility (P = 0.002), between the exposed and unexposed groups. In addition there were significant differences between two groups concerning the GSI (P = 0.045) and the PSDI (P sulfur mustard gas were suffering from a number of psychological symptoms even 20 years after exposure. Providing mental health services and more resource allocation for this community are highly recommended.

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

    Directory of Open Access Journals (Sweden)

    Bita Najafian

    2014-01-01

    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.

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  11. Determination of the sulfur mustard hydrolysis product thiodiglycol by microcolumn liquid chromatography coupled on-line with sulfur flame photometric detection using large-volumn injections and peak compression.

    NARCIS (Netherlands)

    Hooijschuur, E.W.J.; Kientz, C.E.; Brinkman, U.A.T.

    1999-01-01

    A selective, direct and relatively rapid method has been developed for the determination of thiodiglycol (TDG) in aqueous samples. TDG is the main hydrolysis product of the chemical warfare agent sulfur mustard. The method of analysis is based on the on-line coupling of reversed-phase microcolumn

  12. Mental health status following severe sulfur mustard exposure: a long-term study of Iranian war survivors.

    Science.gov (United States)

    Khateri, Shahriar; Soroush, Mohammadreza; Mokhber, Naghmeh; Sedighimoghaddam, Mohammadreza; Modirian, Ehsan; Mousavi, Batool; Mousavi, Seyed Javad; Hosseini, Maryam

    2017-06-01

    This study aimed to describe the mental health status of sulfur mustard-exposed survivors suffering from severe respiratory and ophthalmological problems. Out of 450 invited Iran-Iraq War survivors of sulfur mustard exposure with severe symptoms, 350 participated in this cross-sectional study. Mental health status was assessed using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria. Fisher exact test, Pearson chi-square test, and chi-square test were used to assess any relationship, and the independent-sample t test was employed to compare differences between the veterans with ocular and pulmonary injuries. There were 60.9% (n = 213) survivors who suffered from mental disorders. Among them, 39.7% (n = 139) were previously untreated and required the initiation of psychiatric treatment. The prevalence of anxiety and mood disorders among all survivors was 40.6% (n = 142) and 32.0% (n = 112), respectively. The most common anxiety and mood disorders were posttraumatic stress disorder (32.9%, n = 115) and major depressive disorder (22.3%, n = 78), respectively. Psychiatric disorders were more prevalent in cases with severe pulmonary chemical injury than in subjects with severe ophthalmologic chemical injury. Significant relationships were found between the types of psychiatric disorders and age, education, and occupation (P < .05). The psychiatric morbidity in the chemically injured populations was remarkable and significantly different between the populations. The prevalence of mental illness in these groups highlights the need for the appropriate provision of mental health services. © 2016 John Wiley & Sons Australia, Ltd.

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

    Science.gov (United States)

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

    2013-01-01

    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, were instilled into the trachea. Arterial O2 saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma 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 were 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. PMID:23727623

  14. Evaluation of the pharmacoeconomics of drugs used for the treatment of long-term complications of sulfur mustard

    Directory of Open Access Journals (Sweden)

    Yunes Panahi

    2016-08-01

    Full Text Available Sulfur Mustard (SM, a cytotoxic vesicant chemical warfare agent, has powerful irritant and blistering effects on the skin, eyes and respiratory tract. Since during the Iraq-Iran war, many Iranian soldiers and civilians were exposed to SM, there are several victims still suffering from long-term cutaneous, ocular and pulmonary complications. Currently, there is no definite treatment for long-term complications of SM, and only supportive medical care is being taken to minimize the symptoms. In this study, we compared the cost-effectiveness of common drugs that are used against long-term SM-induced complications in Iranian patients. In this review article, electronic databases were checked using the following key words: sulfur mustard, lung, skin, eye, cost-effectiveness, pharmacoeconomics and treatment. Abstracts of non-English papers and proceedings of congresses on SM were also assessed. Among the studied drugs, high-dose oral N-acetyl cysteine and long-acting inhaled corticosteroids against respiratory complications, topical corticosteroids and oral antihistamines against cutaneous complications and non-steroidal anti-inflammatory drugs and corticosteroids ophthalmic drops against ocular complications were found to be cost-effective. Usage of different drugs in the treatment of SM injuries in Iran, have imposed a significant economic burden to patients and their families because many drugs that are effective against chemical injuries are not covered by insurance. In addition, the development of more effective drugs in this field is considered as an urgent demand that should be noticed by the pharmaceutical industry.

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

    Science.gov (United States)

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

    2016-09-01

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

  16. Protective potential of different compounds and their combinations with MESNA against sulfur mustard-induced cytotoxicity and genotoxicity.

    Science.gov (United States)

    Jost, Petr; Fikrova, Petra; Svobodova, Hana; Pejchal, Jaroslav; Stetina, Rudolf

    2017-06-05

    The purpose of this study was to evaluate the efficacy of potential candidate molecules or their combinations against strong alkylation agent sulfur mustard (SM) on the human lung alveolar epithelial cell line A-549. Candidate molecules were chosen on the basis of their previously observed protective effects in vitro. The tested compounds, including antioxidants, sulfhydryl or other sulfur-containing molecules, nitrogen-containing molecules, PARP inhibitors and a NO synthase inhibitor, were applicated 30min before SM treatment. The efficiency of candidate molecules to protect cells against DNA damage and cell death induced by SM was determined using single-cell gel electrophoresis (comet assay) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction by viable cells. The damage of DNA was assessed 1 and 24h after dose 50μM SM. Cell survival was assessed 24 and 72h after the exposure. To achieve maximal cytoprotection, combinations of selected compounds with sodium 2-mercaptoethane sulphonate (MESNA) were tested. We found significant protective effects by several drugs used individually and also in combination with MESNA. High protection was achieved by sodium thiosulphate, which was further potentiated when combined with MESNA. Most of the selected compounds or mixture provided only moderate genoptotection without having any effect towards cell viability. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog

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    Victor Paromov

    2011-01-01

    Full Text Available Sulfur mustard or mustard gas (HD and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES, or “half-mustard gas,” are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated using in vitro model systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes increased cell viability and attenuated production of reactive oxygen species (ROS in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously described in vivo protective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.

  18. Long-term complications of sulfur mustard poisoning: retinal electrophysiological assessment in 40 severely intoxicated Iranian veterans.

    Science.gov (United States)

    Shoeibi, Nasser; Mousavi, Mir Naghi; Balali-Mood, Mahdi; Moshiri, Mohammad; Darchini-Maragheh, Emadodin; Mousavi, Seyed Reza; Abrishami, Mojtaba

    2017-01-01

    The eye is one of the most sensitive organs to sulfur mustard (SM) [C 4 H 8 Cl 2 S], and preliminary symptoms of exposure usually become evident in the eyes. In this study we aim to evaluate the possible long-term retinal electrophysiologic complications of SM poisoning in Iranian veterans during Iran-Iraq war (1980-1988). In a cross-sectional study forty Iranian veterans who were exposed to mustard gas during the Iran-Iraq war (1980-1988) were included. All the cases underwent complete ocular exam and retinal electrophysiological evaluation, including electroretinography (ERG) and electrooculography (EOG). Data was analyzed using SPSS software. The normal distribution was checked using the Shapiro-Wilk test. Comparison of electrophysiologic values with maximum standard levels was performed using one-sample Student t-test and test of significance was one-tailed. Foreign body sensation (70%), dry eye (50%), photophobia (30%), lacrimation (20%) and pain sensation (10%) were among the common symptoms. ERG showed significant reduced amplitude in rod response, maximal combined response, oscillatory potentials, cone response and 30 Hz flicker waves compared to normal values ( p  < 0.05). Implicit time of b-wave rod response ERG recording was significantly decreased ( p  < 0.05). Implicit time of cone response b-wave was within normal limits. In EOG, Arden ratio did not decrease (total average of 2.311 and 2.48 in right and left eyes, respectively). Delayed toxic effects of SM poisoning in the veterans were observed in the retina, but not in the retinal pigment epithelium layer. As the retina is a neural tissue, long-term effects of SM on neural tissues are presumed.

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

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    Panahi Yunes

    2011-01-01

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

  20. A convenient fluorometric method to study sulfur mustard-induced apoptosis in human epidermal keratinocytes monolayer microplate culture.

    Science.gov (United States)

    Ray, Radharaman; Hauck, Stephanie; Kramer, Rachel; Benton, Betty

    2005-01-01

    Sulfur mustard [SM; bis-(2-chloroethyl) sulfide], which causes skin blistering or vesication [(1991). Histo- and cytopathology of acute epithelial lesions. In: Papirmeister, B., Feister, A. J., Robinson, S. I., Ford, R. D., eds. Medical Defense Against Mustard Gas: Toxic Mechanisms and Pharmacological Implications. Boca Raton: CRC Press, pp. 43-78.], is a chemical warfare agent as well as a potential terrorism agent. SM-induced skin blistering is believed to be due to epidermal-dermal detachment as a result of epidermal basal cell death via apoptosis and/or necrosis. Regarding the role of apoptosis in SM pathology in animal skin, the results obtained in several laboratories, including ours, suggest the following: 1) cell death due to SM begins via apoptosis that proceeds to necrosis via an apoptotic-necrotic continuum and 2) inhibiting apoptosis decreases SM-induced microvesication in vivo. To study the mechanisms of SM-induced apoptosis and its prevention in vitro, we have established a convenient fluorometric apoptosis assay using monolayer human epidermal keratinocytes (HEK) adaptable for multiwell plates (24-, 96-, or 384-well) and high-throughput applications. This assay allows replication and multiple types of experimental manipulation in sister cultures so that the apoptotic mechanisms and the effects of test compounds can be compared statistically. SM affects diverse cellular mechanisms, including endoplasmic reticulum (ER) Ca2+ homeostasis, mitochondrial functions, energy metabolism, and death receptors, each of which can independently trigger apoptosis. However, the biochemical pathway in any of these apoptotic mechanisms is characterized by a pathway-specific sequence of caspases, among which caspase-3 is a key member. Therefore, we exposed 80-90% confluent HEK cultures to SM and monitored apoptosis by measuring the fluorescence generated due to hydrolysis of a fluorogenic caspase-3 substrate (acetyl- or benzyl oxycarbonyl

  1. Discrepancy between mRNA and Protein Expression of Neutrophil Gelatinase-Associated Lipocalin in Bronchial Epithelium Induced by Sulfur Mustard

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    Majid Ebrahimi

    2010-01-01

    Full Text Available Sulfur mustard (SM is a potent vesicant that has been employed as a chemical weapon in various conflicts during the 20th century. More recently, mustard was used in the Iraq conflict against Iranian troops and civilians. At the present time there are more than 40.000 people suffering from pulmonary lesions special bronchiolitis obliterans (BOs due to mustard gas. SM increases the endogenous production of reactive oxygen species (ROS. Neutrophil Gelatinase-associated Lipocalin 2 (Lcn2, NGAL is a member of the lipocalin superfamily for which a variety of functions such as cellular protection against oxidative stress have been reported. Ten normal and Twenty SM-induced COPD patient individuals were studied. Assessment of NGAL expressions in healthy and the patients endobrinchial biopsies were performed by semiquantitative RT-PCR, real-time RT-PCR, and Immunohistochemistry analysis. While Normal control samples expressed same level of mRNA NGAL, expression level of mRNA-NGAL was upregulated about 1.4- to 9.8-folds compared to normal samples. No significant immunoreactivity was revealed in both samples. As we are aware this is the first report of induction of NGAL in patients exposed to SM. NGAL may play an important role in cellular protection against oxidative stress toxicity induced by mustard gas in airway wall of patients.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

    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 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 (14-3-3σ) 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Jung, H., E-mail: junghs@add.re.kr; Lee, H.W.

    2014-05-01

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

  4. Glutathione as an antidote for sulfur mustard poisoning: Mass spectrometric investigations of its potency as a chemical scavenger.

    Science.gov (United States)

    Siegert, Markus; Kranawetvogl, Andreas; Thiermann, Horst; John, Harald

    2017-12-23

    The banned chemical warfare agent sulfur mustard (SM) still represents a serious threat to civilians and military personnel. Therefore, identification of antidotes and scavengers is of high concern. One promising substance is glutathione (GSH). GSH is known to mitigate symptoms of SM poisoning in vitro and in vivo. However, the mechanism of action remains unclear with respect to physiological impact as well as chemical scavenging by reaction between GSH and SM. Therefore, a novel in vitro method was used to characterize the scavenging potential of GSH. Accordingly, alkylation of human serum albumin (HSA), which represents an established biomarker for SM intoxication, was used as a measure for remaining SM. Coincubation of GSH and SM in human serum was performed, and time-dependent degradation of SM was monitored in the presence and absence of GSH. Protein-derived and small molecular reaction products between GSH, HSA, and SM were analyzed using microbore liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry. Although covalent modification of GSH by SM was observed, measurements clearly documented no significant reduction of SM concentration in the presence of GSH. Accordingly, beneficial therapeutic mechanisms of GSH in the case of SM poisoning would appear to be based on physiological effects than on chemical scavenging. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Pro-oxidant-antioxidant balance in Iranian veterans with sulfur mustard toxicity and different levels of pulmonary disorders.

    Science.gov (United States)

    Nobakht M Gh, B Fatemeh; Oskouie, Afsaneh Arefi; Aliannejad, Rasoul; Rezaei-Tavirani, Mostafa; Tavallaie, Shima; Baghban, Alireza Akbarzadeh; Taheri, Salman; Keramati, Mohammad Reza; Alamdari, Daryoush Hamidi

    2016-10-01

    Sulfur mustard (SM) is a strong alkylating agent that primarily targets the skin, eye and lung. The current study evaluated the pro-oxidant-antioxidant balance (PAB) assay in human serum of SM-exposed patients. sera of 35 SM-exposed patients and 19 healthy volunteers were recruited. Both groups had nonsmoker and nonalcoholic people with no diseases such as diabetes, heart disease and other pulmonary diseases (COPD because of smoking, asthma and so on). All patients had documented exposure to SM. The PAB was measured. SM-exposed patients with normal values for pulmonary function test and severe obstructive pulmonary disease demonstrated a significant increase in PAB value in compared with healthy volunteers (the PAB values in healthy volunteers, normal and severe patients were 48.74 ± 21.07 HK, 101.45 ± 32.68 HK and 120.23 ± 31.55 HK, respectively). However, the level of oxidation is not related to the severity of disease defined by spirometry findings. A significant negative correlation was established between the PAB value and FEV1. The increased PAB value in chemical casualties showed that these patients are exposed to oxidative stress.

  6. Characterization of FM2382 from Fulvimarina manganoxydans sp. Nov. 8047 with potential enzymatic decontamination of sulfur mustard.

    Science.gov (United States)

    Zhao, Yuan-Zhong; Guo, Xuan; Zhong, Jin-Yi; Guo, Nan; Chen, Lin-Cai; Dong, Zhi-Yang

    2018-01-01

    Sulfur mustard (SM) can be hydrolyzed by haloalkane dehalogenases such as DhaA, LinB and DmbA. However, the low resistance to the elevated temperatures limited the practical application of haloalkane dehalogenases. Here we reported a new thermotolerant dehalogenase FM2382 from Fulvimarina manganoxydans sp. nov. 8047. The specific activity of FM2382 to SM is 0.6 U/mg. FM2382 possessed high heat stability (45 °C) in slight alkali environment (pH 7.5) and retained approximately 50% activity after incubation at 70 °C for 40 min. The catalytic activity of FM2382 was activated by Co 2+ and Mg 2+ , and inhibited by Zn 2+ , Cu 2+ and Fe 3+ . Furthermore, site-specific mutagenesis proved that D34, K207 D232, D237 were amino acid residues related to the catalytic activity of SM. In conclusion, we found a thermostable haloacid dehalogenases (HAD) family dehalogenase showing SM-degradation activity, which may be useful for practical application in the future. Copyright © 2017. Published by Elsevier Inc.

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

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    Majid Shohrati

    2015-07-01

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

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

    International Nuclear Information System (INIS)

    Jung, H.; Lee, H.W.

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Watson, Annetta Paule [ORNL; Opresko, Dennis M [ORNL; Young, Robert A [ORNL; Hauschild, Veronique [U.S. Environmental Protection Agency

    2006-01-01

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

  10. DNA damage and repair proteins in cellular response to sulfur mustard in Iranian veterans more than two decades after exposure.

    Science.gov (United States)

    Khateri, Shahriar; Balali-Mood, Mahdi; Blain, Peter; Williams, Faith; Jowsey, Paul; Soroush, Mohammad Reza; Behravan, Effat; Sadeghi, Mahmood

    2017-12-05

    Delayed effects of sulfur mustard (SM) exposure on the levels of five important damage/repair proteins were investigated in 40 SM-exposed veterans of Iran-Iraq war and 35 unexposed controls. A major DNA damage biomarker protein - phosphorylated H2AX - along with four DNA repair proteins in cell response to the genome damage MRE11, NBS1, RAD51, and XPA were evaluated in blood lymphocytes from the veterans and controls using western blotting. Mean levels of XPA, MRE11, RAD51 and NBS1 were lower in SM-exposed patients and the decrease in NBS1 was significant. Even though the raised level of phosphor-H2AX in SM-poisoned group compared to the controls was not significant it was consistent with DNA damage findings confirming the severity of damage to the DNA after exposure to SM. There were correlations between the values of RAD51 and NBS1 proteins as well as XPA and MRE11 proteins. More than two decades after exposure to SM, there is still evidences of DNA damage as well as impaired repair mechanisms in cells of exposed individuals. Such disorders in cellular level may contribute to long term health problems of the SM veterans. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-12-31

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

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

    Science.gov (United States)

    Jung, H; Lee, H W

    2014-05-30

    We report herein the evaporation rates and mechanism of a drop of distilled sulfur mustard (HD) agent from stainless steel and aluminum substrates. For systematic analysis, we used a laboratory-sized wind tunnel, thermal desorption (TD) connected to gas chromatograph/mass spectrometry (GC/MS) and drop shape analysis (DSA). We found that the evaporation rates of HD from stainless steel and aluminum increased with temperature. The rates were also linearly proportional to drop size. The time-dependent contact angle measurement showed that the evaporation of the drop of HD proceeded only by constant contact area mechanism from stainless steel surface. On the other hand, the evaporation of HD from aluminum proceeded by a combined mechanism of constant contact area mode and constant contact angle mode. Our experimental data sets and analysis could be used to predict vapor and contact hazard persistence of chemical warfare agents (CWAs) in the air and on exterior surfaces with chemical releases, which assists the military decision influencing personnel safety and decontamination of the site upon a chemical attack event. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Risks of on-pump coronary artery bypass grafting surgery in patients with chronic obstructive pulmonary disease due to sulfur mustard

    Directory of Open Access Journals (Sweden)

    Mehdi Dehghani Firoozabadi

    2017-10-01

    Full Text Available Sulfur mustard (SM is a toxic chemical agent that belongs to a class of vesicant compounds. In the 1980s it was used by the Iraqi army against Iranian forces. Sulfur mustard severely irritates the skin, eyes and lungs. The highest side effects seen in patients affected by this gas are pulmonary complications including different types of lung diseases such as bronchiolitis. It has also led to a certain type of chronic obstructive pulmonary disease called mustard lung. Similar extra-pulmonary, molecular and hormonal effects can be observed in these patients and patients with chronic obstructive pulmonary disease. Here cardiovascular complications may be one of the most dangerous visible effects. And atherosclerosis is probable following the direct effects or consequential long-term effects of SM. The development of atherosclerosis in these patients is associated with an increased risk of cardiovascular and coronary artery disease. Coronary artery bypass grafting surgery is the treatment of coronary artery disease. Doing this surgery by bypass pump has its own morbidity and due to local and systemic inflammation changes in patients with SM pulmonary disorders it may have more side effects. Therefore, detailed knowledge of inflammatory diseases as well as the serum level or even the local lung fluid of the inflammatory factors in these patients before surgery are needed so that it would be possible to reduce the rate of morbidity and mortality by normalizing the inflammatory conditions of the patients before cardiac surgery.

  14. Risks of on-pump coronary artery bypass grafting surgery in patients with chronic obstructive pulmonary disease due to sulfur mustard.

    Science.gov (United States)

    Firoozabadi, Mehdi Dehghani; Sheikhi, Mohammad Ali; Rahmani, Hossein; Ebadi, Ahmad; Heidari, Amanollah; Gholizadeh, Behnam; Sharifi, Khosrow

    2017-10-01

    Sulfur mustard (SM) is a toxic chemical agent that belongs to a class of vesicant compounds. In the 1980s it was used by the Iraqi army against Iranian forces. Sulfur mustard severely irritates the skin, eyes and lungs. The highest side effects seen in patients affected by this gas are pulmonary complications including different types of lung diseases such as bronchiolitis. It has also led to a certain type of chronic obstructive pulmonary disease called mustard lung. Similar extra-pulmonary, molecular and hormonal effects can be observed in these patients and patients with chronic obstructive pulmonary disease. Here cardiovascular complications may be one of the most dangerous visible effects. And atherosclerosis is probable following the direct effects or consequential long-term effects of SM. The development of atherosclerosis in these patients is associated with an increased risk of cardiovascular and coronary artery disease. Coronary artery bypass grafting surgery is the treatment of coronary artery disease. Doing this surgery by bypass pump has its own morbidity and due to local and systemic inflammation changes in patients with SM pulmonary disorders it may have more side effects. Therefore, detailed knowledge of inflammatory diseases as well as the serum level or even the local lung fluid of the inflammatory factors in these patients before surgery are needed so that it would be possible to reduce the rate of morbidity and mortality by normalizing the inflammatory conditions of the patients before cardiac surgery.

  15. Prevalence of chronic complications of sulfur mustard on the oral soft tissues Zahedan veterans

    Directory of Open Access Journals (Sweden)

    Somayeh Salari Seddigh

    2014-10-01

    Full Text Available Background: Chemical gas, especially sulfate mustard (SM was used against Iranian forces repeatedly during the Iraq war. Gas effects on various tissues within the body depend on amount and duration of exposure. According to the prevalence of oral lesions, this study was conducted in Zahedan city on the chemical warfare. Material and Methods: This descriptive cross-sectional study was performed on 70 patients. After obtaining the patient's consent form, a demographic questionnaire was completed by patients and the patients were examined. If there was soft tissue lesions, the cases were examined more closely. All data were collected on special forms and statistical analysis was performed by the SPSS computer program. Results: Among the 82 patients, 52 patients were with oral lesions and 18 patients were with healthy oral mucosa. The most common oral lesions seen in the study were pigmentation (52.8 %, ulcer (42.8% and bleeding and gingival enlargement (34.2 % and white lesions [picking (28.5 % and Peel off (22.8 %], respectively. Conclusion: The most common lesion sites were in the gums and tongue. Many patients referring were not informed of the lesions in their mouth and this problem emphasizes that the periodic oral examinations are required by specialists.

  16. Effects of paraoxonase 1 activity and gene polymorphisms on long-term pulmonary complications of sulfur mustard-exposed veterans.

    Science.gov (United States)

    Taravati, Ali; Ardestani, Sussan K; Ziaee, Abed-Ali; Ghorbani, Atefeh; Soroush, Mohammad-Reza; Faghihzadeh, Soghrat; Kazemi, Hadi; Rezaei, Abbas; Hoseini, Habibollah; Ghazanfari, Tooba

    2013-11-01

    Sulfur mustard (SM) is an alkylating agent with prolonged adverse effects. The antioxidant paraoxonase 1 (PON1), an endogenous free radical scavenger, plays a protective role against oxidative stress. The possible roles of oxidative stress in the pathogenesis of SM, together with the antioxidant activity of PON1, are enough to warrant the analysis of PON1 polymorphisms and allelic variants in incapacitated veterans. PON1 55 L/M and 192 Q/R polymorphisms were assayed in 289 male veterans with severe pulmonary conditions, who were exposed to SM 20-25 years ago, and 66 gender-, age- and ethnic-matched healthy controls. As we showed previously the PON1 activity decreased significantly in veterans. However, PON1 55 L/M and 192 Q/R genotype distributions were not significantly different between the veterans and the controls. R and L allele carriers have also significantly higher basal and salt-stimulated PON1 activity than Q and M allele carriers. Paraoxonase and arylesterase activities in individuals with the QQ+(MM or LM) genotype were significantly lower than those with the (RR or QR)+LL genotype. Furthermore, basal and salt-stimulated paraoxonase activity in veterans with the (RR or QR)+LL genotype was significantly lower than that in the controls. A positive correlation has been determined between serum PON1 activity and pulmonary function test in QR/LL genotypes. Some of the veterans with RR+QR genotypes have also shown a novel missense change of Asn227Ser in exon 6 of the enzyme. This substitution is close to the binding domain of PON1 and so modifies enzyme activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. The Role of Oxidative Stress in Severity of Obstructive Pulmonary Complications in Sputum of Sulfur Mustard-Injured Patients

    Directory of Open Access Journals (Sweden)

    Javad Heydari

    2017-09-01

    Full Text Available Background: Sulfur mustard (SM is a strong bifunctional alkylating agent that causes delayed complications in organs such as lung. Oxidative stress plays a pivotal role in the pathogenesis and progression of many pulmonary diseases. The aim of this study was to investigate the oxidative stress in sputum of SM exposed patients with mild, moderate and severe pulmonary dysfunction and assessing their relationship with pulmonary function. Methods: In this cross–sectional study, oxidative stress biomarkers in sputum were examined on 26 patients with SM-induced bronchiolitis obliterans (9 mild, 14 moderate and 3 severe and 12 matched healthy controls referred to Baqiyatallah Hospital, Tehran between October 2015 and April 2016. Results: Sputum superoxide dismutase, catalase and glutathione S-transferase activities and malondialdehyde level in moderate and severe groups were significantly higher than in the control group (P=0.002, P=0.004, P=0.014 and P=0.009, respectively. Glutathione (GSH level in moderate (22.29%, P=0.025 and severe (45.07%, P=0.004 groups were significantly lower than the control. A decreased in GSH level in severe (41.7% groups was observed as compared with the mild group. Pearson analysis revealed strong correlations between disease severity and oxidative stress biomarkers in sputum of patients with moderate and severe injuries. Conclusions: Oxidative stress is involved in the pathogenesis of patients with moderate and severe pulmonary dysfunction following SM exposure. The presence of enhanced oxidative stress relates to the decline lung function and the progression of the disease. Sputum induction in SM-injured patients can be used to the assessment of the antioxidant status of bronchial secretions.

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

    Science.gov (United States)

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

    2011-01-01

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

  19. Development and comparison of HPLC and MEKC methods for the analysis of cyclic sulfur mustard degradation products.

    Science.gov (United States)

    Lees, Heidi; Vaher, Merike; Kaljurand, Mihkel

    2017-04-01

    In this study, novel, fast, and simple methods based on RP-HPLC and MEKC with DAD are developed and validated for the qualitative and quantitative determination of five cyclic sulfur mustard (HD) degradation products (1,4-thioxane, 1,3-dithiolane, 1,4-dithiane, 1,2,5-trithiepane, and 1,4,5-oxadithiepane) in water samples. The HPLC method employs a C18 column and an isocratic water-ACN (55:45, v/v) mobile phase. This method enables separation of all five cyclic compounds within 8 min. With the CE method, the baseline separation of five compounds was achieved in less than 11 min by applying a simple BGE composed of a 10 mM borate buffer and 90 mM SDS (pH 9.15). Both methods showed good linear correlation (R 2 > 0.9904). The detection limits were in the range of 0.08-0.1 μM for the HPLC method and 10-20 μM for MEKC. The precision tests resulted in RSDs for migration times and peak areas less than 0.9 and 5.5%, respectively, for the HPLC method, and less than 1.1 and 7.7% for the MEKC method, respectively. The developed methods were successfully applied to the analysis of five cyclic HD degradation products in water samples. With the HPLC method, the LODs were lowered using the SPE for sample purification and concentration. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Directory of Open Access Journals (Sweden)

    Pouran Layegh

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jianzhong Li

    2015-10-01

    Full Text Available 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.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

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

    Science.gov (United States)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ham, Hwa-Yong [Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon (Korea, Republic of); Hong, Chang-Won, E-mail: chyj7983@hallym.ac.kr [Department of Chemical and Biological Warfare Research, The Armed Forces Medical Research Institute, Daejeon (Korea, Republic of); Lee, Si-Nae [Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon (Korea, Republic of); Kwon, Min-Soo [Department of Pharmacology, School of Medicine, CHA University, Seongnam (Korea, Republic of); Kim, Yeon-Ja [Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon (Korea, Republic of); Song, Dong-Keun, E-mail: dksong@hallym.ac.kr [Department of Pharmacology, Infectious Diseases Medical Research Center, College of Medicine, Hallym University, Chuncheon (Korea, Republic of)

    2012-01-01

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

  6. Caffeic acid, morin hydrate and quercetin partially attenuate sulfur mustard-induced cell death by inhibiting the lipoxygenase pathway.

    Science.gov (United States)

    Kim, Shin; Jeong, Kwang-Joon; Cho, Sung Kweon; Park, Joo-Won; Park, Woo-Jae

    2016-11-01

    Sulfur mustard (SM) is an alkylating agent, which has been used as in chemical warfare in a number of conflicts. As the generation of reactive oxygen species (ROS), and adducts in DNA and proteins have been suggested as the mechanism underlying SM‑induced cytotoxicity, the present study screened several antioxidant candidates, including tannic acid, deferoxamine mesylate, trolox, vitamin C, ellagic acid and caffeic acid (CA) to assess their potential as therapeutic agents for SM‑induced cell death. Among several antioxidants, CA partially alleviated SM‑induced cell death in a dose‑dependent manner. Although CA treatment decreased the phosphorylation of p38 mitogen‑activated protein (MAP) kinase and p53, p38 MAP kinase inhibition by SB203580 did not affect SM‑induced cell death. As CA has also been reported as a 15‑lipoxygenase (15‑LOX) inhibitor, the role of 15‑LOX in SM‑induced cytotoxicity was also examined. Similar to the results observed with CA, treatment with PD146176, a specific 15‑LOX inhibitor, decreased SM‑induced cytotoxicity, accompanied by decreases in the production of tumor necrosis factor‑α and 15‑hydroxyeicosatetraenoic acid. Furthermore, the present study investigated the protective effects of two natural 15‑LOX inhibitors, morin hydrate and quercetin, in SM‑induced cytotoxicity. As expected, these inhibitors had similar protective effects against SM‑induced cytotoxicity. These antioxidants also reduced the generation of ROS and nitrate/nitrite. Therefore, the results of the present study indicated that the natural products, CA, quercetin and morin hydrate, offer potential as adjuvant therapeutic agents for SM‑induced toxicity, not only by reducing inflammation mediated by the p38 and LOX signaling pathways, but also by decreasing the generation of ROS and nitrate/nitrite.

  7. Four sulfur mustard exposure cases: Overall analysis of four types of biomarkers in clinical samples provides positive implication for early diagnosis and treatment monitoring.

    Science.gov (United States)

    Xu, Hua; Nie, Zhiyong; Zhang, Yajiao; Li, Chunzheng; Yue, Lijun; Yang, Wenfeng; Chen, Jia; Dong, Yuan; Liu, Qin; Lin, Ying; Wu, Bidong; Feng, Jianlin; Li, Hua; Guo, Lei; Xie, Jianwei

    2014-01-01

    In one event, Chinese male individuals accidentally exposed to unknown chemicals and emerged erythema or blisters on contacted organism derma, then hospitalized. To identify the causative agents, blood, urine and exudate samples were collected from the patients during the therapeutic course. Five established liquid chromatography-mass spectrometry (LC-MS) and gas chromatography (GC)-MS methods were employed to analyze the samples. Here, an overall analysis of four types of sulfur mustard biomarkers, including the hydrolysis/oxidation products, β-lyase metabolites, DNA adducts and hemoglobin adducts, was conducted toward the samples from exposed individuals. The results of all the four types of biomarkers in different biomedical matrices showed high relevance, and verified that this exposure is indeed originated from sulfur mustard. The concentrations of the biomarkers in specimens revealed a good correlation with the severity of the patient's symptom. The concentration-time profile demonstrated that most of the biomarkers quickly achieved maximum at the beginning of the course, and then decreased and kept a detectable level until the 7th day after exposure. The DNA adducts in urine samples still appeared on the 30th day, and the N-terminal valine adducts in hemoglobin could be monitored for over 90 days, which was meaningful for the concurrent study of clinical samples. To the best of our knowledge, this work provides the total analysis and profile of four categories of biomarkers in human specimens for the first time, and the good accordance between concentration and level of burns, between time course and biomarkers will be of great importance for early diagnosis and medical treatment monitoring of sulfur mustard exposure.

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

    Science.gov (United States)

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

    2016-05-01

    Comparison of solvent-wetted gauze with body paint, a peelable surface sampling media, for the sampling of the chemical warfare agents VX and sulfur mustard from nine surfaces was performed. The nine surfaces sampled are those typical of interior public venues and include smooth, rough, porous, and non-porous surfaces. Overall, solvent-wetted gauze (wipes) performed better for the recovery of VX from non-porous surfaces while body paint (BP) performed better for the porous surfaces. The average percent VX recoveries using wipes and BP, respectively, are: finished wood flooring, 86.2%, 71.4%; escalator handrail, 47.3%, 26.7%; stainless steel, 80.5%, 56.1%; glazed ceramic tile, 81.8%, 44.9%; ceiling tile, 1.77%, 13.1%; painted drywall 7.83%, 21.1%; smooth cement, 0.64%, 10.3%; upholstery fabric, 24.6%, 23.1%; unfinished wood flooring, 9.37%, 13.1%. Solvent-wetted gauze performed better for the recovery of sulfur mustard from three of the relatively non-porous surfaces while body paint performed better for the more porous surfaces. The average percent sulfur mustard recoveries using wipes and BP, respectively, are: finished wood flooring, 30.2%, 2.97%; escalator handrail, 4.40%, 4.09%; stainless steel, 21.2%, 3.30%; glazed ceramic tile, 49.7%, 16.7%; ceiling tile, 0.33%, 11.1%; painted drywall 2.05%, 10.6%; smooth cement, 1.20%, 35.2%; upholstery fabric, 7.63%, 6.03%; unfinished wood flooring, 0.90%, 1.74%. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Four sulfur mustard exposure cases: Overall analysis of four types of biomarkers in clinical samples provides positive implication for early diagnosis and treatment monitoring

    Directory of Open Access Journals (Sweden)

    Hua Xu

    2014-01-01

    Full Text Available In one event, Chinese male individuals accidentally exposed to unknown chemicals and emerged erythema or blisters on contacted organism derma, then hospitalized. To identify the causative agents, blood, urine and exudate samples were collected from the patients during the therapeutic course. Five established liquid chromatography–mass spectrometry (LC–MS and gas chromatography (GC–MS methods were employed to analyze the samples. Here, an overall analysis of four types of sulfur mustard biomarkers, including the hydrolysis/oxidation products, β-lyase metabolites, DNA adducts and hemoglobin adducts, was conducted toward the samples from exposed individuals. The results of all the four types of biomarkers in different biomedical matrices showed high relevance, and verified that this exposure is indeed originated from sulfur mustard. The concentrations of the biomarkers in specimens revealed a good correlation with the severity of the patient's symptom. The concentration-time profile demonstrated that most of the biomarkers quickly achieved maximum at the beginning of the course, and then decreased and kept a detectable level until the 7th day after exposure. The DNA adducts in urine samples still appeared on the 30th day, and the N-terminal valine adducts in hemoglobin could be monitored for over 90 days, which was meaningful for the concurrent study of clinical samples. To the best of our knowledge, this work provides the total analysis and profile of four categories of biomarkers in human specimens for the first time, and the good accordance between concentration and level of burns, between time course and biomarkers will be of great importance for early diagnosis and medical treatment monitoring of sulfur mustard exposure.

  10. Postsynthetic Incorporation of a Singlet Oxygen Photosensitizer in a Metal-Organic Framework for Fast and Selective Oxidative Detoxification of Sulfur Mustard.

    Science.gov (United States)

    Howarth, Ashlee J; Buru, Cassandra T; Liu, Yangyang; Ploskonka, Ann M; Hartlieb, Karel J; McEntee, Monica; Mahle, John J; Buchanan, James H; Durke, Erin M; Al-Juaid, Salih S; Stoddart, J Fraser; DeCoste, Jared B; Hupp, Joseph T; Farha, Omar K

    2017-01-01

    A fullerene-based photosensitizer is incorporated postsynthetically into a Zr 6 -based MOF, NU-1000, for enhanced singlet oxygen production. The structural organic linkers in the MOF platform also act as photosensitizers which contribute to the overall generation of singlet oxygen from the material under UV irradiation. The singlet oxygen generated by the MOF/fullerene material is shown to oxidize sulfur mustard selectively to the less toxic bis(2-chloroethyl)sulfoxide with a half-life of only 11 min. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Department of Environmental Science, New York Medical College, Valhalla, NY (United States); Heindel, Ned D. [Department of Chemistry, Lehigh University, Bethlehem, PA (United States); Young, Sherri C. [Department of Chemistry, Muhlenberg College, Allentown, PA (United States); Sinko, Patrick J. [Department of Pharmaceutics, Rutgers University, Piscataway, NJ (United States); Casillas, Robert P. [MRIGlobal, Kansas City, MO (United States); Laskin, Jeffrey D. [Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Gerecke, Donald R., E-mail: gerecke@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States)

    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

    International Nuclear Information System (INIS)

    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 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

  13. Efficacy of omeprazole on cough, pulmonary function and quality of life of patients with sulfur mustard lung injury: A placebo-control, cross-over clinical trial study

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Emami

    2014-01-01

    Full Text Available Background: Gastro-esophageal reflux disease (GERD is prevalent and related to more severe disease in patients with respiratory problems. We evaluated the effects of antireflux therapy in warfare victims of exposure to Mustard gas with chronic cough. Materials and Methods: This randomized, double-blind, placebo-controlled, cross-over study was conducted on 45 cases of sulfur mustard injury with chronic cough (≥8 weeks and GERD. Patients were randomized into two groups, receiving either 20 mg twice daily omeprazole-placebo (OP or matching placebo (placebo-omeprazole [PO] for 4 months, followed by a 1-month washout period and the alternative treatment for 4 months. Assessments included GERD and cough, quality of life, and pulmonary function using spirometry. Leicester Cough Questionnaire and SF-36 were used for measuring quality of life. Results: Patients in the OP group experienced a more decrease than those in the PO group in severity of Leicester cough scores during the first 4-month of trial. After crossing the groups, the OP group experienced an increase (P = 0.036 and the PO group experienced a nonsignificant decrease (P = 0.104 in the severity of scores. The OP group also experienced improvement in GERD symptoms and quality of life at the end of the trial, but changes in the PO group was not significant. There was no significant change in respiratory function indices in any groups. Conclusion: Long-term treatment with high-dose omeprazole improved GERD as well as cough, and quality of life, but not changed respiratory function indices in sulfur mustard injured cases with respiratory symptoms.

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Sulfur mustard induced mast cell degranulation in mouse skin is inhibited by a novel anti-inflammatory and anticholinergic bifunctional prodrug.

    Science.gov (United States)

    Joseph, Laurie B; Composto, Gabriella M; Perez, Roberto M; Kim, Hong-Duck; Casillas, Robert P; Heindel, Ned D; Young, Sherri C; Lacey, Carl J; Saxena, Jaya; Guillon, Christophe D; Croutch, Claire R; Laskin, Jeffrey D; Heck, Diane E

    2017-11-07

    Sulfur mustard (SM, bis(2-chloroethyl sulfide) is a potent vesicating agent known to cause skin inflammation, necrosis and blistering. Evidence suggests that inflammatory cells and mediators that they generate are important in the pathogenic responses to SM. In the present studies we investigated the role of mast cells in SM-induced skin injury using a murine vapor cup exposure model. Mast cells, identified by toluidine blue staining, were localized in the dermis, adjacent to dermal appendages and at the dermal/epidermal junction. In control mice, 48-61% of mast cells were degranulated. SM exposure (1.4g/m 3 in air for 6min) resulted in increased numbers of degranulated mast cells 1-14days post-exposure. Treatment of mice topically with an indomethacin choline bioisostere containing prodrug linked by an aromatic ester-carbonate that targets cyclooxygenases (COX) enzymes and acetylcholinesterase (1% in an ointment) 1-14days after SM reduced skin inflammation and injury and enhanced tissue repair. This was associated with a decrease in mast cell degranulation from 90% to 49% 1-3days post SM, and from 84% to 44% 7-14days post SM. These data suggest that reduced inflammation and injury in response to the bifunctional indomethacin prodrug may be due, at least in part, to abrogating mast cell degranulation. The use of inhibitors of mast cell degranulation may be an effective strategy for mitigating skin injury induced by SM. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Inhibition of sulfur mustard-induced cytotoxicity and inflammation by the macrolide antibiotic roxithromycin in human respiratory epithelial cells

    Directory of Open Access Journals (Sweden)

    Barker Peter E

    2007-05-01

    Full Text Available Abstract Background Sulfur mustard (SM is a potent chemical vesicant warfare agent that remains a significant military and civilian threat. Inhalation of SM gas causes airway inflammation and injury. In recent years, there has been increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE cells and bronchial/tracheal epithelial (BTE cells. Cell viability, expression of proinflammatory cytokines including interleukin (IL-1β, IL-6, IL-8 and tumor necrosis factor (TNF, and expression of inducible nitric oxide synthase (iNOS were examined, since these proinflammatory cytokines/mediators are import indicators of tissue inflammatory responses. We suggest that the influence of roxithromycin on SM-induced inflammatory reaction could play an important therapeutic role in the cytotoxicity exerted by this toxicant. Results MTS assay and Calcein AM/ethidium homodimer (EthD-1 fluorescence staining showed that roxithromycin decreased SM cytotoxicity in both SAE and BTE cells. Also, roxithromycin inhibited the SM-stimulated overproduction of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNF at both the protein level and the mRNA level, as measured by either enzyme-linked immunosorbent assay (ELISA or real-time RT-PCR. In addition, roxithromycin inhibited the SM-induced overexpression of iNOS, as revealed by immunocytochemical analysis using quantum dots as the fluorophore. Conclusion The present study demonstrates that roxithromycin has inhibitory effects on the cytotoxicity and inflammation provoked by SM in human respiratory epithelial cells. The decreased cytotoxicity in roxithromycin-treated cells likely depends on the ability of the macrolide to down-regulate the production of proinflammatory

  17. Inhibition of sulfur mustard-induced cytotoxicity and inflammation by the macrolide antibiotic roxithromycin in human respiratory epithelial cells

    Science.gov (United States)

    Gao, Xiugong; Ray, Radharaman; Xiao, Yan; Barker, Peter E; Ray, Prabhati

    2007-01-01

    Background Sulfur mustard (SM) is a potent chemical vesicant warfare agent that remains a significant military and civilian threat. Inhalation of SM gas causes airway inflammation and injury. In recent years, there has been increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE) cells and bronchial/tracheal epithelial (BTE) cells. Cell viability, expression of proinflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF), and expression of inducible nitric oxide synthase (iNOS) were examined, since these proinflammatory cytokines/mediators are import indicators of tissue inflammatory responses. We suggest that the influence of roxithromycin on SM-induced inflammatory reaction could play an important therapeutic role in the cytotoxicity exerted by this toxicant. Results MTS assay and Calcein AM/ethidium homodimer (EthD-1) fluorescence staining showed that roxithromycin decreased SM cytotoxicity in both SAE and BTE cells. Also, roxithromycin inhibited the SM-stimulated overproduction of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNF at both the protein level and the mRNA level, as measured by either enzyme-linked immunosorbent assay (ELISA) or real-time RT-PCR. In addition, roxithromycin inhibited the SM-induced overexpression of iNOS, as revealed by immunocytochemical analysis using quantum dots as the fluorophore. Conclusion The present study demonstrates that roxithromycin has inhibitory effects on the cytotoxicity and inflammation provoked by SM in human respiratory epithelial cells. The decreased cytotoxicity in roxithromycin-treated cells likely depends on the ability of the macrolide to down-regulate the production of proinflammatory cytokines and

  18. Comparison of bronchial responsiveness to ultrasonically nebulized distilled water (UNDW), methacholine, and ultrasonically nebulized distilled cold water (UDCW) in patients with sulfur mustard gas-induced asthma

    Science.gov (United States)

    Emad, Ali; Emad, Yasaman

    2007-01-01

    Objective To evaluate bronchial challenges using three different stimuli as screening tools for bronchial hyper-responsiveness in sulfur mustard gas-induced asthma. Design Randomized, cross-over clinical study. Setting University hospital. Patients Eighteen veterans with mustard gas-induced asthma and 18 normal veterans as the control group. Intervention Pulmonary function tests and inhalation challenges with ultrasonically nebulized distilled water (UNDW), methacholine, and ultrasonically nebulized cold water (UNDCW) were performed on all patients and subjects. Results Six mustard gas-induced asthmatic veterans did not respond to a 20% in FEV1 after distilled water (13.3%), and two of them (11.11%) did not respond with distilled cold water; all responded with methacholine. Only one healthy subject developed a PC20 FEV1 after methacholine but did not with both distilled water and distilled cold water challenges. The asthmatic patients were sensitive to distilled water with a median PD20 of 7.24 ± 3.83 ml (range 2.54 ml to 15.83 ml), and sensitive to cold water with a median PD20 of 6.42 ± 6.24 ml (range 1.92 ml to 25.15 ml). The median PC20 methacholine was 1.90 ± 1.88 mg/ml (range 0.14 mg/ml to 6.20 mg/ml). In patients with a positive response to the distilled water challenge test, no significant correlation was found between PC20 of methacholine and PD20 of distilled water (Rho = −0.34, p = 0.25), whereas in patients whose responses to distilled cold water (DCW) were positive, PD20 of distilled cold water (DCW) correlated well with PC20 of methacholine (Rho = −0.69, p = 0.006). Conclusion Overall, the methacholine challenge test is the best method to distinguish these asthmatic patients from normal subjects in this study. When compared to the methacholine challenge, although the airway response to ultrasonically nebulized distilled cold water test was somewhat less sensitive, it may be used as a simple, fast, inexpensive, and relatively reliable method to

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

    Science.gov (United States)

    Magnusson, R; Nordlander, T; Östin, A

    2016-01-15

    Sampling teams performing work at sea in areas where chemical munitions may have been dumped require rapid and reliable analytical methods for verifying sulfur mustard leakage from suspected objects. Here we present such an on-site analysis method based on dynamic headspace GC-MS for analysis of five cyclic sulfur mustard degradation products that have previously been detected in sediments from chemical weapon dumping sites: 1,4-oxathiane, 1,3-dithiolane, 1,4-dithiane, 1,4,5-oxadithiephane, and 1,2,5-trithiephane. An experimental design involving authentic Baltic Sea sediments spiked with the target analytes was used to develop an optimized protocol for sample preparation, headspace extraction and analysis that afforded recoveries of up to 60-90%. The optimized method needs no organic solvents, uses only two grams of sediment on a dry weight basis and involves a unique sample presentation whereby sediment is spread uniformly as a thin layer inside the walls of a glass headspace vial. The method showed good linearity for analyte concentrations of 5-200 ng/g dw, good repeatability, and acceptable carry-over. The method's limits of detection for spiked sediment samples ranged from 2.5 to 11 μg/kg dw, with matrix interference being the main limiting factor. The instrumental detection limits were one to two orders of magnitude lower. Full-scan GC-MS analysis enabled the use of automated mass spectral deconvolution for rapid identification of target analytes. Using this approach, analytes could be identified in spiked sediment samples at concentrations down to 13-65 μg/kg dw. On-site validation experiments conducted aboard the research vessel R/V Oceania demonstrated the method's practical applicability, enabling the successful identification of four cyclic sulfur mustard degradation products at concentrations of 15-308μg/kg in sediments immediately after being collected near a wreck at the Bornholm Deep dumpsite in the Baltic Sea. Copyright © 2015 Elsevier B.V. All

  20. Simultaneous determination of sulfur mustard and related oxidation products by isotope-dilution LC-MS/MS method coupled with a chemical conversion.

    Science.gov (United States)

    Qi, Meiling; Xu, Bin; Wu, Jianfeng; Zhang, Yajiao; Zong, Cheng; Chen, Jia; Guo, Lei; Xie, Jianwei

    2016-08-15

    Sulfur mustard (SM) is a highly reactive alkylating vesicant with high toxicity and complicated metabolism, the in vivo profile of its oxidation metabolism is not still fully known and urgently needs to be clarified well. In this work, an isotope-dilution high performance liquid chromatography-tandem mass spectrometric method coupled with chemical conversion was developed for the simultaneous quantification of SM and its oxidation products, i.e., mustard sulfoxide (SMO) and mustard sulfone (SMO2). The accurate measurement of SM and its oxidation products with high reaction activity was achived via the method of chemical conversion of 2-(3,5-bis(mercaptomethyl)phenoxy) acetic acid into stable derivative products. Method validation was performed in whole blood matrix, the linear range of the method was between 0.2 and 1000μg/L with correlation coefficients (r(2))>0.99, and the lower limits of quantification for SM, SMO and SMO2 were 1, 1, 0.2μg/L, respectively. The validated method was successfully applied to a toxicokinetics research of SM and its oxidation products after SM dermal exposed rats in a single dose. All three target analytes were found in whole blood samples from poisoned rats, and significant time-dependent responses were also observed. Among them, SMO2 with relatively high toxicity was identified and quantified in vivo for the first time, while SMO was the major product in whole blood and some of them continued to be oxidized to SMO2in vivo. These results give a direct experimental evidence to support that a large amount of SM is converted into the corresponding SMO and SMO2, and these oxidation products might cause potential combined toxic effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Reaction of sulfur mustard gas, soman and agent VX with nanosized anatase TiO2 and ferrihydrite

    Czech Academy of Sciences Publication Activity Database

    Štengl, Václav; Maříková, Monika; Bakardjieva, Snejana; Šubrt, Jan; Opluštil, F.; Olšanská, M.

    2005-01-01

    Roč. 80, č. 7 (2005), s. 754-758 ISSN 0268-2575 R&D Projects: GA MPO(CZ) FD-K/005; GA AV ČR KSK4050111 Institutional research plan: CEZ:AV0Z40320502 Keywords : anatese TiO2 * ferrihydrite * mustard gas Subject RIV: CA - Inorganic Chemistry Impact factor: 0.981, year: 2005

  2. The Toxicity of Inhaled Sulphur Mustard

    Science.gov (United States)

    2012-10-01

    investigated as a potential COTS treatment for HD-induced ALI. 30 Reportable Outcomes Manuscripts Fairhall SJ, Brown RFR , Jugg BJA, Smith AJ...countermeasures for inhaled sulfur mustard. CBD S&T 2011. Presentations Brown RFR . Preliminary studies of the effects of inhaled sulphur mustard in the...gelatinases in sulfur mustard-induced acute airway injury in guinea pigs. Am J Physiol. 276(5:1): L754-762. Fairhall SJ, Brown RFR , Jugg BJA, Smith

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

    Science.gov (United States)

    Liu, Feng; Jiang, Ning; Xiao, Zhi-Yong; Cheng, Jun-Ping; Mei, Yi-Zhou; Zheng, Pan; Wang, Li; Zhang, Xiao-Rui; Zhou, Xin-Bo; Zhou, Wen-Xia; Zhang, Yong-Xiang

    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.

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

    Directory of Open Access Journals (Sweden)

    Feng Liu

    2016-04-01

    Full Text Available 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.

  5. Electrochemical sensing of thiodiglycol, the main hydrolysis product of sulfur mustard, by using an electrode composed of an ionic liquid, graphene nanosheets and silver nanoparticles

    International Nuclear Information System (INIS)

    Mahyari, Mojtaba

    2016-01-01

    The authors describe a method for amperometric determination of thiodiglycol (TDG), the main hydrolysis product of sulfur mustard. The electrode consists of a mixture of graphene nanosheets, silver nanoparticles and the ionic liquid octylpyridinium hexafluorophosphate. Electrochemical oxidation of TDG was performed by cyclic voltammetry at pH 4 and revealed a pair of well-defined redox peaks at potentials of 0.43 and 0.19 V (vs. Ag/AgCl). Amperometric detection was accomplished over a dynamic range that is linear in the 10–3700 μM concentration range. The detection limit (at an S/N of 3) is 6 μM. The electrode was applied to the determination of TDG in (spiked) waste water and gave recoveries that ranged from 98.2 to 103.3 %. (author)

  6. 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)

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-12-31

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

  8. Monitoring urinary metabolites resulting from sulfur mustard exposure in rabbits, using highly sensitive isotope-dilution gas chromatography-mass spectrometry.

    Science.gov (United States)

    Nie, Zhiyong; Zhang, Yajiao; Chen, Jia; Lin, Ying; Wu, Bidong; Dong, Yuan; Feng, Jianlin; Liu, Qin; Xie, Jianwei

    2014-08-01

    A highly sensitive method for the determination of sulfur mustard (SM) metabolites thiodiglycol (TDG) and thiodiglycol sulfoxide (TDGO) in urine was established and validated using isotope-dilution negative-ion chemical ionization (NICI) gas chromatography-mass spectrometry (GC-MS). TDGO in the samples was reduced with TiCl3, and then determined together with TDG as a single analyte. The sample preparation procedures, including two solid-phase-extraction (SPE) clean-up steps, were optimized to improve the sensitivity of the method. The limits of detection (LOD) for both TDG and TDG plus TDGO (TDG + TDGO) were 0.1 ng mL(-1), and the limits of quantitation (LOQ) for both were 0.3 ng mL(-1). The method was used in a rabbit cutaneous SM exposure model. Domestic rabbits were exposed to neat liquid SM at three dosage levels (0.02, 0.05, and 0.15 LD50), and the urinary excretion of four species of hydrolysis metabolites, namely free TDG, free plus conjugated TDG (total TDG), free TDG + TDGO, and free plus conjugated TDG + TDGO (total TDG + TDGO), was evaluated to investigate the metabolic processes. The total urinary excretion profiles of the metabolites, including the peak time, time window, and dose-response and time-response relationships, were clarified. The results revealed that the concentrations of TDG and TDG + TDGO in the urine increased quickly and then decreased rapidly in the first two days after SM exposure. The cumulative amount of total TDG + TDGO excreted in urine during the first five days accounted for 0.5-1% of the applied dose of SM. It is also concluded that TDG and TDGO in urine existed mainly in free form, the levels of glucuronide and of sulfate conjugates of TDG or TDGO were very low, and most hydrolysis metabolites were present in the oxidized form (TDGO). The study indicates that the abnormal increase of TDG and TDGO excretion levels can be used as a diagnostic indicator and establishes a reference time-window for retrospective analysis and

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

    Science.gov (United States)

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

    2017-02-01

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

  10. Altered expression of cyclooxygenase-2, 12-lipoxygenase, inducible nitric oxide synthase-2 and surfactant protein D in lungs of patients with pulmonary injury caused by sulfur mustard.

    Science.gov (United States)

    Tahmasbpour, Eisa; Ghanei, Mostafa; Khor, Abolfazl; Panahi, Yunes

    2018-03-14

    Sulfur mustard (SM) is a strong alkylating toxicant that targets different organs, particularly human lung tissue. Change in genes expression is one of the molecular mechanisms of SM toxicity in damaged tissue. The purpose of this investigation is to characterize the expression of cyclooxygenase-2 (COX-2), 12-lipoxygenase (12-LO), inducible nitric oxide synthase 2 (iNOS2), and surfactant protein D (SFTPD) in lungs of patients who exposed to SM. Lung biopsies were provided from SM-exposed patients (n = 6) and controls (n = 5). Total RNA were extracted from all specimens and then cDNA was synthesized for each sample. Changes in gene expression were measured using RT 2 Profiler ™PCR Array. Pulmonary function tests revealed more obstructive and restrictive spirometric patterns among patients compared to the control group. Expression of COX-2 and 12-LO in the lung of patients was increased by 6.2555 (p = 0.004) and 6.2379-folds (p = 0.002), respectively. In contrast, expression of SF-D and iNOS genes was reduced by 8.5869-fold (p = 0.005) and 2.4466-folds (p = 0.011), respectively. Mustard lungs were associated with overexpression of COX-2 and 12-LO, which are responsible for inflammation, overproduction of free radicals and oxidative stress. Downregulation of iNOS2 and SF-D are probably the reason for lung disease and dysfunction among these patients. Therefore, the expression of these genes could be an important, routine part of the management of such patients.

  11. CD4/CD8 ratio and cytokine levels of the BAL fluid in patients with bronchiectasis caused by sulfur mustard gas inhalation

    Directory of Open Access Journals (Sweden)

    Emad Yasaman

    2007-01-01

    Full Text Available Abstract Objective To analyze cytokine levels in BAL fluid of patients with bronchiectasis due to mustard gas inhalation. Patients 29 victims with mustard gas-induced bronchiectasis and 25 normal veterans as control group. Intervention PFTs,, high-resolution CT scans of the chest, analyses of BAL fluids for five cytokines (IL-8, IL-1β, IL-6, TNF-α, IL-12 and analyses of BAL fluids for cellular and flow-cytometric analysis of the phenotype of bronchoalveolar cells were performed in all cases. Results CD4 lymphocytes expressed as percentage or absolute number were significantly higher in patients with bronchiectasis than in controls (32.17 ± 16.00 vs 23.40 ± 6.97%, respectively; p = 0.01; and 3.31 ± 2.03 vs 1.88 ± 0.83 × 103 cells/ml, respectively; p = 0.001. The CD4/CD8 ratio was significantly higher in patients with bronchiectasis than in controls (3.08 ± 2.05 vs 1.68 ± 0.78; p = 0.002. There were significant differences in cytokine (IL-8, IL-1β, IL-6, TNF-α, IL-12 levels of BAL fluid between patients with bronchiectasis and healthy controls. A significant correlation was observed between the HRCT scores and both the percentage and the absolute number of CD4 lymphocytes in BAL fluid in patients with bronchiectasis (r = -0.49, p = 0.009; r = -0.50, p = 0.008; respectively. HRCT scores showed a significant correlation with CD4/CD8 ratios (r = 0.54, p = 0.004 too. Of measured BAL cytokines, only IL-8 (r = -0.52, p = 0.005 and TNF-aα (r = 0.44, p = 0.01 showed significant correlations with the HRCT scores. Conclusion The increased levels of cytokines CD4 lymphocytes in the BAL fluid suggest the possible causative mechanism in the lung in sulfur mustard gas-induced bronchiectasis by the recruitment of neutrophils into the lung.

  12. A mediational model of PTSD in World War II veterans exposed to mustard gas.

    Science.gov (United States)

    Jankowski, M Kay; Schnurr, Paula P; Adams, Gary A; Green, Bonnie L; Ford, Julian D; Friedman, Matthew J

    2004-08-01

    Structural equation modeling (SEM) was used to examine associations among trauma-related contextual factors, initial psychological reactions, social support, and subsequent disclosure on posttraumatic stress disorder (PTSD) symptoms in a sample of World War II (WWII) veterans exposed to mustard gas (N = 305). A structural model suggested that initial psychological reaction mediated the relationship between variables related to the context of mustard gas exposure and severity of PTSD symptoms 50 years later. Unexpectedly, social support appeared to be positively related to PTSD symptoms, and not related to the contextual variables or initial psychological reactions. These findings contribute to our understanding of PTSD in older veterans, and have relevance for early intervention services to prevent PTSD among those at risk for exposure to toxic agents.

  13. Study on Effectiveness of Low Dose Theophylline as Add-on to Inhaled Corticosteroid for Patients with Sulfur Mustard Induced Bronchiolitis

    Directory of Open Access Journals (Sweden)

    Yunes Panahi

    2013-12-01

    Full Text Available Background: Theophylline may reverse steroid resistance and decrease inflammation in patients with chronic pulmonary disease and sulfur mustard (SM induced bronchiolitis. This study was designed to assess the effects of low-dose theophylline on improvement of pulmonary function tests (PFTs of SM exposed patients.Methods: In this comparative observational study, a group of SM-exposed victims during the Iraq-Iran war who were treated with oral slow releasing (SR theophylline, salmetrol, fluxitide, omeprazole and NAC (study group were compared to a group of age and gender matched SM-exposed patients who received same medications except oral SR theophylline (historical control group. PFTs were measured at the beginning of the study and after 8 weeks of the treatment.Results: In total, 33 subjects in the study group and 27 subjects in the control group were studied. Mean (SD age of all subjects was 51 (14.1 years. In the study group, on the 8th week post-treatment, PFTs decreased, though the differences of tests between before and after treatment were not significant. In the control group, all the tests decreased in the same period and these reductions were not also significant. However, the changes in PFTs were significantly different between the two groups. The results of most PFTs in the controls decreased in greater extents compared to theophylline treated patients. This shows that despite theophylline was unable to improve the patients; it was partially able to decelerate the reductions in PFTs.Conclusion: Theophylline may not improve PFTs of SM exposed patients but it may decelerate the progress of the underlying respiratory disease. Further studies in this setting with higher doses of theophylline and longer term of evaluation are needed to better understand the pathophysiological mechanism of SM induced bronchiolitis and the effectiveness of the treatment with theophylline.   How to cite this article: Panahi Y, Poursaleh Z, Amini-Harandi A

  14. Malignant cutaneous T-cell lymphoma among 1100 Iranian victims, two decades after exposure to sulfur mustard: a long term investigation

    International Nuclear Information System (INIS)

    Emadi, S. N.; Emadi, S. E.

    2009-01-01

    Sulfur Mustard ((SM; 2, 2 -dichlorethyl sulfide)) is a potent chemical warfare agent that was widely used during First World War and Iran -Iraq conflict. Over 100,000 Iranians were injured by sulfur mustard. This vesicant agent has a lot of acute and chronic destructive influences on the skin, eye and respiratory system. SM via the alkylation of DNA and several cellular proteins (structural, cytoplasmic and enzymes) and cell nuclei; produce several toxic, mutagenic and carcinogenic effects on epidermis, dermis, dermal appendix and hypodermics. In acute phases flexural locations and thin epidermal area such as groin, scrotum, and axilla and eyelids showed the most severe complication. According to scientific studies on chemical victims depression of cell-mediated immunity and also lower percentage of NK cell has been observed in SM exposure furthermore cytokines and other growth factors produced and secreted during epidermal and dermal regeneration of healing skin blisters. In reference to the last study about long term effect of SM the cutaneous signs and disorders could be categorized into 3 different groups. Conclusion Human data on the carcinogenicity of SM are from (a) battlefield exposures, (b) accidents, and (c) workers in chemical factories. Both British and American studies and other researchers have investigated the increased incidences of leukemia, pulmonary and skin carcinoma arising from World War I battlefield exposure. Clinical documentation in our cases shows notable and common signs, symptoms and data such as 1- Middle ages 2- Location of CTCL (folds and exposed areas) 3- The similarity between CTCL and SM scar (pigmentory and vascular changes) 4- Chronic dermatitis especially xerosis and eczema with itching before the beginning of CTCL. All of this study and data leads us to the conclusion that SM can possibly cause CTCL in indirect and direct way. CTCL can be caused indirectly due to prolonged period of chronic dermatitis (xerosis, eczema

  15. MUSTARD GAS EXPOSURE AND CARCINOGENESIS OF LUNG

    OpenAIRE

    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.

  16. Efficacy of probiotic supplementation on quality of life and pulmonary symptoms due to sulfur mustard exposure: a randomized double-blind placebo-controlled trial.

    Science.gov (United States)

    Panahi, Yunes; Ghanei, Mostafa; Vahedi, Ensieh; Mousavi, Seyyed Hossein; Imani, Saber; Sahebkar, Amirhossein

    2017-01-01

    This study investigated the efficacy and safety of supplementation with probiotics in improving chronic pulmonary symptoms due to sulfur mustard (SM) exposure. In a randomized double-blind placebo-controlled study, 65 subjects suffering from chronic pulmonary complications of SM were assigned to one probiotic capsule (1 × 10 9 CFU containing seven strains of lactic acid-producing bacteria) every 12 h or an identical placebo for six weeks. Serum high-sensitivity C-reactive protein (CRP) concentrations, pulmonary function tests (FEV1, FEV1/FVC and MMEF 25-75%) and COPD assessment test (CAT) were assessed at baseline and at the end of trial. The groups were comparable in baseline characteristics. There were significant improvements in FEV1/FVC in the probiotic but not in placebo group. CAT scores were decreased in both study groups. However, between-group comparison of changes in the assessed parameters reached statistical significance only for CAT score (p < 0.001). There was no report of adverse events during the course of trial. Findings of the present trial favor the efficacy of probiotic supplementation in improving the pulmonary symptoms of SM-exposed subjects.

  17. Efficacy and Safety of Immunotherapy with Interferon-Gamma in the Management of Chronic Sulfur Mustard-Induced Cutaneous Complications: Comparison with Topical Betamethasone 1%

    Directory of Open Access Journals (Sweden)

    Yunes Panahi

    2012-01-01

    Full Text Available The present trial investigated the efficacy of immunotherapy with interferon-gamma (IFN-γ in the treatment of sulfur mustard (SM-induced chronic skin complications. Forty subjects who were suffering from chronic skin complications of SM and were diagnosed to have severe atopic dermatitis, were assigned to IFN-γ (50 μg/m2 subcutaneously three times per week (n=20 or betamethasone valerate topical cream 0.1% (n=20 every night for 30 days. Extent and intensity of cutaneous complications was evaluated using scoring atopic dermatitis (SCORAD index, and quality of life using dermatology life quality index (DLQI at baseline and at the end of trial. SCORAD-A and SCORAD-B scores were significantly decreased in both IFN-γ and betamethasone. However, SCORAD-C score was decreased only in the IFN-γ group. There were significant reductions in overall as well as objective SCORAD scores in both groups. As for the magnitude of changes, treatment with IFN-γ was associated with greater reductions in overall, objective and segmented SCORAD scores compared to betamethasone. DLQI reduction was found to be significantly greater in the IFN-γ group. Promising improvements in quality life and clinical symptoms that was observed in the present study suggest the application of IFN-γ as an effective therapy for the management of SM-induced chronic skin complications.

  18. Adipose-Derived Mesenchymal Stem Cells for Treatment of Airway Injuries in A Patient after Long-Term Exposure to Sulfur Mustard.

    Science.gov (United States)

    Nejad-Moghaddam, Amir; Ajdari, Soheila; Tahmasbpour, Eisa; Goodarzi, Hassan; Panahi, Yunes; Ghanei, Mostafa

    2017-01-01

    Sulfur mustard (SM) is a potent mutagenic agent that targets several organs, particularly lung tissue. Changes in morphological structure of the airway system are associated with chronic obstructive pulmonary deficiency following exposure to SM. Although numerous studies have demonstrated pathological effects of SM on respiratory organs, unfortunately there is no effective treatment to inhibit further respiratory injuries or induce repair in these patients. Due to the extensive progress and achievements in stem cell therapy, we have aimed to evaluate safety and potential efficacy of systemic mesenchymal stem cell (MSC) administration on a SM-exposed patient with chronic lung injuries. In this clinical trial study, our patient received 100×106cells every 20 days for 4 injections over a 2-month period. After each injection we evaluated the safety, pulmonary function tests (PFT), chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), Borg Scale Dyspnea Assessment (BSDA), and 6 Minute Walk Test (6MWT). One-way ANOVA test was used in this study which was not significant (P>0.05). There were no infusion toxicities or serious adverse events caused by MSC administration. Although there was no significant difference in PFTs, we found a significant improvement for 6MWT, as well as BSDA, SGRQ, and CAT scores after each injection. Systemic MSC administration appears to be safe in SM-exposed patients with moderate to severe injuries and provides a basis for subsequent cell therapy investigations in other patients with this disorder (Registration Number: IRCT2015110524890N1).

  19. In vitro the differences of inflammatory and oxidative reactions due to sulfur mustard induced acute pulmonary injury underlying intraperitoneal injection and intratracheal instillation in rats.

    Science.gov (United States)

    Yu, Dan; Bei, Yuan-Yuan; Li, Yuan; Han, Wei; Zhong, Yu-Xu; Liu, Fei; Zhao, Yu-Ling; Zhu, Xiao-Ji; Zhao, Jian

    2017-06-01

    This study was to investigate the differences of inflammatory reaction and oxidative stress due to sulfur mustard (SM)-induced acute pulmonary injury via two ways in rats. In intraperitoneal and tracheal SM groups, injected intraperitoneally and instilled intratracheally with 0.1mL diluted SM (0.96 LD 50 =8mg/kg) and SM (0.98 LD 50 =2mg/kg) were administered in rats. In bronchoalveolar lavage fluid, serum, and alveolar septum, lactate dehydrogenase, glutathione peroxidase, tumor necrosis factor-α, interleukin-1β, interleukin-6, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, l-selectin, r-glutamyl transpeptidase, thiobarbituric acid reactive substances levels as well as the expression of CD4, CD20, CD68, 8-hydroxy deoxyguanosine, nuclear factor-E2-related factor 2, and heme oxygenase-1 measured by ELISA, immune scatter turbidimetry and immunohistochemical method in the intraperitoneal SM group were increased at each time-point compared with the tracheal SM groups, respectively. These data demonstrated an increased inflammatory reaction and oxidative stress indices in rat via intraperitoneal injection under similar SM LD 50 doses. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Mustards and Vesicants

    Energy Technology Data Exchange (ETDEWEB)

    Young, Robert A [ORNL; Bast, Cheryl B [ORNL

    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.

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

    Science.gov (United States)

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

    2014-08-01

    We studied the response of ethylene-sensitive (Pusa Jai Kisan) and ethylene-insensitive (SS2) mustard (Brassica juncea) cultivars to 0, 0.5, 1.0 and 2.0 mM SO₄(2-), and the effect of 1.0 mM SO₄(2-) was studied in the amelioration of 50 µM cadmium (Cd). The Cd-induced oxidative stress and Cd accumulation were greater in SS2 than Pusa Jai Kisan, but sulfur (S) application alleviated Cd-induced oxidative stress more prominently in Pusa Jai Kisan by increasing S-metabolism and synthesis of reduced glutathione (GSH) and ethylene production; and promoted photosynthesis and plant dry mass under Cd stress. The ethylene-sensitive cultivar responded more to S treatment under Cd stress and showed increased activity of antioxidant system resulting in increased photosynthesis and growth. Cadmium treatment resulted in rapid increase in ethylene formation which adversely influenced photosynthesis and plant dry mass. However, S and ethephon application to Cd-treated plants lowered ethylene formation to optimal range responsible for maximal GSH synthesis and protection against Cd-induced oxidative stress. The similarity of the effectiveness of 1.0 mM SO₄(2-) with 200 µL L(-1) ethylene source as ethephon in alleviation of 50 µM Cd further verifies that differential alleviation of Cd toxicity in the two cultivars by S was dependent on ethylene production. The results suggest that ethylene production determines Cd stress alleviation by S via regulatory interaction with antioxidant metabolism. Thus, ethylene production and sensitivity bear a prominent role in alleviation of Cd stress by S and can be used as a criterion for developing Cd tolerant genotypes. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-02-26

    Exposure of the skin to sulfur mustard (SM) results in long-term complications such as impaired tissue regeneration. Previous own studies in normal human epidermal keratinocytes (NHEK) treated with SM demonstrated reduced proliferation, premature differentiation and a restricted functionality of hypoxia-mediated signaling in the cells. Here, we investigated the involvement of microRNAs, miR-203 and miR-210, in these mechanisms. SM significantly upregulated the expression of miR-203 in NHEK when cultivated under normoxic and hypoxic conditions. SM had no effect on miR-210 under normoxia. However, miR-210 levels were greatly increased in NHEK when grown in hypoxia and further elevated upon exposure of the cells to SM. In normoxia and hypoxia, inhibition of miR-203 by transfection of NHEK with complementary oligonucleotides, anti-miR-203, attenuated the SM-induced impairment of metabolic activity and proliferation, and counteracted SM-promoted keratin-1 expression in these cells. Consistent ameliorating effects on dysregulated metabolic activity, proliferation and keratin-1 expression in SM-treated NHEK were obtained upon inhibition of miR-210 in these cells grown in hypoxia. Our findings provide evidence that miR-203 and miR-210 are key regulators in normal and SM-impaired keratinocyte functionality, and suggest potential usefulness of inhibitors against miR-203 and miR-210 for target-directed therapeutical intervention to improve re-epithelialization of SM-injured skin. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. From the Cover: ImpairedProliferation and Differentiation of the Conducting Airway Epithelium Associated With Bronchiolitis Obliterans After Sulfur Mustard Inhalation Injury in Rats.

    Science.gov (United States)

    McGraw, Matthew D; Rioux, Jaqueline S; Garlick, Rhonda B; Rancourt, Raymond C; White, Carl W; Veress, Livia A

    2017-06-01

    Sulfur mustard (SM) is a chemical warfare agent that causes chronic airway remodeling. This study's objective was to assess for changes to the bronchiolar epithelium after SM exposure to explain its contribution to chronic airway remodeling. Adult male rats were exposed to a sublethal dose of SM inhalation (1.0-1.2 mg/kg) for 50 min. Histological sections of the bronchiolar epithelium were analyzed for changes using hematoxylin and eosin, trichrome, and immunofluorescent staining for acetylated tubulin (AT) and club cell secretory protein (CCSP). CCSP in bronchoalveolar lavage fluid was assessed using western blot. A bromodeoxyuridine (BRDU) assay was used to assess for epithelial proliferation, and real-time PCR measured changes in Notch mRNA expression. SM caused significant proximal bronchiolar epithelial injury with epithelial denudation, loss of acetylated tubulin and CCSP staining, and reduced bronchoalveolar lavage fluid CCSP levels. bromodeoxyuridine (BRDU) + staining of proximal bronchiolar epithelial cells was not increased, but staining was increased in the distal bronchiolar epithelium. One month after injury, the proximal bronchiolar epithelium was not fully repaired. Significant collagen deposition surrounded proximal bronchioles with luminal obstruction, consistent with bronchiolitis obliterans. These changes corresponded with a downregulation of Notch1, Notch3, and Hes1 mRNA expressions. This study demonstrates that SM exposure resulted in severe proximal airway epithelial injury, persistent morphological changes, impaired epithelial proliferation and, ultimately, bronchiolitis obliterans. These changes occurred at the same time that the Notch signaling genes were downregulated. Thus, the lung epithelium and the Notch signaling pathway may be worthy targets for the prevention of chronic airway remodeling after SM inhalation injury. Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by US

  4. Delayed Complications and Long-term Management of Sulfur Mustard Poisoning: Recent Advances by Iranian Researchers (Part І of ІІ

    Directory of Open Access Journals (Sweden)

    Emadodin Darchini-Maragheh

    2018-03-01

    Full Text Available Chemical warfare agents are the most brutal weapons among the weapons of mass destruction. Sulfur mustard (SM is a potent toxic alkylating agent known as “the King of the Battle Gases”. SM has been the most widely used chemical weapon during the wars. It was widely used in World War I. Thereafter, it was extensively employed by the Iraqi troops against the Iranian military personnel and even civilians in the border cities of Iran and Iraq in the period between 1983 and 1988. Long-term incapacitating properties, significant environmental persistence, lack of an effective antidote, and relative ease of manufacturing have kept SM a potential agent for both terrorist and military uses. Even 3 decades after SM exposure, numerous delayed complications among Iranian victims are still being reported by researchers. The most common delayed complications have been observed in the respiratory tracts of chemically injured Iranian war veterans. Also, skin lesions and eye disorders have been observed in most Iranian SM-exposed war veterans in the delayed phase of SM intoxication. Thus, extensive research has been conducted on Iranian war veterans during the past decades. Nevertheless, major gaps still continue to exist in the SM literature. Part І of this paper will discuss the delayed complications and manifestations of exposure to SM among Iranian victims of the Iran–Iraq conflict. Part ІІ, which will appear in the next issue of Iran J Med Sci, will discuss the long-term management and therapy of SM-exposed patients.

  5. Evaluation of carbon aerogel-based solid-phase extraction sorbent for the analysis of sulfur mustard degradation products in environmental water samples.

    Science.gov (United States)

    Jõul, Piia; Vaher, Merike; Kuhtinskaja, Maria

    2018-05-01

    In this study, SPE method using a carbon aerogel(CA)-based sorbent was developed and evaluated for the simultaneous extraction of sulfur mustard (HD) degradation products from environmental water samples. Applied CAs proved to be very promising materials for use as SPE sorbents, due to their high porosity, very low density and a large specific surface area. 10 degradation products of HD, both aliphatic and cyclic (thiodiglycol (TDG), TDG sulfoxide, TDG sulfone, 3,5-dithia-1,7-heptanediol, 3,6-dithia-1,8-octanediol, 1,4-thioxane, 1,3-dithiolane, 1,4-dithiane, 1,2,5-trithiepane, and 1,4,5-oxadithiepane) were extracted on a CA-based SPE cartridge. The concentrations of target analytes in the eluate were determined by HPLC-DAD and CE-DAD. Several parameters affecting the extraction efficiency, including the kind and volume of the eluting solvent, sample loading flow rate, volume and ionic strength as well as the reusability of the cartridge, were investigated and optimized to achieve the best performance for the analytes. A series of quantitative parameters such as linear range, coefficient of determination, LOD, LOQ and precision were examined under the optimized conditions. High sensitivity (LODs 0.17-0.50 μM) and high precision (intraday RSD = 2.0-7.7% and interday RSD = 2.7-9.9%) for all the analytes were achieved. The performance of the CA-based sorbent was compared with that of commonly used SPE sorbents. Applied for the analysis of spiked pore water samples collected from the Bornholm Basin, one of the largest chemical warfare dumping sites in the Baltic Sea, the proposed method allowed high SPE recoveries of all the analytes ranging from 83.5 to 99.7% to be obtained. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Oxidative stress and altered expression of peroxiredoxin genes family (PRDXS) and sulfiredoxin-1 (SRXN1) in human lung tissue following exposure to sulfur mustard.

    Science.gov (United States)

    Tahmasbpour Marzony, Eisa; Ghanei, Mostafa; Panahi, Yunes

    2016-05-01

    Sulfur mustard (SM) is a potent and mutagenic agent that targets human lung tissue. The purpose of this investigation is to characterize the expression of sulfiredoxin-1 (SRXN1) and peroxiredoxin (PRDXs) genes and oxidative stress (OS) status in human lung after exposure to SM. Lung biopsy specimens bronchoalveolar lavage (BAL) fluids were provided from SM-exposed patients (n = 6) and controls (n = 5). Changes in gene expression were measured using RT(2) Profiler PCR Array. OS was considered by measuring BAL fluid levels of malondialdehyde (MDA) and protein carbonyls (PC). Mean of MDA and PC values in BAL fluid of patients (0.6467 ± 0.05922 nmol/l and 1.391 ± 0.421 nmol/mg, respectively) was higher than in controls (0.486 ± 0.04615 nmol/l and 0.949 ± 0.149 nmol/mg, respectively). Expression of all examined genes was in the order PRDX1> PRDX3> PRDX6> SRXN1> PRDX2> PRDX4> PRDX5. Among the most upregulated genes was the PRDX1, which was overexpressed by 10.1029-fold (p = 0.000634). SM-exposed individuals demonstrated expression of PRDX3 4.6231 (p = 0.000134), PRDX6 3.4964 (p = 0.001102), SRXN1 3.3719 (p < 0.0001) and PRDX2 2.7725-folds (p = 0.000383) higher than those of controls that reveal. Upregulation of PRDXs and SRXN1 genes may be because of reactive oxygen species (ROS) production and OS in lung tissue of patients after SM exposure. Expression of SRXN1 and PRDXNs genes, especially I, II, III, and VI is increased in SM-injured lungs, suggesting the induction of cellular responses to increased production of ROS and OS in lung of the patients. Therefore, sulfiredoxin and peroxiredoxins can be targeted as biomarkers of OS in these patients.

  7. Are generic and disease-specific health related quality of life correlated? The case of chronic lung disease due to sulfur mustard

    Directory of Open Access Journals (Sweden)

    Shervin Assari

    2009-09-01

    Full Text Available

    • BACKGROUND: The aim of this study was to investigate the association between the two most commonly used generic and disease specific health-related quality of life (HRQoL measures in patients with chronic lung disease due to SM: Medical Outcomes Study Short Form 36-Item (SF-36 and St George's Respiratory Questionnaire (SGRQ.
    • METHODS: This is a secondary analysis of Iranian Chemical Warfare Victims Health Assessment Study (ICWVHAS during October 2007 in Isfahan, Iran. In that survey, conducted in an outpatient setting, 292 patients with chronic lung disease due to SM were selected from all provinces in Iran. The total score and sub scores of correlations of SGRQ and SF-36 were assessed. Correlation of quality-of-life scores were evaluated using Pearson’s coefficient.
    • RESULTS: Samples were 276 patients who were selected for our analysis. No significant correlation was found between the total score or sub scores of SF-36 and the total score or sub scores of SGRQ (p > 0.05.
    • CONCLUSIONS: In patients with chronic lung disease due to SM, the SF-36 and SGRQ assess different aspects of HRQoL. Therefore applying both of them together, at least in the research setting is suggested.
    • KEYWORDS: Chronic Lung Disease, Health Related Quality of Life, Generic Health Related Quality of Life, Disease Specific Health Related Quality of Life, Sulfur Mustard.

  8. Evaluation of Association Between the Serum Levels of MMP-9 and MMP-9/TIMPs With Soluble Forms of Selectins and Itching Induced by Sulfur Mustard

    Science.gov (United States)

    Askari, Nayere; Ghazanfari, Tooba; Naghizadeh, Mohammad Mehdi; Moin, Athar; Khamesipour, Ali; Pourfarzam, Shahryar; Hassan, Zuhair Mohammad

    2017-01-01

    Background & objective: Pruritus is the most frequent chronic dermal complication of sulfur mustard (SM), which negatively influences the quality of life. Exact pathophysiology of SM-induced itching is unknown. The current study aimed at evaluating the possible association between SM-induced itching and the serum levels of matrix metalloproteinase (MMP)-9 and their endogenous inhibitors, and serum levels of soluble forms of selectins (sL-, sP-, and sE-selectins) as adhesion molecules involved in the development of different inflammatory reactions. Methods: Serum levels of MMP-9, MMP-9/ tissue inhibitors of metalloproteinases (TIMPs), and selectins were measured by the enzyme-linked immunosorbent assay (ELISA), and compared between the groups (n=368) with and without itching, and matched control groups (n=126). Results: Serum levels of MMP-9 were significantly higher in the SM exposed group with itching, compared with that of the group without itching (medians: 894 and 624 pg/mL respectively; P-value =0.034). There was no relationship between the serum levels of MMP-9/TIMP-1, MMP-9/TIMP-2, MMP-9/TIMP-4, and itching in the patients exposed to SM. Median serum levels of sE- and sL-selectins in the exposed group with itching were higher than those of the exposed group without itching. These differences were statistically insignificant (P-values =0.084 and 0.095, respectively). Conclusion: According to the results of the current study, the increased serum levels of MMP-9 and selectins 20 years after exposure may play role in the pathogenesis and persistence of SM-induced itching in the exposed individuals. PMID:29531551

  9. The effect of Zataria multiflora on pulmonary function tests, hematological and oxidant/antioxidant parameters in sulfur mustard exposed veterans, a randomized doubled-blind clinical trial.

    Science.gov (United States)

    Khazdair, Mohammad Reza; Rajabi, Omid; Balali-Mood, Mahdi; Beheshti, Farimah; Boskabady, Mohammad Hossein

    2018-03-01

    Sulfur mustard is an alkylating agent which cause to short and long term incapacitations on various organs including lung. There is no definite treatment for lung disorders induced by SM exposure. In the present study, the preventive effect of Zataria multiflora (Z. multiflora) on hematological parameters, oxidant/antioxidant markers and pulmonary function tests (PFT) in veterans, 27-30 years after exposed to SM were studied. Forty seven veterans allocated to three groups included: placebo group (P) and two groups treated with 5 and 10 mg/kg/day of Z. multiflora (Zat 5 and Zat 10). Drugs were prescribed in a double-blind manner for two months. Total and different WBC, hematological indices, oxidant/antioxidant markers and PFT values included; force vital capacity (FVC) and peak expiratory flow (PEF) were assessed at the beginning (step 0), one and two month (step I and II, respectively) after starting treatment. Total and different white blood cell in Zat 5 and 10 mg/kg treated groups in Step I and II were significantly decreased compared to Step 0 (p < 0.05 to p < 0.001). The levels of thiol, superoxide dismutase (SOD) and catalase (CAT) in Zat 5 and 10 mg/kg treated groups in step I and II were significantly increased (p < 0.05 to p < 0.001) but the level of malondialdehyde (MDA) significantly decreased in two treatment groups compared to Step 0 (p < 0.05 and p < 0.001 respectively). FVC and PEF values were significant increase in Zat 5 and 10 mg/kg treated groups in step I and II compared to step 0 (p < 0.05 to p < 0.001). Furthermore, FVC and PEF values in Zat 5 mg/kg were also increased in step II compared to step I (p < 0.01 for both). The percentage improvement of total and differential WBC, oxidant/antioxidant markers, FVC and PEF values during two moth treatment period significantly improved in the treated groups compared to the placebo group. Z. multiflora reduces inflammatory cells and oxidant biomarkers

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

    Science.gov (United States)

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

    2011-03-15

    Sulfur mustard, an agent used in chemical warfare, is an alkylating substance with carcinogenic potential. However, the precise long-term carcinogenic effects of mustard gas are unclear. Since 1952, the authors have conducted health surveys of former workers who were employed from 1929 to 1945 in a poisonous gas factory in Okuno-jima, Hiroshima, Japan. This prospective study was undertaken from 1952 to 2005 to examine the incidence of lung cancer among the workers who were exposed to mustard gas (n=480), lewisite (n=55), and/or diphenylcyanarsine (n=178), as well as the incidence among unexposed workers (n=969). The stochastic relation between exposure and lung cancer was explored on the basis of multistage carcinogenesis by using an accelerated hazard model with a transformed age scale. Mustard gas exposure was found to transform the age scale for developing lung cancer. One year of exposure in subjects ≤18 or >18 years old at first exposure shifted the age scale down by 4.9 years and 3.3 years, respectively. On the basis of the long-term follow-up of former workers in the poisonous gas factory, the authors concluded that sulfur mustard decreased the age at which people were at risk of developing lung cancer and that the effect declined with aging. © The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.

  11. Acidithiobacillus caldus sulfur oxidation model based on transcriptome analysis between the wild type and sulfur oxygenase reductase defective mutant.

    Directory of Open Access Journals (Sweden)

    Linxu Chen

    Full Text Available Acidithiobacillus caldus (A. caldus is widely used in bio-leaching. It gains energy and electrons from oxidation of elemental sulfur and reduced inorganic sulfur compounds (RISCs for carbon dioxide fixation and growth. Genomic analyses suggest that its sulfur oxidation system involves a truncated sulfur oxidation (Sox system (omitting SoxCD, non-Sox sulfur oxidation system similar to the sulfur oxidation in A. ferrooxidans, and sulfur oxygenase reductase (SOR. The complexity of the sulfur oxidation system of A. caldus generates a big obstacle on the research of its sulfur oxidation mechanism. However, the development of genetic manipulation method for A. caldus in recent years provides powerful tools for constructing genetic mutants to study the sulfur oxidation system.An A. caldus mutant lacking the sulfur oxygenase reductase gene (sor was created and its growth abilities were measured in media using elemental sulfur (S(0 and tetrathionate (K(2S(4O(6 as the substrates, respectively. Then, comparative transcriptome analysis (microarrays and real-time quantitative PCR of the wild type and the Δsor mutant in S(0 and K(2S(4O(6 media were employed to detect the differentially expressed genes involved in sulfur oxidation. SOR was concluded to oxidize the cytoplasmic elemental sulfur, but could not couple the sulfur oxidation with the electron transfer chain or substrate-level phosphorylation. Other elemental sulfur oxidation pathways including sulfur diooxygenase (SDO and heterodisulfide reductase (HDR, the truncated Sox pathway, and the S(4I pathway for hydrolysis of tetrathionate and oxidation of thiosulfate in A. caldus are proposed according to expression patterns of sulfur oxidation genes and growth abilities of the wild type and the mutant in different substrates media.An integrated sulfur oxidation model with various sulfur oxidation pathways of A. caldus is proposed and the features of this model are summarized.

  12. Acidithiobacillus caldus sulfur oxidation model based on transcriptome analysis between the wild type and sulfur oxygenase reductase defective mutant.

    Science.gov (United States)

    Chen, Linxu; Ren, Yilin; Lin, Jianqun; Liu, Xiangmei; Pang, Xin; Lin, Jianqiang

    2012-01-01

    Acidithiobacillus caldus (A. caldus) is widely used in bio-leaching. It gains energy and electrons from oxidation of elemental sulfur and reduced inorganic sulfur compounds (RISCs) for carbon dioxide fixation and growth. Genomic analyses suggest that its sulfur oxidation system involves a truncated sulfur oxidation (Sox) system (omitting SoxCD), non-Sox sulfur oxidation system similar to the sulfur oxidation in A. ferrooxidans, and sulfur oxygenase reductase (SOR). The complexity of the sulfur oxidation system of A. caldus generates a big obstacle on the research of its sulfur oxidation mechanism. However, the development of genetic manipulation method for A. caldus in recent years provides powerful tools for constructing genetic mutants to study the sulfur oxidation system. An A. caldus mutant lacking the sulfur oxygenase reductase gene (sor) was created and its growth abilities were measured in media using elemental sulfur (S(0)) and tetrathionate (K(2)S(4)O(6)) as the substrates, respectively. Then, comparative transcriptome analysis (microarrays and real-time quantitative PCR) of the wild type and the Δsor mutant in S(0) and K(2)S(4)O(6) media were employed to detect the differentially expressed genes involved in sulfur oxidation. SOR was concluded to oxidize the cytoplasmic elemental sulfur, but could not couple the sulfur oxidation with the electron transfer chain or substrate-level phosphorylation. Other elemental sulfur oxidation pathways including sulfur diooxygenase (SDO) and heterodisulfide reductase (HDR), the truncated Sox pathway, and the S(4)I pathway for hydrolysis of tetrathionate and oxidation of thiosulfate in A. caldus are proposed according to expression patterns of sulfur oxidation genes and growth abilities of the wild type and the mutant in different substrates media. An integrated sulfur oxidation model with various sulfur oxidation pathways of A. caldus is proposed and the features of this model are summarized.

  13. Two Lung Cancer Development-Related Genes, Forkhead Box M1 (FOXM1) and Apolipoprotein E (APOE), are overexpressed in Bronchial of Patients after Long-Term Exposure to Sulfur Mustard.

    Science.gov (United States)

    Tahmasbpour, Eisa; Ghanei, Mostafa; Panahi, Yunes

    2017-01-01

    Sulfur mustard (SM) is a strong alkylating and mutagenic compound that targets human airway system. We considered the expression of Forkhead box M1 ( FOXM1 ) and apolipoprotein E ( APOE ) genes, which are responsible for cell proliferation, differentiation, tumorigenesis, and increased risk of lung cancer, in the lung bronchial tissue of patients exposed to SM. After performing pulmonary functional tests (PFTs), 11 human subjects (five controls and six SM-exposed patients) were entered in this study. Total RNA were extracted from all biopsy samples and then cDNA was synthesised for each specimen using RT-PCR. Changes in gene expression were measured using a RT 2 Profiler ™PCR Array. PFTs have demonstrated more obstructive and restrictive spirometric patterns among patients compared to the controls. A higher expression was recorded for both examined genes in bronchial of SM-exposed patients. Expression of FOXM1 and APOE genes in bronchial of the patients was significantly ( p < 0.001) overexpressed by 14.8316 and 3.9504-folds, respectively. Mustard lungs were associated with increased expression of FOXM1 and APOE genes, which suggests an increased risk of lung cancer among these patients. Since FOXM1 and APOE are considered as oxidative stress responsive genes, we speculate that increased expression of these genes is more likely linked to overproduction of reactive oxygen species (ROS) and oxidative stress (OS) in mustard lungs. Further studies are required at protein level among SM-exposed patients with lung cancer to use these genes as lung cancer biomarkers among these patients.

  14. Caustic Hydrolysis of Sulfur Mustard

    National Research Council Canada - National Science Library

    Harvey, Steven

    1997-01-01

    The reactions of HD with aqueous calcium hydroxide and aqueous sodium hydroxide were investigated with respect to their potential applicability to a neutralization-based chemical demilitarization process...

  15. Complications and Carcinogenic Effects of Mustard Gas--a Systematic Review and Meta-Analysis in Iran.

    Science.gov (United States)

    Panahi, Yunes; Gholami, Nasrin; Ghojazadeh, Morteza; Moslemi, Farnaz; Naghavi-Behzad, Mohammad; Azami-Aghdash, Saber; Ghaffari, Alireza; Piri, Reza

    2015-01-01

    Catastrophic effects of mustard gas as a chemical warfare agent have always been a major problem for those exposed to this agent. In this meta-analysis it was tried to evaluate carcinogenesis, ocular, cutaneous and respiratory complications of mustard gas exposure among Iranians who had been exposed to this agent during the Iran-Iraq war. In this meta-analysis, the required data were collected using keywords "mustard gas", "sulfur mustard", "cancer", "neoplasm", "respiratory complications", "ocular complications" , "lung disease", "chronic complication", "eye", "skin", "cutaneous complication", "carcinogenesis" and their combination with keywords "Iran", "Iranian", "prevalence", "mortality" and their Farsi equivalent terms from the databases of SID, Iranmedex, Magiran, Pubmed, Science Direct, Google Search engine, Gray Literature and Reference of References. To determine the prevalence of each complication and perform meta-analysis, CMA: 2 (Comprehensive Meta-Analysis) software with a randomized model was used. Of the 542 articles found, 7 national articles, consistent with the aims of this study were selected. Meta- analysis of seven papers revealed that cancer risk, especially cancer of the respiratory system was elevated, so that the relative risk (RR) of cancer role of mustard gas was inconsistent from 2/1 to 4 in this survey. Also prevalence of delayed skin disorders due to sulfur mustard was 94.6%, pulmonary complications 94.5% and ocular complications 89.9%. The incidence of various cancers in victims exposed to mustard gas was 1.7% worldwide where the rate was 2.2% in Iranian victims of the Iraq-Iran war. Based on present study the prevalence of delayed mustard gas related cutaneous, pulmonary and ocular complications is above 90% and risk of carcinogenesis is higher in comparison to worldwide statistics. This may suggest need for long-term and persistent follow-up and rehabilitation procedures for populations exposed to this agent.

  16. Multiphysics Modelling of Sodium Sulfur Battery

    Science.gov (United States)

    Mason, Jerry Hunter

    Due to global climate change and the desire to decrease greenhouse gas emissions, large scale energy storage has become a critical issue. Renewable energy sources such as wind and solar will not be a viable energy source unless the storage problem is solved. One of the practical and cost effective solutions for this problem is sodium sulfur batteries. These batteries are comprised of liquid electrode materials suspended in porous media and operate at relatively high temperatures (>300°C). The sodium anode and the sulfur/sodium-polysulfide cathode are separated by a solid electrolyte made of beta-alumina or NASICON material. Due to the use of porous materials in the electrodes, capillary pressure and the combination of capillary action and gravity become important. Capillary pressure has a strong dependence on the wetting phase (liquid electrode material) saturation; therefore sharp concentration gradients can occur between the inert gas and the electrode liquid, especially within the cathode. These concentration gradients can have direct impacts on the electrodynamics of the battery as they may produce areas of high electrical potential variation, which can decrease efficiency and even cause failures. Then, thermal management also becomes vital since the electrochemistry and material properties are sensitive to temperature gradients. To investigate these phenomena in detail and to attempt to improve upon battery design a multi-dimensional, multi-phase code has been developed and validated in this study. Then a porous media flow model is implemented. Transport equations for charge, mass and heat are solved in a time marching fashion using finite volume method. Material properties are calculated and updated as a function of time. The porous media model is coupled with the continuity equation and a separate diffusion equation for the liquid sodium in the melt. The total mass transport model is coupled with charge transport via Faraday's law. Results show that

  17. A robust high-throughput sample preparation and liquid chromatography/tandem mass spectrometry method for the quantitation of β-lyase metabolites of sulfur mustard as 1,1'-sulfonylbis-[2-(methylthio)ethane] in human urine.

    Science.gov (United States)

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

    2013-05-30

    Sulfur mustard (HD) is a major chemical warfare agent threat to humans. Since World War I, several incidents of human exposure to sulfur mustard have been reported. In order to assist health professionals during an exposure event and support biological monitoring, a rapid analytical method is required to measure the exposure of humans to HD. The β-lyase metabolites of HD, 1-methylsulfinyl-2-[2-(methylthio)ethylsulfonyl]ethane (MSMTESE) and 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] (SBMSE) were reduced to the single biomarker, 1,1'-sulfonylbis-[2-(methylthio)ethane] (SBMTE), using titanium(III) chloride. High-throughput sample preparation was performed on a Tecan Freedom EVO liquid handler and analysis was performed by electrospray ionization liquid chromatography and tandem mass spectrometry (LC/MS/MS) in the multiple-reaction monitoring mode. Each analytical run consisted of a matrix blank, calibration standards (0.1-100 ng/mL), low quality controls (QCs), 2.5 ng/mL, and high QCs, 25.0 ng/mL, of SBMTE in human urine. The method was validated with 20 analytical runs performed by four analysts. The mean calculated concentrations of the low and high QCs were 2.52 and 25.5 ng/mL with relative standard deviations of 3.6% and 2.3%, respectively. This semi-automated method has few manual transfer steps, thus minimizing common manual errors and saving time. Therefore, this method would be very helpful to responding laboratories in a large-scale exposure event related to HD. Copyright © 2013 John Wiley & Sons, Ltd.

  18. Sulfur self-retention in ash a grain model approach

    Directory of Open Access Journals (Sweden)

    Manović Vasilije

    2002-01-01

    Full Text Available A developed overall model for sulfur self-retention in ash during coal particle combustion is presented in the paper. The total sulfur content in char, after devolatilization, is evaluated using a derived correlation. It is assumed that sulfur retention during char combustion occurs due to the reaction between SO2 and the active part of the Ca in the form of uniformly distributed CaO grains. Parametric analysis shows that the process is limited by solid diffusion through the product layer formed on the CaO grains and that the most important coal characteristics which influence sulfur self-retention are coal rank, content of sulfur forms, molar Ca/S ratio and particle radius. The model predicts relatively well the levels of the experimentally obtained values of SSR efficiencies, as well as the influence of temperature, particle size and the surrounding conditions.

  19. Sulfur deposition simulations over China, Japan, and Korea: a model intercomparison study for abating sulfur emission.

    Science.gov (United States)

    Kim, Cheol-Hee; Chang, Lim-Seok; Meng, Fan; Kajino, Mizuo; Ueda, Hiromasa; Zhang, Yuanhang; Son, Hye-Young; Lee, Jong-Jae; He, Youjiang; Xu, Jun; Sato, Keiichi; Sakurai, Tatsuya; Han, Zhiwei; Duan, Lei; Kim, Jeong-Soo; Lee, Suk-Jo; Song, Chang-Keun; Ban, Soo-Jin; Shim, Shang-Gyoo; Sunwoo, Young; Lee, Tae-Young

    2012-11-01

    In response to increasing trends in sulfur deposition in Northeast Asia, three countries in the region (China, Japan, and Korea) agreed to devise abatement strategies. The concepts of critical loads and source-receptor (S-R) relationships provide guidance for formulating such strategies. Based on the Long-range Transboundary Air Pollutants in Northeast Asia (LTP) project, this study analyzes sulfur deposition data in order to optimize acidic loads over the three countries. The three groups involved in this study carried out a full year (2002) of sulfur deposition modeling over the geographic region spanning the three countries, using three air quality models: MM5-CMAQ, MM5-RAQM, and RAMS-CADM, employed by Chinese, Japanese, and Korean modeling groups, respectively. Each model employed its own meteorological numerical model and model parameters. Only the emission rates for SO(2) and NO(x) obtained from the LTP project were the common parameter used in the three models. Three models revealed some bias from dry to wet deposition, particularly the latter because of the bias in annual precipitation. This finding points to the need for further sensitivity tests of the wet removal rates in association with underlying cloud-precipitation physics and parameterizations. Despite this bias, the annual total (dry plus wet) sulfur deposition predicted by the models were surprisingly very similar. The ensemble average annual total deposition was 7,203.6 ± 370 kt S with a minimal mean fractional error (MFE) of 8.95 ± 5.24 % and a pattern correlation (PC) of 0.89-0.93 between the models. This exercise revealed that despite rather poor error scores in comparison with observations, these consistent total deposition values across the three models, based on LTP group's input data assumptions, suggest a plausible S-R relationship that can be applied to the next task of designing cost-effective emission abatement strategies.

  20. in Patients with Mustard Lung

    Directory of Open Access Journals (Sweden)

    ShahrzadM Lari

    2013-05-01

    Full Text Available   Introduction: Chronic Obstructive Pulmonary Disease (COPD secondary to sulfur mustard exposure, known as mustard lung, is an important late pulmonary complication. The BODE (Body mass index, Obstruction, Dyspnea, and Exercise index has been established as a valuable tool for determining the adverse consequences of COPD. The aim of this study was to evaluate the role of the BODE index in patients with mustard lung.   Materials and Methods: Eighty-two consecutively stable patients with mustard lung with all levels of severity were entered this study. The following parameters were recorded in all patients: standard spirometry, pulse oximetry, health-related quality of life, the BODE index. Additionally, the severity of COPD was determined by GOLD (Global initiative for chronic Obstructive Lung Disease staging. The correlation of the BODE index with pulmonary parameters was determined. Results: The mean age of the patients was 47.30±7.08 SD years. The mean BODE index was 3.16±2.25 SD. There was a statistically significant inverse correlation between the BODE index and oxygen saturation (r=-0.30, p=0.007. Also a statistically significant correlation was found between the BODE index and quality of life (r=0.80, p=0.001. The BODE index was not correlated with age of the patients and duration of disease. Conclusions: The results of this study showed that the BODE index is correlated with important clinical parameters and can be used in clinical practice

  1. SOME IMMUNOLOGICAL CHARACTERISTICS IN MUSTARD EXPOSED PATIENTS

    Directory of Open Access Journals (Sweden)

    M ADIB

    2001-06-01

    Full Text Available Introduction. Mutagenesis, carsinogenesis and cytotoxicity effects on body tissues are side effects of sulfur mustard which in turn, causes the bone marrow and lymphoid system dysfunction. Previous investigation in 31 Iranian chemical casualties, indicated the presence of persistant atypical lymphocytes and the decrease of T lymphocyte subsets and surface markers. The present study was performed to evaluate the changes of B lymphocyte surface markers in the above mentioned group and compare the changes with two other control groups. Methods.The first control group consisted of 30 chemical casaulities with the same clinical conditions and the same history of exposure to mustard but absence of atypical lymphocytes in their blood, and the second control group were consisted of 30 completely normal indivduals. Monoclonal antibodies congugated to fluoroscein isothiocyanate were used to determine B lymphocyte markers.The monoclonal antibodies used in this study were against human immunoglobuline δ and µ heavy chain, λ and κ light chains, anti human HLADR and anti human CD10. The tests were performed on 100 ml of peripheral blood, using flow cytometer model EPICS®XL. Results. In comparsion with normal controls, k and λ light chains showed a significant decrease (P < 0.001 while HLADR showed a significant increase (P < 0.001 in the two groups of poison gas injury. No significant difference could be seen in µ and δ chain. Two patients of victims group with atypical lymphocytes were CD10 positive. Discussion. Results of this investigation on B lymphocyte markers, suggests the increasing risk of neoplasuc or Iymphopro fife rative disorder with B cell origin, in chemical casaulties with mustard gas.

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

    Science.gov (United States)

    2010-07-01

    ... effects of exposure to mustard gas and Lewisite. 3.316 Section 3.316 Pensions, Bonuses, and Veterans... mustard gas and Lewisite. (a) Except as provided in paragraph (b) of this section, exposure to the... connection for that condition: (1) Full-body exposure to nitrogen or sulfur mustard during active military...

  3. An Updated Gas/grain Sulfur Network for Astrochemical Models

    Science.gov (United States)

    Laas, Jacob; Caselli, Paola

    2017-06-01

    Sulfur is a chemical element that enjoys one of the highest cosmic abundances. However, it has traditionally played a relatively minor role in the field of astrochemistry, being drowned out by other chemistries after it depletes from the gas phase during the transition from a diffuse cloud to a dense one. A wealth of laboratory studies have provided clues to its rich chemistry in the condensed phase, and most recently, a report by a team behind the Rosetta spacecraft has significantly helped to unveil its rich cometary chemistry. We have set forth to use this information to greatly update/extend the sulfur reactions within the OSU gas/grain astrochemical network in a systematic way, to provide more realistic chemical models of sulfur for a variety of interstellar environments. We present here some results and implications of these models.

  4. Performance and cost models for the direct sulfur recovery process. Task 1 Topical report, Volume 3

    Energy Technology Data Exchange (ETDEWEB)

    Frey, H.C. [North Carolina State Univ., Raleigh, NC (United States); Williams, R.B. [Carneigie Mellon Univ., Pittsburgh, PA (United States)

    1995-09-01

    The purpose of this project is to develop performance and cost models of the Direct Sulfur Recovery Process (DSRP). The DSRP is an emerging technology for sulfur recovery from advanced power generation technologies such as Integrated Gasification Combined Cycle (IGCC) systems. In IGCC systems, sulfur present in the coal is captured by gas cleanup technologies to avoid creating emissions of sulfur dioxide to the atmosphere. The sulfur that is separated from the coal gas stream must be collected. Leading options for dealing with the sulfur include byproduct recovery as either sulfur or sulfuric acid. Sulfur is a preferred byproduct, because it is easier to handle and therefore does not depend as strongly upon the location of potential customers as is the case for sulfuric acid. This report describes the need for new sulfur recovery technologies.

  5. High throughput quantitative analysis of the β-lyase sulfur mustard metabolite, 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] in urine via high performance liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Bevan, Martin J; Wogen, Matthew T; Lunda, Mark D; Saravia, Stefan A

    2017-04-15

    Sulfur Mustard (HD) has a 100year history of use as a chemical warfare agent and recent events in the Middle East are causing it to once again be a potential concern. We report a new high-throughput method for the determination of HD exposure by the analysis of the β-lyase metabolite 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] (SBMSE) in human urine. This method features a hydrogen peroxide (H 2 O 2 ) oxidative conversion of the β-lyase metabolites to SBMSE, followed by sample extraction and concentration using solid phase extraction in 96-well plate format. Subsequent high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) analysis gave linear quantitation over a calibration range of 0.1-100ng/mL, with a method detection limit of 0.03ng/mL. Liquid chromatographic separation was achieved using a hydrophilic interaction liquid chromatography (HILIC) column with an analyte retention time of 0.9min and method time of 1.5min (cycle time=2.0min). Users of this method could prepare and analyze approximately 650 samples in 24h which would be important for an emergency response. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  7. The Respiratory Toxicities of Mustard Gas

    Directory of Open Access Journals (Sweden)

    Mostafa Ghanei

    2010-12-01

    Full Text Available Sulfur mustard is one of the major potent chemical warfareagents. It was widely used against not only military personnelbut also civilian people of Iran during the last years (1984–1988 of the Iraq–Iran war. A number of studies were performedregarding the acute and long-term consequences ofsulfur mustard on respiratory system. Currently, many aspectsof leading respiratory disorder that was prescribed as “mustardlung” have been revealed. However, there is growing concernabout pathophysiological mechanisms behind the mustardlung. Herein available published materials about mustard lungare summarized, and it has been tried to highlight practicalpoints relevant to the diagnosis and treatment of the disease.Iran J Med Sci 2010; 35(4: 273-280.

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

    Science.gov (United States)

    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. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Abel, E.L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); Boulware, S. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); Fields, T.; McIvor, E.; Powell, K.L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); DiGiovanni, J.; Vasquez, K.M. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); MacLeod, M.C., E-mail: mcmacleod@mdanderson.org [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States)

    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.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    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.

  11. Determination of hydrolysis products of sulfur mustards by reversed-phase microcolumn liquid chromatography coupled on-line with sulfur flame photometric detection and electrospray ionization mass spectrometry using large-volume injections and peak compression

    NARCIS (Netherlands)

    Hooijschuur, E.W.J.; Kientz, C.E.; Hulst, A.G.; Brinkman, U.A.T.

    2000-01-01

    On-line coupling of reversed-phase microcolumn liquid chromatography (micro-RPLC) and sulfur-selective flame photometric detection (S-FPD) was studied for the selective and direct determination of thiodiglycol, bis(2- hydroxyethylthio)methane, 1,2-bis(2-hydroxyethylthio)ethane, 1,3-bis(2-

  12. Sulfur Deactivation of NOx Storage Catalysts: A Multiscale Modeling Approach

    Directory of Open Access Journals (Sweden)

    Rankovic N.

    2013-09-01

    Full Text Available Lean NOx Trap (LNT catalysts, a promising solution for reducing the noxious nitrogen oxide emissions from the lean burn and Diesel engines, are technologically limited by the presence of sulfur in the exhaust gas stream. Sulfur stemming from both fuels and lubricating oils is oxidized during the combustion event and mainly exists as SOx (SO2 and SO3 in the exhaust. Sulfur oxides interact strongly with the NOx trapping material of a LNT to form thermodynamically favored sulfate species, consequently leading to the blockage of NOx sorption sites and altering the catalyst operation. Molecular and kinetic modeling represent a valuable tool for predicting system behavior and evaluating catalytic performances. The present paper demonstrates how fundamental ab initio calculations can be used as a valuable source for designing kinetic models developed in the IFP Exhaust library, intended for vehicle simulations. The concrete example we chose to illustrate our approach was SO3 adsorption on the model NOx storage material, BaO. SO3 adsorption was described for various sites (terraces, surface steps and kinks and bulk for a closer description of a real storage material. Additional rate and sensitivity analyses provided a deeper understanding of the poisoning phenomena.

  13. Mucilage in Yellow Mustard (Brassica Hirta) Seeds

    OpenAIRE

    Siddiqui, I. R.; Yiu, S. H.; Jones, J. D.; Kalab, M.

    1986-01-01

    Release of mucilage from yellow mustard (brassica hirta, also known as Sinapis alba) seed coats (hulls) was studied by optical and scanning electron microscopy. Micrographs were obtained of the mucilage which had exuded from briefly moistened seeds and dried subsequently in the form of small droplets on the seed surface. The mucilage collected from the seed surface and mucilage isolated on a larger scale from seed hulls was hydrolyzed with sulfuric acid and the hydrolyzates were analyzed f...

  14. Atmospheric sulfur and climate changes: a modelling study at mid and high-southern latitudes

    International Nuclear Information System (INIS)

    Castebrunet, H.

    2007-09-01

    The mid and high-southern latitudes are still marginally affected by anthropogenic sulfur emissions. They are the only regions in the world where the natural cycle of the atmospheric sulfur may still be observed. Sulfur aerosols are well-known for their radiative impact, and thus interact with climate. Climate can in turn affect atmospheric sulfur sources, distribution and chemistry. Antarctic ice cores provide information on the evolution of climate and sulfur deposition at the surface of the ice sheet at glacial-interglacial time scales. The aim of this thesis is to develop and use modeling towards a better understanding of the atmospheric sulfur cycle in antarctic and sub-antarctic regions. Ice core data are used to validate model results under glacial climate conditions. An Atmospheric General Circulation Model (AGCM) coupled to a sulfur chemistry module is used: the LMD-ZTSulfur model, version 4. An update of both the physical and chemical parts of the model. The model was first performed. The impact of there changes on modelled sulfur cycle are evaluated for modern climate. Further, boundary conditions are adapted to simulate the atmospheric circulation and sulfur cycle at the Last Glacial Maximum, approximately 20,000 years ago. In the model, sulfur is found to be highly sensitive to antarctic sea-ice coverage, which is still poorly known during the ice age. An original dataset of ice-age sea-ice coverage was developed. Its impact on the oceanic emissions of dimethyl sulfide, main precursor of sulfur aerosols at high-southern latitudes, is discussed. Using the same oceanic sulfur reservoirs as for present day climate, the model broadly reproduces the glacial deposits of sulfur aerosols on the Antarctic plateau, suggesting little impact of climate on oceanic sulfur production in the Antarctic region. Sensitivity tests were carried out to draw an up-to-date status of major uncertainties and difficulties facing future progress in understanding atmospheric

  15. Mustard gas exposure and carcinogenesis of lung.

    Science.gov (United States)

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

    2009-08-01

    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. 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. 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. 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.

  16. 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.

    Science.gov (United States)

    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

  17. New Approaches towards the Elucidation of Epidermal-Dermal Separation in Sulfur Mustard-Exposed Human Skin and Directions for Therapy

    National Research Council Canada - National Science Library

    Mol, Marijke

    2005-01-01

    .... Results of experiments with a human skin ex vivo model show that apoptosis and metalloprotease activity are key elements in HD-induced skin pathogenesis, and that intervention in these two processes...

  18. Contact Hwersensitaity to Mustard Khal and Mustard Oil

    Directory of Open Access Journals (Sweden)

    J S Pasricha

    1985-01-01

    Full Text Available This report describes 2 females patients having contact dermatitis due to mustard khal the residue of,mustard seeds after the oil hasbeen extracted out. The dermatitis was caused by mbdng mustard khal with the cattle feed and was occurring on the hands and forearms, though the face, ear lobules and neck were also mvolved because of the practice of applying mustard oil on the hair. Patch tests were positive with the mustard khal and its fractionation products in both the patients and with mustard oil in one patient.

  19. Aromatic sulfonation with sulfur trioxide: mechanism and kinetic model.

    Science.gov (United States)

    Moors, Samuel L C; Deraet, Xavier; Van Assche, Guy; Geerlings, Paul; De Proft, Frank

    2017-01-01

    Electrophilic aromatic sulfonation of benzene with sulfur trioxide is studied with ab initio molecular dynamics simulations in gas phase, and in explicit noncomplexing (CCl 3 F) and complexing (CH 3 NO 2 ) solvent models. We investigate different possible reaction pathways, the number of SO 3 molecules participating in the reaction, and the influence of the solvent. Our simulations confirm the existence of a low-energy concerted pathway with formation of a cyclic transition state with two SO 3 molecules. Based on the simulation results, we propose a sequence of elementary reaction steps and a kinetic model compatible with experimental data. Furthermore, a new alternative reaction pathway is proposed in complexing solvent, involving two SO 3 and one CH 3 NO 2 .

  20. Evaluation of JAK2 (V617F Mutation in Iranian Veterans with Delayed Complications of Sulphur Mustard Poisoning

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Keramati

    2016-06-01

    Full Text Available Background: Sulfur mustard was the most widely applied chemical warfare agent by the Iraqi army in Iran–Iraq war (1983-1988. Considering the role of sulfur mustard toxicity in hematopoietic neoplasms and also new role of JAK2 mutation in these neoplasms, we assessed this mutation and delayed hematologic complications in veterans exposed to sulfur mustard. Methods: This case control study was performed in Mashhad University of Medical Sciences, Mashhad, Iran in collaboration with Janbasan Foundation of Khorasan Razavi, Iran in 2012. The case group consists of 42 patients who exposed to sulfur mustard about 30 yr ago and the control group includes 30 healthy persons. For all subjects complete blood counts and ARMSpolymerase chain reaction for JAK2 (V617F mutation was carried out. Data were analyzed by statistical software using independent sample t-testand Mann- Whitney U test. Results: JAK2 (V617F mutation was detected, neither in the sulfur mustardveterans nor in the control group. Moreover no significant difference was detected in hematologic parameters between the two groups. Conclusion: Despite sulfur mustard can increase risk of tumor genesis especially hematologic neoplasms but this is probablyas result of other genetic mechanism apart from JAK2 mutation. Considering the health and importance of preventive measure for the sulfur mustard victims, we suggest other genetic aspects of tumor genesis to be assessed in these patients.

  1. Medical Management of Cutaneous Sulfur Mustard Injuries

    Science.gov (United States)

    2009-01-01

    negative pressure, (2) Amino-Plex® Spray (biO2 Cosmeceuticals International, Inc., Beverly Hills, CA), a nutritive cosmeceutical product that is...such as vitiligo and discoid lupus rthematosis than the general population (Balali-Mood andHefazi, 006; Hafazi et al., 2006). Lower incidences of...Inc., Beverly Hills, CA) is a nutritive cosmeceutical product that is designed to increase oxygen in cells, stimulate ATP synthesis, improve glucose

  2. Mustard gas exposure in Iran-Iraq war - A scientometric study.

    Science.gov (United States)

    Nokhodian, Zary; ZareFarashbandi, Firoozeh; Shoaei, Parisa

    2015-01-01

    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. 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. 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. 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.

  3. Contact Hwersensitaity to Mustard Khal and Mustard Oil

    OpenAIRE

    J S Pasricha; Ramji Gupta; S K Gupta

    1985-01-01

    This report describes 2 females patients having contact dermatitis due to mustard khal the residue of,mustard seeds after the oil hasbeen extracted out. The dermatitis was caused by mbdng mustard khal with the cattle feed and was occurring on the hands and forearms, though the face, ear lobules and neck were also mvolved because of the practice of applying mustard oil on the hair. Patch tests were positive with the mustard khal and its fractionation products in both the patients and with must...

  4. An improved LTE model of a high pressure sulfur discharge

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, C W; Heijden, H W P van der; Hartgers, A; Garloff, K; Dijk, J van; Mullen, J J A M van der [Department of Applied Physics, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven (Netherlands)

    2004-01-21

    An existing LTE model (Johnston C W et al 2002 J. Phys. D: Appl. Phys. 35 342) of a high pressure sulfur discharge is improved upon by more accurate and complete treatment of each term in the energy balance. The simulation program PLASIMO (Janssen G M et al 1999 Plasma Sources Sci. Technol. 8 1, van Dijk J 2001 Modelling of plasma light sources: an object-oriented approach PhD Thesis Eindhoven University of Technology, The Netherlands, ISBN 90-386-1819-0), which is an integrated environment for construction and execution of plasma models, has been used to define and solve all aspects of the model. The electric field is treated as being dc, and the temperature dependent nature of species interactions is incorporated in determination of transport coefficients. In addition to the main radiative transition, B3{sup {sigma}}{sub g}{sup -}, several others in S{sub 2} are included. These are B''3{sup {pi}}{sub u} {yields} X3{sup {sigma}}{sub g}{sup -}, B'3{sup {pi}}{sub g} {yields} {l_brace}A3{sup {sigma}}{sub u}{sup +}, A'3{sup {delta}}{sub u}{r_brace} and e1{sup {pi}}{sub g} {yields} c1{sup {sigma}}{sub u}{sup -}. The S{sub 3} molecule is also included in the composition as an absorbing particle. Furthermore, radiation production is treated quantum mechanically. The principle improvement over the previous work is that both the position of the spectral maximum and the pressure shift are quantitatively described by the current model. Both are chiefly due to the presence of S{sub 3}.

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

    Science.gov (United States)

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

    2015-01-01

    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. 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. 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. 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.

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

    Directory of Open Access Journals (Sweden)

    Gila Pirzad Jahromi

    Full Text Available 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.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.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.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.

  7. Laboratory measurements and modeling of molecular photoabsorption in the ultraviolet for planetary atmospheres applications: diatomic sulfur and sulfur monoxide

    Science.gov (United States)

    Stark, Glenn

    2016-07-01

    Our research program comprises the measurement and modeling of ultraviolet molecular photoabsorption cross sections with the highest practical resolution. It supports efforts to interpret and model observations of planetary atmospheres. Measurement and modeling efforts on diatomic sulfur (S _{2}) and sulfur monoxide (SO) are in progress. S _{2}: Interpretations of atmospheric (Io, Jupiter, cometary comae) S _{2} absorption features are hindered by a complete lack of laboratory cross section data in the ultraviolet. We are working to quantify the photoabsorption spectrum of S _{2} from 240 to 300 nm based on laboratory measurements and theoretical calculations. We have constructed an experimental apparatus to produce a stable column of S _{2} vapor at a temperature of 800 K. High-resolution measurements of the absorption spectrum of the strong B - X system of S _{2} were completed using the NIST VUV-FTS at Gaithersburg, Maryland. These measurements are currently being incorporated into a coupled-channel model of the absorption spectrum of S _{2} to quantify the contributions from individual band features and to establish the mechanisms responsible for the strong predissociation signature of the B - X system. A successful coupled channels model can then be used to calculate the B - X absorption spectrum at any temperature. SO: There has been a long-standing need for high-resolution cross sections of sulfur monoxide radicals in the ultraviolet and vacuum ultraviolet regions, where the molecule strongly predissociates, for modeling the atmospheres of Io and Venus, and most recently for understanding sulfur isotope effects in the ancient (pre-O _{2}) atmosphere of Earth. We have produced a measurable column of SO in a continuous-flow DC discharge cell, using SO _{2} as a parent molecule. Photoabsorption measurements were recently recorded on the DESIRS beamline of the SOLEIL synchrotron, taking advantage of the high-resolution VUV-FTS on that beamline. A number of

  8. Thermal Behavior and Heat Generation Modeling of Lithium Sulfur Batteries

    DEFF Research Database (Denmark)

    Stroe, Daniel-Ioan; Knap, Vaclav; Swierczynski, Maciej Jozef

    2017-01-01

    Lithium Sulfur batteries are receiving a lot of research interest because of their intrinsic characteristics, such as very high energy density and increased safety, which make them a suitable solution for zero-emission vehicles and space application. This paper analyses the influence of the tempe......Lithium Sulfur batteries are receiving a lot of research interest because of their intrinsic characteristics, such as very high energy density and increased safety, which make them a suitable solution for zero-emission vehicles and space application. This paper analyses the influence...

  9. Breeding of oilseed mustard

    Indian Academy of Sciences (India)

    admin

    transcriptome sequencing using NGS. There are three major diseases in mustard – Alternaria blight, white rust and stem rot. Germplasm is available for white rust resistance and loci conferring resistance have been mapped. No germplasm is available within Brassica species for resistance to Alternaria and stem rot.

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

    Science.gov (United States)

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

    2011-01-01

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

  11. Pulmonary Complications of Mustard Gas Exposure: A Study on Cadavers

    Directory of Open Access Journals (Sweden)

    Behnam Behnoush

    2011-04-01

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

  12. Stoichiometric modeling of oxidation of reduced inorganic sulfur compounds (Riscs) in Acidithiobacillus thiooxidans.

    Science.gov (United States)

    Bobadilla Fazzini, Roberto A; Cortés, Maria Paz; Padilla, Leandro; Maturana, Daniel; Budinich, Marko; Maass, Alejandro; Parada, Pilar

    2013-08-01

    The prokaryotic oxidation of reduced inorganic sulfur compounds (RISCs) is a topic of utmost importance from a biogeochemical and industrial perspective. Despite sulfur oxidizing bacterial activity is largely known, no quantitative approaches to biological RISCs oxidation have been made, gathering all the complex abiotic and enzymatic stoichiometry involved. Even though in the case of neutrophilic bacteria such as Paracoccus and Beggiatoa species the RISCs oxidation systems are well described, there is a lack of knowledge for acidophilic microorganisms. Here, we present the first experimentally validated stoichiometric model able to assess RISCs oxidation quantitatively in Acidithiobacillus thiooxidans (strain DSM 17318), the archetype of the sulfur oxidizing acidophilic chemolithoautotrophs. This model was built based on literature and genomic analysis, considering a widespread mix of formerly proposed RISCs oxidation models combined and evaluated experimentally. Thiosulfate partial oxidation by the Sox system (SoxABXYZ) was placed as central step of sulfur oxidation model, along with abiotic reactions. This model was coupled with a detailed stoichiometry of biomass production, providing accurate bacterial growth predictions. In silico deletion/inactivation highlights the role of sulfur dioxygenase as the main catalyzer and a moderate function of tetrathionate hydrolase in elemental sulfur catabolism, demonstrating that this model constitutes an advanced instrument for the optimization of At. thiooxidans biomass production with potential use in biohydrometallurgical and environmental applications. Copyright © 2013 Wiley Periodicals, Inc.

  13. Sulfur retention by ash during coal combustion. Part I. A model of char particle combustion

    Directory of Open Access Journals (Sweden)

    BORISLAV GRUBOR

    2003-02-01

    Full Text Available A model for the combustion of porous char particles as a basis for modeling the process of sulfur retention by ash during coal combustion is developed in this paper. The model belongs to the microscopic intrinsic models and describes the dynamic behavior of a porous char particle during comustion, taking into account temporal and spatial changes of all important physical properties of the char particle and various combustion parameters. The parametric analysis of the enhanced model shows that the model represents a good basis for the development of a model for the process of sulfur retention by ash during coal combustion. The model enables the prediction of the values of all parameters necessary for the introduction of reactions between sulfur compounds and mineral components in ash, primarily calcium oxide.

  14. Effects of native herbs and light on garlic mustard (Alliaria petiolata) invasion

    Science.gov (United States)

    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

  15. Absence of respiratory inflammatory reaction of elemental sulfur using the California Pesticide Illness Database and a mouse model.

    Science.gov (United States)

    Lee, Kiyoung; Smith, Jodi L; Last, Jerold A

    2005-01-01

    Elemental sulfur, a natural substance, is used as a fungicide. Elemental sulfur is the most heavily used agricultural chemical in California. In 2003, annual sulfur usage in California was about 34% of the total weight of pesticide active ingredient used in production agriculture. Even though sulfur is mostly used in dust form, the respiratory health effects of elemental sulfur are not well documented. The purpose of this paper is to address the possible respiratory effect of elemental sulfur using the California Pesticide Illness Database and laboratory experiments with mice. We analyzed the California Pesticide Illness Database between 1991 and 2001. Among 127 reports of definite, probable, and possible illness involving sulfur, 21 cases (16%) were identified as respiratory related. A mouse model was used to examine whether there was an inflammatory or fibrotic response to elemental sulfur. Dust solutions were injected intratracheally into ovalbumin sensitized mice and lung damage was evaluated. Lung inflammatory response was analyzed via total lavage cell counts and differentials, and airway collagen content was analyzed histologically and biochemically. No significant differences from controls were seen in animals exposed to sulfur particles. The findings suggest that acute exposure of elemental sulfur itself may not cause an inflammatory reaction. However, further studies are needed to understand the possible health effects of chronic sulfur exposure and environmental weathering of sulfur dust.

  16. Modeling of a Large-Scale High Temperature Regenerative Sulfur Removal Process

    DEFF Research Database (Denmark)

    Konttinen, Jukka T.; Johnsson, Jan Erik

    1999-01-01

    model that does not account for bed hydrodynamics. The pilot-scale test run results, obtained in the test runs of the sulfur removal process with real coal gasifier gas, have been used for parameter estimation. The validity of the reactor model for commercial-scale design applications is discussed.......Regenerable mixed metal oxide sorbents are prime candidates for the removal of hydrogen sulfide from hot gasifier gas in the simplified integrated gasification combined cycle (IGCC) process. As part of the regenerative sulfur removal process development, reactor models are needed for scale......-up. Steady-state kinetic reactor models are needed for reactor sizing, and dynamic models can be used for process control design and operator training. The regenerative sulfur removal process to be studied in this paper consists of two side-by-side fluidized bed reactors operating at temperatures of 400...

  17. Mustard Gas Inhalation Injury: Therapeutic Strategy.

    Science.gov (United States)

    Keyser, Brian M; Andres, Devon K; Holmes, Wesley W; Paradiso, Danielle; Appell, Ashley; Letukas, Valerie A; Benton, Betty; Clark, Offie E; Gao, Xiugong; Ray, Prabhati; Anderson, Dana R; Ray, Radharaman

    2014-07-01

    Mustard gas (sulfur mustard [SM], bis-[2-chloroethyl] sulfide) is a vesicating chemical warfare agent and a potential chemical terrorism agent. Exposure of SM causes debilitating skin blisters (vesication) and injury to the eyes and the respiratory tract; of these, the respiratory injury, if severe, may even be fatal. Therefore, developing an effective therapeutic strategy to protect against SM-induced respiratory injury is an urgent priority of not only the US military but also the civilian antiterrorism agencies, for example, the Homeland Security. Toward developing a respiratory medical countermeasure for SM, four different classes of therapeutic compounds have been evaluated in the past: anti-inflammatory compounds, antioxidants, protease inhibitors and antiapoptotic compounds. This review examines all of these different options; however, it suggests that preventing cell death by inhibiting apoptosis seems to be a compelling strategy but possibly dependent on adjunct therapies using the other drugs, that is, anti-inflammatory, antioxidant, and protease inhibitor compounds. © The Author(s) 2014.

  18. Modeling the Distribution of Sulfur Compounds in a Large Two Stroke Diesel Engine

    DEFF Research Database (Denmark)

    Cordtz, Rasmus Lage; Schramm, Jesper; Andreasen, Anders

    2013-01-01

    In many years large low speed marine diesel engines have consumed heavy fuel oils with sulfur contents in the order of 2.5 - 4.5wt%. Present legislations require that the fuel sulfur is reduced and in near future the limit will be 0.5wt% globally. During combustion most of the sulfur is oxidized...... conditions and sulfur feed. This work presents a computational model of a large low speed two-stroke diesel engine where a 0D multi-zone approach including a detailed reaction mechanism is employed in order to investigate in cylinder formation of gaseous SO3 where fuel injection rates are determined using...... to SO2 from which a fraction is further oxidized to SO3. SO3 may combine with H2O and condense as liquid sulfuric acid that promotes corrosive wear on e.g. cylinder liners. To extend engine lifetime and reduce costs for lubrication it is pivotal to identify formation of SO3 with respect to operational...

  19. Electrical circuit models for performance modeling of Lithium-Sulfur batteries

    DEFF Research Database (Denmark)

    Knap, Vaclav; Stroe, Daniel Ioan; Teodorescu, Remus

    2015-01-01

    Energy storage technologies such as Lithium-ion (Li-ion) batteries are widely used in the present effort to move towards more ecological solutions in sectors like transportation or renewable-energy integration. However, today's Li-ion batteries are reaching their limits and not all demands...... of the industry are met yet. Therefore, researchers focus on alternative battery chemistries as Lithium-Sulfur (Li-S), which have a huge potential due to their high theoretical specific capacity (approx. 1675 Ah/kg) and theoretical energy density of almost 2600 Wh/kg. To analyze the suitability of this new...... emerging technology for various applications, there is a need for Li-S battery performance model; however, developing such models represents a challenging task due to batteries' complex ongoing chemical reactions. Therefore, the literature review was performed to summarize electrical circuit models (ECMs...

  20. Quantitative Reconstruction of Sulfur Deposition Using a Mixing Model Based on Sulfur Isotope Ratios in Tree Rings.

    Science.gov (United States)

    Ishida, Takuya; Tayasu, Ichiro; Takenaka, Chisato

    2015-11-01

    Quantification of sulfur (S) deposition is critical to deciphering the environmental archive of S in terrestrial ecosystems. Here we propose a mixing model that quantifies S deposition based on the S isotope ratio (δS) in tree rings. We collected samples from Japanese cedar ( D. Don) stumps from two sites: one near Yokkaichi City (YOK), which is well known for having the heaviest S air pollution in the world, and one at Inabu-cho (INA) in central Japan, which has been much less affected by air pollution. The δS profiles at both sites are consistent with S air pollution and contributions of anthropogenic S. The minimum value in YOK is lower than the δS values of anthropogenic S or any other possible source. Because the δS in the tree rings is affected by fractionation in the forest ecosystems, we used a mixing model to account for the isotope effects and to distinguish the sources of S. Based on the model results, we infer that the peak of S emissions at YOK occurred sometime between the late 1960s and early 1970s (489 mmol m yr). This estimated value is comparable with the highest reported values in Europe. This is the first quantitative estimate of anthropogenic input of S in forest systems based on δS in tree rings. Our results suggest that tree ring data can be used when monitoring stations of atmospheric S are lacking and that estimates of S deposition using δS in tree rings will advance our understanding of the local-scale S dynamics and the effect of human activities on it. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  1. A dynamic mathematical model for microbial removal of pyritic sulfur from coal.

    Science.gov (United States)

    Kargi, F; Weissman, J G

    1984-06-01

    A dynamic mathematical model has been developed to describe microbial desulfurization of coal by Thiobacillus ferrooxidans. The model considers adsorption and desorption of cells on coal particles and microbial oxidation of pyritic sulfur on particle surfaces. The influence of certain parameters, such as microbial growth rate constants, adsorption-description constants, pulp density, coal particle size, initial cell and solid phase substrate concentration on the maximum rate of pyritic sulfur removal, have been elucidated. The maximum rate of pyritic sulfur removal was strongly dependent upon the number of attached cells per coal particle. At sufficiently high initial cell concentrations, the surfaces of coal particles are nearly saturated by the cells and the maximum leaching rate is limited either by total external surface area of coal particles or by the concentration of pyritic sulfur in the coal phase. The maximum volumetric rate of pyritic sulfur removal (mg S/h cm(3) mixture) increases with the pulp density of coal and reaches a saturation level at high pulp densities (e.g. 45%). The maximum rate also increases with decreasing particle diameter in a hyperbolic form. Increases in adsorption coefficient or decreases in the desorption coefficient also result in considerable improvements in this rate. The model can be applied to other systems consisting of suspended solid substrate particles in liquid medium with microbial oxidation occurring on the particle surfaces (e.g., bacterial ore leaching). The results obtained from this model are in good agreement with published experimental data on microbial desulfurization of coal and bacterial ore leaching.

  2. The serum levels of adiponectin and leptin in mustard lung patients.

    Science.gov (United States)

    Rokni Yazdi, H; Lari, S M; Attaran, D; Ayatollahi, H; Mohsenizadeh, A

    2014-06-01

    Chronic obstructive pulmonary disease (COPD) due to sulfur mustard (SM), known as mustard lung, is an important late pulmonary complication of SM poisoning. Due to the possible role of systemic inflammation in mustard lung, we evaluated the serum levels of adiponectin and leptin in these patients. Thirty nonsmoker mustard lung patients in stable phase were enrolled into this study. Also, 30 COPD and 21 healthy participants were entered as control groups. Complete lung function tests were performed in the participants. The serum levels of adiponectin and leptin were measured in all groups. There were no statistically significant differences in mean adiponectin and leptin levels among the groups (p = 0.38 and p = 0.35, respectively). There was a downward trend in leptin to adiponectin ratio from lower to higher stages of global initiative for chronic obstructive lung disease guidelines in mustard lung patients, which was not statistically significant (p = 0.8). Our results showed that there is no difference in mean adipokine levels in stable mustard lung patients compared with control groups. There was a foot-point in the alterations of serum adipokines regarding the severity of COPD, which needs to be documented by larger sample group. © The Author(s) 2014.

  3. Extending the models for iron and sulfur oxidation in the extreme Acidophile Acidithiobacillus ferrooxidans

    Directory of Open Access Journals (Sweden)

    Holmes David S

    2009-08-01

    Full Text Available Abstract Background Acidithiobacillus ferrooxidans gains energy from the oxidation of ferrous iron and various reduced inorganic sulfur compounds at very acidic pH. Although an initial model for the electron pathways involved in iron oxidation has been developed, much less is known about the sulfur oxidation in this microorganism. In addition, what has been reported for both iron and sulfur oxidation has been derived from different A. ferrooxidans strains, some of which have not been phylogenetically characterized and some have been shown to be mixed cultures. It is necessary to provide models of iron and sulfur oxidation pathways within one strain of A. ferrooxidans in order to comprehend the full metabolic potential of the pangenome of the genus. Results Bioinformatic-based metabolic reconstruction supported by microarray transcript profiling and quantitative RT-PCR analysis predicts the involvement of a number of novel genes involved in iron and sulfur oxidation in A. ferrooxidans ATCC23270. These include for iron oxidation: cup (copper oxidase-like, ctaABT (heme biogenesis and insertion, nuoI and nuoK (NADH complex subunits, sdrA1 (a NADH complex accessory protein and atpB and atpE (ATP synthetase F0 subunits. The following new genes are predicted to be involved in reduced inorganic sulfur compounds oxidation: a gene cluster (rhd, tusA, dsrE, hdrC, hdrB, hdrA, orf2, hdrC, hdrB encoding three sulfurtransferases and a heterodisulfide reductase complex, sat potentially encoding an ATP sulfurylase and sdrA2 (an accessory NADH complex subunit. Two different regulatory components are predicted to be involved in the regulation of alternate electron transfer pathways: 1 a gene cluster (ctaRUS that contains a predicted iron responsive regulator of the Rrf2 family that is hypothesized to regulate cytochrome aa3 oxidase biogenesis and 2 a two component sensor-regulator of the RegB-RegA family that may respond to the redox state of the quinone pool

  4. Influence of Sea Ice on Arctic Marine Sulfur Biogeochemistry in the Community Climate System Model

    Energy Technology Data Exchange (ETDEWEB)

    Deal, Clara [Univ. of Alaska, Fairbanks, AL (United States); Jin, Meibing [Univ. of Alaska, Fairbanks, AL (United States)

    2013-06-30

    Global climate models (GCMs) have not effectively considered how responses of arctic marine ecosystems to a warming climate will influence the global climate system. A key response of arctic marine ecosystems that may substantially influence energy exchange in the Arctic is a change in dimethylsulfide (DMS) emissions, because DMS emissions influence cloud albedo. This response is closely tied to sea ice through its impacts on marine ecosystem carbon and sulfur cycling, and the ice-albedo feedback implicated in accelerated arctic warming. To reduce the uncertainty in predictions from coupled climate simulations, important model components of the climate system, such as feedbacks between arctic marine biogeochemistry and climate, need to be reasonably and realistically modeled. This research first involved model development to improve the representation of marine sulfur biogeochemistry simulations to understand/diagnose the control of sea-ice-related processes on the variability of DMS dynamics. This study will help build GCM predictions that quantify the relative current and possible future influences of arctic marine ecosystems on the global climate system. Our overall research objective was to improve arctic marine biogeochemistry in the Community Climate System Model (CCSM, now CESM). Working closely with the Climate Ocean Sea Ice Model (COSIM) team at Los Alamos National Laboratory (LANL), we added 1 sea-ice algae and arctic DMS production and related biogeochemistry to the global Parallel Ocean Program model (POP) coupled to the LANL sea ice model (CICE). Both CICE and POP are core components of CESM. Our specific research objectives were: 1) Develop a state-of-the-art ice-ocean DMS model for application in climate models, using observations to constrain the most crucial parameters; 2) Improve the global marine sulfur model used in CESM by including DMS biogeochemistry in the Arctic; and 3) Assess how sea ice influences DMS dynamics in the arctic marine

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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.

  6. Panceratic Complications of Mustard Gas Exposure: A Study on Cadavers

    Directory of Open Access Journals (Sweden)

    Amir Farshid Fayyaz

    2015-06-01

    Full Text Available Background: Sulfur mustard is one of the chemical warfare gases that has been known as a vesicant or blistering agents. It is a chemical alkylating compound agent that can be frequently absorbed through skin, respiratory system, genital tract, and ocular system. This study was done to pathologically analyze the microscopic pancreatic lesions in cadavers. Methods: This case series study was performed during 2007 to 2012 in Legal Medicine Organization. Exposure was confirmed by the written reports of the field hospitals, based on acute presentation of eye, skin and pulmonary symptoms of the exposure. Results: Pancreatic autopsy findings were chronic inflammation, fibrosis and duct ectasia; acinar atrophy was also seen in 4 cases. All 4 cases had chronic pancreatic disease with abdominal pain, steatorrhea and weight loss that was confirmed by sonography. CT scan and Endoscopic Retrograde Cholangio-Pancreatography (ERCP have also demonstrated the chronic pancreatitis. Conclusion: According to the chronic progressive lesions caused by mustard gas exposure such as pulmonary lesions and also its high mortality rate, suitable programming for protection of the mustard gas exposed people in chemical factories is necessary.

  7. 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.

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Multi-temperature state-dependent equivalent circuit discharge model for lithium-sulfur batteries

    DEFF Research Database (Denmark)

    Propp, Karsten; Marinescu, Monica; Auger, Daniel J.

    2016-01-01

    pulse profile at four temperatures from 10 °C to 50 °C, giving linearized ECN parameters for a range of states-of-charge, currents and temperatures. These are used to create a nonlinear polynomial-based battery model suitable for use in a battery management system. When the model is used to predict......Lithium-sulfur (Li-S) batteries are described extensively in the literature, but existing computational models aimed at scientific understanding are too complex for use in applications such as battery management. Computationally simple models are vital for exploitation. This paper proposes a non......-linear state-of-charge dependent Li-S equivalent circuit network (ECN) model for a Li-S cell under discharge. Li-S batteries are fundamentally different to Li-ion batteries, and require chemistry-specific models. A new Li-S model is obtained using a ‘behavioural’ interpretation of the ECN model; as Li...

  9. Lipid Profile Status in Mustard Lung Patients and its Relation to Severity of Airflow Obstruction

    Directory of Open Access Journals (Sweden)

    Davood Attaran

    2014-02-01

    Full Text Available Introduction: Chronic obstructive pulmonary disease (COPD secondary to sulfur mustard gas poisoning, known as mustard lung, is a major late pulmonary complications in chemical warfare patients. Serious comorbidities like dyslipidemia are frequently encountered in COPD. The aim of this study was to measure the serum lipid profile and evaluate the relation of lipid parameters with the severity of airway obstruction in mustard lung patients. Materials and Methods: Thirty-six non-smoker mustard lung patients with no history of cardiovascular disease, diabetes mellitus, and dyslipidemia were entered into this cross-sectional study. Control group consisted of 36 healthy non-smoker men were considered in this study. Serum lipid profile was performed in the patients and the controls. Spirometry was done in mustard lung patients. Results: The mean age of the patients was 47±6.80 SD years. The mean duration of COPD was 18.50±7.75 SD years. There were statistically significant differences in mean serum triglycerides and total cholesterol levels between patients and controls (p=0.04 and p=0.03, respectively.The mean levels of lipid parameters were not statistically significant different among the 4 stages of COPD severity (p>0.05. Conclusion: The current study revealed that the serum levels of triglycerides and cholesterol are elevated in mustard lung patients compared with the healthy controls. Since lipid profile abnormalities are considered as a major risk factor for cardiovascular disease, especial attention to this matter is recommended in mustard lung patients

  10. Mathematical modeling of simultaneous carbon-nitrogen-sulfur removal from industrial wastewater.

    Science.gov (United States)

    Xu, Xi-Jun; Chen, Chuan; Wang, Ai-Jie; Ni, Bing-Jie; Guo, Wan-Qian; Yuan, Ye; Huang, Cong; Zhou, Xu; Wu, Dong-Hai; Lee, Duu-Jong; Ren, Nan-Qi

    2017-01-05

    A mathematical model of carbon, nitrogen and sulfur removal (C-N-S) from industrial wastewater was constructed considering the interactions of sulfate-reducing bacteria (SRB), sulfide-oxidizing bacteria (SOB), nitrate-reducing bacteria (NRB), facultative bacteria (FB), and methane producing archaea (MPA). For the kinetic network, the bioconversion of C-N by heterotrophic denitrifiers (NO 3 - →NO 2 - →N 2 ), and that of C-S by SRB (SO 4 2- →S 2- ) and SOB (S 2- →S 0 ) was proposed and calibrated based on batch experimental data. The model closely predicted the profiles of nitrate, nitrite, sulfate, sulfide, lactate, acetate, methane and oxygen under both anaerobic and micro-aerobic conditions. The best-fit kinetic parameters had small 95% confidence regions with mean values approximately at the center. The model was further validated using independent data sets generated under different operating conditions. This work was the first successful mathematical modeling of simultaneous C-N-S removal from industrial wastewater and more importantly, the proposed model was proven feasible to simulate other relevant processes, such as sulfate-reducing, sulfide-oxidizing process (SR-SO) and denitrifying sulfide removal (DSR) process. The model developed is expected to enhance our ability to predict the treatment of carbon-nitrogen-sulfur contaminated industrial wastewater. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Destruction Chemistry of Mustard Simulants

    Science.gov (United States)

    2008-07-04

    organosulfur compounds under both pyrolytic and oxidative conditions. We focus on the destruction of alkyl sulfides that are surrogates for chemical... organosulfur , oxidation, pyrolysis, chemical kinetic mechanism, thermochemistry, reaction, kinetics, flow reactor, GC/MS, FTIR, mustard agent simulant, CWA...destruction chemistry of organosulfur compounds under both pyrolytic and oxidative conditions. We focus on the destruction of alkyl sulfides that are

  12. Mustard vesicants alter expression of the endocannabinoid system in mouse skin

    International Nuclear Information System (INIS)

    Wohlman, Irene M.; Composto, Gabriella M.; Heck, Diane E.; Heindel, Ned D.; Lacey, C. Jeffrey; Guillon, Christophe D.; Casillas, Robert P.; Croutch, Claire R.; Gerecke, Donald R.; Laskin, Debra L.; Joseph, Laurie B.; Laskin, Jeffrey D.

    2016-01-01

    Vesicants including sulfur mustard (SM) and nitrogen mustard (NM) are bifunctional alkylating agents that cause skin inflammation, edema and blistering. This is associated with alterations in keratinocyte growth and differentiation. Endogenous cannabinoids, including N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoyl glycerol (2-AG), are important in regulating inflammation, keratinocyte proliferation and wound healing. Their activity is mediated by binding to cannabinoid receptors 1 and 2 (CB1 and CB2), as well as peroxisome proliferator-activated receptor alpha (PPARα). Levels of endocannabinoids are regulated by fatty acid amide hydrolase (FAAH). We found that CB1, CB2, PPARα and FAAH were all constitutively expressed in mouse epidermis and dermal appendages. Topical administration of NM or SM, at concentrations that induce tissue injury, resulted in upregulation of FAAH, CB1, CB2 and PPARα, a response that persisted throughout the wound healing process. Inhibitors of FAAH including a novel class of vanillyl alcohol carbamates were found to be highly effective in suppressing vesicant-induced inflammation in mouse skin. Taken together, these data indicate that the endocannabinoid system is important in regulating skin homeostasis and that inhibitors of FAAH may be useful as medical countermeasures against vesicants. - Highlights: • Sulfur mustard and nitrogen mustard are potent skin vesicants. • The endocannabinoid system regulates keratinocyte growth and differentiation. • Vesicants are potent inducers of the endocannabinoid system in mouse skin. • Endocannabinoid proteins upregulated are FAAH, CB1, CB2 and PPARα. • FAAH inhibitors suppress vesicant-induced inflammation in mouse skin.

  13. Serpentinization of abyssal peridotites from the MARK area, Mid-Atlantic Ridge: Sulfur geochemistry and reaction modeling

    Science.gov (United States)

    Alt, J.C.; Shanks, Wayne C.

    2003-01-01

    The opaque mineralogy and the contents and isotope compositions of sulfur in serpentinized peridotites from the MARK (Mid-Atlantic Ridge, Kane Fracture Zone) area were examined to understand the conditions of serpentinization and evaluate this process as a sink for seawater sulfur. The serpentinites contain a sulfur-rich secondary mineral assemblage and have high sulfur contents (up to 1 wt.%) and elevated ??34Ssulfide (3.7 to 12.7???). Geochemical reaction modeling indicates that seawater-peridotite interaction at 300 to 400??C alone cannot account for both the high sulfur contents and high ??34Ssulfide. These require a multistage reaction with leaching of sulfide from subjacent gabbro during higher temperature (???400??C) reactions with seawater and subsequent deposition of sulfide during serpentinization of peridotite at ???300??C. Serpentinization produces highly reducing conditions and significant amounts of H2 and results in the partial reduction of seawater carbonate to methane. The latter is documented by formation of carbonate veins enriched in 13C (up to 4.5???) at temperatures above 250??C. Although different processes produce variable sulfur isotope effects in other oceanic serpentinites, sulfur is consistently added to abyssal peridotites during serpentinization. Data for serpentinites drilled and dredged from oceanic crust and from ophiolites indicate that oceanic peridotites are a sink for up to 0.4 to 6.0 ?? 1012 g seawater S yr-1. This is comparable to sulfur exchange that occurs in hydrothermal systems in mafic oceanic crust at midocean ridges and on ridge flanks and amounts to 2 to 30% of the riverine sulfate source and sedimentary sulfide sink in the oceans. The high concentrations and modified isotope compositions of sulfur in serpentinites could be important for mantle metasomatism during subduction of crust generated at slow spreading rates. ?? 2003 Elsevier Science Ltd.

  14. Apoptotic cell death in rat lung following mustard gas inhalation.

    Science.gov (United States)

    Andres, Devon K; Keyser, Brian M; Melber, Ashley A; Benton, Betty J; Hamilton, Tracey A; Kniffin, Denise M; Martens, Margaret E; Ray, Radharaman

    2017-06-01

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

  15. Coupled sulfur isotopic and chemical mass transfer modeling: Approach and application to dynamic hydrothermal processes

    International Nuclear Information System (INIS)

    Janecky, D.R.

    1988-01-01

    A computational modeling code (EQPSreverse arrowS) has been developed to examine sulfur isotopic distribution pathways coupled with calculations of chemical mass transfer pathways. A post processor approach to EQ6 calculations was chosen so that a variety of isotopic pathways could be examined for each reaction pathway. Two types of major bounding conditions were implemented: (1) equilibrium isotopic exchange between sulfate and sulfide species or exchange only accompanying chemical reduction and oxidation events, and (2) existence or lack of isotopic exchange between solution species and precipitated minerals, parallel to the open and closed chemical system formulations of chemical mass transfer modeling codes. All of the chemical data necessary to explicitly calculate isotopic distribution pathways is generated by most mass transfer modeling codes and can be input to the EQPS code. Routines are built in to directly handle EQ6 tabular files. Chemical reaction models of seafloor hydrothermal vent processes and accompanying sulfur isotopic distribution pathways illustrate the capabilities of coupling EQPSreverse arrowS with EQ6 calculations, including the extent of differences that can exist due to the isotopic bounding condition assumptions described above. 11 refs., 2 figs

  16. In-depth study on the solubility of elemental sulfur in sour gas mixtures based on the Chrastil's association model

    Directory of Open Access Journals (Sweden)

    Qiao Wang

    2016-12-01

    Full Text Available Accurately predicting the solubility of elemental sulfur in sour gas mixtures is a primary task. As a current and widely-used model on the solubility of elemental sulfur in sour gas mixtures, Chrastil's association model has a big error in the process of predicting experimental data based on different fitting methods. This paper combined with experimental data reported by relevant scholars about elemental sulfur solubility in sour gases and selected density, temperature and pressure as three important influential factors. According to different fitting methods, we can calculate the correlation parameters in Chrastil's model. Then different solubility formulas can be used to predict the solubility of elemental sulfur in sour gas mixtures. Through in-depth research and analysis of Chrastil's solubility model from numerical aspects, it's easy to find the irrationality about Chrastil's solubility model and fitting methods. Especially in fitting methods, further improvement of the fitting method is proposed and used to predict the solubility of elemental sulfur in sour gas mixtures. The calculation results show that some improvements of the predicting precision have been achieved by using the improved fitting method in Chrastil's association model.

  17. Model for estimating air pollutant uptake by forests: calculation of forest absorption of sulfur dioxide from dispersed sources

    International Nuclear Information System (INIS)

    Murphy, C.E. Jr.; Sinclair, T.R.; Knoerr, K.R.

    1975-01-01

    The computer model presented in this paper is designed to estimate the uptake of air pollutants by forests. The model utilizes submodels to describe atmospheric diffusion immediately above and within the canopy, and into the sink areas within or on the trees. The program implementing the model is general and can be used with only minor changes for any gaseous pollutant. To illustrate the utility of the model, estimates are made of the sink strength of forests for sulfur dioxide. The results agree with experimentally derived estimates of sulfur dioxide uptake in crops and forest trees. (auth)

  18. Architectural and biochemical expressions of mustard gas keratopathy: preclinical indicators and pathogenic mechanisms.

    Directory of Open Access Journals (Sweden)

    Patrick McNutt

    Full Text Available 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

  19. RELY: A reliability modeling system for analysis of sodium-sulfur battery configurations

    Energy Technology Data Exchange (ETDEWEB)

    Hostick, C.J.; Huber, H.D.; Doggett, W.H.; Dirks, J.A.; Dovey, J.F.; Grinde, R.B.; Littlefield, J.S.; Cuta, F.M.

    1987-06-01

    In support of the Office of Energy Storage and Distribution of the US Department of Energy (DOE), Pacific Northwest Laboratory has produced a microcomputer-based software package, called RELY, to assess the impact of sodium-sulfur cell reliability on constant current discharge battery performance. The Fortran-based software operates on IBM microcomputers and IBM-compatibles that have a minimum of 512K of internal memory. The software package has three models that provide the following: (1) a description of the failure distribution parameters used to model cell failure, (2) a Monte Carlo simulation of battery life, and (3) a detailed discharge model for a user-specified battery discharge cycle. 6 refs., 31 figs., 4 tabs.

  20. Experimental studies and mathematical modeling of an up-flow biofilm reactor treating mustard oil rich wastewater.

    Science.gov (United States)

    Chakraborty, Chandrima; Chowdhury, Ranjana; Bhattacharya, Pinaki

    2011-05-01

    Bioremediation of lipid-rich model wastewater was investigated in a packed bed biofilm reactor (anaerobic filter). A detailed study was conducted about the influence of fatty acid concentration on biomethanation of the high-fat liquid effluent of edible oil refineries. The biochemical methane potential (BMP) of the liquid waste was reported and maximum cumulative methane production at the exit of the reactor is estimated to be 785 ml CH(4) (STP)/(gVSS added). The effects of hydraulic retention time (HRT), organic loading rate (OLR) and bed porosity on the cold gas efficiency or energy efficiency of the bioconversion process were also investigated. Results revealed that the maximum cold gas efficiency of the process is 42% when the total organic load is 2.1 g COD/l at HRT of 3.33 days. Classical substrate uninhibited Monod model is used to generate the differential system equations which can predict the reactor behavior satisfactorily. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Identification and ranking of poly (ADP-ribose) polymerase inhibitors as protectors against sulfur mustard induced decrease in cellular energy and viability in in vitro assays with human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Meier, H.L.; Kelly, S.A.

    1993-05-13

    Lymphocyte were utilized as a model for investigating HD effects on resting cells. Lymphocytes exposed to HD demonstrated a concentration dependent decrease in ATP, NAD, and viability. The decrease began in 15 minutes for ATP, 2 hours for NAD, and 6 hours for viability. All three of these HD initiated biochemical changes can be blocked by poly (ADP-ribose) polymerase inhibitors (PADPRPI). To completely inhibit HD initiated ATP, NAD, and viability decreases the PADPRPI had to be present at time 0, 1, and 4 hours respectfully. The amount of protection conferred by the PADPRPI in the viability assay decreased in a linear manner with the delay of the addition and the concentration of the inhibitor from 6-12 hours post HD exposure. There was a good correlation between IC50 to inhibit poly (ADP-ribose) polymerase and EC50 prevention of HD initiated cell death (r=O.94). Thus, three in vitro assays which can measure biochemical and pathologic changes induced by HD in G sub 0 lymphocytes have been developed. These assays have been employed to study the ability of candidate antidotes to prevent HD initiated changes. Benzamidine analogs, including the F.D.A. approved vitamin niacinamide, have been shown to be effective at inhibiting all of these changes.

  2. A self-consistent LTE model of a microwave-driven, high-pressure sulfur lamp

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, C.W.; Mullen, J.J.A.M. van der [Department of Applied Physics, Eindhoven University of Technology (Netherlands)]. E-mails: C.W.Johnston@tue.nl; J.J.A.M.v.d.Mullen@tue.nl; Heijden, H.W.P. van der; Janssen, G.M.; Dijk, J. van [Department of Applied Physics, Eindhoven University of Technology (Netherlands)

    2002-02-21

    A one-dimensional LTE model of a microwave-driven sulfur lamp is presented to aid our understanding of the discharge. The energy balance of the lamp is determined by Ohmic input on one hand and transport due to conductive heat transfer and molecular radiation on the other. We discuss the origin of operational trends in the spectrum, present the model and discuss how the material properties of the plasma are determined. Not only are temperature profiles and electric field strengths simulated but also the spectrum of the lamp from 300 to 900 nm under various conditions of input power and lamp filling pressure. We show that simulated spectra demonstrate observed trends and that radiated power increases linearly with input power as is also found from experiment. (author)

  3. Electric circuit modeling of lithium-sulfur batteries during discharging state

    DEFF Research Database (Denmark)

    Stroe, Daniel-Ioan; Knap, Vaclav; Swierczynski, Maciej Jozef

    2017-01-01

    Lithium-ion batteries are characterized by having very good performance in terms of efficiency, lifetime, and selfdischarge, which allowed them to become the major player in the electric vehicle applications. However, they were not able to totally overcome the EV range anxiety. Thus, research...... is carried out nowadays to develop batteries with even higher gravimetric energy density, which should allow a substantial range increase. One of the technologies, which should be able to meet the range requirements is the Lithium-Sulfur (Li-S) battery. Thanks to the extensive research and development...... efforts, these cells are close to enter the market, being evaluate in various projects. In this paper, we have proposed an electrical circuit model for a Li-S pouch cell, which was parameterized based on extensive electrochemical impedance spectroscopy measurements. The developed model was verified using...

  4. Multi-temperature state-dependent equivalent circuit discharge model for lithium-sulfur batteries

    Science.gov (United States)

    Propp, Karsten; Marinescu, Monica; Auger, Daniel J.; O'Neill, Laura; Fotouhi, Abbas; Somasundaram, Karthik; Offer, Gregory J.; Minton, Geraint; Longo, Stefano; Wild, Mark; Knap, Vaclav

    2016-10-01

    Lithium-sulfur (Li-S) batteries are described extensively in the literature, but existing computational models aimed at scientific understanding are too complex for use in applications such as battery management. Computationally simple models are vital for exploitation. This paper proposes a non-linear state-of-charge dependent Li-S equivalent circuit network (ECN) model for a Li-S cell under discharge. Li-S batteries are fundamentally different to Li-ion batteries, and require chemistry-specific models. A new Li-S model is obtained using a 'behavioural' interpretation of the ECN model; as Li-S exhibits a 'steep' open-circuit voltage (OCV) profile at high states-of-charge, identification methods are designed to take into account OCV changes during current pulses. The prediction-error minimization technique is used. The model is parameterized from laboratory experiments using a mixed-size current pulse profile at four temperatures from 10 °C to 50 °C, giving linearized ECN parameters for a range of states-of-charge, currents and temperatures. These are used to create a nonlinear polynomial-based battery model suitable for use in a battery management system. When the model is used to predict the behaviour of a validation data set representing an automotive NEDC driving cycle, the terminal voltage predictions are judged accurate with a root mean square error of 32 mV.

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

    Science.gov (United States)

    2006-05-01

    manipulated at the level of a cell surface (Fas/TNF) receptor, these two molecules represent attractive targets for the modulation of the effects of SM in...and Catsoulacos, P. (1990). Effects of alkylating antineoplastics alone or in combination with 3- aminobenzamide on genotoxicity, antitumor

  6. Gas Chromatographic Analysis of Sulfur Mustard in Diethyl Phthalate

    National Research Council Canada - National Science Library

    Lancaster, Paul

    1998-01-01

    ...) that had been trapped in the solvent, diethyl phthalate (DEP) is described. The method utilises the improved sensitivity and selectivity offered by the new Pulsed Flame Photometric Detector to detect routinely samples containing...

  7. The Role of Energy Metabolism in Cutaneous Sulfur Mustard Injury

    Science.gov (United States)

    2006-11-01

    Depletion Effects of Niacinamide : Niacinamide , which is both a PARP inhibitor and a precursor for the synthesis of NAD+, has been shown to protect...inhibition of glycolysis, we pretreated HEK with varying concentrations of niacinamide prior to exposure and then assayed for both NAD+ content and the...rate of glycolysis. In these experiments (Martens and Smith, 1993), 1 mM niacinamide increased NAD+ levels at all time points in both control and

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

    National Research Council Canada - National Science Library

    Rosenthal, Dean

    2003-01-01

    .... We made significant headway in elucidating several important pathways by which SM induces cell death in cultured keratinocytes and dermal fibroblasts, as well as in intact mouse and grafted human skin...

  9. Electrosorption in lithium-sulfur batteries: modeling of solvation and adsorption at nanostructured cathodes

    OpenAIRE

    Lück, Jessica; Danner, Timo; Latz, Arnulf

    2016-01-01

    Since the energy density of lithium-ion batteries is reaching its ceiling so that improvements are just of minor nature, researchers have moved their focus to systems beyond lithium-ion. One of the most promising candidates besides the lithium-air technology for future energy storage both for automotive and stationary applications are lithium-sulfur batteries. The use of sulfur as an active material offers many benefits compared to lithium-ion systems. First of all sulfur is expec...

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

    Science.gov (United States)

    2006-09-01

    A. M. Hossini, L. F. Fecker, C. E. Orfanos, and B. Tebbe (2002). The role of nuclear factor-kappa B and melanogenesis in tumor necrosis factor...chemical warfare agents. A further goal in conjunction with consortium members is to design rat and mouse microarrays and QPCR reagents , which will be

  11. Sinalbin degradation products in mild yellow mustard paste

    OpenAIRE

    Paunović, Dragana; Šolević-Knudsen, Tatjana; Krivokapić, Mirjana; Zlatković, Branislav; Antić, Mališa

    2012-01-01

    Sinalbin degradation products in mild yellow mustard paste were investigated. The analyzed material consisted of a mild yellow mustard paste condiment and ground white mustard seeds which were originally used in the mustard paste production process. The samples were extracted in a Soxhlet extraction system and analyzed by gas chromatography - mass spectrometry (GC-MS) technique. The only sinalbin degradation product in ground mustard seeds was 2-(4-hydroxyphenyl)acetonitrile. The most a...

  12. The Significance of BODE (BMI, Obstruction, Dyspnea, Exercise Index in Patients with Mustard Lung

    Directory of Open Access Journals (Sweden)

    OmidShadkam

    2013-05-01

    Full Text Available Introduction: Chronic Obstructive Pulmonary Disease (COPD secondary to sulfur mustard exposure, known as mustard lung, is an important late pulmonary complication. The BODE (Body mass index, Obstruction, Dyspnea, and Exercise index has been established as a valuable tool for determining the adverse consequences of COPD. The aim of this study was to evaluate the role of the BODE index in patients with mustard lung. Materials and Methods: Eighty-two consecutively stable patients with mustard lung with all levels of severity were entered this study. The following parameters were recorded in all patients: standard spirometry, pulse oximetry, health-related quality of life, the BODE index. Additionally, the severity of COPD was determined by GOLD (Global initiative for chronic Obstructive Lung Disease staging. The correlation of the BODE index with pulmonary parameters was determined. Results: The mean age of the patients was 47.30±7.08 SD years. The mean BODE index was 3.16±2.25 SD. There was a statistically significant inverse correlation between the BODE index and oxygen saturation (r=-0.30, p=0.007. Also a statistically significant correlation was found between the BODE index and quality of life (r=0.80, p=0.001. The BODE index was not correlated with age of the patients and duration of disease. Conclusions: The results of this study showed that the BODE index is correlated with important clinical parameters and can be used in clinical practice

  13. Development of alternative sulfur dioxide control strategies for a metropolitan area and its environs, utilizing a modified climatological dispersion model

    Science.gov (United States)

    K. J. Skipka; D. B. Smith

    1977-01-01

    Alternative control strategies were developed for achieving compliance with ambient air quality standards in Portland, Maine, and its environs, using a modified climatological dispersion model (CDM) and manipulating the sulfur content of the fuel oil consumed in four concentric zones. Strategies were evaluated for their impact on ambient air quality, economics, and...

  14. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Two-Generation Reproduction Study of Sulfur Mustard (HD) in Rats

    Science.gov (United States)

    1989-09-30

    ACO6.76RLO 78&0 1ECURITY CLASIFICATION or. TWIS AfE REPORT DOCUMENTATION PAGE OIN 7Ŝ I&. REPORT SECURITY CLASSIFICATION 1b. RESTRICTIVE MARKINGS...particle filters and a carbon filter. Near the end of quarantine 11 rats were subjected to a health evaluation and tested for antibodies to viral

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

    Science.gov (United States)

    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. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  16. Modeling the electron transport chain of purple non-sulfur bacteria.

    Science.gov (United States)

    Klamt, Steffen; Grammel, Hartmut; Straube, Ronny; Ghosh, Robin; Gilles, Ernst Dieter

    2008-01-01

    Purple non-sulfur bacteria (Rhodospirillaceae) have been extensively employed for studying principles of photosynthetic and respiratory electron transport phosphorylation and for investigating the regulation of gene expression in response to redox signals. Here, we use mathematical modeling to evaluate the steady-state behavior of the electron transport chain (ETC) in these bacteria under different environmental conditions. Elementary-modes analysis of a stoichiometric ETC model reveals nine operational modes. Most of them represent well-known functional states, however, two modes constitute reverse electron flow under respiratory conditions, which has been barely considered so far. We further present and analyze a kinetic model of the ETC in which rate laws of electron transfer steps are based on redox potential differences. Our model reproduces well-known phenomena of respiratory and photosynthetic operation of the ETC and also provides non-intuitive predictions. As one key result, model simulations demonstrate a stronger reduction of ubiquinone when switching from high-light to low-light conditions. This result is parameter insensitive and supports the hypothesis that the redox state of ubiquinone is a suitable signal for controlling photosynthetic gene expression.

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

    Science.gov (United States)

    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.

  18. Variable trajectory model for regional assessments of air pollution from sulfur compounds.

    Energy Technology Data Exchange (ETDEWEB)

    Powell, D.C.; McNaughton, D.J.; Wendell, L.L.; Drake, R.L.

    1979-02-01

    This report describes a sulfur oxides atmospheric pollution model that calculates trajectories using single-layer historical wind data as well as chemical transformation and deposition following discrete contaminant air masses. Vertical diffusion under constraints is calculated, but all horizontal dispersion is a funcion of trajectory variation. The ground-level air concentrations and deposition are calculated in a rectangular area comprising the northeastern United States and southeastern Canada. Calculations for a 29-day assessment period in April 1974 are presented along with a limited verification. Results for the studies were calculated using a source inventory comprising 61% of the anthropogenic SO/sub 2/ emissions. Using current model parameterization levels, predicted concentration values are most sensitive to variations in dry deposition of SO/sub 2/, wet deposition of sulfate, and transformation of SO/sub 2/ to sulfate. Replacing the variable mixed-layer depth and variable stability features of the model with constant definitions of each results in increased ground-level concentration predicions for SO/sub 2/ and particularly for sulfate.

  19. 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

    International Nuclear Information System (INIS)

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

    2010-01-01

    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 μM) 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 4 (LTA 4 ) hydrolase and leukotriene C 4 (LTC 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 4 hydrolase and LTC 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.

  20. Modeling the condensation of sulfuric acid and water on the cylinder liner of a large two-stroke marine diesel engine

    DEFF Research Database (Denmark)

    Cordtz, Rasmus Faurskov; Mayer, Stefan; Eskildsen, Svend S.

    2018-01-01

    Corrosive wear of cylinder liners in large two-stroke marine diesel engines that burn heavy fuel oil containing sulfur is coupled to the formation of gaseous sulfur trioxide (SO3) and subsequent combined condensation of sulfuric acid (H2SO4) and water (H2O) vapor. The present work seeks to address...... vapor liquid equilibrium. By assuming homogenous cylinder gas mixtures condensation is modeled using a convective heat and mass transfer analogy combined with realistic liner temperature profiles. Condensation of water is significantly altered by the liner temperature and charge air humidity while...... how fuel sulfur content, charge air humidity and liner temperature variations affects the deposition of water and sulfuric acid at low load operation. A phenomenological engine model is applied to simulate the formation of cylinder/bulk gas combustion products and dew points comply with H2O–H2SO4...

  1. Development of Efficient Flowsheet and Transient Modeling for Nuclear Heat Coupled Sulfur Iodine Cyclefor Hydrogen Production

    Energy Technology Data Exchange (ETDEWEB)

    Shripad T. Revankar; Nicholas R. Brown; Cheikhou Kane; Seungmin Oh

    2010-05-01

    The realization of the hydrogen as an energy carrier for future power sources relies on a practical method of producing hydrogen in large scale with no emission of green house gases. Hydrogen is an energy carrier which can be produced by a thermochemical water splitting process. The Sulfur-Iodine (SI) process is an example of a water splitting method using iodine and sulfur as recycling agents.

  2. Thermodynamic modeling of HIx part of the Iodine – Sulfur thermocycle

    OpenAIRE

    Hadj-Kali, Mohamed; Gerbaud, Vincent; Borgard, Jean-Marc; Floquet, Pascal; Joulia, Xavier; Carles, Philippe

    2007-01-01

    The thermochemical water splitting cycle is an environmentally attractive way to produce hydrogen without using fossil fuels. Among a hundreds possible cycles, the sulfur – iodine (IS) is a promising one, expected to become a major source of hydrogen production from nuclear or solar energy. The IS process cycle is divided into three sections; namely: (1) the Bunsen section whose purpose is to produce the two immiscible liquid acid phases: one containing mainly sulfuric acid and the other h...

  3. Sinalbin degradation products in mild yellow mustard paste

    Directory of Open Access Journals (Sweden)

    Paunović Dragana

    2012-01-01

    Full Text Available Sinalbin degradation products in mild yellow mustard paste were investigated. The analyzed material consisted of a mild yellow mustard paste condiment and ground white mustard seeds which were originally used in the mustard paste production process. The samples were extracted in a Soxhlet extraction system and analyzed by gas chromatography - mass spectrometry (GC-MS technique. The only sinalbin degradation product in ground mustard seeds was 2-(4-hydroxyphenylacetonitrile. The most abundant sinalbin degradation product in yellow mustard paste was 4-(hydroxymethylphenol. Other compounds identified in this sample were: 4-methyl phenol, 4-ethyl phenol, 4-(2-hydroxyethylphenol and 2-(4-hydroxyphenyl ethanoic acid.

  4. Mass-dependent sulfur isotope fractionation during reoxidative sulfur cycling

    DEFF Research Database (Denmark)

    Pellerin, André; Bui, Thi Hao; Rough, Mikaella

    2015-01-01

    The multiple sulfur isotope composition of porewater sulfate from the anoxic marine sapropel of Mangrove Lake, Bermuda was measured in order to establish how multiple sulfur isotopes are fractionated during reoxidative sulfur cycling. The porewater-sulfate d34S and D33S dataset exhibits the disti......The multiple sulfur isotope composition of porewater sulfate from the anoxic marine sapropel of Mangrove Lake, Bermuda was measured in order to establish how multiple sulfur isotopes are fractionated during reoxidative sulfur cycling. The porewater-sulfate d34S and D33S dataset exhibits......, informed by the chemistry of sulfur intermediate compounds in Mangrove Lake, reveals that sulfate reduction produces a relatively small intrinsic fractionation and that an active reoxidative sulfur cycle increases the fractionation of the measured values. Based on the model results, the reoxidative cycle...... of Mangrove Lake appears to include sulfide oxidation to elemental sulfur followed by the disproportionation of the elemental sulfur to sulfate and sulfide. This model also indicates that the reoxidative sulfur cycle of Mangrove Lake turns over from 50 to 80% of the sulfide produced by microbial sulfate...

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

    Directory of Open Access Journals (Sweden)

    Neera Tewari-Singh

    Full Text Available 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.

  6. Tribological Characteristics Evaluation of Mustard Oil Blends

    Directory of Open Access Journals (Sweden)

    Mohammed Hassan Jabal

    2018-03-01

    Full Text Available A progressive increase in the desire for environmentally friendly lubricants by users and strict government regulations for the use of these lubricants has provided an opportunity to use plant oils as biodegradable lubricants, therefore vegetable oils have been investigated to replace oil lubricants because of their maintaining the conditions of nature (environment properties. In this paper, the influences of the blending ratio of mustard seeds oil with commercial mineral oil (SAE40 on the tribological characteristics were investigated and compared with mineral oil using the four-ball tribotester. Mustard seeds oil was blended with mineral oil at a volumetric ratio ranging from 22.5 to 90%. All experimental works were confirmed to ASTM D4172-B standard. The results exhibit that some blends of mustard seeds oil with mineral oil have lower wear scar diameter, friction torque, Friction coefficient and a higher parameter of flash temperature value compared to mineral oil and neat mustard seed oil. In conclusion, the mustard seed oil blend (MU22.5 shows a better anti-wear and anti-friction performance compared to oil samples. Therefore, mustard seeds oil has the potential to be used as a lubricant of mating surfaces.

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

    Directory of Open Access Journals (Sweden)

    Fabiana Arduini

    2015-02-01

    Full Text Available 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-chloroethylamine 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.

  8. Sulfur dioxide AQI modeling by artificial neural network in Tehran between 2007 and 2013

    Directory of Open Access Journals (Sweden)

    Saeed Motesaddi

    2015-12-01

    Full Text Available Background: Air pollution and concerns about health impacts have been raised in metropolitan cities like Tehran. Trend and prediction of air pollutants can show the effectiveness of strategies for the management and control of air pollution. Artificial neural network (ANN technique is widely used as a reliable method for modeling of air pollutants in urban areas. Therefore, the aim of current study was to evaluate the trend of sulfur dioxide (SO2 air quality index (AQI in Tehran using ANN. Methods: The dataset of SO2 concentration and AQI in Tehran between 2007 and 2013 for 2550 days were obtained from air quality monitoring fix stations belonging to the Department of Environment (DOE. These data were used as input for the ANN and nonlinear autoregressive (NAR model using Matlab (R2014a software. Results: Daily and annual mean concentration of SO2 except 2008 (0.037 ppm was less than the EPA standard (0.14 and 0.03 ppm, respectively. Trend of SO2 AQI showed the variation of SO2 during different days, but the study declined overtime and the predicted trend is higher than the actual trend. Conclusion: The trend of SO2 AQI in this study, despite daily fluctuations in ambient air of Tehran over the period of the study have decreased and the difference between the predicted and actual trends can be related to various factors, such as change in management and control of SO2 emissions strategy and lack of effective parameters in SO2 emissions in predicting model.

  9. Estimates of methionine and sulfur amino acid requirements for laying hens using different models

    Directory of Open Access Journals (Sweden)

    AA Saki

    2012-09-01

    Full Text Available This experiment was conducted to evaluate the effects of dietary methionine (Met content on the performance of white commercial laying hens and to determine Met and total sulfur amino acids requirements (TSAA. These requirements were estimated using three statistical models (broken-line regression, exponential and second order equations to evaluate their abilit to determine amino acid requirements. A total of 216 laying hens (23 wks of age was used in a completely randomized design (CRD with six treatments with four replicates of nine birds each. The basal diet contained 15.25% crude protein, 2830.16 kcal/kg ME and 0.24% Met. Synthetic DL-Met was added to the deficient (basal diet in 0.05% increments to make the other five experimental diets (0.29, 0.34, 0.39, 0.44 and 0.49% Met. Increasing Met level from 0.24 to 0.34% significantly increased egg production, egg weight, egg mass, egg content, and feed intake and decreased feed conversion ratio (p<0.05. However, further Met increases, from 0.34 to 0.49%, no longer influenced these parameters. Out of the three models, the broken-line regression model presented better estimates of AA requirements. Based on broken-line equations, average Met and TSAA requirements of the laying hens were 0.31 and 0.60% (245.50 and 469.25 mg/hen/day from 22 to 36 wks of age, respectively.

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

    Science.gov (United States)

    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.

  11. Atmospheric sulfur and climate changes: a modelling study at mid and high-southern latitudes; Soufre atmospherique et changements climatiques: une etude de modelisation pour les moyennes et hautes latitudes Sud

    Energy Technology Data Exchange (ETDEWEB)

    Castebrunet, H

    2007-09-15

    The mid and high-southern latitudes are still marginally affected by anthropogenic sulfur emissions. They are the only regions in the world where the natural cycle of the atmospheric sulfur may still be observed. Sulfur aerosols are well-known for their radiative impact, and thus interact with climate. Climate can in turn affect atmospheric sulfur sources, distribution and chemistry. Antarctic ice cores provide information on the evolution of climate and sulfur deposition at the surface of the ice sheet at glacial-interglacial time scales. The aim of this thesis is to develop and use modeling towards a better understanding of the atmospheric sulfur cycle in antarctic and sub-antarctic regions. Ice core data are used to validate model results under glacial climate conditions. An Atmospheric General Circulation Model (AGCM) coupled to a sulfur chemistry module is used: the LMD-ZTSulfur model, version 4. An update of both the physical and chemical parts of the model. The model was first performed. The impact of there changes on modelled sulfur cycle are evaluated for modern climate. Further, boundary conditions are adapted to simulate the atmospheric circulation and sulfur cycle at the Last Glacial Maximum, approximately 20,000 years ago. In the model, sulfur is found to be highly sensitive to antarctic sea-ice coverage, which is still poorly known during the ice age. An original dataset of ice-age sea-ice coverage was developed. Its impact on the oceanic emissions of dimethyl sulfide, main precursor of sulfur aerosols at high-southern latitudes, is discussed. Using the same oceanic sulfur reservoirs as for present day climate, the model broadly reproduces the glacial deposits of sulfur aerosols on the Antarctic plateau, suggesting little impact of climate on oceanic sulfur production in the Antarctic region. Sensitivity tests were carried out to draw an up-to-date status of major uncertainties and difficulties facing future progress in understanding atmospheric

  12. Sulfur hexafluoride (SF6) emissions in East Asia determined by inverse modeling

    Science.gov (United States)

    Fang, X.; Thompson, R. L.; Saito, T.; Yokouchi, Y.; Kim, J.; Li, S.; Kim, K. R.; Park, S.; Graziosi, F.; Stohl, A.

    2014-05-01

    Sulfur hexafluoride (SF6) has a global warming potential of around 22 800 over a 100-year time horizon and is one of the greenhouse gases regulated under the Kyoto Protocol. Around the year 2000 there was a reversal in the global SF6 emission trend, from a decreasing to an increasing trend, which was likely caused by increasing emissions in countries that are not obligated to report their annual emissions to the United Nations Framework Convention on Climate Change. In this study, SF6 emissions during the period 2006-2012 for all East Asian countries - including Mongolia, China, Taiwan, North Korea, South Korea and Japan - were determined by using inverse modeling and in situ atmospheric measurements. We found that the most important sources of uncertainty associated with these inversions are related to the choice of a priori emissions and their assumed uncertainty, the station network as well as the meteorological input data. Much lower uncertainties are due to seasonal variability in the emissions, inversion geometry and resolution, and the measurement calibration scale. Based on the results of these sensitivity tests, we estimate that the total SF6 emission in East Asia increased rapidly from 2404 ± 325 Mg yr-1 in 2006 to 3787 ± 512 Mg yr-1 in 2009 and stabilized thereafter. China contributed 60-72% to the total East Asian emission for the different years, followed by South Korea (8-16%), Japan (5-16%) and Taiwan (4-7%), while the contributions from North Korea and Mongolia together were less than 3% of the total. The per capita SF6 emissions are highest in South Korea and Taiwan, while the per capita emissions for China, North Korea and Japan are close to global average. During the period 2006-2012, emissions from China and from South Korea increased, while emissions from Taiwan and Japan decreased overall.

  13. 7 CFR 457.168 - Mustard crop insurance provisions.

    Science.gov (United States)

    2010-01-01

    ... contained in the Basic Provisions, mustard seed must be planted in rows. Acreage planted in any other manner... placing into windrows without removal of the seed from the pod. Type. A category of mustard identified as... Directive for Inspection of Mustard Seed, provided by the Federal Grain Inspection Service or such other...

  14. Hydrogen peroxide oxidation of mustard-model sulfides catalyzed by iron and manganese tetraarylporphyrines. Oxygen transfer to sulfides versus H(2)O(2) dismutation and catalyst breakdown.

    Science.gov (United States)

    Marques, A; Marin, M; Ruasse, M F

    2001-11-16

    Fe(III)- and Mn(III)-meso-tetraarylporphyrin catalysis of H(2)O(2) oxidation of dibenzyl and phenyl-2-chloroethyl sulfides, 1, is investigated in ethanol with the aim of designing catalytic systems for mustard decontamination. The sulfide conversion, the sulfoxide and sulfone yields, the oxygen transfer from H(2)O(2) to the sulfide, and the catalyst stability depend markedly on the metal, on the substituents of its ligand, and on the presence or the absence of a cocatalyst, imidazole or ammonium acetate. With Fe, sulfones, the only oxidation products, are readily obtained whatever the ligand (TPP, F(20)TPP, or TDCPP) and the cocatalyst; the oxygen transfer is fairly good, up to 95% when the catalyst concentration is small ([1]/[Cat] = 420); the catalyst breakdown is insignificant only in the absence of any cocatalyst. With Mn, the sulfide conversion is achieved completely when the ligand is TDCPP or TSO(3)PP, but not F(20)TPP or TPP; a mixture of sulfoxide, 2, and sulfone, 3, is always obtained with [2]/[3] = 3.5-0.85 depending on the ligand and the cocatalyst (electron withdrawing substituents favor 3 and NH(4)OAc, 2). The catalyst stability is very good, but the oxygen transfer is poor whatever the ligand and the cocatalyst. These results are discussed in terms of a scheme in which sulfide oxygenation, H(2)O(2) dismutation, and oxidative ligand breaking compete. It is shown that the efficiency of the oxygen transfer is related not only to the rate constant of the dismutation route but also to the concentration of the active metal-oxo intermediate, most likely a perferryl or permanganyl species, i.e., to the rate of its formation.

  15. Bioterrorism Agents/Diseases

    Science.gov (United States)

    ... Poisoning Methyl isocyanate Case Definition: Methyl Isocyanate Poisoning Mustard gas (H) (sulfur mustard) Facts About Sulfur Mustard Case ... About Strychnine Case Definition: Strychnine Sulfur mustard (H) (mustard gas) Facts About Sulfur Mustard Case Definition: Vesicant (Mustards, ...

  16. Chemical Agents

    Science.gov (United States)

    ... Poisoning Methyl isocyanate Case Definition: Methyl Isocyanate Poisoning Mustard gas (H) (sulfur mustard) Facts About Sulfur Mustard Case ... About Strychnine Case Definition: Strychnine Sulfur mustard (H) (mustard gas) Facts About Sulfur Mustard Case Definition: Vesicant (Mustards, ...

  17. Sodium Azide

    Science.gov (United States)

    ... Poisoning Methyl isocyanate Case Definition: Methyl Isocyanate Poisoning Mustard gas (H) (sulfur mustard) Facts About Sulfur Mustard Case ... About Strychnine Case Definition: Strychnine Sulfur mustard (H) (mustard gas) Facts About Sulfur Mustard Case Definition: Vesicant (Mustards, ...

  18. Facts about Benzene

    Science.gov (United States)

    ... Poisoning Methyl isocyanate Case Definition: Methyl Isocyanate Poisoning Mustard gas (H) (sulfur mustard) Facts About Sulfur Mustard Case ... About Strychnine Case Definition: Strychnine Sulfur mustard (H) (mustard gas) Facts About Sulfur Mustard Case Definition: Vesicant (Mustards, ...

  19. Pneumonic Plague

    Science.gov (United States)

    ... Poisoning Methyl isocyanate Case Definition: Methyl Isocyanate Poisoning Mustard gas (H) (sulfur mustard) Facts About Sulfur Mustard Case ... About Strychnine Case Definition: Strychnine Sulfur mustard (H) (mustard gas) Facts About Sulfur Mustard Case Definition: Vesicant (Mustards, ...

  20. Modeling and observational constraints on the sulfur cycle in the marine troposphere: a focus on reactive halogens and multiphase chemistry

    Science.gov (United States)

    Chen, Q.; Breider, T.; Schmidt, J.; Sherwen, T.; Evans, M. J.; Xie, Z.; Quinn, P.; Bates, T. S.; Alexander, B.

    2017-12-01

    The radiative forcing from marine boundary layer clouds is still highly uncertain, which partly stems from our poor understanding of cloud condensation nuclei (CCN) formation. The oxidation of dimethyl sulfide (DMS) and subsequent chemical evolution of its products (e.g. DMSO) are key processes in CCN formation, but are generally very simplified in large-scale models. Recent research has pointed out the importance of reactive halogens (e.g. BrO and Cl) and multiphase chemistry in the tropospheric sulfur cycle. In this study, we implement a series of sulfur oxidation mechanisms into the GEOS-Chem global chemical transport model, involving both gas-phase and multiphase oxidation of DMS, DMSO, MSIA and MSA, to improve our understanding of the sulfur cycle in the marine troposphere. DMS observations from six locations around the globe and MSA/nssSO42- ratio observations from two ship cruises covering a wide range of latitudes and longitudes are used to assess the model. Preliminary results reveal the important role of BrO for DMS oxidation at high latitudes (up to 50% over Southern Ocean). Oxidation of DMS by Cl radicals is small in the model (within 10% in the marine troposphere), probably due to an underrepresentation of Cl sources. Multiphase chemistry (e.g. oxidation by OH and O3 in cloud droplets) is not important for DMS oxidation but is critical for DMSO oxidation and MSA production and removal. In our model, about half of the DMSO is oxidized in clouds, leading to the formation of MSIA, which is further oxidized to form MSA. Overall, with the addition of reactive halogens and multiphase chemistry, the model is able to better reproduce observations of seasonal variations of DMS and MSA/nssSO42- ratios.

  1. Sulfur dioxide estimations in the planetary boundary layer using dispersion models and satellite retrievals

    Science.gov (United States)

    Zarauz, Jorge V.

    The health and environmental conditions in the Central Andes city La Oroya, Peru, have been seriously damaged by the heavy metal mining activities in the region. The situation has been exacerbated by the complex topography, which prevents proper mixing and dissolution of particles and gases released into the atmosphere. Understanding how pollutants are dispersed in populated regions, especially in complex terrain, would help to create mitigation strategies. The present study uses CALPUFF and HYSPLIT dispersion/deposition models to estimate sulfur dioxide (SO2) dispersion from the main stack of the La Oroya metallurgical plant. Due to the lack of meteorological data in the area, the Weather Research and Forecasting model (WRF) is used with observational nudging for temperature, relative humidity, and wind fields of three surface meteorological stations specifically installed for the study. The pollutant dispersion models are sensitive to a precise estimation of the turbulent vertical transport of mass, energy and moisture in the low atmosphere; therefore, two planetary boundary layer (PBL) schemes are tested, the Mellor-Yamada-Janjic and Yonsei University models. The dispersion models are run and results compared with field measurements at La Oroya, and Huancayo. The observation-nudging and YSU scheme considerably improved the prognostic variables. CALPUFF and HYSPLIT models showed similar patterns; however, HYSPLIT overestimated SO2 concentrations for low PBLs. Moreover, recent enhancements on spectral, spatial and temporal resolution of atmospheric scanning sensors of chemical constituents from the space, have led to detecting trace gases of anthropogenic origin in the lower troposphere. This contribution also explores the SO2 level 2 dataset from Ozone Mapping Instrument (OMI), in conjunction with atmospheric optical depth and Angstrom coefficient data products, extracted from MODerate Resolution Imaging Spectroradiometer (MODIS) to estimate SO2 loads in the PBL

  2. The effect of nightly nasal CPAP treatment on nocturnal hypoxemia and sleep disorders in mustard gas-injured patients.

    Science.gov (United States)

    Vahedi, Ensieh; Fazeli Varzaneh, Ali Reza; Ghanei, Mostafa; Afsharpaiman, Shahla; Poursaleh, Zohre

    2014-12-01

    Sleep-related breathing disorders are associated with unusual respiratory pattern or an abnormal reduction in gas exchange during sleep that is common in sulfur mustard (SM) exposure. We compared 57 Iranian male patients injured with SM and had any complaints of sleep problems with an age-matched group of 21 Iranian male patients who had complaints of sleep problems and were not chemically injured; this group had Epworth Sleepiness Scale (ESS) above 10 and whom referred for polysomnography. Split-night studies were performed for patients with diagnostic polysomnography for obstructive sleep apnea (OSA) and respiratory events. We then studied respiratory events including episodes of OSA, apnea-hypopnea index (AHI) and respiratory disturbance index (RDI). The mean age in mustard-exposed patients was 48.14±8.04 years and in age-matched group, 48.19±8.39 years. In mustard exposed patients, there were statistical differences for the episodes of OSA (p=0.001), AHI (p=0.001), and RDI (p=0.001) between two segments of split-night studies. In the age-matched group, there were statistically differences for each parameter (episodes of OSA (p=0.001), AHI (p=0.001), and RDI (p=0.001)). There were no significant differences between two groups. This study indicated that the incidence of respiratory events and nocturnal hypoxemia during sleep in mustard-exposed patients were high and treatment with CPAP significantly reduced all these events.

  3. High resolution computed tomography findings and pulmonary function tests among mustard gas exposed patients: is there a remarkable relationship

    International Nuclear Information System (INIS)

    Adibi, A.; Niroomand, P.

    2012-01-01

    Objective: High resolution computed tomography (HRCT) and pulmonary function tests (PFT) are the two main methods, currently used for investigation of pulmonary complications in sulfur mustard gas exposed patients. According to different types of injuries in mustard gas exposed individuals, we decided to test the correlation between PFT and HRCT in these victims. Methodology: Fifty one randomly selected cases from 12000 mustard gas exposed patients during Iran-Iraq war (1983-1989) were studied. HRCT and PFT were conducted based on standard protocols. HRCT scores were tested for correlation to PFT measures. Results: A significant differences between PFT findings were found within HRCT groups (score=3, score 4-6 and score =7). There was a significant correlation between HRCT scores and FEV1, MMEF and FEV1: FVC ratio (P<0.05) in all subjects. Conclusion: HRCT and PFT results showed an acceptable correlation in mustard gas exposed patients. It seems to be useful to use each of these two diagnostic tools based on clinical judgment and feasibility. (author)

  4. Estimating Sulfur hexafluoride (SF6) emissions in China using atmospheric observations and inverse modeling

    Science.gov (United States)

    Fang, X.; Thompson, R.; Saito, T.; Yokouchi, Y.; Li, S.; Kim, J.; Kim, K.; Park, S.; Graziosi, F.; Stohl, A.

    2013-12-01

    With a global warming potential of around 22800 over a 100-year time horizon, sulfur hexafluoride (SF6) is one of the greenhouse gases regulated under the Kyoto Protocol. Global SF6 emissions have been increasing since circa the year 2000. The reason for this increase has been inferred to be due to rapidly increasing emissions in developing countries that are not obligated to report their annual emissions to the United Nations Framework Convention on Climate Change, notably China. In this study, SF6 emissions during the period 2006-2012 for China and other East Asian countries were determined using in-situ atmospheric measurements and inverse modeling. We performed various inversion sensitivity tests, which show the largest uncertainties in the a posteriori Chinese emissions are associated with the a priori emissions used and their uncertainty, the station network, as well as the meteorological input data. The overall relative uncertainty of the a posteriori emissions in China is estimated to be 17% in 2008. Based on sensitivity tests, we employed the optimal parameters in our inversion setup and performed yearly inversions for the study period. Inversion results show that the total a posteriori SF6 emissions from China increased from 1420 × 245 Mg/yr in 2006 to 2741 × 472 Mg/yr in 2009 and stabilized thereafter. The rapid increase in emissions reflected a fast increase in SF6 consumption in China, a result also found in bottom-up estimates. The a posteriori emission map shows high emissions concentrated in populated parts of China. During the period 2006-2012, emissions in northwestern and northern China peaked around the year 2009, while emissions in eastern, central and northeastern China grew gradually during almost the whole period. Fluctuating emissions are observed for southwestern China. These regional differences should be caused by changes of provincial SF6 usage and by shifts of usage among different sectors. Fig. 1. Footprint emission sensitivity

  5. Aircraft exhaust sulfur emissions

    Energy Technology Data Exchange (ETDEWEB)

    Brown, R.C.; Anderson, M.R.; Miake-Lye, R.C.; Kolb, C.E. [Aerodyne Research, Inc., Billerica, MA (United States). Center for Chemical and Environmental Physics; Sorokin, A.A.; Buriko, Y.I. [Scientific Research Center `Ecolen`, Moscow (Russian Federation)

    1997-12-31

    The extent to which fuel sulfur is converted to SO{sub 3} during combustion and the subsequent turbine flow in supersonic and subsonic aircraft engines is estimated numerically. The analysis is based on: a flamelet model with non-equilibrium sulfur chemistry for the combustor, and a one-dimensional, two-stream model with finite rate chemical kinetics for the turbine. The results indicate that between 2% and 10% of the fuel sulfur is emitted as SO{sub 3}. It is also shown that, for a high fuel sulfur mass loading, conversion in the turbine is limited by the level of atomic oxygen at the combustor exit, leading to higher SO{sub 2} oxidation efficiency at lower fuel sulfur loadings. While SO{sub 2} and SO{sub 3} are the primary oxidation products, the model results further indicate H{sub 2}SO{sub 4} levels on the order of 0.1 ppm for supersonic expansions through a divergent nozzle. This source of fully oxidized S(6) (SO{sub 3} + H{sub 2}SO{sub 4}) exceeds previously calculated S(6) levels due to oxidation of SO{sub 2} by OH in the exhaust plume outside the engine nozzle. (author) 26 refs.

  6. Sulfur Earth

    Science.gov (United States)

    de Jong, B. H.

    2007-12-01

    Variations in surface tension affect the buoyancy of objects floating in a liquid. Thus an object floating in water will sink deeper in the presence of dishwater fluid. This is a very minor but measurable effect. It causes for instance ducks to drown in aqueous solutions with added surfactant. The surface tension of liquid iron is very strongly affected by the presence of sulfur which acts as a surfactant in this system varying between 1.9 and 0.4 N/m at 10 mass percent Sulfur (Lee & Morita (2002), This last value is inferred to be the maximum value for Sulfur inferred to be present in the liquid outer core. Venting of Sulfur from the liquid core manifests itself on the Earth surface by the 105 to 106 ton of sulfur vented into the atmosphere annually (Wedepohl, 1984). Inspection of surface Sulfur emission indicates that venting is non-homogeneously distributed over the Earth's surface. The implication of such large variation in surface tension in the liquid outer core are that at locally low Sulfur concentration, the liquid outer core does not wet the predominantly MgSiO3 matrix with which it is in contact. However at a local high in Sulfur, the liquid outer core wets this matrix which in the fluid state has a surface tension of 0.4 N/m (Bansal & Doremus, 1986), couples with it, and causes it to sink. This differential and diapiric movement is transmitted through the essentially brittle mantle (1024 Pa.s, Lambeck & Johnson, 1998; the maximum value for ice being about 1030 Pa.s at 0 K, in all likely hood representing an upper bound of viscosity for all materials) and manifests itself on the surface by the roughly 20 km differentiation, about 0.1 % of the total mantle thickness, between topographical heights and lows with concomitant lateral movement in the crust and upper mantle resulting in thin skin tectonics. The brittle nature of the medium though which this movement is transmitted suggests that the extremes in topography of the D" layer are similar in range to

  7. HIGH-Resolution CT in Chronic Pulmonary Changes after Mustard Gas Exposure

    International Nuclear Information System (INIS)

    Bagheri, M.H.; Mostafavi, S.H.

    2003-01-01

    Purpose: To identify the findings of high-resolution CT (HRCT) of the lung in patients with previous sulfur mustard gas exposure, and to correlate these findings with clinical and chest X-ray (CXR) results. Material and Methods: 50 consecutive patients were studied prospectively. The clinical data were recorded. Standard p.a. CXR and HRCT of the lung and spirometry were performed. The findings of CXR, HRCT and clinical and spirometry results were scored between 0 and 3 according to the severity of the findings. Results: HRCT abnormality was detected in all 50 patients (100%), while CXR was abnormal in 40 patients (80%). The most common HRCT findings was airway abnormalities (bronchial wall thickening in 100% of cases). Other important findings were suggestive of interstitial lung disease (ILD) (80%), bronchiectasis (26%), and emphysema (24%). A statistically significant correlation was found between the severity of clinical presentation and that of the HCTR scores in patients with bronchiectasis, bronchitis and ILD (p< 0.05), but not with severity scores of HRCT in patients with emphysema. No significant correlation was found between severity scores of CXR findings. HRCT evidence of bronchial wall thickening and with a lower frequency ILD were present despite normal CXR in 20% of the patients. Conclusion: The results of this study suggest that bronchial wall thickening, ILD and emphysema are common chronic pulmonary sequelae of sulfur mustard injury. HRCT of the chest should be considered as the imaging modality of choice in chemical war injury

  8. HIGH-Resolution CT in Chronic Pulmonary Changes after Mustard Gas Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Bagheri, M.H.; Mostafavi, S.H. [Shiraz Univ. of Medical Siences (Iran, Islamic Republic of). Dept. of Radiology; Hosseini, S.K. [Shiraz Univ. of Medical Siences (Iran, Islamic Republic of). Dept. of Internal Medicine; Alavi, S.A. [Medical Center for Chemical Warfare Victims Foundation, Shiraz (Iran, Islamic Republic of)

    2003-05-01

    Purpose: To identify the findings of high-resolution CT (HRCT) of the lung in patients with previous sulfur mustard gas exposure, and to correlate these findings with clinical and chest X-ray (CXR) results. Material and Methods: 50 consecutive patients were studied prospectively. The clinical data were recorded. Standard p.a. CXR and HRCT of the lung and spirometry were performed. The findings of CXR, HRCT and clinical and spirometry results were scored between 0 and 3 according to the severity of the findings. Results: HRCT abnormality was detected in all 50 patients (100%), while CXR was abnormal in 40 patients (80%). The most common HRCT findings was airway abnormalities (bronchial wall thickening in 100% of cases). Other important findings were suggestive of interstitial lung disease (ILD) (80%), bronchiectasis (26%), and emphysema (24%). A statistically significant correlation was found between the severity of clinical presentation and that of the HCTR scores in patients with bronchiectasis, bronchitis and ILD (p< 0.05), but not with severity scores of HRCT in patients with emphysema. No significant correlation was found between severity scores of CXR findings. HRCT evidence of bronchial wall thickening and with a lower frequency ILD were present despite normal CXR in 20% of the patients. Conclusion: The results of this study suggest that bronchial wall thickening, ILD and emphysema are common chronic pulmonary sequelae of sulfur mustard injury. HRCT of the chest should be considered as the imaging modality of choice in chemical war injury.

  9. Effect of sulfur fertilization on the sanitary state of plants of the family Brassicaceae

    Directory of Open Access Journals (Sweden)

    Tomasz P. Kurowski

    2012-12-01

    Full Text Available The experiment was carried out in the years 2006-2008 in Bałcyny (N=53°35'49"; E=19°51'20". The aim of this study was to determine the effect of sulfur fertilization on the sanitary state of spring oilseed rape, winter oilseed rape, white mustard and Chinese mustard as well as on the species composition of fungi colonizing their seeds. Sulfur fertilization had a beneficial effect on the health of Brassicaceae plants infested by Alternaria blight, grey mould, Sclerotinia stem rot, Phoma stem canker and Verticillium wilt, but it had a varying effect on the occurrence of powdery mildew. Alternaria alternata and Penicillium spp. were isolated most frequently from Brassicaceae seeds. In general, more fungi (including pathogenic to Brassicaceae were isolated from the seeds of plants grown in non-sulfur fertilized plots. Pathogens occurred primarily on the seed surface, and their number decreased after surface disinfection of seeds.

  10. Sulfur cycle

    Digital Repository Service at National Institute of Oceanography (India)

    LokaBharathi, P.A.

    energy. At the end of the anaerobic food chain in bacteria they serve to purify the system of sulfide and other metabolic end products. In the process sulfur is returned to the system as sulfate. In transition zones from anaerobic to aerobic...

  11. A novel diffusion-biphasic hydrolysis coupled kinetic model for dilute sulfuric acid pretreatment of corn stover.

    Science.gov (United States)

    Chen, Longjian; Zhang, Haiyan; Li, Junbao; Lu, Minsheng; Guo, Xiaomiao; Han, Lujia

    2015-02-01

    Kinetic experiments on the dilute sulfuric acid pretreatment of corn stover were performed. A high xylan removal and a low inhibitor concentration were achieved by acid pretreatment. A novel diffusion-hydrolysis coupled kinetic model was proposed. The contribution to the xylose yield was analyzed by the kinetic model. Compared with the inhibitor furfural negatively affecting xylose yield, the fast and slow-hydrolyzing xylan significantly contributed to the xylose yield, however, their dominant roles were dependent on reaction temperature and time. The impact of particle size and acid concentration on the xylose yield were also investigated. The diffusion process may significantly influence the hydrolysis of large particles. Increasing the acid concentration from 0.15 M to 0.30 M significantly improved the xylose yield, whereas the extent of improvement decreased to near-quantitative when further increasing acid loading. These findings shed some light on the mechanism for dilute sulfuric acid hydrolysis of corn stover. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. 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.

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  14. Reactivity of volatile thiols with polyphenols in a wine-model medium: impact of oxygen, iron, and sulfur dioxide.

    Science.gov (United States)

    Nikolantonaki, Maria; Chichuc, Igor; Teissedre, Pierre-Louis; Darriet, Philippe

    2010-02-15

    As volatile thiols are nucleophiles, they are capable of additional reactions with electrophiles. In enology, this concerns reactions between volatile or non-volatile thiols and oxidized phenolic compounds. Initial studies concerning the reactivity of volatile thiols with polyphenols showed that (+)-catechin played a detrimental role in the level of 3-sulfanylhexan-1-ol (3SH), in the absence of sulfur dioxide. Our experiment revealed that (-)-epicatechin was more reactive with volatile thiols than (+)-catechin. Furthermore, Fe (III) was shown to play a crucial role in catalyzing polyphenol oxidation reactions, by affecting the direct reaction of phenolic compounds with oxygen. It was noted that, even if the volatile thiols studied were members of the same chemical family, they exhibited a different behavior pattern under oxidation conditions. 2-furanmethanethiol (2FMT) was more reactive than 3-sulfanylhexan-1-ol with both (+)-catechin and (-)-epicatechin. In contrast, 4-methyl-4-sulfanylpentan-2-one (4MSP) was less reactive with these phenolics. Additionally, the vital role of sulfur dioxide in protecting 3-sulfanylhexan-1-ol, 2-furanmethanethiol, and 4-methyl-4-sulfanylpentan-2-one was demonstrated in the model medium. Copyright 2009 Elsevier B.V. All rights reserved.

  15. Oxidants and antioxidants in sulfur mustard–induced injury

    Science.gov (United States)

    Laskin, Jeffrey D.; Black, Adrienne T.; Jan, Yi-Hua; Sinko, Patrick J.; Heindel, Ned D.; Sunil, Vasanthi; Heck, Diane E.; Laskin, Debra L.

    2014-01-01

    Sulfur mustard (SM) is a chemical weapon that targets the skin, eyes, and lung. It was first employed during World War I and it remains a significant military and civilian threat. As a bifunctional alkylating agent, SM reacts with a variety of macromolecules in target tissues including nucleic acids, proteins and lipids, as well as small molecular weight metabolites such as glutathione. By alkylating subcellular components, SM disrupts metabolism, a process that can lead to oxidative stress. Evidence for oxidative stress in tissues exposed to SM or its analogs include increased formation of reactive oxygen species, the presence of lipid peroxidation products and oxidized proteins, and increases in antioxidant enzymes such as superoxide dismutase, catalase, and glutathione-S-transferase. Inhibition of antioxidant enzymes including thioredoxin reductase by SM can also disrupt cellular redox homeostasis. Consistent with these findings, SM-induced toxicity has been shown to be reduced by antioxidants in both in vitro and in vivo models. These data indicate that drugs that target oxidative stress pathways may represent important candidates for reducing SM-induced tissue injury. PMID:20716289

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Features of accumulation of inorganic elements in seeds of white mustard (Sinapis alba L.) and black mustard (Brassica nigra L.)

    OpenAIRE

    О. І. Рудник-Іващенко; Л. М. Михальська; В. В. Швартау

    2016-01-01

    Purpose. To investigate special aspects of accumulation of inorganic elements including heavy metals in seeds of white and black mustard to be grown for obtaining drugs. Methods. Field experiments, microwave digestion, ICP-MS and statistical analysis. Results. The content of inorganic elements including heavy metals was determined in the seeds of white and black mustard grown in Kiev Oblast. It was revealed that during the growing season plants of white mustard were able to accumulate...

  18. Graviditet efter Mustards operation for transpositio vasorum

    DEFF Research Database (Denmark)

    Pank, Marie; Larsen, Signe Holm; Sørensen, Keld

    2009-01-01

    INTRODUCTION: Previously, the Mustard operation was the preferred surgical technique in patients with transposition of the great arteries. After this procedure the anatomical right ventricle remains the systemic ventricle, which entails long-term complications, especially heart failure. The Mustard....... MATERIAL AND METHODS: Information on diagnosis, procedure, functional status, pregnancy, delivery and congenital heart disease in the off-spring were found in registers (The National Register of Health, The National Birth Register) and in medical records. Questionnaires were mailed to the 16 surviving...... women over 15 years of age. RESULTS: Four women gave birth to nine children. Two women temporally had heart symptoms during pregnancy and delivery, but this caused no objective changes. The women who had children were older than those who did not. None of the children had congenital heart disease nor...

  19. Tribological Characteristics Evaluation of Mustard Oil Blends

    OpenAIRE

    Mohammed Hassan Jabal; Muhannad Zaidan Khalefa

    2018-01-01

    A progressive increase in the desire for environmentally friendly lubricants by users and strict government regulations for the use of these lubricants has provided an opportunity to use plant oils as biodegradable lubricants, therefore vegetable oils have been investigated to replace oil lubricants because of their maintaining the conditions of nature (environment) properties. In this paper, the influences of the blending ratio of mustard seeds oil with commercial mineral oil (SAE40) on the ...

  20. Biologically produced sulfur

    NARCIS (Netherlands)

    Kleinjan, W.E.; Keizer, de A.; Janssen, A.J.H.

    2003-01-01

    Sulfur compound oxidizing bacteria produce sulfur as an intermediate in the oxidation of hydrogen sulfide to sulfate. Sulfur produced by these microorganisms can be stored in sulfur globules, located either inside or outside the cell. Excreted sulfur globules are colloidal particles which are

  1. Experimental and Kinetic Modeling Studies on the Conversion of Sucrose to Levulinic Acid and 5-Hydroxymethylfurfural Using Sulfuric Acid in Water

    NARCIS (Netherlands)

    Tan-Soetedjo, Jenny N. M.; van de Bovenkamp, Henk H.; Abdilla, Ria M.; Rasrendra, Carolus B.; van Ginkel, Jacob; Heeres, Hero J.

    2017-01-01

    We here report experimental and kinetic modeling studies on the conversion of sucrose to levulinic acid (LA) and 5-hydroxymethylfurfural (HMF) in water using sulfuric acid as the catalyst. Both compounds are versatile building blocks for the synthesis of various biobased (bulk) chemicals. A total of

  2. Teaching Human Genetics with Mustard: Rapid Cycling "Brassica rapa" (Fast Plants Type) as a Model for Human Genetics in the Classroom Laboratory

    Science.gov (United States)

    Wendell, Douglas L.; Pickard, Dawn

    2007-01-01

    We have developed experiments and materials to model human genetics using rapid cycling "Brassica rapa", also known as Fast Plants. Because of their self-incompatibility for pollination and the genetic diversity within strains, "B. rapa" can serve as a relevant model for human genetics in teaching laboratory experiments. The experiment presented…

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

    Science.gov (United States)

    2010-01-01

    ...) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Germination Tests in the Administration of the Act § 201.56-3 Mustard family, Brassicaceae (Cruciferae). Kinds of seed: Broccoli, brussels sprouts, cabbage... 7 Agriculture 3 2010-01-01 2010-01-01 false Mustard family, Brassicaceae (Cruciferae). 201.56-3...

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

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Anil K.; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep [Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); Orlicky, David J. [Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); Agarwal, Chapla [Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); White, Carl W. [Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045USA (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@UCDenver.edu [Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States)

    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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  6. Sulfur metabolism in phototrophic sulfur bacteria

    DEFF Research Database (Denmark)

    Frigaard, Niels-Ulrik; Dahl, Christiane

    2008-01-01

    Phototrophic sulfur bacteria are characterized by oxidizing various inorganic sulfur compounds for use as electron donors in carbon dioxide fixation during anoxygenic photosynthetic growth. These bacteria are divided into the purple sulfur bacteria (PSB) and the green sulfur bacteria (GSB......). They utilize various combinations of sulfide, elemental sulfur, and thiosulfate and sometimes also ferrous iron and hydrogen as electron donors. This review focuses on the dissimilatory and assimilatory metabolism of inorganic sulfur compounds in these bacteria and also briefly discusses these metabolisms...... in other types of anoxygenic phototrophic bacteria. The biochemistry and genetics of sulfur compound oxidation in PSB and GSB are described in detail. A variety of enzymes catalyzing sulfur oxidation reactions have been isolated from GSB and PSB (especially Allochromatium vinosum, a representative...

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

    NARCIS (Netherlands)

    Koppelman, S.J.; Vlooswijk, R.; Bottger, G.; Duijn, G. van; Schaft, P. van der; Dekker, J.; Bemgen, H. van

    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

  8. Sulfuric acid-sulfur heat storage cycle

    Science.gov (United States)

    Norman, John H.

    1983-12-20

    A method of storing heat is provided utilizing a chemical cycle which interconverts sulfuric acid and sulfur. The method can be used to levelize the energy obtained from intermittent heat sources, such as solar collectors. Dilute sulfuric acid is concentrated by evaporation of water, and the concentrated sulfuric acid is boiled and decomposed using intense heat from the heat source, forming sulfur dioxide and oxygen. The sulfur dioxide is reacted with water in a disproportionation reaction yielding dilute sulfuric acid, which is recycled, and elemental sulfur. The sulfur has substantial potential chemical energy and represents the storage of a significant portion of the energy obtained from the heat source. The sulfur is burned whenever required to release the stored energy. A particularly advantageous use of the heat storage method is in conjunction with a solar-powered facility which uses the Bunsen reaction in a water-splitting process. The energy storage method is used to levelize the availability of solar energy while some of the sulfur dioxide produced in the heat storage reactions is converted to sulfuric acid in the Bunsen reaction.

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

    Science.gov (United States)

    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. Copyright © 2013 John Wiley & Sons, Ltd.

  10. Transcriptome analysis of stem development in the tumourous stem mustard Brassica juncea var. tumida Tsen et Lee by RNA sequencing

    Directory of Open Access Journals (Sweden)

    Sun Quan

    2012-04-01

    Full Text Available Abstract Background Tumourous stem mustard (Brassica juncea var. tumida Tsen et Lee is an economically and nutritionally important vegetable crop of the Cruciferae family that also provides the raw material for Fuling mustard. The genetics breeding, physiology, biochemistry and classification of mustards have been extensively studied, but little information is available on tumourous stem mustard at the molecular level. To gain greater insight into the molecular mechanisms underlying stem swelling in this vegetable and to provide additional information for molecular research and breeding, we sequenced the transcriptome of tumourous stem mustard at various stem developmental stages and compared it with that of a mutant variety lacking swollen stems. Results Using Illumina short-read technology with a tag-based digital gene expression (DGE system, we performed de novo transcriptome assembly and gene expression analysis. In our analysis, we assembled genetic information for tumourous stem mustard at various stem developmental stages. In addition, we constructed five DGE libraries, which covered the strains Yong'an and Dayejie at various development stages. Illumina sequencing identified 146,265 unigenes, including 11,245 clusters and 135,020 singletons. The unigenes were subjected to a BLAST search and annotated using the GO and KO databases. We also compared the gene expression profiles of three swollen stem samples with those of two non-swollen stem samples. A total of 1,042 genes with significantly different expression levels occurring simultaneously in the six comparison groups were screened out. Finally, the altered expression levels of a number of randomly selected genes were confirmed by quantitative real-time PCR. Conclusions Our data provide comprehensive gene expression information at the transcriptional level and the first insight into the understanding of the molecular mechanisms and regulatory pathways of stem swelling and development

  11. submitter Modeling the thermodynamics and kinetics of sulfuric acid-dimethylamine-water nanoparticle growth in the CLOUD chamber

    CERN Document Server

    Ahlm, L; Schobesberger, S; Praplan, A P; Kim, J; Tikkanen, O -P; Lawler, M J; Smith, J N; Tröstl, J; Acosta Navarro, J C; Baltensperger, U; Bianchi, F; Donahue, N M; Duplissy, J; Franchin, A; Jokinen, T; Keskinen, H; Kirkby, J; Kürten, A; Laaksonen, A; Lehtipalo, K; Petäjä, T; Riccobono, F; Rissanen, M P; Rondo, L; Schallhart, S; Simon, M; Winkler, P M; Worsnop, D R; Virtanen, A; Riipinen, I

    2016-01-01

    Dimethylamine (DMA) has a stabilizing effect on sulfuric acid (SA) clusters, and the SA and DMA molecules and clusters likely play important roles in both aerosol particle formation and growth in the atmosphere. We use the monodisperse particle growth model for acid-base chemistry in nanoparticle growth (MABNAG) together with direct and indirect observations from the CLOUD4 and CLOUD7 experiments in the cosmics leaving outdoor droplets (CLOUD) chamber at CERN to investigate the size and composition evolution of freshly formed particles consisting of SA, DMA, and water as they grow to 20 nm in dry diameter. Hygroscopic growth factors are measured using a nano-hygroscopicity tandem differential mobility analyzer (nano-HTDMA), which combined with simulations of particle water uptake using the thermodynamic extended-aerosol inorganics model (E-AIM) constrain the chemical composition. MABNAG predicts a particle-phase ratio between DMA and SA molecules of 1.1–1.3 for a 2 nm particle and DMA gas-phase mixing ratio...

  12. Comparison of Optimal Thermodynamic Models of the Tricarboxylic Acid Cycle from Heterotrophs, Cyanobacteria, and Green Sulfur Bacteria.

    Science.gov (United States)

    Thomas, Dennis G; Jaramillo-Riveri, Sebastian; Baxter, Douglas J; Cannon, William R

    2014-12-26

    We have applied a new stochastic simulation approach to predict the metabolite levels, material flux, and thermodynamic profiles of the oxidative TCA cycles found in E. coli and Synechococcus sp. PCC 7002, and in the reductive TCA cycle typical of chemolithoautotrophs and phototrophic green sulfur bacteria such as Chlorobaculum tepidum. The simulation approach is based on modeling states using statistical thermodynamics and employs an assumption similar to that used in transition state theory. The ability to evaluate the thermodynamics of metabolic pathways allows one to understand the relationship between coupling of energy and material gradients in the environment and the self-organization of stable biological systems, and it is shown that each cycle operates in the direction expected due to its environmental niche. The simulations predict changes in metabolite levels and flux in response to changes in cofactor concentrations that would be hard to predict without an elaborate model based on the law of mass action. In fact, we show that a thermodynamically unfavorable reaction can still have flux in the forward direction when it is part of a reaction network. The ability to predict metabolite levels, energy flow, and material flux should be significant for understanding the dynamics of natural systems and for understanding principles for engineering organisms for production of specialty chemicals.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-01

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

  14. Mustard Group Chemical War Agents from Preventive Medicine Perspective

    Directory of Open Access Journals (Sweden)

    Muharrem Ucar

    2007-06-01

    Full Text Available Although many preventive efforts and treaties, chemical warfare agents have still been a severe assault form against both military and civilian individuals. The most important chemical warfare agents sulphur mustard and others are easy to handle and cheap those the important reasons to accept sulphur mustard as a chemical warfare agent. Many individuals attacked by sulphur mustard have severe health problems such as respiratory system diseases. After ten years of sulphur mustard exposure, several health problems such as respiratory tract problems (%42.5, eye problems (%40 and other systemic diseases have been observed to insist on induviduals when examined. Exposure of even single sulphur mustard exposure has been seen to result high level of disability and early deaths. In spite of the fact that there is no available antidote and/or remedy against sulphur mustard exposure, our country has an incremental chemical assault threat for both military personels and civilians because of its jeopolitics position. Experimental studies regarding sulphur mustard toxicity will be helpful for novel preventive strategies and antidot devolepment. [TAF Prev Med Bull 2007; 6(3.000: 209-214

  15. PERFORMANCE AND ANALYSIS OF MUSTARD FARMING IN JAYAPURA PAPUA

    Directory of Open Access Journals (Sweden)

    Herman Tangkelayuk

    2014-01-01

    Full Text Available Research aim was to see variability, feasibility, and mustard farm income cultivated in Jayapura . The experiment was conducted in Kampung Yobeh, District of Sentani, Jayapura regency, on November to December 2013, using data growing season in October 2013, in form of a survey involving 30 mustard farmers as respondents . Determination of respondent using simple random method by getting farmers planting mustard continuously. Results: average mustard farmers area of 0,099 ha, seed expenses of IDR 37,400, the use of 9.20 kg Urea, NPK 2.80 kg, 526 kg manure , and cost of medicines IDR 26.366, male workers 2.66 HOK and women 2.03 HOK , and other expenses (shrinkage values and land tax .The level of productivity of mustard is 538.6 kg/0.99 ha/cropping season. Total revenue mustard farming with land size 0,099 ha/growing season is IDR 1.615.800, total spending is IDR 562 18. Benefit of farmers is IDR 1,053,618 with value of R/C ratio of 2.87. Analysis shows that mustard farming in Yobeh village, Sentani, Jayapura profitable, it is advisable for further development. Need guidance from Field Extension so that increased production increased.

  16. Multi-model mean nitrogen and sulfur deposition from the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP: evaluation of historical and projected future changes

    Directory of Open Access Journals (Sweden)

    J.-F. Lamarque

    2013-08-01

    Full Text Available We present multi-model global datasets of nitrogen and sulfate deposition covering time periods from 1850 to 2100, calculated within the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP. The computed deposition fluxes are compared to surface wet deposition and ice core measurements. We use a new dataset of wet deposition for 2000–2002 based on critical assessment of the quality of existing regional network data. We show that for present day (year 2000 ACCMIP time slice, the ACCMIP results perform similarly to previously published multi-model assessments. For this time slice, we find a multi-model mean deposition of approximately 50 Tg(N yr−1 from nitrogen oxide emissions, 60 Tg(N yr−1 from ammonia emissions, and 83 Tg(S yr−1 from sulfur emissions. The analysis of changes between 1980 and 2000 indicates significant differences between model and measurements over the United States but less so over Europe. This difference points towards a potential misrepresentation of 1980 NH3 emissions over North America. Based on ice core records, the 1850 deposition fluxes agree well with Greenland ice cores, but the change between 1850 and 2000 seems to be overestimated in the Northern Hemisphere for both nitrogen and sulfur species. Using the Representative Concentration Pathways (RCPs to define the projected climate and atmospheric chemistry related emissions and concentrations, we find large regional nitrogen deposition increases in 2100 in Latin America, Africa and parts of Asia under some of the scenarios considered. Increases in South Asia are especially large, and are seen in all scenarios, with 2100 values more than double their 2000 counterpart in some scenarios and reaching > 1300 mg(N m−2 yr−1 averaged over regional to continental-scale regions in RCP 2.6 and 8.5, ~ 30–50% larger than the values in any region currently (circa 2000. However, sulfur deposition rates in 2100 are in all regions lower than in 2000 in

  17. Multi-model mean nitrogen and sulfur deposition from the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP): evaluation of historical and projected future changes

    Science.gov (United States)

    Lamarque, J.-F.; Dentener, F.; McConnell, J.; Ro, C.-U.; Shaw, M.; Vet, R.; Bergmann, D.; Cameron-Smith, P.; Dalsoren, S.; Doherty, R.; Faluvegi, G.; Ghan, S. J.; Josse, B.; Lee, Y. H.; MacKenzie, I. A.; Plummer, D.; Shindell, D. T.; Skeie, R. B.; Stevenson, D. S.; Strode, S.; Zeng, G.; Curran, M.; Dahl-Jensen, D.; Das, S.; Fritzsche, D.; Nolan, M.

    2013-08-01

    We present multi-model global datasets of nitrogen and sulfate deposition covering time periods from 1850 to 2100, calculated within the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP). The computed deposition fluxes are compared to surface wet deposition and ice core measurements. We use a new dataset of wet deposition for 2000-2002 based on critical assessment of the quality of existing regional network data. We show that for present day (year 2000 ACCMIP time slice), the ACCMIP results perform similarly to previously published multi-model assessments. For this time slice, we find a multi-model mean deposition of approximately 50 Tg(N) yr-1 from nitrogen oxide emissions, 60 Tg(N) yr-1 from ammonia emissions, and 83 Tg(S) yr-1 from sulfur emissions. The analysis of changes between 1980 and 2000 indicates significant differences between model and measurements over the United States but less so over Europe. This difference points towards a potential misrepresentation of 1980 NH3 emissions over North America. Based on ice core records, the 1850 deposition fluxes agree well with Greenland ice cores, but the change between 1850 and 2000 seems to be overestimated in the Northern Hemisphere for both nitrogen and sulfur species. Using the Representative Concentration Pathways (RCPs) to define the projected climate and atmospheric chemistry related emissions and concentrations, we find large regional nitrogen deposition increases in 2100 in Latin America, Africa and parts of Asia under some of the scenarios considered. Increases in South Asia are especially large, and are seen in all scenarios, with 2100 values more than double their 2000 counterpart in some scenarios and reaching > 1300 mg(N) m-2 yr-1 averaged over regional to continental-scale regions in RCP 2.6 and 8.5, ~ 30-50% larger than the values in any region currently (circa 2000). However, sulfur deposition rates in 2100 are in all regions lower than in 2000 in all the RCPs. The new

  18. A self-discharge model of Lithium-Sulfur batteries based on direct shuttle current measurement

    DEFF Research Database (Denmark)

    Knap, Vaclav; Stroe, Daniel Loan; Swierczynski, Maciej Jozef

    2016-01-01

    . A simple but comprehensive mathematical model of the Li-S battery cell self-discharge based on the shuttle current was developed and is presented. The shuttle current values for the model parameterization were obtained from the direct shuttle current measurements. Furthermore, the battery cell depth......-of-discharge values were recomputed in order to account for the influence of the self-discharge and provide a higher accuracy of the model. Finally, the derived model was successfully validated against laboratory experiments at various conditions....

  19. The Global Garlic Mustard Field Survey: challenges and opportunities of a unique, large-scale collaboration for invasion biology

    Czech Academy of Sciences Publication Activity Database

    Colautti, R. I.; Franks, S. J.; Hufbauer, R. A.; Kotanen, P. M.; Torchin, M.; Byers, J. E.; Pyšek, Petr; Bossdorf, O.

    2014-01-01

    Roč. 21, č. 1 (2014), s. 29-47 ISSN 1619-0033 Grant - others:AV ČR(CZ) AP1002 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:67985939 Keywords : garlic mustard * citizen science * model system Subject RIV: EH - Ecology, Behaviour

  20. Formation and Control of Sulfur Oxides in Sour Gas Oxy-Combustion: Prediction Using a Reactor Network Model

    KAUST Repository

    Bongartz, Dominik

    2015-11-19

    © 2015 American Chemical Society. Sour natural gas currently requires expensive gas cleanup before it can be used in power generation because it contains large amounts of hydrogen sulfide (H2S) and carbon dioxide (CO2) that entail a low heating value and highly corrosive combustion products. A potential alternative is to use the gas directly in a gas turbine process employing oxy-fuel combustion, which could eliminate the need for gas cleanup while also enabling the application of carbon capture and sequestration, possibly combined with enhanced oil recovery (EOR). However, the exact influence of an oxy-fuel environment on the combustion products of sour gas has not been quantified yet. In this work, we used a reactor network model for the combustor and the gas turbine together with our recently assembled and validated detailed chemical reaction mechanism for sour gas combustion to investigate the influence of some basic design parameters on the combustion products of natural gas and sour gas in CO2 or H2O diluted oxy-fuel combustion as well as in conventional air combustion. Our calculations show that oxy-fuel combustion produces up to 2 orders of magnitude less of the highly corrosive product sulfur trioxide (SO3) than air combustion, which clearly demonstrates its potential in handling sulfur containing fuels. Unlike in air combustion, in oxy-fuel combustion, SO3 is mainly formed in the flame zone of the combustor and is then consumed as the combustion products are cooled in the dilution zone of the combustor and the turbine. In oxy-fuel combustion, H2O dilution leads to a higher combustion efficiency than CO2 dilution. However, if the process is to be combined with EOR, CO2 dilution makes it easier to comply with the very low levels of oxygen (O2) required in the EOR stream. Our calculations also show that it might even be beneficial to operate slightly fuel-rich because this simultaneously decreases the O2 and SO3 concentration further. The flame zone