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Sample records for sulfur mustard exposed

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

    DTIC Science & Technology

    2015-06-01

    USAMRICD‐TR‐15‐02  A Histological Assessment of Lung Injury in Rats  Exposed to Inhaled  Sulfur  Mustard across Dose  and Time    Derron A...Lung Injury in rats Exposed to Inhaled Sulfur Mustard across Dose and Time 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...Histological Assessment of Lung Injury in Rats Exposed to Inhaled Sulfur Mustard across Dose and Time 5a. CONTRACT NUMBER 5b. GRANT NUMBER   5c

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

    PubMed

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

    2016-09-01

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

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

    SciTech Connect

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

    2013-12-15

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

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

    PubMed

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

    2017-06-28

    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.

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

    PubMed

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

    2008-05-01

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

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

    PubMed

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

    2016-12-01

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

  7. Comparative proteome analysis of peripheral neutrophils from sulfur mustard-exposed and COPD patients.

    PubMed

    Shahriary, Alireza; Mehrani, Hossein; Ghanei, Mostafa; Parvin, Shahram

    2015-01-01

    Respiratory disorders in sulfur mustard (SM)-exposed and chronic obstructive pulmonary disease (COPD) patients are mostly associated with neutrophilic inflammation, severe airflow limitation, and oxidative stress. The objective of this study was to establish whether neutrophil (PMN) proteomes in these diseases were similar or differed. Blood neutrophil proteomes from healthy, SM-exposed, and COPD subjects were analyzed using two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF MS). Elastase activity was determined kinetically. The results showed that levels of S100 calcium-binding protein (CBP) A12, S100 CBP A8, glyceraldehyde-3-phosphate dehy-drogenase, superoxide dismutase, and protein disulfide isomerase proteins - as well as elastase activity - were significantly increased in PMN from 'diseased' hosts compared to in cells from healthy controls. In contrast, coactosin-like protein, RhoGDP dissociation inhibitor, and actin isoforms were significantly decreased in diseased subjects' PMN compared to PMN of healthy controls. Moreover, serpin B1 and coronin-1A were expressed only in PMN of the healthy subjects. Lastly, S100 CBP A9, endoplasmic reticulum (ER)-60 protease, and glutathione-S-transferase isoforms were differentially expressed in the cells from the SM-exposed and COPD subjects. These results show that serpin B1, an efficient inhibitor of neutrophil serine proteases, was not detectable, and elastase activity significantly increased in PMN from both SM-exposed and COPD patients. It seems that, apart from inflammation and oxidative stress, a protease:anti-protease imbalance exists within PMN of both COPD and SM-exposed patients.

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

    PubMed

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

    2014-08-01

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

  9. Cytokine regulation by MAPK activated kinase 2 in keratinocytes exposed to sulfur mustard.

    PubMed

    Yego, E Chepchumba K; Dillman, James F

    2013-10-01

    Uncontrolled inflammation contributes to cutaneous damage following exposure to the warfare agent bis(2-chloroethyl) sulfide (sulfur mustard, SM). Activation of the p38 mitogen activated protein kinase (MAPK) precedes SM-induced cytokine secretion in normal human epidermal keratinocytes (NHEKs). This study examined the role of p38-regulated MAPK activated kinase 2 (MK2) during this process. Time course analysis studies using NHEK cells exposed to 200μM SM demonstrated rapid MK2 activation via phosphorylation that occurred within 15 min. p38 activation was necessary for MK2 phosphorylation as determined by studies using the p38 inhibitor SB203580. To compare the role of p38 and MK2 during SM-induced cytokine secretion, small interfering RNA (siRNA) targeting these proteins was utilized. TNF-α, IL-1β, IL-6 and IL-8 secretion was evaluated 24h postexposure, while mRNA changes were quantified after 8h. TNF-α, IL-6 and IL-8 up regulation at the protein and mRNA level was observed following SM exposure. IL-1β secretion was also elevated despite unchanged mRNA levels. p38 knockdown reduced SM-induced secretion of all the cytokines examined, whereas significant reduction in SM-induced cytokine secretion was only observed with TNF-α and IL-6 following MK2 knockdown. Our observations demonstrate potential activation of other p38 targets in addition to MK2 during SM-induced cytokine secretion.

  10. The immunostatus of natural killer cells in people exposed to sulfur mustard.

    PubMed

    Ghotbi, Ladan; Hassan, Zuhair

    2002-06-01

    Sulfur mustard (2,2-dichloroethyl sulfide, SM) has been documented as an alkylating agent. It has been widely used as a chemical weapon during the last two decades. Despite extensive worldwide research, no effective therapy has yet been devised for the treatment of patients exposed to SM. A severe suppression of the immune system still remains as the major cause of opportunistic infections, septicemia and death in such patients. The aim of this study was to determine the possible effect of SM on natural killer (NK) cells in patients suffering from SM injuries. Patients were classified into three groups: mild, moderate and severe. Blood sample obtained from each patient was examined using flowcytometric technique. Results showed that the percentage of NK cells (CD45+/CD56+) is significantly lower in severe patients than that of the control group (P<0.05). It was also observed that the activity of NK cells (CD56+/CD25+) in severe alkylating group is noticeably higher compared with the control group (P<0.1).

  11. Cytokine Regulation by MAPK Activated Kinase 2 in Keratinocytes Exposed to Sulfur Mustard

    DTIC Science & Technology

    2013-07-10

    sulfur mustard (bis(2-chloroethyl) sulfide; SM) is a bifunctional alkylating agent that leads to cutane- ous damage. Changes that characterize skin ...cytokine secretion (Sabourin et al., 2000). The skin provides a protective barrier from the environment, and keratinocytes are the predominant cell type...al., 2010). Uncontrolled activation of this kinase in epidermal tissue is also associated with inflammatory skin conditions such as psoriasis and

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

    PubMed

    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

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

    PubMed

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

    2016-04-01

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

  14. The effect of vitamin E on tracheal responsiveness and lung inflammation in sulfur mustard exposed guinea pigs.

    PubMed

    Boskabady, Mohammad Hossein; Amery, Sediqa; Vahedi, Nassim; Khakzad, Mohammad Reza

    2011-02-01

    Pulmonary complications of sulfur mustard (SM) range from mild respiratory symptoms to even severe bronchial stenosis. In the present study, the protective effect of vitamin E on tracheal responsiveness (TR) and lung inflammation of SM-exposed guinea pigs were examined. Guinea pigs were exposed to ethanol (control group), 40 mg/m(3) inhaled SM and ethanol vehicle (sulfur mustard exposed (SME) group), SME treated with vitamin E (SME + E), SME with dexamethasone (SME + D) and both drugs (SME + E + D), (n = 8 for each group). TR to methacholine, total and differential white blood cell (WBC) count of lung lavage and serum cytokines were evaluated 14 days post-exposure. TR, WBC, interleukin 4 (IL-4), interferon gamma (INF-γ), eosinophil, and monocyte levels in SME guinea pigs were significantly higher, but lymphocyte was lower than those of controls (P < 0.05 to P < 0.001). TR, IL-4, and eosinophil levels in SME + E, SME + D and SME + E + D, INF-γ in SME + E and SME + E + D and WBC in SME + E were significantly decreased compared to that of the SME group (P < 0.01 to P < 0.001). In addition, the TR of SME + D + E was significantly higher than that of SME + E (P < 0.01) and SME + D (P < 0.05) groups. The results showed a preventive effect of vitamin E, dexamethasone and their combination on TR and lung inflammation in SME guinea pigs.

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

    PubMed

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

    2015-12-01

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

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

    PubMed

    Wattana, Monica; Bey, Tareg

    2009-01-01

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

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

    SciTech Connect

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

    1991-12-31

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

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

    DTIC Science & Technology

    2000-01-01

    niacin - amide; however, indomethacin did protect against HD-induced inflammatory mediators and pathological injury [51]. Volume 14, Number 6, 2000...mustard vapor exposure by pretreatment with niacin - amide, promethazinc and indomethacin. J Appl Toxicol 1995;15:133-138. 50. Mol MAE, De Vries R...Pharmacol 1991;107:439-449. 51. Zhang Z, Riviere JE, Monterio-Riviere N A. Evaluation of protective effects of sodium thiosulfate, cysteine, niacin

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

    PubMed

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

    2011-01-01

    Exposure to sulfur mustard (SM) causes a variety of respiratory symptoms, such as chronic bronchitis and constrictive bronchiolitis. This study assessed the effectiveness of noninvasive positive-pressure ventilation, adjunct with 79:21 helium:oxygen instead of 79:21 air:oxygen, in 24 patients with a previous exposure to SM presenting with acute respiratory failure. Both air:oxygen and helium:oxygen significantly decreased systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse rate, respiratory rate, dyspnea, and increased oxygen saturation (P values: .007, .029, .002, <.001, <.001, <.001, and .002 for air:oxygen, respectively, and <.001, .020, .001, <.001, <.001, <.001, and .002, for helium:oxygen, respectively). Moreover, helium:oxygen more potently improved systolic pressure, mean arterial pressure, pulse rate, respiratory rate, and dyspnea (P values: .012, .048, <.001, <.001, and .012, respectively). The results of our study support the benefit of using helium:oxygen adjunct with noninvasive positive-pressure ventilation in patients exposed to SM with acute respiratory decompensation. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. 2,6-Dithiopurine blocks toxicity and mutagenesis in human skin cells exposed to sulfur mustard analogues, 2-chloroethyl ethyl sulfide and 2-chloroethyl methyl sulfide.

    PubMed

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

    2010-03-15

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

  1. 2,6-Dithiopurine blocks toxicity and mutagenesis in human skin cells exposed to sulfur mustard analogs, 2-chloroethyl ethyl sulfide and 2-chloroethyl methyl sulfide

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  4. Ultrastructural Correlates of Sulfur Mustard Toxicity

    DTIC Science & Technology

    1989-10-01

    number) FIELD GROUP SUBGROUP -)Sulfur mustard (HD), toxicity, lymphocytes in vitro, keratinocytes in culture, skin , ultrastructure, pathology. 19...sulfur mustard (HD) on 1) human lymphocytes in vitro, 2) human keratinocytes in culture, and 3) the skin of the hairless guiiea pig. While doses of...germinativum and the generation of microblisters at the dermal-epidermal junction were une ivocal to that reported for human- skin grafted to congenitally

  5. Evaluation of the effects of hypochlorite solutions in the decontamination of wounds exposed to either vx or sulfur mustard

    SciTech Connect

    Hobson, D.W.; Snider, T.H.; Korte, D.W.

    1993-05-13

    The decontamination safety and efficacy of aqueous solutions of sodium hypochlorite (NaOCl) and calcium hypochlorite Ca(OC1)2 against sulfur mustard (HD) and the organophosphonate O-ethyl S-(2-Diisopropylnmino)-ethyl methylphosphonothioate (VX) were examined in the New Zealand White rabbit. Tests on shaved rabbit dorsa indicated moderate irritation due to either NaOC1 or Ca(OCI)2 at 5 percent but no appreciable irritation at 0.5 percent concentrations. Against VX applied topically on shaved rabbit dorsa, significant protection, as indicated by higher 24-hr median lethality doses, was afforded by 0.5 and 5.0 percent NaOC1. However, when VX was applied either directly into a dermal wound or onto a swatch of fabric sampled from battle dress uniform (BDU) and subsequently placed into a wound, only 5.0 percent NaOC1 offered significant protection. Against HD, 0.5 and 5.0 percent NaOC1 were equally effective decontaminants as indexed by dermal lesion areas resulting from 1- to 60-min exposures. Neither NaOC1 solution demonstrated sustained efficacy against HD applied on fabric and placed in wounds.

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

    SciTech Connect

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

    1993-12-31

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

  7. The chronic effects of sulfur mustard exposure.

    PubMed

    Rowell, Mike; Kehe, Kai; Balszuweit, Frank; Thiermann, Horst

    2009-09-01

    Whilst the acute effects of sulfur mustard have been relatively well characterised, the chronic effects of short term but significant exposures are still evolving. The approximately 30,000 Iranian victims of CW exposure from the 1980 to 1988 Iran-Iraq war who are currently being followed form a key population who are now 20 years post-exposure. The key chronic findings in this population reflect the common acute effects of sulfur mustard, and are related to the skin, eye and respiratory system. Excluding pruritus, skin changes appear to settle. Eye symptoms are slowly progressive, however a severe, rapid onset form of keratitis is seen to develop in a number of patients after a latent period of 15-20 years. The respiratory tract also shows progressive deterioration, with bronchiolitis obliterans now being considered the main pathological feature of "mustard lung". In addition, there are other potential effects of sulfur mustard exposure which become evident only in the longer term and which are being investigated, including the development of cancer, immunological and neuropsychiatric changes, and reproductive effects. Finally, a chronic effect of sulfur mustard exposure that is now becoming apparent is the wider long-term social and economic effects of these illnesses on individuals and their families.

  8. Wound Healing of Cutaneous Sulfur Mustard Injuries

    PubMed Central

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

    2005-01-01

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

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

    PubMed

    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.

  10. The effect of Nigella sativa alone, and in combination with dexamethasone, on tracheal muscle responsiveness and lung inflammation in sulfur mustard exposed guinea pigs.

    PubMed

    Boskabady, Mohammad Hossein; Vahedi, Nassim; Amery, Sediqa; Khakzad, Mohammad Reza

    2011-09-02

    ETHNOMEDICAL RELEVANCE: The anti-inflammatory activity of both systemic and local administrations of essential oil from Nigella sativa L. has been shown. Therefore, the effect of Nigella sativa on tracheal responsiveness (TR) and lung inflammation of sulfur mustard (SM) exposed guinea pigs was examined. Guinea pigs were exposed to diluent solution (control group), inhaled SM (SME group), SME treated with Nigella sativa (SME+N), SME treated with dexamethasone (SME+D) and SME treated with both drugs (SME+N+D), (n=7 for each group). TR to methacholine, total white blood cell (WBC) and differential WBC count of lung lavage, and serum cytokines were measured 14 days post-exposure. The values of TR, eosinophil, monocyte, lymphocyte, interleukine-4 (IL-4) and interferon gamma (IFN-γ) of SME group were significantly higher than those of controls (p<0.05 to p<0.001). The TR in SME+N, SME+D and SME+N+D was significantly lower compared to that of SME group (p<0.01 for all cases). The percentage of eosinophil in SME+D, and the percentage of monocyte in SME+N+D (p<0.05 to p<0.01) were significantly lower than those in SME group. The neutrophil number was decreased in SME+N and SME+N+D groups compared to SME animals (p<0.05 to p<0.01). IL-4 levels in serum of SME+N (p<0.01), SME+D (p<0.05), SME+N+D (p<0.01) and IFN-γ in SME+N (p<0.05) were greater than those in SME animals. These results showed a preventive effect of Nigella sativa on TR and lung inflammation of SM exposed guinea pigs. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  11. Mass Spectrometric Detection of Sulfur Mustard Adducts to Proteins and DNA: Dosimetry of Exposure to Sulfur Mustard

    DTIC Science & Technology

    1993-05-13

    agents. In this context, we developed immunochemical analysis procedures for sulfur mustard adducts to DNA which allow to detect exposure of human...We did not succeed so far in developing a suitable immunochemical method for detection of sulfur mustard-protein adducts . Presently, we are extending...Verification, dosimetry and biomonitoring of mustard gas exposure via immunochemical detection of mustard gas adducts to DNA and proteins. Final

  12. Salivary levels of secretary IgA, C5a and alpha 1-antitrypsin in sulfur mustard exposed patients 20 years after the exposure, Sardasht-Iran Cohort Study (SICS).

    PubMed

    Yarmohammadi, Mohammad Ebrahim; Hassan, Zuhair Mohammad; Mostafaie, Ali; Ebtekar, Massoumeh; Yaraee, Roya; Pourfarzam, Shahryar; Jalali-Nadoushan, Mohammadreza; Faghihzadeh, Soghrat; Vaez-Mahdavi, Mohammad-Reza; Soroush, Mohammad-Reza; Khamesipour, Ali; Faghihzadeh, Elham; Sharifnia, Zarin; Naghizadeh, Mohammad-Mehdi; Ghazanfari, Tooba

    2013-11-01

    Sulfur mustard (SM) is a strong toxic agent that causes acute and chronic health effects on a myriad of organs following exposure. Although the primary targets of inhaled mustard gas are the epithelia of the upper respiratory tract, the lower respiratory tract is the focus of the current study, and upper tract complications remain obscure. To our knowledge there is no study addressing the secretory IgA (S-IgA), C5a, alpha 1 antitrypsin (A1AT) in the saliva of SM-exposed victims. In this study, as many as 500 volunteers, including 372 SM-exposed cases and 128 control volunteers were recruited. A 3 ml sample of saliva was collected from each volunteer, and the level of secretory IgA, C5a, and alpha 1 antitrypsin in the samples were compared between the two groups. The SM-exposed group showed a significantly higher amount of salivary alpha 1 antitrypsin and secretary IgA compared to the control group (p<.006 and p<.018 respectively). The two groups showed no significant difference (p=0.192) in the level of C5a. The results also showed that the level of salivary A1AT is more than that of IgA in severely injured cases. The findings presented here provide valuable insight for both researchers and practitioners dealing with victims of the chemical warfare agent, sulfur mustard. This research indicates that certain branches of the inflammatory processes mandate serious attention in therapeutic interventions.

  13. Neutralization and Biodegradation of Sulfur Mustard.

    DTIC Science & Technology

    1997-02-01

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

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

    DTIC Science & Technology

    1989-05-01

    strains TA98 or TAI00. Sulfur mustard has been reported to induce a linear increase in the mutation of L5178Y cells as determined by reversion from...PNL-6945 Tokicology Studies on Lewisite and Sulfur Mustard Agents: Modified Dominant Lethal Study of to Sulfur Mustard in RatsiU) if) Final Report 6t...Frederick, MD 21701-5010 Approved for public release; distribution unlimited The findings in this report are not to be construed as an official

  15. Inhibitors of Apoptosis Affect DNA Degradation and Repair in Sulfur Mustard (HD)-Exposed Human Epidermal Keratinocytes (HEK)

    DTIC Science & Technology

    2003-07-01

    accompanied by DNA ligase I activation via DNA-dependent protein kinase (DNA-PK) mediated phosphorylation, and is retarded in the presence of a poly (ADP...ATCC No. HB 11726). Bovine DNA ligase I monoclonal antibody was a kind gift from Dr. Tomas Lindahl of the Imperial Cancer Research Fund, UK...metabolic 33P labeling of DNA ligase in HEK and other cells: The experimental and control cells were washed with 37oC saline and then exposed to 1 mM HD

  16. Sulfur Mustard Toxicity Following Dermal Exposure

    PubMed Central

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

    2007-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    SciTech Connect

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

    1997-02-01

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

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

    SciTech Connect

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

    1991-03-11

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

  20. Effects of Exposure to Sulfur Mustard on Speech Aerodynamics

    ERIC Educational Resources Information Center

    Heydari, Fatemeh; Ghanei, Mostafa

    2011-01-01

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

  1. Effects of Exposure to Sulfur Mustard on Speech Aerodynamics

    ERIC Educational Resources Information Center

    Heydari, Fatemeh; Ghanei, Mostafa

    2011-01-01

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

  2. Decreased expression of miR-20a and miR-92a in the serum from sulfur mustard-exposed patients during the chronic phase of resulting illness.

    PubMed

    Alvanegh, Akbar Ghorbani; Edalat, Houri; Fallah, Parviz; Tavallaei, Mahmood

    2015-01-01

    Sulfur mustard (SM), with extensive nucleophilic and alkylating properties, was employed during the Iran-Iraq war by Iraqi forces. The most critical complications attributed to SM are related to dangerous pulmonary disorders collectively known as "mustard lung". The symptoms gradually emerge over a long period, becoming chronic, and are dependent on time and the amount of exposed SM. Because of the unknown and complex nature of the disease, no differential diagnostic method or absolute treatment strategy has been formally developed. The aim of our study was to determine the expression pattern of the microRNAs (miRNAs) miR-92a and miR-20a in the serum of patients with mustard lung along with that of normal individuals. miRNAs have been shown to possess stable persistence in biofluids like plasma and serum and are considered non-aggressive biomarkers helpful for diagnosis and treatment of many diseases. A highly sensitive approach called stem-loop real-time quantitative polymerase chain reaction was employed to study the expression of miRNAs. The expression of miR-92a and miR-20a was significantly down-regulated in the serum of patients with mustard lung compared to the control group. Down-regulation of miR-92a and miR-20a may be due to chronic epigenetic alterations after SM exposure, which finally leads to changes in vital cellular processes such as differentiation, proliferation and so forth. Our findings may provide a differential diagnostic method that is effective for diagnosing lung diseases caused by SM exposure. Additionally, these miRNAs may be regarded as probable targets for treatment of lung injuries.

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

    PubMed

    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

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

    PubMed

    van der Schans, Govert P; Noort, Daan; Mars-Groenendijk, Roos H; Fidder, Alex; Chau, Lai F; de Jong, Leo P A; Benschop, Hendrik 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 2-hydroxyethylthioethyl group at the omega-amide function were synthesized and used as antigens for raising antibodies. After immunization, monoclonal antibodies were obtained with affinity for keratin isolated from human callus exposed to 50 microM sulfur mustard. These antibodies showed binding to the stratum corneum of human skin exposed to low levels of sulfur mustard, as evidenced by immunofluorescence microscopy. This approach opens the way for development of a detection kit that can be applied directly to the skin. To the best of our knowledge, this is the first example of immunochemical detection of adduct formation of toxic chemicals with skin proteins. A similar approach can be followed for skin exposure to environmental pollutants.

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

    PubMed Central

    2012-01-01

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

  6. Activation of Poly(ADP-Ribose) Polymerase by Sulfur Mustard in Hela Cell Cultures

    DTIC Science & Technology

    1993-05-13

    predicted by this hypothesis, research have shown that HD exposure will reduce NAD+ levels in several models, including human skin on nude mice (Gross et. al...C.L., MEIER, H.L., PAPIRMEISTER, B., BRINKELY, F.B. AND JOHNSON, B. (1985) Sulfur mustard lowers NAD+ levels in human skin , Toxicol. Appl. Pharmacol...L.W., (1991) Niacinamide Pretreatment Reduces Microvesicle Formation in Hairless Guinea Pigs Cutaneously Exposed to Sulfur Mustard. Fundam. Appl. Toxicol., 17 : 533-542. •!4’ " %

  7. Cytometric analysis of DNA changes induced by sulfur mustard

    SciTech Connect

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

    1993-05-13

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

  8. Effects of exposure to sulfur mustard on speech aerodynamics.

    PubMed

    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 speech are still evolving. We evaluated aerodynamics of speech in male patients following sulfur mustard inhalation. In a case-control study patients with chemical injuries (n=19) along with age and sex-matched healthy control group (n=20) were selected. Aerodynamic analyses were performed by using the Glasgow Airflow Measurement System (known as ST1 dysphonia). Results indicated that except mean flow rate, there were statistically significant differences in vital capacity, phonation time, phonation volume, vocal velocity index, total expired volume and phonation quotient of patients between experimental and control groups (P<0.05). This study demonstrated mustard gas can impair different parameters of speech aerodynamics. As a result of this activity, the reader will be able to describe: (1) the evaluation of air flow in relation to speech system dysfunction and efficiency; (2) the effect of sulfur mustard known as mustard gas on respiratory physiology. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2004-11-01

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

  10. An epidemiologic study to screen for chronic myelocytic leukemia in war victims exposed to mustard gas.

    PubMed Central

    Ghanei, Mostafa; Vosoghi, Ali Akbar

    2002-01-01

    Chemical agents such as mustard gas (or sulfur mustard), which has alkylating characteristics, were used against Iranian combatants in the Iraq-Iran war. Previous studies have not shown a strong link between these chemical agents and the development of chronic myelocytic leukemia (CML). The purpose of this study was to evaluate the increased risk of CML development in Iranian soldiers exposed to mustard gas during the war. Based on a descriptive study of 2,500 cases with documented exposure to various chemical warfare agents, 665 patients had documented exposure to mustard gas. We screened the latter using the leukocyte alkaline phosphatase (LAP) test and performed further cytochemical studies on cases with positive results. From among the 665 cases with documented exposure to mustard gas, 9 cases had LAP scores < 20; 2 of these 9 cases had CML and a score of zero (0.3%). We detected cytogenetic abnormalities in 7 patients with low LAP scores and atypical lymphocytes of 5-11% in 40 patients. The risk ratio of CML developing in victims exposed to mustard gas (cutaneous or respiratory) may be higher in comparison with the normal population, although confounding factors (e.g., the possibility of exposure to combined chemical agents, excluding patients who did not manifest blisters) limited our results. Because the increased development of CML in young patients with a documented history of exposure to mustard gas cannot be disregarded, further studies are needed. PMID:12003756

  11. Sulfur Mustard Induces Immune Sensitization in Hairless Guinea Pigs

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2010-02-01

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

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

    SciTech Connect

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

    1987-09-30

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

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

    NASA Astrophysics Data System (ADS)

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

    2003-07-01

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

  15. Teratogenic effects of sulfur mustard on mice fetuses.

    PubMed

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

    2012-05-01

    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. 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. Craniofacial and septal defects as well as the limb malformations were the most common types of birth defects, displaying an extremely complex biomedical problem. 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.

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

    PubMed

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

    2013-12-05

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

  17. Inflammatory effects of inhaled sulfur mustard in rat lung

    SciTech Connect

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

    2010-10-15

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

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

    PubMed

    Graham, John S; Schoneboom, Bruce A

    2013-12-05

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

  19. Teratogenic Effects of Sulfur Mustard on Mice Fetuses

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    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.

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

    PubMed

    Ahmad, Shama; Ahmad, Aftab

    2016-06-01

    Sulfur mustard (SM; bis-(2-chlororethyl) sulfide) is a highly reactive, potent warfare agent that has recently reemerged as a major threat to military and civilians. Exposure to SM is often fatal, primarily due to pulmonary injuries and complications caused by its inhalation. Profound inflammation, hypercoagulation, and oxidative stress are the hallmarks that define SM-induced pulmonary toxicities. Despite advances, effective therapies are still limited. This current review focuses on inflammatory and coagulation pathways that influence the airway pathophysiology of SM poisoning and highlights the complexity of developing an effective therapeutic target. © 2016 New York Academy of Sciences.

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

    SciTech Connect

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

    1995-04-05

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

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

    SciTech Connect

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

    1993-05-13

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

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

    DTIC Science & Technology

    1993-05-13

    AD-P008 756 EFFECT OF SULFUR MUSTARD ON MAST CELLS IN HAIRLESS GUINEA PIG SKIN JOHN S. GRAHAM, MARK A . BRYANT and ERNEST H. BRAUE U.S. Army Medical...with their granules of vasoactive histamine, mast cells might be expected to play a role in HD-induced injury. Changes in mast cells exposed to low...histopathology 94-07918 Best Available Copy C0t PONENT PART NOTICE THIS PAPER IS A CCWPOWENT PART OF THE FOLLOWING COIPILATION REPORT: TITLE: Proceedins of the

  5. Multiphoton imaging the disruptive nature of sulfur mustard lesions

    NASA Astrophysics Data System (ADS)

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

    2005-03-01

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

  6. Pathogenesis and treatment of skin lesions caused by sulfur mustard.

    PubMed

    Poursaleh, Zohreh; Ghanei, Mostafa; Babamahmoodi, Farhang; Izadi, Morteza; Harandi, Ali Amini; Emadi, Seyed Emad; Taghavi, Nez'hat-o-Sadat; Sayad-Nouri, Seyede Somaye; Emadi, Seyed Naser

    2012-09-01

    Sulfur mustard (SM) exposure intensely causes lesions that range in severity from mild erythema to blister formation and necrosis. This review will discuss acute and long-term skin consequences due to exposure to SM and different kinds of medical prophylaxis and therapeutics against SM-induced skin lesions. Literature survey of medical case reports, clinical studies, and original articles was performed using PubMed, Medline, and the Cochrane Database (1917-2011 March). Key words included sulfur mustard, skin, toxicity, pathogenesis, cancer, treatment. SM-induced damage to the skin is characterized by edema, inflammation, and cell death mainly of the basal keratinocyte layer, with varying immunological and pathological changes in the acute phase. Also, xerosis, hypo or hyper pigmentation, scars, and rarely, skin cancers are long-term cutaneous effects. So far,the combination therapy of topical drugs and oral antihistamines, also iodine and antitumor necrosis factor alpha antibodies, are effective remedies in the treatment of skin lesions. The requirement for preparedness in the dermatological community concerning SM exposure is underlined. Novel treatments for prevention and therapeutics against SM toxicity and carcinogenicity are reviewed.

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

    SciTech Connect

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

    1992-12-31

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

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

    PubMed

    Jost, Petr; Svobodova, Hana; Stetina, Rudolf

    2015-07-25

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

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

    SciTech Connect

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

    1989-05-01

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

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

    SciTech Connect

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

    1989-06-30

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

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

    PubMed

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

    2010-03-15

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

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

    PubMed Central

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

    2010-01-01

    Sulfur mustard (bis-(2-chloroethyl)sulfide) has been used in chemical warfare since World War I, and is well known as an acutely toxic vesicant. It has been implicated as a carcinogen after chronic low-level exposure, and is known to form inter-strand crosslinks in DNA. Sulfur and nitrogen mustards are currently of interest as potential chemical threat agents for terrorists due to ease of synthesis. Sulfur mustard and monofunctional analogs (half-mustards, 2-[chloroethyl] alkyl sulfides) react as electrophiles, damaging cellular macromolecules, and thus are potentially subject to scavenging by nucleophilic agents. We have determined rate constants for the reaction of four purine derivatives that contain nucleophilic thiol moieties with several sulfur-half-mustards. Three of these compounds, 2,6-dithiopurine, 2,6-dithiouric acid, and 9-methyl-6-mercaptopurine, exhibit facile reaction with the electrophilic mustard compounds. At near neutral pH, these thiopurines are much better nucleophilic scavengers of mustard electrophiles than other low molecular weight thiols such as N-acetyl cysteine and glutathione. Progress curves calculated by numerical integration techniques indicate that equimolar concentrations of thiopurine provide significant reductions in the overall exposure to the episulfonium ions, which are the major reactive, electrophiles produced when sulfur mustards are dissolved in aqueous solution. PMID:20050632

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

    PubMed

    Jiang, Austin; Maibach, Howard

    2017-09-19

    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.

  14. N-acetyl-L-Cysteine as prophylaxis against sulfur mustard.

    PubMed

    Bobb, Andrew J; Arfsten, Darryl P; Jederberg, Warren W

    2005-01-01

    Sulfur mustard (HD) is a blister agent targeting the eyes, respiratory system, skin, and possibly other organs. Extensive exposure can destroy the immune system by destruction of bone marrow cells. There is no antidote for HD or effective treatment other than rapid decontamination. Clinical trials have demonstrated activity for N-acetyl-L-cysteine (NAC) against a number of significant human pathologies involving free radicals, and animal and tissue studies have suggested efficacy for NAC as a chemoprotectant against many toxic chemicals. Among these are studies demonstrating that NAC significantly reduces the effects of HD and HD simulants, both in cultured cells and animals. Given the historical effectiveness of HD, the lack of any effective treatment, the demonstrated chemoprotective properties of NAC, its low toxicity, the lack of regulatory controls, and the data supporting efficacy against HD effects, we suggest daily oral administration of the maximum safe dose of NAC to personnel entering combat zones.

  15. Ocular Effects of Sulfur Mustard and Therapeutic Approaches.

    PubMed

    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.

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

    PubMed

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

    2013-12-05

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

  17. Development of Protective Agent Against Sulfur Mustard-Induced Skin Lesions

    DTIC Science & Technology

    2005-03-01

    AD Award Number: DAMD17-03-2-0013 TITLE: Development of Protective Agent Against Sulfur Mustard- Induced Skin Lesions PRINCIPAL INVESTIGATOR: Uri...Protective Agent Against Sulfur Mustard- DAMDl7-03-2-0013 Induced Skin Lesions 6. A UTHOR(S) Uri Wormser, Ph.D. 7. PERFORMING ORGANIZA TION NAME(S) AND...5 The involvement of inflammatory mediators in SM-induced skin toxicity ......... 6 Experimental procedures

  18. Immunochemical and Biochemical Analysis of Adducts to DNA and Proteins After Exposure to Sulfur Mustard

    DTIC Science & Technology

    1993-05-13

    cQ.00o~33/o/ /9 IMMUNOCHEMICAL AND BIOCHEMICAL ANALYSIS OF O• ADDUCTS TO DNA AND PROTEINS AFTER EXPOSURE TO SULFUR MUSTARD _ == M G.P. van der Schans...chosen to define exposure to sulfur mustard (HD), based on immunochemical analysis of adducts of HD to DNA and proteins. These adducts are agent...calibration of the immunochemical assays. Analogous to HD-DNA adducts , reaction products with blood proteins may be used to establish HD exposure. Since it

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

    SciTech Connect

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

    1989-07-31

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

  20. Extraction and Analysis of Sulfur Mustard (HD) from Various Food Matrices by Gas ChromatographyMass Spectrometry

    DTIC Science & Technology

    2016-01-01

    EXTRACTION AND ANALYSIS OF SULFUR MUSTARD (HD) FROM VARIOUS FOOD MATRICES BY GAS CHROMATOGRAPHY–MASS...Sulfur Mustard (HD) from Various Food Matrices by Gas Chromatography–Mass Spectrometry 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...spectrometry was used to analyze sulfur mustard (HD) in various food matrices . The development of a solid-phase extraction method using a normal

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

    PubMed

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

    2003-01-01

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

  2. Assessment of sulfur mustard interaction with basement membrane components

    SciTech Connect

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

    1995-08-01

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

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

    PubMed

    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.

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

    PubMed

    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.

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

    DTIC Science & Technology

    2005-10-01

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

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

    PubMed

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

    2016-08-15

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

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

    SciTech Connect

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

    1987-09-30

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

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

    SciTech Connect

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

    1993-05-13

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

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

    PubMed

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

    2013-12-05

    Sulfur mustard (SM) is an old chemical warfare agent causing blisters (vesicant). Skin toxicity is thought to be partly caused by SM induced DNA damage. SM and the hemi mustard 2-chloroethyl ethyl sulfide (CEES) are bi- and monofunctional DNA alkylating agents, respectively. Both chemicals react especially with N7 guanine. The most abundant adducts are 7-hydroxyethylthioethylguanine for SM (61%) and 7-ethyl thioethylguanine for CEES. Thus, DNA alkylation should serve as a biomarker of SM exposure. A specific monoclonal antibody (2F8) was previously developed to detect SM and CEES adducts at N7 position by means of immunoslotblot (ISB) technique (van der Schans et al. (2004) [16]). Nitrogen mustards (HN-1, HN-2, HN-3) are alkylating agents with structural similarities, which can form DNA adducts with N7 guanine. The aim of the presented work was to modify the van der Schans protocol for use in a field laboratory and to test the cross reactivity of the 2F8 antibody against nitrogen mustards. Briefly, human keratinocytes were exposed to SM and CEES (0-300μM, 60min) or HN-1, HN-2, HN-3 (120min). After exposure, cells were scraped and DNA was isolated and normalized. 1μg DNA was transferred to a nitrocellulose membrane using a slotblot technique. After incubation with 2F8 antibody, the DNA adducts were visualized with chromogen staining (3,3'-diaminobenzidine (DAB), SeramunGrün). Blots were photographed and signal intensity was quantified. In general, DAB was superior to SeramunGrün stain. A staining was seen from 30nM to 300μM of SM or CEES, respectively. However, statistically significant DNA adducts were detected after CEES and SM exposure above 30μM which is below the vesicant threshold. No signal was observed after HN-1, HN-2, HN-3 exposure. The total hands-on time to complete the assay was about 36h. Further studies are necessary to validate SM or CEES exposure in blister roofs of exposed patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

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

    PubMed

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

    2009-02-15

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

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

    DTIC Science & Technology

    2005-01-05

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

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

    USDA-ARS?s Scientific Manuscript database

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

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

    SciTech Connect

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

    1997-12-31

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

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

    SciTech Connect

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

    1998-07-01

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

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

    PubMed Central

    2013-01-01

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

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

    PubMed

    Jung, Hyunsook; Choi, Seungki

    2017-07-24

    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.

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

    PubMed

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

    2015-01-01

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

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

    DTIC Science & Technology

    2006-09-01

    and Beneficial Effects of N- Acetyl Cysteine ( NAC ), J. Biochem. Mol. Toxicol. 18: 150-153, 2004. 4. Mukhopadhyay, S., Das, S. K., and Mukherjee, S...Mustard Consortium have documented protection against 2- chloroethyl-ethyl sulfide (CEES) induced lung injury using n- Acetyl Cysteine ( NAC ) alone or...and was its primary mechanism of action. Consequently, NAC (N- acetyl cystiene) was found to be protective as a prophylaxis and treatment. A

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

    PubMed Central

    Paromov, Victor; Kumari, Sudha; Brannon, Marianne; Kanaparthy, Naga S.; Yang, Hongsong; Smith, Milton G.; Stone, William L.

    2011-01-01

    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. PMID:21776256

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

    PubMed

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

    2016-01-01

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

  3. Pepsin and Bile Acid Concentrations in Sputum of Mustard Gas Exposed Patients

    PubMed Central

    Karbasi, Ashraf; Goosheh, Hassan; Aliannejad, Rasoul; Saber, Hamid; Salehi, Maryam; Jafari, Mahvash; Imani, Saber; Saburi, Amin; Ghanei, Mostafa

    2013-01-01

    Background/Aim: Gastro-esophageal reflux has been suggested to be associated with several pulmonary complications such as asthma, and post-transplant bronchiolitis obliterans (BO). Pepsin or bile salts in the sputum is shown to be an optimal molecular marker of gastric contents macro/micro aspiration. In this study, we investigated sputum pepsin as a marker of micro-aspiration in sulfur mustard (SM) exposed cases compared to healthy controls. Materials and Methods: In a case controlled study, 26 cases with BO and 12 matched healthy controls were recruited and all cases were symptomatic and their exposure to SM was previously documented during Iran-Iraq conflict. Pepsin levels in sputum and total bile acids were measured using enzymatic assay. The severity of respiratory disorder was categorized based upon the spirometric values. Result: The average concentration of pepsin in sputum was higher in the case group (0.29 ± 0.23) compared with healthy subjects (0.13 ± 0.07; P ± 0.003). Moreover, the average concentration of bile acids in the sputum cases was not significantly different in comparison to the controls (P = 0.5). Conclusion: Higher pepsin concentrations in sputum of SM exposed patients compared with healthy control subjects indicate the occurrence of significantly more gastric micro-aspiration in SM exposed patients. PMID:23680709

  4. Poly (ADP-Ribose) Polymerase is Involved in the Repair of DNA Damage Due to Sulfur Mustard by a Mechanism Other Than DNA Ligase I Activation

    DTIC Science & Technology

    2004-11-16

    agents including sulfur mustard (SM). We observed concurrent activation of PARP and DNA ligase in SM-exposed human epidermal keratinocytes (HEK...Previous reports from other laboratories suggested that DNA ligase activation could be due to its modification by PARP. In humans, there are three distinct...DNA ligases, I, II and IV of which DNA ligase I participates in DNA replication and repair. By metabolically labeling HEK using 3H-adenosine

  5. Development of Medical Countermeasures to Sulfur Mustard Vesication

    DTIC Science & Technology

    2002-01-01

    vesicating properties. Its use on the battlefield results in debilitating injuries to skin , eyes and the respiratory system (1, 2). To elucidate the toxic...PARP Inhibitors Niacinamide Disruption of Calcium Calcium Modulators BAPTA* Proteolytic Activation Protease Inhibitors AEBSF* Inflammation...Mustard Injury.” Toxicology Methods, Vol. 7. pp. 381-397, 1997. 6. Yourick, JJ, Clark, CR and Mitcheltree, L. “ Niacinamide Pretreatment Reduces

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

    SciTech Connect

    1996-05-01

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

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

    DTIC Science & Technology

    2005-08-01

    mechanism of action of sulfur mustard using proteomics , which has led to new hypotheses concerning how the toxic effects of sulfur mustard come to be...i.e., treatment with blocking solution, 1st antibody (2F8, directed against N7- HETE-Gua in DNA) and 2 nd antibody (rabbit-anti-mouse-Ig-horse radish ...HETE-Gua, culture supematant, TNO-PML, Rijswijk, The Netherlands 2nd Antibody Rabbit-anti-mouse-Ig-horse radish peroxidase, Dakopatts, Glostrup, Denmark

  8. Ultrastructural Correlates of the Protection Afforded by Niacinamide against Sulfur Mustard-Induced Cytotoxicity of Human Lymphocytes in Vitro

    DTIC Science & Technology

    1988-12-01

    niacinamide could be extended to include a similar mechanism of prctection in skin . It is not possible to conclude whether the ultrastructural changes...ULTRASTRUCTURAL CORRELATES OF THE PROTECTION AFFORDED BY NIACINAMIDE AGAINST SULFUR MUSTARD-INDUCED CYTOTOXICITY OF HUMAN LY.lPHOCYTES I1 VITRO Jo04N P...TITLE (Include Secunriy Clawtication) Ultrastruetural Correlates of the Protection Afforded by Niacinamide against’Sulfur Mustard- induced

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Airway Obstruction Due to Bronchial Vascular Injury after Sulfur Mustard Analog Inhalation

    PubMed Central

    Veress, Livia A.; O'Neill, Heidi C.; Hendry-Hofer, Tara B.; Loader, Joan E.; Rancourt, Raymond C.; White, Carl W.

    2010-01-01

    Rationale: Sulfur mustard (SM) is a frequently used chemical warfare agent, even in modern history. SM inhalation causes significant respiratory tract injury, with early complications due to airway obstructive bronchial casts, akin to those seen after smoke inhalation and in single-ventricle physiology. This process with SM is poorly understood because animal models are unavailable. Objectives: To develop a rat inhalation model for airway obstruction with the SM analog 2-chloroethyl ethyl sulfide (CEES), and to investigate the pathogenesis of bronchial cast formation. Methods: Adult rats were exposed to 0, 5, or 7.5% CEES in ethanol via nose-only aerosol inhalation (15 min). Airway microdissection and confocal microscopy were used to assess cast formation (4 and 18 h after exposure). Bronchoalveolar lavage fluid (BALF) retrieval and intravascular dye injection were done to evaluate vascular permeability. Measurements and Main Results: Bronchial casts, composed of abundant fibrin and lacking mucus, occluded dependent lobar bronchi within 18 hours of CEES exposure. BALF contained elevated concentrations of IgM, protein, and fibrin. Accumulation of fibrin-rich fluid in peribronchovascular regions (4 h) preceded cast formation. Monastral blue dye leakage identified bronchial vessels as the site of leakage. Conclusions: After CEES inhalation, increased permeability from damaged bronchial vessels underlying damaged airway epithelium leads to the appearance of plasma proteins in both peribronchovascular regions and BALF. The subsequent formation of fibrin-rich casts within the airways then leads to airways obstruction, causing significant morbidity and mortality acutely after exposure. PMID:20639443

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

    PubMed Central

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

    2013-01-01

    The endoplasmic reticulum (ER) stress response is a cell survival pathway upregulated when cells are under severe stress. Severely damaged mouse ear skin exposed to the vesicant, sulfur mustard (bis-2-chloroethyl sulfide, SM), resulted in increased expression of ER chaperone proteins that accompany misfolded and incorrectly made proteins targeted for degradation. Time course studies with SM using the mouse ear vesicant model (MEVM) showed progressive histopathologic changes including edema, separation of the epidermis from the dermis, persistent inflammation, upregulation of laminin γ2 (one of the chains of laminin-332, a heterotrimeric skin glycoprotein required for wound repair), and delayed wound healing from 24 h to 168 h post exposure. This was associated with time related increased expression of the cell survival ER stress marker, GRP78/BiP, and the ER stress apoptosis marker, GADD153/CHOP, suggesting simultaneous activation of both cell survival and non-mitochondrial apoptosis pathways. Dual immunofluorescence labeling of a keratinocyte migration promoting protein, laminin γ2 and GRP78/BIP, showed colocalization of the two molecules 72 h post exposure indicating that the laminin γ2 was misfolded after SM exposure and trapped within the ER. Taken together, these data show that ER stress is induced in mouse skin within 24 h of vesicant exposure in a defensive response to promote cell survival; however, it appears that this response is rapidly overwhelmed by the apoptotic pathway as a consequence of severe SM-induced injury. PMID:23357548

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    2013-10-01

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

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

    DTIC Science & Technology

    2010-01-01

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

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

    DTIC Science & Technology

    2004-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-09-30

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

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

    DTIC Science & Technology

    2000-01-01

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

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

    DTIC Science & Technology

    1987-12-31

    semen donors were trained to service an AV during a 2- to 3-week period (Gregoire et al., 1958). On the day of AI, semen samples from at least 3... Semen samples of satisfactory quality were pooled and diluted with buffered citrate/egg-yolk extender to a concentration of 21 to 30 million sperm/ml...V) ,NI REPORT NO. PNL-6408 00 TERATOLOGY STUDIES OF LEWISITE AND SULFUR MUSTARD AGENTS: EFFECTS OF LEWISITE IN RATS AND RABBITS FINAL REPORT P. L

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

    SciTech Connect

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

    1991-12-31

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

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

    SciTech Connect

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

    1993-12-31

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

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

    PubMed

    Gold, M B; Scharf, B A

    1995-01-01

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

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

    PubMed

    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.

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

    PubMed

    Lee, Jin Young; Lee, Yong Han

    2016-01-01

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

  7. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Two-Generation Reproduction Study of Sulfur Mustard (HD) in Rats

    DTIC Science & Technology

    1989-09-30

    ACO6.76RLO 78&0 1ECURITY CLASIFICATION or. TWIS AfE REPORT DOCUMENTATION PAGE OIN 7" 8 I&. REPORT SECURITY CLASSIFICATION 1b. RESTRICTIVE MARKINGS...Sotae and ZICcJ~r 7b. ADDRESS (City, SUMt. &W WVCode) P.O. Box 999 Richland, WA 99352-0999 8 .NAME OF FUNDING ISPONSORING ftb OFFICE SYMBOL 9. PROCUREMENT...jACSSION NO. 63751A I6375ID993 IC? 1003 11. TITLE (bidui Secunftya~ktO1 (U) Toxicology’Studies on Levisite and Su ~ifur Mustard Agents: Two-Goneration

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

    PubMed

    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.

  9. Improved Wound Healing of Cutaneous Sulfur Mustard Injuries in a Weanling Pig Model

    PubMed Central

    Graham, John S.; Stevenson, Robert S.; Mitcheltree, Larry W.; Simon, Marcia; Hamilton, Tracey A.; Deckert, Robin R.; Lee, Robyn B.

    2006-01-01

    Objective: The objective was to examine the efficacy of several treatment regimens in improving wound healing of cutaneous sulfur mustard (HD) injuries. Methods: Wound healing studies were conducted in weanling pigs. Superficial dermal HD injuries were debrided at 48 hours postexposure using an erbium-doped yttrium aluminum garnet (Er:YAG) laser, followed by application of a treatment adjunct. A variety of noninvasive bioengineering methods were conducted during the postsurgical observation period to examine the various cosmetic and functional aspects of the skin. Histopathology was performed at the end of each study (14 or 21 days postsurgery). Results: As noted clinically, reepithelialization was nearly complete by 7 days postsurgery for many of the sites treated with petrolatum and scarlet red dressings. By 21 days, the skin elasticity of the petrolatum-dressed sites was not significantly different from that of sham-exposed skin. Upon dressing removal on postsurgery day 4, the neoepidermis of allograft- and thin film-dressed sites was partially removed, with resultant petechial hemorrhaging. Mean pathology scores for hydrocolloid-dressed sites were significantly lower than those of untreated HD-exposed sites on postsurgery day 14. Conclusions: Care must be taken during bandage changes, and a nonadherent dressing that could be left in place for a longer period of time (eg, 7 days) would be beneficial. The use of cultured epithelial allograft material may have a potential role if grown on a completely nonadherent backing and left undisturbed for at least a week. Xeroform Petrolatum and Scarlet Red Ointment dressings are effective and inexpensive treatment adjuncts for HD injuries. PMID:17111042

  10. Immunochemical detection of adducts of sulfur mustard to DNA of calf thymus and human white blood cells.

    PubMed

    van der Schans, G P; Scheffer, A G; Mars-Groenendijk, R H; Fidder, A; Benschop, H P; Baan, R A

    1994-01-01

    As part of a program to develop methods for dosimetry of exposure to sulfur mustard, we developed immunochemical methods for the detection of the major adduct, N7-[2-[(hydroxyethyl)thio]ethyl]guanine (N7-HETE-Gua), formed after alkylation of DNA with sulfur mustard. After immunization of rabbits with calf thymus DNA treated with sulfur mustard, we obtained the antiserum W7/10 with a high specificity for DNA adducts of sulfur mustard. With this serum, a competitive enzyme-linked immunosorbent assay was developed in which sulfur mustard adducts to DNA could be detected with a minimum detectable amount of 1-5 fmol per well and a selectivity that allows detection of one N7-HETE-Gua among 5 x 10(6) unmodified nucleotides in single-stranded DNA. The complications that arise to isolate double-stranded DNA from biological samples and to make the DNA single-stranded without destruction of the sulfur mustard adducts result in about a 20-fold higher limit for adduct detection in DNA from human blood than in single-stranded DNA. Presently, adducts in white blood cells can be detected after exposure of human blood to sulfur mustard concentrations > or = 2 microM. We synthesized N7-HETE-GMP for use as a hapten to generate monoclonal antibodies against this adduct. After immunization of mice with this adduct coupled to the carrier protein keyhole limpet hemocyanin we obtained several hybridomas producing monoclonal antibodies that recognize N7-HETE-Gua, containing an intact imidazolium ring. The sensitivity of the competitive ELISA with the monoclonal antibodies was comparable to that of the assays performed with the rabbit antiserum.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    NASA Astrophysics Data System (ADS)

    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.

  12. The effect of sulfur mustard and nitrogen mustard on corneal collagen degradation induced by the enzyme collagenase.

    PubMed

    Naderi, Mostafa; Jadidi, Khosro; Falahati, Farzaneh; Alavi, Saayyed Ali

    2010-12-01

    Sulfur mustard (SM) is an alkylating agent that can affect cornea and induce various complications. With regard to the role of the enzyme collagenase in dermatologic complications induced by sm and its role in other ocular disorders, we studied the effect of SM and nitrogen mustard (NM) on collagen degradation by collagenase. This study included 7 groups of samples: The negative control group contained collagen without collagenase and toxins, the control group contained collagen and collagenase without any toxin, the positive control groups of NM and SM contained collagen and NM or SM without collagenase, the experimental groups of NM and SM contained collagen that was affected by NM or SM and collagenase, and the control group of collagenase contained only collagenase without containing collagen or receiving toxins. After incubation for 3.5 hours, the amount of hydroxyproline and the protein content of the samples were measured. Data were analyzed by analysis of variance (ANOVA). The protein concentrations of the negative control group and the positive control groups of SM and NM were significantly lower than those for all other groups of the study. There was a significant difference in hydroxyproline concentration of control group and negative control group; however, there was no significant difference between experimental group of SM and the positive control group of SM. There was no significant difference between the negative control group and the positive control group of SM in the hydroxyproline concentration of sediment samples. According to the results of this study, SM can affect the corneal collagen in a way in which collagenase cannot degrade it. In addition, it can be hypothesized that ineffective activity of this enzyme can result in increasing concentration of collagenase, which can lead to the destruction of the normal collagen of the cornea. The main result of this study confirms the hypothesis that SM inhibits the effect of collagenase on corneal

  13. 1H and 13C{1H} NMR spectral parameters of sulfur mustards, nitrogen mustards, and lewisites: computing and predicting of reference spectra for chemical identification.

    PubMed

    Haapaniemi, Esa; Mesilaakso, Markku

    2012-03-01

    The (1)H and (13)C{(1)H} chemical shifts and (1)H spin-spin couplings of sulfur mustards, nitrogen mustards, and lewisites scheduled in the Chemical Weapons Convention, and those of bis(2-chloromethyl)disulfide, were determined in CDCl(3), CD(2)Cl(2), and (CD(3))(2)CO. Accurate parameters of this kind of series can be used for evaluating the current molecular modeling programs and the chemical shift and coupling constant prediction possibilities of the programs. Several prediction tests were made with commercial programs, and the results are reported here. Copyright © 2012 John Wiley & Sons, Ltd.

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

    PubMed

    Smith, C N; Lindsay, C D

    2001-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2010-12-15

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

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

    SciTech Connect

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

    1992-12-31

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

  18. The role of interleukin-6 (IL-6) in human sulfur mustard (HD) toxicology.

    PubMed

    Arroyo, C M; Broomfield, C A; Hackley, B E

    2001-01-01

    The authors applied in vitro models of controlled damage to human epidermal keratinocytes (HEKs), human skin fibroblasts (HSFs), and human breast skin tissue (HBST) to examine the mechanism responsible for sulfur mustard (HD)-induced interleukin-6 (IL-6) alterations. Treatment with 100 microM HD for 24 hours resulted in a significant increased amount of IL-6 being secreted by HEKs (HD-exposed to control ratio [E/C] = 4.15 +/- 0.07) and by HSFs (E/C = 7.66 +/- 0.04). Furthermore, the HD-induced secretion of IL-6 in HEKs was neutralized with monoclonal human IL-6 antibodies. The secretion of IL-6 in HBST supernatant exposed to HD produced conflicting results. Although an increase of IL-6 was observed in control superfusion media from HBST, IL-6 levels were observed to decrease as the concentration of HD increased. Time course of IL-6 mRNA levels were performed using a competitive polymerase chain reaction (PCR) and human IL-6 mRNA assay detection kit in control and HD (100 microM)-treated HEKs cells. IL-6 mRNA transcripts in HD-exposed HEKs were first observed within 2 hours, dropped at 5 to 6 hours, and increased by approximately 2.2-fold and 8.5-fold at 24 to 48 hours after HD exposure, respectively, as detected by the Xplore mRNA Quantification System. Surface-enhanced laser desorption ionization (SELDI) mass spectrometry was also applied to study the secretion pattern of IL-6 on lysate preparations of HBST. A peak in the area of 23,194 to 23,226 Da was detected using antibody coupled to the chip. This peak was assigned to correspond to the mass of the IL-6 glycoprotein. Recombinant human IL-6 (rhIL-6) exposed to HD lacked the second disulfide bridge and was partially unfolded, as determined by nuclear magnetic resonance-nuclear Overhauser enhancement and exchange spectroscopy (NMR-NOESY). The disappearance of the resonance peak at 3.54 ppm and the appearance of a new chemical shift at 1.85 ppm suggested that a change in structure had occurred in the presence of

  19. Serum cytokine profiles of Khorasan veterans 23 years after sulfur mustard exposure.

    PubMed

    Riahi-Zanjani, Bamdad; Balali-Mood, Mahdi; Mousavi, Seyed-Reza; Karimi, Gholamreza; Sadeghi, Mahmood; Shirmast, Elham; Mahmoudi, Mahmoud

    2014-12-01

    Sulfur mustard (SM) is an incapacitating chemical warfare agent that was used against Iranian soldiers during the period from 1983 to 1988. We have investigated serum cytokines profiles of Khorasan veterans who were exposed to SM >23 years earlier. Forty-four male Iranian veterans who had >40% disabilities due to delayed complications of SM poisoning and had disabilities were investigated. A total of 30 healthy male volunteers (relatives of the veterans) were selected as the control group. Cytokine levels were measured in the serum of case and control subjects using commercial ELISA kits. Hematologic parameters (white/red blood cell counts, hemoglobin levels, immune cell differentials) were also performed on blood samples from the study subjects. The results indicated that serum levels of ICAM-1 were significantly higher in the samples from SM-exposed veterans (772.8 [± 15.1] ng/ml [p=0.014] vs. control values of 710.2 [± 20.0] ng/ml). On the other hand, serum IL-1β, IL-8 levels and TNFα, were significantly lower for the veterans than the controls (IL-1β: 3.8 [± 0.1] vs. 4.3 [± 0.2] pg/ml, p=0.037; IL-8: 21.0 [± 6.1] vs. 84.6 [± 20.3] pg/ml, p=0.002; TNFα: 4.5 [± 0.1] vs. 5.5 [± 0.1] pg/ml, p=0.027). Levels of other assayed cytokines, e.g., IL-2, -4, -5, -6, -10, and -12, IFNγ, TNFβ, and sVCAM-1 were not significantly different between the study populations. None of the assayed hematologic parameters appeared to differ as well. It seems possible that dysfunctions could have been induced in the innate immune functions of the SM-exposed veterans as a result of these changes in cytokine expression and that these, in turn, may have contributed to the increased incidence of a myriad of diseases that have been documented in these veterans, including cancers. Future studies must focus on examining the significance of these changes in circulating cytokines and their potential contribution to the development of different diseases in veterans exposed to SM.

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

    PubMed

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

    2016-02-26

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

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

    SciTech Connect

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

    2013-04-15

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

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

    PubMed Central

    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

  3. Beneficial effects of activated macrophages on sulfur mustard-induced cutaneous burns, an in vivo experience.

    PubMed

    Dachir, Shlomit; Cohen, Maayan; Sahar, Rita; Graham, John; Eisenkraft, Arik; Horwitz, Vered; Kadar, Tamar

    2014-12-01

    Macrophages are known to have key functions in almost every stage of wound healing and there is evidence for their beneficial effects in treating decubital ulcers and deep sternal wound infections in human. This study aimed to investigate the efficacy of a treatment with activated macrophages on ameliorating acute and long-term sulfur mustard (SM) induced skin injuries in the hairless guinea pig (HGP) model. HGP were exposed to SM vapor and treated with either a single or multiple intra-dermal injections of human activated macrophages in suspension (hAMS) into the wound bed. Clinical and histological evaluations were conducted up to 4 weeks post-exposure. A single treatment with hAMS early after exposure (15 min and 6 h) resulted in a reduction in the number of damaged cells and vesications in the epidermis at 24 h. A substantial increase in cellular infiltration, mostly polymorphonuclears, was taking place in the hAMS-treated animals starting as early as 1 h after exposure. This flow of inflammatory cells continued, in the treated group, for at least 4 weeks, long after the injected macrophages were not detected. Repeated injections of hAMS (15 min, 48 h and 7 d post-exposure) decreased significantly the area of the wounds and improved the integrity of the barrier function as expressed by measuring trans-epidermal water loss up to 10 d. Our results indicate that the role of macrophages in wound healing is complex; their efficacy may depend on the timing of administration. Further investigation is required to determine whether they are required during the early phase of wound development and/or during the late phase of scar formation and remodeling.

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

    PubMed

    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.

  5. Mechanistic insights of sulfur mustard-induced acute tracheal injury in rats.

    PubMed

    Zhu, Xiao-Ji; Xu, Rui; Meng, Xiao; Chu, Hai-Bo; Zhao, Chao; Lian, Cheng-Jin; Wang, Tao; Guo, Wen-Jun; Zhang, Sheng-Ming

    2014-01-01

    Sulfur mustard (SM) is believed to be a major threat to civilian populations because of the persistent asymmetric threat by nonstate actors, such as terrorist groups, the ease of synthesis and handling, and the risk of theft from stockpiles. The purpose of this study was to establish mechanisms of acute tracheal injury in rats induced by SM using histopathologic, immunohistochemical, and biochemical parameters. Male rats (Sprague-Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM. Animals were euthanized 6-, 24-, 48-, and 72-hour postexposure, and intracavitary blood samples from the heart and tracheal tissues were collected. Exposure of rats to SM resulted in rapid tracheal injury, including tracheal epithelial cell shedding, focal ulceration, and abundant lymphocyte invasion of the submucosa. There was also evidence of a large number of apoptotic cells in the epithelium and submucosa, the serum levels of tumor necrosis factor α, interleukin 1β (IL) 1β, IL-6, and γ-glutamyl transferase peaked at 24 hours, and the serum levels of lactate dehydrogenase, glutathione peroxidase, and thiobarbituric acid reactive substance peaked at 6 hours. The SM exposure also resulted in a loss of the cellular membrane, leakage of cytoplasm, fuzzy mitochondrial cristae, medullary changes in ciliated and goblet cells, and the nuclear chromatin appeared marginated in basal cells and fibroblasts. The results in the propylene glycol group were the same as the control group. These data demonstrated the histologic changes, inflammatory reactions, apoptosis, oxidative stress, and DNA damage following SM (2 mg/kg)-induced acute tracheal injury; the severity of changes was time dependent. © The Author(s) 2014.

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

    PubMed

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

    2009-04-01

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

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

    PubMed Central

    Ebrahimi, Majid; Roudkenar, Mehryar Habibi; Imani Fooladi, Abbas Ali; Halabian, Raheleh; Ghanei, Mostafa; Kondo, Hisatake; Nourani, Mohammad Reza

    2010-01-01

    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. PMID:20508729

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

    PubMed

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

    2012-05-01

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

  9. Biochemical evaluation of sulfur and nitrogen assimilation potential of mustard (Brassica juncea L. Czern. & Coss.) under application of slow-release sulfur fertilizer.

    PubMed

    Ahmad, A; Abraham, G; Abdin, M Z

    2001-01-01

    Pot experiments were conducted to study the efficacy of a slow sulfur-releasing fertilizer, sulfur glass fritz (SGF 1), on growth, photosynthesis, and sulfur, and nitrogen assimilation potentials of brown mustard (Brassicajuncea L. Czern. & Coss. cv. Pusa Jaikisan). Growth as indicated by biomass accumulation slowed down in response to the application of sulfur glass fritz. A similar trend was observed in the case of photosynthesis rate. The activity of two marker enzymes, ATP-sulfurylase and nitrate reductase, showed very low levels of activity, indicating poor assimilation of sulfur and nitrogen by the plant under sulfur glass fritz. It is therefore concluded that the release of sulfur by sulfur glass fritz is too slow and that the initial nonavailability of sulfur to the plants could lead to suboptimization of both sulfur- and nitrogen-assimilating enzymes. These factors may contribute to low rates of photosynthesis and poor growth.

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

    PubMed

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

    2009-11-06

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

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

    SciTech Connect

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

    1993-05-13

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

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

    PubMed Central

    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

  13. Elemental sulfur effects on Pb and Zn uptake by Indian mustard and winter wheat.

    PubMed

    Yan-shan, Cui; Qing-ren, Wang; Yi-ting, Dong; Hai-feng, Li

    2003-11-01

    A pot experiment was conducted to investigate the influence of elemental sulfur to contaminated soil on plant uptake by a heavy metal hyperaccumulator, Indian mustard (Brassica juncea) and a field crop, winter wheat (Triticum. aestivum). Elemental sulfur (S) with different rates was carried out, they were 0 (S0), 20 (S20), 40 (S40), 80 (S80), and 160 (S160) mmol/kg respectively. Extra pots with the same rates of S but without plants were used for soil sampling to monitor pH and CaCl2-extractable heavy metal changes. The results showed that S enhanced phytoextraction of Pb and Zn from contaminated soil. Application S effectively decreased soil pH down to 1.1 as the most at the rate of S160. The concentrations of CaCl2-extractable Pb and Zn in soil and uptake of Pb and Zn by the plants were increased with soil pH decreased. A good correlation between CaCl2-extractable Pb/Zn and soil pH was found (R2Pb = 0.847 and R2Zn = 0.991, n = 25). With S application, soil CaCl2-extractable Pb and Zn concentrations, concentration of Pb and Zn in plants and the amount of removal by plant uptake were significantly higher than those without S. Under the treatment of S160, the highest CaCl2-extractable Pb and Zn were observed, they were 4.23 mg/kg and 0.40 mg/kg, 2.7 and 2.0 times as that of the control (S0) respectively. At the highest rates of S (S160), both Indian mustard and winter wheat reached the highest uptake of Pb and Zn. The highest Pb concentrations in wheat and Indian mustard were 32.8 mg/kg and 537.0 mg/kg, all 1.8 times as that of the control, and the highest Zn concentrations in wheat and Indian mustard were 215.5 mg/kg and 404.0 mg/kg, 2.4 and 2.0 times as that of the control respectively. The highest removals of Pb and Zn from the contaminated soil were 0.41 mg/pot and 0.31 mg/pot by Indian mustard in the treatment of S160 through 50 days growth.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-12

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

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

    PubMed

    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.

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

    PubMed

    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.

  18. Comparative study of skin sebum and elasticity level in patients with sulfur mustard-induced dermatitis and healthy controls.

    PubMed

    Davoudi, Seyyed Masoud; Sadr, Bardia; Hayatbakhsh, Mohammad R; Keshavarz, Saeed; Shohrati, Majid; Naghizadeh, Mohammad Mehdi; Babakoohi, Shahab; Rashighi-Firouzabadi, Mehdi; Firooz, Alireza

    2010-05-01

    Sulfur mustard (SM) - a chemical agent - has both acute and chronic effects on skin. Xerosis, which is deemed to be due to the damage of hydrolipidic barrier of the skin, is the most common complaint of veterans exposed to the chemical. This study was designed to evaluate skin sebum and elasticity in veterans with a history of SM contact. Three hundred and ten subjects were enrolled in this study and were divided into four groups: SM-exposed patients with current skin lesions (n=87); SM-exposed patients without skin lesions (n=71); patients with dermatitis (n=78); and normal controls (n=74). The skin sebum and elasticity were measured in four areas (forehead, suprasternal, palm and back of the hands) using a Sebumeter and a Reviscometer. Skin sebum was higher in participants who presented with dermatitis and had history of contact with SM than others; the difference was only statistically significant on the forehead. There was no significant difference in the skin elasticity between the four groups. While SM may increase skin sebum in long term, there is no evidence that it has a substantial effect on skin elasticity.

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

    SciTech Connect

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

    1993-05-13

    Hypochlorite solutions are thought to be efficacious when used to topically decontaminate intact skin. However, few studies have examined the efficacy of decontamination of chemically contaminated wounds. Therefore, we compared the decontamination efficacy of sodium hypochlorite (0.5% and 2.5% solutions), calcium hypochlorite (0.5% and 2.5% solutions) and sterile water to untreated controls in wounds exposed to sulfur mustard (HD). Anesthetized euthymic hairless guinea pigs (EHGP) (n=6) were exposed to 0.4 LD50 HD in a full-thickness 8 mm surgical biopsy skin defect (i.e., wound). Each animal was subsequently decontaminated, after a two-minute intra-wound exposure to liquid HD, with one of the decontamination solutions. Decontamination efficacy was determined by the visual grading of the HD-traumatized wound lesion and by comparison of the expected HD-induced leukocyte suppression. Leukocyte suppression was inconsistent in all animals; therefore, the visual grading was the only viable evaluation method. No significant differences were observed among wounds decontaminated with any of the solutions. However, the skin surrounding undecontaminated (but exposed) control animals showed the least visual pathology. The lesions induced following decontamination are presumed to be due to the mechanical flushing HD onto the peri-lesional skin, or by chemical damage induced by the solution, or HD-solution interaction. Further studies are required to best delineate the optimal decontamination process for HD contaminated wounds.

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

    SciTech Connect

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

    1994-12-31

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

  1. Association of physical activity and IL-10 levels 20 years after sulfur mustard exposure: Sardasht-Iran cohort study.

    PubMed

    Ghazanfari, Zeinab; Ghazanfari, Tooba; Kermani-Jalilvand, Arezou; Yaraee, Roya; Vaez-Mahdavi, Mohammad R; Foroutan, Abbas; Araghizadeh, Hassan; Faghihzadeh, Soghrat; Moaiedmohseni, Sakine; Soroush, Mohammad R; Naghizadeh, Mohammad M; Hassan, Zuhair M

    2009-12-01

    IL-10 is an anti-inflammatory cytokine that is important in the regulation of inflammatory processes in different conditions. Sulfur mustard (SM) intoxicated patients are suffering from different inflammatory diseases in their lung, skin and eyes. Physical activity (PA) is reported to control inflammation by reducing pro-inflammatory and inducing anti-inflammatory cytokines. Our previous study revealed lower PA and more sedentary lifestyle among SM exposed population. This study aimed to determine the relationship of PA with IL-10 production in SM exposed subjects. Baseline, mitogen-induced and the serum levels of IL-10 were evaluated. In a historical cohort study, Sardasht-Iran Cohort Study (SICS), 372 SM exposed participants were studied 20 years after exposure and were compared with 128 unexposed control participants. The Global Physical Activity Questionnaire (GPAQ; developed by WHO) was used to obtain a self-reported measure of physical activity. Whole blood culture supernatants and serum samples were used for IL-10 measurement by ELISA technique. In both the control and exposed groups mitogen-induced IL-10 production was significantly elevated with severity of PA intensity (p<0.05). In the control subjects with moderate PA intensity, the mitogen-induced IL-10 production was higher than the corresponding in the exposed group (p<0.05). In the exposed group, mitogen-induced IL-10 production had significant positive correlation with total PA, total transport PA, total recreational PA and total moderate intensity work (p<0.05). The positive relationship between high PA and the levels of anti-inflammatory cytokine IL-10 indicates a need to encourage a more active lifestyle among the SM exposed subjects who have various inflammatory complications.

  2. The effects of atorvastatin on mustard-gas-exposed patients with chronic obstructive pulmonary disease: A randomized controlled trial

    PubMed Central

    Ghobadi, Hassan; Lari, Shahrzad M.; Pourfarzi, Farhad; Mahmoudpour, Afsoun; Ghanei, Mostafa

    2014-01-01

    Background: Statins have anti-inflammatory effects in patients with chronic obstructive pulmonary disease (COPD). This study designed to evaluate the effects of atorvastatin on serum highly sensitive C-reactive protein (hs-CRP) and pulmonary function in sulfur mustard exposed patients with COPD. Materials and Methods: Fifty patients with chronic obstructive pulmonary disease due to sulfur mustard and high serum hs-CRP entered in this study. Participants were randomized to receive 40 mg atorvastatin or placebo in a double-blind clinical trial. Forty-five patients completed the study (n = 23 atorvastatin and n = 22 placebo). Pulse oximetry (SpO2), pulmonary function test (PFT), and 6 min walk distance test (6MWD) was measured. COPD assessment test (CAT) and St. George's respiratory questionnaire (SGRQ) were also completed by patients at the beginning of trial and after 9 weeks of prescription of 40 mg/day atorvastatin or placebo. At fourth week, SpO2, PFT, and 6MWD were again measured. After 9 weeks serum hs-CRP was re-measured. Results: There was no significant difference between atorvastatin and the placebo group in SpO2, FEV1, and 6MWD after fourth week (P = 0.79, P = 0.12, P = 0.12, respectively). The difference between baseline and ninth week was calculated for two groups of trial and control in term of serum hs-CRP, SpO2, FEV1, and 6MWD. Significant improvement was not observed between two groups in above mentioned variables (P = 0.35, P = 0.28, P = 0.94, P = 0.43, respectively). However, the quality of life was improved by administration of atorvastatin using the CAT score (P < 0.001) and SGRQ total score (P = 0.004). Conclusion: Atorvastatin does not alter serum hs-CRP and lung functions but may improve quality of life in SM-injured patients with COPD. PMID:24778661

  3. Sulfur Mustard-induced Neutropenia: Treatment with Granulocyte Colony-stimulating Factor

    DTIC Science & Technology

    2006-01-01

    pegylated G-CSF ( peg -G-CSF) Hematological data from rats exposed to HD by inhalation have been approved by the U.S. Food and Drug Administration as...study was to determine the phocytes, at 24 hours after exposure. 4 Gold and Scharfd re- effectiveness of G-CSF and peg -G-CSF in ameliorating HD-in- ported...includ- exposure, G-CSF therapy (10 Ag/kg per day for 21 days) was ing nitrogen mustard, also induce severe neutropenia," an ex- initiated. Peg -G-CSF

  4. Sulfur Mustard

    MedlinePlus

    ... Training Related Bioterrorism Resources Bacillus anthracis (Anthrax) Botulism (Clostridium botulinum toxin) Brucella species (brucellocis) Laboratory Information Surveillance & Investigation Burkholderia mallei (glanders) ...

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

    SciTech Connect

    Ludlum, D.B.

    1996-04-01

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

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

    PubMed

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

    2016-02-26

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

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

    SciTech Connect

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

    1988-01-01

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

  8. Cellular and molecular mechanisms of acute exposure to sulfur mustard: a systematic review.

    PubMed

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

    2017-04-01

    Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent in several battles and is still a potential worldwide menace. Besides local absorption, particularly in the skin, eyes and lungs, systemic spread of the agent also has detrimental effects on gonads, bone marrow and nervous system. Moreover, chronic exposure of SM to respiratory system causes death. Inducing oxidative stress, and disturbing DNA and tissue repair systems, inflammation and cell death signaling pathways have been introduced as molecular mechanisms of the injury. In this systematic review, more than 1200 (2000-2014) articles focusing on gross or molecular pathological reports in the acute phase of the respiratory injury after SM exposure were reviewed, followed by two different layers of gross and molecular pathological data (clinic and laboratory) integrated together in a spatio-temporal order. Role of epithelial, neutrophil and macrophage cells and three signaling pathways of inflammation, oxidative stress and cell death are covered in details. Our results propose a critical role of interleukin-17 producing cells in acute and chronic inflammatory responses.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

    The potential of exogenous ethylene and sulfur (S) in reversal of cadmium (Cd)-inhibited photosynthetic and growth responses in mustard (Brassica juncea L. cv. Pusa Jai Kisan) were studied. Plants grown with 50 μM Cd showed increased superoxide and H2O2 accumulation and lipid peroxidation together with increased activity of 1-aminocyclopropane carboxylic acid synthase (ACS) and ethylene production and inhibition of photosynthesis and growth. Application of 1 mM SO4(2-) or 200 μL L(-1) ethephon (ethylene source) influenced photosynthetic and growth performance equally in presence or absence of Cd. However, their combined application synergistically improved photosynthetic performance more in presence of Cd and reduced oxidative stress (lower superoxide and H2O2 accumulation) by decreasing ethylene and glucose sensitivity with the increase in cysteine and methionineand a non-proteinogenic thiol (reduced glutathione; GSH) contents. The central role of ethylene in potentiating S-mediated reversal of Cd-induced oxidative stress was evident with the use of ethylene action inhibitor, norbornadiene (NBD). The application of NBD resulted in decreased thiol production and photosynthetic responses. This suggests that ethylene promotes the effects of S in reversal of adverse effects of Cd, and thus, ethylene modulation may be considered as potential tool to substantiate the S effects in reversal of Cd inhibited photosynthesis and growth in mustard.

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1992-03-01

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

  13. HO1 mRNA and Protein do not Change in Parallel in Bronchial Biopsies of Patients After Long Term Exposure to Sulfur Mustard

    PubMed Central

    Nourani, Mohammad Reza; Yazdani, Samaneh; Roudkenar, Mehryar Habibi; Ebrahimi, Majid; Halabian, Raheleh; Mirbagheri, Leila; Ghanei, Mostafa; Fooladi, Abbas Ali Imani

    2010-01-01

    Sulfur mustard (SM), is an alkylating agent and has been emerged as a chemical weapon in various battlefields. More recently, SM was employed in the Iraq conflict against Iranian military forces and civilians. Nowadays there are more than 40,000 people suffering from pulmonary lesions special chronic obstructive pulmonary disease (COPD) due to mustard gas in Iran. SM causes the endogenous production of reactive oxygen species (ROS). Heme oxygenases (HOs) are the rate-limiting enzyme for heme metabolism. Numerous studies have confirmed that HOs are concerned in diverse biological processes such as anti-oxidation. The present study was undertaken to consider the regulation of HO-1 and HO-2 n the human airway wall, and to suggest a probable role that HOs may play in cellular defense against oxidative stress due to SM. In this research ten unexposed SM individuals and twenty SM exposed patients were included. Evaluation of HO-1& HO -2 expressions in unexposed and SM exposed patients samples was performed by semiquantitative RT-PCR, real-time RT-PCR and Immunohistochemistry analysis. While unexposed SM samples expressed same levels of HOs, expression level of HO-1 was upregulated about 3.58 ± 1.93 folds in SM exposed patients in comparison with unexposed ones, we could not find any difference in expression of HO-2 n two groups. In contrast, Immunohistochemistry results showed negative HO-1 protein expression in SM injured patients. Our results revealed that HO1 may plays an important role in cellular protection against oxidative stress due to mustard gas toxicity in airway wall of SM exposed patients at mRNA level, but translational modifications might cause decrease in the amount of HO1 protein. PMID:20981135

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

    PubMed Central

    2010-01-01

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

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

    PubMed Central

    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

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

    SciTech Connect

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

    1993-05-13

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

  17. Sulfur mustard causes oxidative stress and depletion of antioxidants in muscles, livers, and kidneys of Wistar rats.

    PubMed

    Pohanka, Miroslav; Stetina, Rudolf; Svobodova, Hana; Ruttkay-Nedecky, Branislav; Jilkova, Martina; Sochor, Jiri; Sobotka, Jakub; Adam, Vojtech; Kizek, Rene

    2013-07-01

    Sulfur mustard (SM) is a chemical warfare agent with cytotoxic effect and a tight link to oxidative stress (OS). Depletion of antioxidants is considered as a cause of detrimental consequence and belongs to the important steps leading to cell death. The oxidative injury appearing after SM exposure is not well understood. Nevertheless, identification of the pathological processes would be a good opportunity to establish an efficient therapy. Here, we focused our effort on an estimation of reactive oxygen species homeostasis and apoptotic processes in Wistar rats exposed to 0-160 mg/kg of SM. We assayed antioxidant activity, thiobarbituric acid reactive substances, reduced glutathione/oxidized glutathione, metallothionein, glutathione reductase, glutathione peroxidase, glutathione S-transferase, caspase 3, and glucose in the livers, kidneys, and muscles of the animals. Significant OS, depletion of low-molecular-mass antioxidants, increase in caspase activity, and some other processes related to SM action were determined. Moreover, we infer a principal role of OS in the tested organs.

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

    PubMed

    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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  1. Long-term ocular consequences of sulfur mustard in seriously eye-injured war veterans.

    PubMed

    Ghasemi, Hassan; Ghazanfari, Tooba; Ghassemi-Broumand, Mohammad; Javadi, Mohammad Ali; Babaei, Mahmoud; Soroush, Mohammad Reza; Yaraee, Roya; Faghihzadeh, Soghrat; Poorfarzam, Shahriar; Owlia, Parviz; Naghizadeh, Mohammad Mehdi; Etezad-Razavi, Mohammad; Jadidi, Khosro; Naderi, Mostafa; Hassan, Zuhair Mohammad

    2009-01-01

    Sulfur mustard (SM) has been used as a dangerous chemical warfare agent since the early 20th century. Although many descriptive studies about SM-induced ocular injuries are present in the medical literature, few of them have been conducted over a large group with serious ocular involvement. This descriptive study was conducted on 149 severe SM-intoxicated war veterans. Ocular history, anterior and posterior segment findings using a slit lamp, and direct and indirect ophthalmoscopic findings were recorded. Severity of the disease was also recorded based on a chart of the Foundation of Martyrs and Veterans Affairs. Ocular complains included photophobia (73.2%), sense of decreased vision (72.5%), dry eye sensation (66.4%), foreign body sensation (61.1%), tearing (46.3%), and pain (43.0%). Slit lamp findings were meibomian gland dysfunction (MGD; 96%), blepharitis, punctal closure, trichiasis, tear break-up time, and tear meniscus layer abnormality (80% to 90%). Conjunctival disturbances included vascular abnormality, ischemia, hyperemia, subconjunctival fibrosis, and pterygium. Limbal changes were abnormal vessels, limbal tissue loss and pigment loss, and pannus formation. Corneal problems included epithelial and stromal disturbances, calcium deposition, and melting. The most frequent previous surgeries were punctal closure, lamellar keratoplasty (LK), and stem cell allograft. Severity of intoxication included mild (17%), moderate (25%), and severe (57%). Chronic blepharitis and decreased tear secretion are the 2 most important and influencing factors in progression of ocular problems in SM injuries. The more severe the initial exposure, percentage of disability, and duration of ocular involvement, the higher the likelihood of mustard gas keratopathy.

  2. Efficacy of Aloe vera/olive oil cream versus betamethasone cream for chronic skin lesions following sulfur mustard exposure: a randomized double-blind clinical trial.

    PubMed

    Panahi, Yunes; Davoudi, Seyyed Masoud; Sahebkar, Amirhossein; Beiraghdar, Fatemeh; Dadjo, Yahya; Feizi, Iraj; Amirchoopani, Golnoush; Zamani, Ali

    2012-06-01

    Chronic pruritic skin lesions are among the common late complications of sulfur mustard intoxication. In the present randomized double-blind clinical trial, therapeutic efficacy of Aloe vera/olive oil combination cream in the alleviation of these lesions was evaluated and compared to that of betamethasone 0.1% cream. Sixty-seven Iranian chemical warfare-injured veterans were randomized to apply A. vera/olive oil (n=34, completers=31) or betamethasone 0.1% (n=33, completers=32) cream twice daily for 6 weeks. Evaluation of pruritus severity was performed using a pruritic score questionnaire and visual analogue scale (VAS). Both treatments were associated with significant reductions in the frequency of pruritus (p<0.05), burning sensation (p<0.01 and p<0.001 in A. vera/olive oil and betamethasone group, respectively), scaling (p<0.01 and p<0.05) and dry skin (p<0.001) at the end of trial. Fissure and excoriation were only reduced in the A. vera group (p<0.05). The change in the frequency of hyper- and hypopigmentation lesions, blisters, erythema and lichenification did not reach statistical significance in any of the groups (p>0.05). Mean pruritus (p<0.05) and VAS scores (p<0.01 and p<0.05) were significantly decreased by the end of trial in both groups. The rate of improvement in the pruritus severity [defined as being classified in a less severe category (mild, moderate and severe)] was found to be comparable between the groups (p>0.05). A. vera/olive oil cream was at least as effective as betamethasone 0.1% in the treatment of sulfur mustard-induced chronic skin complications and might serve as a promising therapeutic option for the alleviation of symptoms in mustard gas-exposed patients.

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

    DTIC Science & Technology

    2004-08-01

    Mol from our laboratory is studying the mechanism of action of sulfur mustard using proteomics , which has led to new hypotheses concerning how the...rabbit-anti-mouse-Ig-horse radish peroxidase), were performed as previously described (Benschop and Van der Schans, 1995). Solutions A and B of the...anti-mouse-Ig-horse radish peroxidase, Dakopatts, Glostrup, Denmark Enhanced Chemiluminescence Blotting Detection System Solution A and B, Boehringer

  4. Vascular hyperpermeability in response to inflammatory mustard oil is mediated by Rho kinase in mice systemically exposed to arsenic.

    PubMed

    Chen, Shih-Chieh; Liu, Chun-Chih; Huang, Shin-Yin; Chiou, Shean-Jaw

    2011-09-01

    The mechanisms underlying vascular dysfunction and cardiovascular disease induced by chronic arsenic exposure are not completely understood. We have previously shown that mice chronically fed sodium arsenite are hypersensitive to the permeability-increasing effects of inflammatory mustard oil. The aim of this study was to investigate whether RhoA/Rho kinase (ROCK)-mediated vascular leakage (hyperpermeability) is induced by mustard oil in mice systemically exposed to arsenic. Animals were orally fed water (control group) or sodium arsenite for 8weeks. We compared the blood pressure and microvessel density of the ears between these two groups. Both control and arsenic groups exhibited a similar mean arterial pressure and microvessel density. Microvessel permeability changes that occurred following mustard oil treatment in the presence of Y-27632, a ROCK inhibitor, were quantified using the Evans blue (EB) technique and vascular labeling with carbon particles. Both the excessive leakiness of EB and the high density of carbon-labeled microvessels upon stimulation with mustard oil in the arsenic-fed mice were reduced by Y-27632 treatment. However, RhoA and ROCK2 expression levels were similar between control and arsenic-fed mice. We further investigated ROCK2 levels and ROCK activity in the ears following mustard oil challenge. ROCK2 levels in mouse ears treated with mustard oil were higher in the arsenic group as compared with the control group. Following mustard oil application, ROCK activity was significantly higher in the arsenic-fed mice compared with the control mice. These findings indicate that increased ROCK2 levels and enhanced ROCK activity are responsible for mustard oil-induced vascular hyperpermeability in arsenic-fed mice. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    SciTech Connect

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

    2009-12-01

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

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

    PubMed

    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.

  7. Evaluation of candidate decontaminants against percutaneous sulfur mustard and thickened soman challenges

    SciTech Connect

    Blank, J.A.; Hobson, D.W.; Menton, R.G.; Olson, C.T.; Korte, D.W.

    1993-05-13

    Studies were conducted to evaluate the efficacy of candidate skin decontaminants relative to a standard control decontaminant, XE-555 resin, against percutaneous sulfur mustard (HD) or thickened soman (TGD) challenge. Male, New Zealand White rabbits were used as the model system with lesion area as the end point for HD exposures and erythrocyte acetylcholinesterase (AChE) inhibition as the endpoint for TGD exposure. Initial studies were performed to establish assay parameters for, and to validate the use of, AChE inhibition as an endpoint for assessing candidate decontaminant efficacy against nerve agent exposures. XE-555 resin was concurrently evaluated with each candidate decontaminant for both assay control and comparative purpose. Decontamination was initiated at 1, 3, or 5 min after HD exposures and 2 min after TGD exposures. U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) compounds 1513, 1514, 1515, 1516, and 1517 were evaluated against HD and against TGD. Results from these studies demonstrated the utility of AChE inhibition for evaluating skin decontaminants. None of the candidate decontaminants evaluated was more effective than the standard control decontaminant against HD or TGD exposures.

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

    PubMed

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

    2013-02-01

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

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

    NASA Astrophysics Data System (ADS)

    Werrlein, Robert; Madren-Whalley, Janna S.

    2002-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2017-01-01

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

  12. Dermal and ocular exposure systems for the development of models of sulfur mustard-induced injury.

    PubMed

    Weber, Waylon M; Kracko, Dean A; Lehman, Mericka R; Cox, Christopher E; Cheng, Yung-Sung; Grotendorst, Gary R; McDonald, Jacob D

    2011-09-01

    Sulfur mustard (SM) is a chemical threat agent for which the effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present article details the techniques used to develop SM laboratory exposure systems for the development of animal models of ocular and dermal injury. These models are critical to enable evaluation of SM injury and therapeutics against that injury. Iterative trials were conducted to optimize dermal and ocular injury models in guinea pigs and rabbits respectively. The goal was a homogeneous and diffuse ocular and dermal injury that compares to the human injury. Dermal exposures were conducted by either a flow-past or static vapor cup system. Ocular exposures were conducted by a static exposure system. Ocular and dermal exposures were conducted with vaporized SM. Vapor concentrations increased with time in the dermal and ocular exposure systems but were stable with varying amounts of applied SM. A dermal deposition estimation study was also conducted. Deposited volumes increased with exposure time.

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

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

  14. Respiratory effects of sulfur mustard exposure, similarities and differences with asthma and COPD.

    PubMed

    Khazdair, Mohammad Reza; Boskabady, Mohammad Hossein; Ghorani, Vahideh

    2015-01-01

    Previous research has found relationships between sulfur mustard (SM) toxicity and its adverse effects. SM is highly toxic to the respiratory system, leading to hacking cough, rhinorrheachest tightness, acute pharyngitis and laryngitis, chronic bronchitis and lung fibrosis. In this review, based on the scientific literature, we provide an updated summary of information on SM exposures and their differences with asthma and COPD. Information of this review was obtained by searching Medline/PubMed, ScienceDirect, Scopus, Google Scholar, ISI Web of Knowledge and Chemical Abstracts. SM exposure can decrease pulmonary function tests (PFTs) values. In addition, inflammatory cell accumulation in the respiratory tract and increased expression of some pro-inflammatory cytokines including tumor necrosis factor-α (TNFα), IL-1a, IL-1β, and reactive oxygen radicals due to SM exposure have been shown. Matrix metalloproteinase (MMP) which degrade extracellular matrix proteins, contributing to inflammatory cell recruitment, tissue injury and fibrosis are also up-regulated in the lung after SM exposure. In the lung, SM exposure also can cause serious pathological changes including airway inflammation, parenchymal tissue destruction and airway obstruction which can lead to asthma or chronic obstructive pulmonary disease (COPD). Following SM poisoning, DNA damage, apoptosis and autophagy are observed in the lung along with the increased expression of activated caspases and DNA repair enzymes. In the present article, respiratory symptoms, changes in PFTs, lung pathology and lung inflammation due to SM exposure and the similarities and differences between them and those observed in asthma and COPD were reviewed.

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

    PubMed Central

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

    2017-01-01

    Acute lung injury due to sulfur mustard (SM) inhalation causes 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 (TFPI) 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 (PAI-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and α2-antiplasmin (α2AP). Airway administration of tissue plasminogen activator (tPA) can overwhelm these effects and be 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. PMID:27384912

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

    PubMed

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

    2016-01-01

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

  17. Inhalation exposure systems for the development of rodent models of sulfur mustard-induced pulmonary injury.

    PubMed

    Weber, Waylon M; Kracko, Dean A; Lehman, Mericka R; Irvin, Clinton M; Blair, Lee F; White, Richard K; Benson, Janet M; Grotendorst, Gary R; Cheng, Yung-Sung; McDonald, Jacob D

    2010-01-01

    Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury. These models are critical for evaluating SM injury and developing therapeutics against that injury. Iterative trials were conducted to optimize a lung injury model. The resulting pathology was used as a guide, with a goal of effecting homogeneous and diffuse lung injury comparable to that of human injury. Inhalation exposures were conducted by either nose-only inhalation or intubated inhalation. The exposures were conducted to either directly vaporized SM or SM that was nebulized from an ethanol solution. Inhalation of SM by nose-only inhalation resulted in severe nasal epithelial degeneration and minimal lung injury. The reactivity of SM did not permit it to transit past the upper airways to promote lower airway injury. Intratracheal inhalation of SM vapors at a concentration of 5400 mg x min/m(3) resulted in homogeneous lung injury with no nasal degeneration.

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

    PubMed Central

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

    2010-01-01

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

  19. Inhalation Exposure Systems for the Development of Rodent Models of Sulfur Mustard-Induced Pulmonary Injury

    PubMed Central

    Weber, Waylon M.; Kracko, Dean A.; Lehman, Mericka R.; Irvin, Clinton M.; Blair, Lee F.; White, Richard K.; Benson, Janet M.; Grotendorst, Gary R.; Cheng, Yung-Sung; McDonald, Jacob D.

    2011-01-01

    Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury. These models are critical for evaluating SM injury and developing therapeutics against that injury. Iterative trials were conducted to optimize a lung injury model. The resulting pathology was used as a guide, with a goal of effecting homogeneous and diffuse lung injury comparable to that of human injury. Inhalation exposures were conducted by either nose-only inhalation or intubated inhalation. The exposures were conducted to either directly vaporized SM or SM that was nebulized from an ethanol solution. Inhalation of SM by nose-only inhalation resulted in severe nasal epithelial degeneration and minimal lung injury. The reactivity of SM did not permit it to transit past the upper airways to promote lower airway injury. Intratracheal inhalation of SM vapors at a concentration of 5400 mg · min/m3 resulted in homogeneous lung injury with no nasal degeneration. PMID:20025432

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

    PubMed Central

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

    2008-01-01

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

  1. External urethral stenosis: a latent effect of sulfur mustard two decades post-exposure.

    PubMed

    Emadi, Seyed Naser; Hosseini-Khalili, Alireza; Soroush, Mohammadreza; Ardakani, Mohammadreza Khodaei; Ghassemi-Broumand, Mohammad; Davoodi, Seyed Masoud; Amirani, Omolbanin; Haines, David

    2009-09-01

    Sulfur mustard (SM), a chemical weapon used widely during World War I and against Iranians during the Iran-Iraq War of the 1980s, causes massive inflammatory tissue damage in the immediate post-exposure period, resulting in debilitating chronic disease in years to decades following contact with the agent. These syndromes most often are pathologies of the lungs, eyes, and skin, the primary target organs of SM. Typically, they are characterized by severe and increasingly painful inflammation, often accompanied by fibrosis and constriction of the anatomic channels needed for normal life, such as the small airways of the lungs and, in the present report, the urethra. The present case study is a 43-year-old man with a history of heavy SM exposure to the groin in 1984. Within 1 year after exposure, the patient was found to have developed meatal stricture, occlusion of the external urethral meatus, and difficulty in urination. Two years post-exposure, he underwent ventral meatotomy and meatoplasty. This case presents a unique example of the latent effects of SM exposure to the groin, and will be of value in the prevention of similar injury and complications to persons at risk of SM exposure in the future.

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

    PubMed

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

    2013-11-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2011-07-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. Gas Chromatographic-Mass Spectrometric Analysis of Sulfur Mustard-Plasma Protein Adducts: Validation and Use in a Rat Inhalation Model

    DTIC Science & Technology

    2008-01-01

    method for detecting HD exposure (13). The technique lever- ages interaction of HD with plasma proteins to form stable adducts . The analytical...Benschop. Immunochemical detection of sulfur mustard adducts with keratins in the stratum corneum of human skin. Chem. Res. Toxicol. 15: 21-25 (2002). 13...mustard-plasma protein adducts : Validation and use of a rat inhalation model 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Capacio

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

    PubMed

    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.

  8. Chewing gum containing allyl isothiocyanate from mustard seed extract is effective in reducing volatile sulfur compounds responsible for oral malodor.

    PubMed

    Tian, Minmin; Hanley, Anthony Bryan; Dodds, Michael W J; Yaegaki, Ken

    2013-08-01

    To evaluate the in vivo effect of chewing gum containing allyl isothiocyanate alone, and in combination with zinc salts on reduction of the level of volatile sulfur compounds responsible for oral malodor. 15 healthy volunteers between the ages of 20-50 chewed either an experimental gum or a placebo gum for 12 minutes. Their mouth air was analyzed for volatile sulfur compounds by a gas chromatograph at baseline, immediately after chewing, and at 60, 120 and 180 minutes after treatment. The study revealed that allyl isothiocyanate, a constituent of mustard seed extract, can effectively reduce the concentration of volatile sulfur compounds in mouth air. Chewing gum containing 0.1% zinc lactate and 0.01% of allyl isothiocyanate eliminated 89%, 55.5%, 48% and 24% of the total VSC concentration immediately after chewing and at 1, 2, and 3 hours after chewing, respectively.

  9. Microbiological evaluation of chronic blepharitis among Iranian veterans exposed to mustard gas: a case-controlled study.

    PubMed

    Karimian, Farid; Zarei-Ghanavati, Siamak; A, Baradaran-Rafii; Jadidi, Khosrow; Lotfi-Kian, Alireza

    2011-06-01

    To evaluate the microbiological characteristics of eyelid margin flora in chronic blepharitis in mustard gas-exposed individuals and compare the results with those in age- and sex-matched unexposed people. In this comparative case series, 289 patients with ocular manifestations of mustard gas exposure (case) were evaluated for signs of chronic blepharitis. Additionally, microbiological evaluation of eyelid margins was conducted in these patients and compared with results of 100 unexposed patients with chronic blepharitis (control). One-hundred fifty (52.0%) of 289 mustard gas casualties had signs of chronic blepharitis. Microbiological evaluation revealed higher isolation rates of Staphylococcus epidermidis (78%) and Staphylococcus aureus (57%) in the case in comparison to control group (P < 0.01). Moreover, S. aureus isolated from the cases exhibited greater resistance to common antibiotics compared with control group. Fungi were isolated more frequent in the case compared with controls (30% vs. 4%, P < 0.01), with Cladosporium and Candida species being most common in the case group. Exposure to mustard gas seems to alter the microbiological flora of the eyelid margin. Staphylococcus spp., including antibiotic-resistant strains, and fungi were more frequently isolated in these patients. The relationship between microbial culture results and the severity of ocular surface manifestations in mustard gas-injured cases warrant further investigation.

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

    NASA Astrophysics Data System (ADS)

    Sadeghi, Meysam; Yekta, Sina; Ghaedi, Hamed

    2016-07-01

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

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

    PubMed

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

    2009-07-22

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

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

    PubMed

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

    2004-01-01

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

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

    PubMed

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

    2014-10-01

    Sulfur (S) assimilation results in the synthesis of cysteine (Cys), a common metabolite for the formation of both reduced glutathione (GSH) and ethylene. Thus, ethylene may have regulatory interaction with GSH in the alleviation of salt stress. The involvement of ethylene in the alleviation of salt stress by S application was studied in mustard (Brassica juncea cv. Pusa Jai Kisan). First, the effects of 0, 0.5, 1.0 and 2.0 mM SO4 (2) (-) were studied on photosynthetic and growth parameters to ascertain the S requirement as sufficient-S and excess-S for the plant. In further experiments, the effects of sufficient-S (1 mM SO4 (2) (-) ) and excess-S (2 mM SO4 (2) (-) ) were studied on the alleviation of salt stress-induced by 100 mM NaCl, and ethylene involvement in the alleviation of salt stress by S. Under non-saline condition, excess-S increased ethylene with less content of Cys and GSH and adversely affected photosynthesis and growth. In contrast, excess-S maximally alleviated salt stress due to high demand for S and optimal ethylene formation, which maximally increased GSH and promoted photosynthesis and growth. The involvement of ethylene in S-mediated alleviation of salt stress was further substantiated by the reversal of the effects of excess-S on photosynthesis by aminoethoxyvinylglycine (AVG), ethylene biosynthesis inhibitor. The studies suggest that plants respond differentially to the S availability under non-saline and salt stress and excess-S was more potential in the alleviation of salt stress. Further, ethylene regulates plants' response and excess S-induced alleviation of salt stress and promotion of photosynthesis. © 2014 Scandinavian Plant Physiology Society.

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

    PubMed

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

    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.

  15. Addition of Epidermal Growth Factor Improves the Rate of Sulfur Mustard Wound Healing in an In Vitro Model

    DTIC Science & Technology

    2008-03-26

    cultures20 and a number of immortalized human skin cell lines , includ- ing G361, SVK14, HaCaT , and NCTC 2544, have also been used to study SM toxicity...148 HENEMYRE-HARRIS ET AL 21. Simpson R, Lindsay CD. Effect of sulphur mustard on human skin cell lines with differential agent sensitivity. J Appl...Methods: The model consisted of normal human epidermal keratinocytes seeded into 6-well plates, exposed to SM, and wounded (disruption of the cell

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    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.

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

    PubMed

    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

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

    PubMed

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

    2010-07-01

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

  20. Long-term right ventricular changes in mustard-exposed patients: A historical cohort.

    PubMed

    Khosravi, Arezoo; Motamedi, Mohamad Ali; Kazemi-Saleh, Davoud; Aslani, Jafar; Ghanei, Mostafa

    2017-10-05

    Mustard gas (MG) is a chemical warfare agent widely used in the Iran-Iraq War. Its catastrophic effects on the lungs, eyes, and skin have been well studied. However, it also affects the cardiovascular system. We aimed to evaluate the long-term effect of MG on right ventricular (RV) function. All patients presenting to the university clinics between May 2014 and September 2015 were consecutively evaluated to enter the study based on the inclusion criteria (documented proof of chemical injury, no past or present cardiovascular disease, not a current smoker, and no history of sleep apnea). A comparable control group of veterans without MG exposure was randomly selected. All patients underwent echocardiographic measurement of RV size and function by a blinded cardiologist. We included 23 patients in the MG-exposed group and 19 subjects in the control group, with a mean age of 48.6 years. Mean chemical injury severity score was 29.7% and mean time from the MG exposure was 29.2 years. The main complaint of MG-exposed patients pertained to respiratory symptoms (91%). Pulmonary artery pressure was higher (32.83 vs. 28.95 mmHg) and RV strain was lower (-17.05% vs. -20.72%) in the MG-exposed than in the control group (P < .05). Our results present baseline RV values for MG-exposed patients and show mild but significant changes after 3 decades. Further cellular and molecular studies are needed to evaluate underlying mechanisms of MG cardiotoxicity. © 2017 Wiley Periodicals, Inc.

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

    SciTech Connect

    Brimfield, A.A.; Hodgson, Ernest

    2006-06-15

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

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

    PubMed

    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.

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

    SciTech Connect

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

    1995-12-31

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

  4. A comparison of decontamination effects of commercially available detergents in rats pre-exposed to topical sulphur mustard.

    PubMed

    Misik, Jan; Jost, Petr; Pavlikova, Ruzena; Vodakova, Eva; Cabal, Jiri; Kuca, Kamil

    2013-06-01

    The genotoxic vesicant sulphur mustard [bis-2-(chloroethyl)sulphide] is a chemical warfare agent which is easily available due to its relatively simple synthesis. Thus, sulphur mustard is a potential agent for mass contamination. In this study, we focused on sulphur mustard toxicity and decontamination in a rat model using commercially available detergent mixtures for dermal decontamination. Male Wistar rats were percutaneously treated with sulphur mustard and subjected to wet decontamination 2 min postexposure. Commercially produced detergents Neodekont™, Argos™, Dermogel™ and FloraFree™ were tested for their decontamination efficacy against an exposed group and their protective ratios determined. The results showed that all tested detergent solutions produced an increase in the median lethal dose [LD(50) = 9.83 (5.87-13.63) mg·kg(-1)] in comparison to controls, which led to increased survival of experimental animals. In general, all tested detergents provided modest decontamination efficacy (PR = 2.0-5.7). The highest protective ratio (5.7) was consistently achieved with Argos™. Accordingly, Argos™ should be considered in further investigation of mass casualty decontamination.

  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

    SciTech Connect

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

    2010-09-01

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

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

    PubMed Central

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

    2015-01-01

    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 P450’s 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. PMID:20561902

  7. Trans-Dermal Fentanyl Patches are a Cost-Effective Method of Long-Term Analgesic Delivery Following Corneal Exposure to Sulfur Mustard Vapor

    DTIC Science & Technology

    2012-01-01

    T., 2000. Beneficial effects of topical anti - inflammatory drugs against sulfur mustard-induced ocular lesions in rabbits. J Appl Toxicol 20 Suppl 1...nibble at food and readily consume fresh fruits and vegetables , although like most animals they exhibit individual preferences. Evidence of a lack of

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

    PubMed Central

    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

  9. Hypochlorite Solution as a Decontaminant in Sulfur Mustard Contaminated Skin Defects in the Euthymic Hairless Guinea Pig

    DTIC Science & Technology

    1993-05-13

    AD-P008 792 Hyochlorte Solution as a Decossitamrsrl nan Sultur Mustard Contaminated Skin Defects in the Euthymesc Hailess Guinea Pig Mark B. Gol, OVM...soilutions are thought to be efficacious when used to topi.cally dft-ontaminaise intact skin . However, lb~w -studios havo exarn-ined the efficacy of...euthymic hairles guinea pigs (EHGP) (n--6) were exposed tn 0 4 LD50 HO in a hA-thickntss 8 mm surgical bmop~sy skin deflect (ioe wound) Each animal was

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

    SciTech Connect

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

    1990-12-01

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

  11. Alterations in serum levels of inflammatory cytokines (TNF, IL-1alpha, IL-1beta and IL-1Ra) 20 years after sulfur mustard exposure: Sardasht-Iran cohort study.

    PubMed

    Yaraee, Roya; Ghazanfari, Tooba; Ebtekar, Massoumeh; Ardestani, Sussan K; Rezaei, Abbas; Kariminia, Amina; Faghihzadeh, Soghrat; Mostafaie, Ali; Vaez-Mahdavi, Mohammad R; Mahmoudi, Mahmoud; Naghizadeh, Mohammad M; Soroush, Mohammad R; Hassan, Zuhair M

    2009-12-01

    Mustard gas, even in low doses, has the ability to inflict damage in multiple organs especially the skin, eyes, as well as the respiratory tract. This damage may cause many complications which persist during the lifespan of exposed subjects. Pro-inflammatory cytokines including TNF, IL-1alpha, IL-1beta and IL-1Ra cause systemic inflammatory reactions and numerous changes including altered cell signaling and migration, changes in cytokine production and fever. The aim of this study was to determine the serum levels of these cytokines in subjects who were exposed to mustard gas 20 years ago in comparison with an unexposed control group. In this historical cohort study 368 sulfur mustard (SM) exposed participants from Sardasht and 126 age-matched unexposed volunteers from Rabat (a nearby town) as controls were chosen by a random systematic sampling. The serum concentrations of IL-1alpha, IL-1beta, IL-1Ra and TNF were measured by a sandwich ELISA technique. Median of the serum levels of cytokines TNF, IL-1alpha, IL-1beta and IL-1Ra in the control group was 23.79, 1.89, 1.91 and 32.9 pg/ml respectively, while in the SM-exposed participants these values were 11.11, 0.81, 1.73 and 26.7 pg/ml respectively. The serum pro-inflammatory cytokine levels were significantly lower in the exposed group than in controls (p<0.01). There was also significant positive correlation between concentration of all of mentioned cytokines, the strongest being between IL-1beta and TNF (r=0.809 in the control group). The observed down-regulation of pro-inflammatory cytokines should be considered in interpretation of diagnosis and therapeutic measures taken to improve clinical complications.

  12. Comparative study of Unna's Boot and betamethasone cream in the treatment of sulfur mustard-related pruritus.

    PubMed

    Shohrati, Majid; Davoudi, Masoud; Almasi, Mahmoud; Sadr, Bardia; Peyman, Mohammadreza

    2007-01-01

    Pruritus, as a chronic lesion caused by sulfur mustard, is a common problem among chemical weapons veterans. Numerous treatments like antihistamines, local anesthetics, and corticosteroids have been prescribed in order to control pruritus in these patients, while long- term and widespread use of each one of them has its own restrictions. Nowadays different mixtures, including Unna's Boot, are being used. They are effective and have limited adverse effects. So in this study we compared this product with corticosteroids. In this double-blind randomized clinical trial in Baqyiatallah hospital, 90 veterans were included and randomly divided into three groups. Subjects of each group received one of the Betamethasone %1 cream, Unna's Boot cream, or placebo cream for three weeks. They used their medication on an itching area of body, one finger tip unit every night. To evaluate the drugs' efficacy we used pruritus score index and Visual Analysis Score index. From 90 patients, 75 patients completely used the medication and the other 15 subjects were excluded from the study. All three drugs caused significant decrease in both pruritus score and VAS (p < .001). Betamethasone and Unna's Boot were significantly more effective than placebo and despite more efficacy of betamethasone rather than Unna's Boot, they did not have any significant differences (p > .05). Pruritus is a chronic lesion in veterans that needs long-term conservation treatment. Regarding definite side effects of local long-term therapy with corticosteroids and nearly equal efficacy of Unna's Boot and betamethasone, Unna's Boot seems to be a better choice in controlling sulfur mustard-related pruritus compared with betamethason.

  13. Blood and Tissue Silver Levels Following Application of Silver-Based Dressings to Sulfur Mustard Chemical Burns.

    PubMed

    Barillo, David J; Croutch, Claire R; Reid, Frances; Culley, Tara; Sosna, William; Roseman, Julie

    Silver-based dressings are commonly used in burn care. Silver sulfadiazine use is associated with elevated blood, urine, and tissue levels of silver ion. We examined wound and tissue levels of silver ion in a two-species model of sulfur mustard chemical burn injury treated with two different silver-based dressings. Superficial dermal and moderate thickness dermal chemical burns were induced in 16 hairless guinea pigs and in 16 Gottingen minipigs by exposure to sulfur mustard vapor. After debridement, silver-nylon burn dressings or silver-calcium alginate dressings were applied and changed every 7 days until wound healing or a maximum of 60 days post exposure. At autopsy, liver, spleen, and wound samples were harvested. Silver ion was measured using inductively coupled plasma-mass spectrography with a lower level of detection of 0.02 parts per billion. Negligible silver ion levels were found in the liver (mean < 0.003 μg/g of tissue) and spleen (mean < 0.05 μg/g) of all 32 animals. Wound biopsies showed silver ion levels ranging from 0.07 to 19.5 μg/g of tissue. Wound levels were higher in minipigs than in hairless guinea pigs and were higher in animals treated with silver-nylon burn wound dressings than with silver-calcium alginate dressings. Silver ion could be detected in some wounds 40 days after dressings were removed. In a chemical burn model, application of silver-nylon or silver-calcium alginate dressings is associated with elevated wound levels but negligible tissue levels of silver ion.

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

    DTIC Science & Technology

    2003-12-01

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

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

    SciTech Connect

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

    1993-05-13

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

  16. Serum levels of IL-8 and IL-6 in the long term pulmonary complications induced by sulfur mustard: Sardasht-Iran Cohort Study.

    PubMed

    Pourfarzam, Shahryar; Ghazanfari, Tooba; Yaraee, Roya; Ghasemi, Hassan; Hassan, Zuhair M; Faghihzadeh, Soghrat; Ardestani, Sussan K; Kariminia, Amina; Fallahi, Faramarz; Soroush, Mohammad R; Merasizadeh, Javad; Mahlojirad, Maryam; Naghizadeh, Mohammad M; Ghanei, Mostafa

    2009-12-01

    Sulfur mustard (SM) is a blistering chemical agent which has short and long term toxicity against many organs. The respiratory tract is one of the main targets, and is the most disabling long term complication of SM. Inflammatory mediators especially IL-8 and IL-6 play the primary role in the various chronic pulmonary diseases. Sardasht-Iran Cohort Study (SICS) was designed to evaluate immunological and molecular parameters in SM exposed people 20 years after exposure. In the present study, the association of the serum levels of IL-8, IL-6, C reactive protein (CRP) and rheumatoid factor (RF) with long term pulmonary involvement was evaluated. There were 348 exposed and 120 control participants. The clinical evaluations were done for all subjects and Spirometry was performed according to American Thoracic Society Criteria. Severity of pulmonary involvement was assessed by Global Initiative for chronic Obstructive Lung Disease (GOLD) classification. The serum levels of IL-8, IL-6 and RF were assessed by ELISA assay. CRP was assessed by photometric method. The serum levels of IL-8 and IL-6 significantly decreased in the SM exposed participants compared to the control group. There were no significant associations between the serum levels of IL-8 and pulmonary symptoms (chronic cough, sputum, hemoptysis, and dyspnea), pulmonary findings (crackles, rales, and wheezing) as well as spirometry parameters. IL-6 was associated with wheezing and CRP was associated with wheezing and rales in SM exposed group. We concluded the serum levels of these inflammatory mediators probably do not have any major role in pathogenesis and persistence of pulmonary complications and do not reflect the degree of severity of pulmonary involvement following SM exposure.

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

    SciTech Connect

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

    1989-05-01

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

  18. Serum levels of interleukins 2, 4, 6, and 10 in veterans with chronic sulfur mustard-induced pruritus: a cross-sectional study.

    PubMed

    Panahi, Yunes; Davoudi, Seyyed Masoud; Beiraghdar, Fatemeh; Amiri, Mojtaba; Saadat, Alireza; Marzony, Eisa Tahmasbpour; Naghizadeh, Mohmad Mehdi; Sahebkar, Amirhossein

    2013-01-01

    Inflammation is a key component in the pathogenesis of sulfur mustard (SM)-induced skin complications. Here, the levels of interleukin (IL) -2, IL-4, IL-6, and IL-10 were evaluated in patients with chronic SM-induced complications. Seventy-four serum samples were collected from SM-injured veterans (SM group; n = 37) and nonchemically injured patients (control group; n = 37) with skin pruritus. The levels of IL-2, IL-4, IL-6, and IL-10 were evaluated by sandwich enzyme-linked immunosorbant assay technique in both nil and mitogen medium. No significant difference was found in pruritus score between SM (74.16 +/- 5.93) and control (74.48 +/- 6.15) groups (P > .05). The mean serum concentrations of IL-2 and IL-6 were found to be significantly elevated in the control compared with the SM group (P < .05). However, no significant difference was observed between the study groups regarding serum levels of IL-4 and IL-10 (P > .05). Serum IL-2 (in both SM and control groups) and IL-6 (in the control group) concentrations were significantly correlated with pruritus score while no significant association was found for IL-4 and IL-10. Serum concentrations of IL-2, IL-6, and IL-10 are significantly decreased in SM-exposed patients with chronic pruritus. Such alterations might represent a plausible mechanism for tissue damage and skin itching following SM exposure. Therefore, variation of ILs may also contribute to skin pruritus induced by SM.

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

    PubMed

    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.

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

    PubMed

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

    2016-07-01

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

  1. Poly (ADP-ribose) polymerase (PARP) is essential for sulfur mustard-induced DNA damage repair, but has no role in DNA ligase activation.

    PubMed

    Bhat, K Ramachandra; Benton, Betty J; Ray, Radharaman

    2006-01-01

    Concurrent activation of poly (ADP-ribose) polymerase (PARP) and DNA ligase was observed in cultured human epidermal keratinocytes (HEK) exposed to the DNA alkylating compound sulfur mustard (SM), suggesting that DNA ligase activation could be due to its modification by PARP. Using HEK, intracellular 3H-labeled NAD+ (3H-adenine) was metabolically generated and then these cells were exposed to SM (1 mM). DNA ligase I isolated from these cells was not 3H-labeled, indicating that DNA ligase I is not a substrate for (ADP-ribosyl)ation by PARP. In HEK, when PARP was inhibited by 3-amino benzamide (3-AB, 2 mM), SM-activated DNA ligase had a half-life that was four-fold higher than that observed in the absence of 3-AB. These results suggest that DNA repair requires PARP, and that DNA ligase remains activated until DNA damage repair is complete. The results show that in SM-exposed HEK, DNA ligase I is activated by phosphorylation catalysed by DNA-dependent protein kinase (DNA-PK). Therefore, the role of PARP in DNA repair is other than that of DNA ligase I activation. By using the DNA ligase I phosphorylation assay and decreasing PARP chemically as well as by PARP anti-sense mRNA expression in the cells, it was confirmed that PARP does not modify DNA ligase I. In conclusion, it is proposed that PARP is essential for efficient DNA repair; however, PARP participates in DNA repair by altering the chromosomal structure to make the DNA damage site(s) accessible to the repair enzymes.

  2. Improvements in the Methodology of Monitoring Sulfur Mustard Exposure by Gas Chromatography-Mass Spectrometry Analysis of Cleaved and Derivatized Blood Protein Adducts

    DTIC Science & Technology

    2008-01-01

    14). The technique involves the formation and monitoring of HD adducts cleaved from blood proteins such as albumin and Reproduction (photocopying) of...metric and immunochemical analysis of covalent adducts to pro- teins and DNA In Chemical Weapons Convention Chemicals Analysis: Sample Collection...D. Noort, R.H. Mars-Groenendijk, A Fidder, L.F. Chau, L.P.A. de long, and H.P. Benschop. Immunochemical detection of sulfur mustard adducts with

  3. Detection and measurement of sulfur mustard (HD) offgassing from the weanling pig following exposure to saturated HD vapor. Technical report, September-October 1994

    SciTech Connect

    Logan, T.P.; Graham, J.S.; Martin, J.L.; Zallnick, J.E.; Jakubowski, E.M.

    1997-11-01

    Sulfur mustard (HD) is a chemical warfare agent for which there is neither antidote nor adequate therapeutic protection. Animal models are employed to investigate mechanisms of injury and to evaluate protective measures against HD exposure. Researchers whose experiments involve cutaneous application of HD vapor to animals benefit from the detection and quantitation of HD at the exposed site. The ability to detect and quantify HD enables the researcher to follow safe procedures in handling skin samples. We have designed an experimental procedure to measure HD offgassing from animal models. A Minicams(R), which is a portable gas chromatograph (GC) equipped with a flame photometric detector (FPD) and with online sorbent collection and desorption, was used to monitor the HD concentration. Confirming measurements were made using a two-step process that trapped HD on a Tenax sorbent offline and then transferred the sample by means of an ACEM 900 to a OC equipped with either FPD or a mass spectrometer (MS). We collected data from six experiments in which weanling pigs were exposed to saturated HD vapor via vapor caps containing 10 micro of HD. HD concentration was measured in time-weighted-average (TWA) units at a specific HD application site. The currently recommended exposure value for HD is 3 ng/l, 1 TWA unit. In five of the six experiments, Minicams HD concentration values were less than 0.5 TWA, 2 hours postexposure, and in one of the experiments, TWA Minicams concentration was less than 0.5 TWA, 5 hours post-exposure. OCIMS detection was used in three of the experiments to confirm Minicams data and to provide greater sensitivity and selectivity at 0.1 TWA. GC/MS data confirmed that HD concentrations fell below 0.1 TWA in less than S hours for a specific site.

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

    PubMed Central

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

    2017-01-01

    Objective 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. Materials and Methods 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). Results 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. Conclusion 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). PMID:28367422

  5. The beneficial effects of doxycycline, an inhibitor of matrix metalloproteinases, on sulfur mustard-induced ocular pathologies depend on the injury stage.

    PubMed

    Horwitz, Vered; Dachir, Shlomit; Cohen, Maayan; Gutman, Hila; Cohen, Liat; Fishbine, Eliezer; Brandeis, Rachel; Turetz, Joseph; Amir, Adina; Gore, Ariel; Kadar, Tamar

    2014-08-01

    Sulfur mustard (SM) induces acute ocular lesions, including erosions and inflammation that may be followed by delayed injuries expressed by epithelial defects and neovascularization (NV). Based on the matrix metalloproteinases (MMPs) activity, we evaluated the clinical and biochemical effects of topical treatment with doxycycline, an MMP inhibitor, targeted to the various injury stages. Rabbit eyes were exposed to SM vapor. A clinical follow-up was carried out up to 2 months. Tear fluid and cornea samples were collected at different time points for measurements of MMPs activity by zymography. Efficacy of a post-exposure topical doxycycline (2 mg/ml in phosphate buffer saline, ×4/d), targeted to the different phases of the clinical injury, was evaluated. Elevated MMP-9 and MMP-2 activities were found in all corneas during the acute injury and in vascularized corneas during the delayed pathology. In the tear fluid, high MMP-9 activity and negligible MMP-2 activity were found in all the exposed eyes until after the appearance of the delayed pathology symptoms. Prolonged doxycycline treatment reduced MMP-9 activity in the tear fluid. During the acute phase, doxycycline treatment reduced corneal MMP-9 activity and the severity of the injury. Targeting the delayed pathology, doxycycline was clinically efficient only when treatment began before NV appearance. This in vivo study showed the involvement of MMP-9 and MMP-2 during different phases of the SM-induced ocular injury, and the potential of doxycycline treatment as a post exposure measure for reducing the acute injury and as a preventive therapy for ameliorating the delayed pathology. The tear fluid provided a non-invasive method for continuous follow-up of MMPs activity and revealed additional beneficial aspects of injury and the treatment.

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

    SciTech Connect

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

    2014-10-15

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

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

    PubMed

    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.

  8. Impact of topical application of sulfur mustard on mice skin and distant organs DNA repair enzyme signature.

    PubMed

    Sauvaigo, Sylvie; Sarrazy, Fanny; Batal, Mohamed; Caillat, Sylvain; Pitiot, Benoit; Mouret, Stéphane; Cléry-Barraud, Cécile; Boudry, Isabelle; Douki, Thierry

    2016-01-22

    Sulfur mustard (SM) is a chemical warfare agent that, upon topical application, damages skin and reaches internal organs through diffusion in blood. Two major toxic consequences of SM exposure are inflammation, associated with oxidative stress, and the formation of alkylated DNA bases. In the present study, we investigated the impact of exposure to SM on DNA repair, using two different functional DNA repair assays which provide information on several Base Excision Repair (BER) and Excision/Synthesis Repair (ESR) activities. BER activities were reduced in all organs as early as 4h after exposure, with the exception of the defense systems against 8-oxo-guanine and hypoxanthine which were stimulated. Interestingly, the resulting BER intermediates could activate inflammation signals, aggravating the inflammation triggered by SM exposure and leading to increased oxidative stress. ESR activities were found to be mostly inhibited in skin, brain and kidneys. In contrast, in the lung there was a general increase in ESR activities. In summary, exposure to SM leads to a significant decrease in DNA repair in most organs, concomitant with the formation of DNA damage. These synergistic genotoxic effects are likely to participate in the high toxicity of this alkylating agent. Lungs, possibly better equipped with repair enzymes to handle exogenous exposure, are the exception.

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

    PubMed

    Jung, H; Lee, H W

    2014-05-30

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

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

    SciTech Connect

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

    2006-01-01

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

  11. Role of cytokines and reactive oxygen intermediates in the inflammatory response produced by sulfur mustard. A progress report

    SciTech Connect

    Dannenberg, A.M.; Tsuruta, J.

    1993-05-13

    Cytokines play a major role in both acute and chronic inflammatory processes, including those produced by sulfur mustard (SM). In situ hybridization of the mRNA of various cytokines with radiolabeled antisense RNA probes enables us to visualize under the microscope which cells in tissue sections of SM lesions are producing which type of cytokine. This technique, therefore, demonstrates cell function histologically, even though the cells are no longer alive at the time of analysis. Cytokines from infiltrating phagocytes. We have successfully demonstrated the mRNAs of four major cytokines in developing and healing rabbit SM lesions: Interleukin 1 beta (IL-1 beta), neutrophil attractant/activation protein 1 (NAP-1 or IL-8), monocyte chemoattractant (activating) protein 1 (MCP-1), and GRO, which is macrophage inflammatory protein 2. The macrophage/fibroblast group in the lesions contained the mRNA of all four cytokines, and granulocytes contained the mRNA of IL-1 beta and NAP-1. More cytokine producing cells were present in the peak lesions than in healing lesions.

  12. Tear total protein analysis in patients with late sulfur mustard-induced ocular complications: a cross-sectional study.

    PubMed

    Panahi, Yunes; Eftekhari Milani, Amir; Sahebkar, Amirhossein; Naderi, Mostafa; Babaei, Mahmoud; Beiraghdar, Fatemeh; Parvin, Shahram; Dadjo, Yahya

    2012-06-01

    Eyes are the most sensitive organs to sulfur mustard (SM). Late ocular complications have been reported even 15-20 years post-exposure. To date, no study has investigated the composition of tear proteins in tear samples of SM-intoxicated patients. Total protein content as well as concentrations of vascular endothelial growth factor (VEGF), calcitonin gene related peptide (CGRP) and substance P were measured in unstimulated tears of chemically-injured patients who suffer from late ocular complications of SM. These levels were compared to corresponding values obtained from tears of healthy control subjects. The concentration of total proteins was measured using the Bradford method and those of VEGF, CGRP and substance P by ELISA. Total protein concentration was significantly lower in tears of the SM compared to control group (p<0.01). In contrast, tear samples of the SM group had significantly higher VEGF and VEGF/total protein compared to control group (p<0.01). Tear CGRP concentration was found to be lower in the SM vs. control group (p<0.05) but no significant difference in CGRP/total protein was observed (p>0.05). Finally, tear substance P concentrations were not found to be significantly different between the two groups (p>0.05). The results of this investigation indicated decreased total protein and CGRP, and elevated VEGF concentration in tears of SM-intoxicated patients who suffer from chronic ocular complications.

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

    PubMed

    Kiani, Armin; Dastafkan, Kamran

    2016-09-15

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

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

    SciTech Connect

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

    2008-07-01

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

  15. Analysis of different fates of DNA adducts in adipocytes post-sulfur mustard exposure in vitro and in vivo using a simultaneous UPLC-MS/MS quantification method.

    PubMed

    Wang, Peng; Zhang, Yajiao; Chen, Jia; Guo, Lei; Xu, Bin; Wang, Lili; Xu, Hua; Xie, Jianwei

    2015-06-15

    Sulfur mustard (SM) is a powerful alkylating vesicant that can rapidly penetrate skin, ocular, and lung bronchus mucous membranes and react with numerous nucleophiles in vivo. Although the lesion mechanisms of SM remain unclear, DNA damage is believed to be the most crucial factor in initiating SM-induced toxicity. Four major DNA adducts were identified for retrospective detection and DNA lesion evaluation, namely, N(7)-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (N(7)-HETEG), bis(2-ethyl-N(7)-guanine)thioether (Bis-G), N(3)-(2-hydroxyethylthioethyl)-2'-adenine (N(3)-HETEA), and O(6)-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (O(6)-HETEG). Because of previous observations that the levels of SM-DNA adducts were relatively higher in adipose-rich organs, such as the brain, we focused on the in vitro and in vivo fates of the DNA adducts in exposed adipocytes. A UPLC-MS/MS method developed in our laboratory was used to profile the N(7)-HETEG, Bis-G, and N(3)-HETEA levels in human mature adipocytes (HA-s) that had differentiated from human subcutaneous preadipocytes (HPA-s). This method was also used to profile three other cell lines related to the targeting of major tissues, including human keratinocytes (HaCaT), human hepatocytes (L-02), and human lung fibroblasts (HLF). Long-lasting adduct persistence and a high proportion of Bis-G were found in exposed adipocytes in vitro. The survival properties of exposed adipocytes were also tested. At the same time, the fate of SM-DNA adducts in vivo was characterized using a rat model exposed to 1 and 10 mg/kg doses of SM. The level of DNA adducts in the exposed adipose tissue (AT) was much lower than those in other organs studied in our previous work. The adduct persistence behavior was observed in AT with an extremely high proportion of Bis-G, which was higher than N(7)-HETEG. In light of these results, we suggest that an adipose-rich environment may promote the formation of Bis-G and that adipocyte-specific DNA repair mechanisms may

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

    SciTech Connect

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

    2010-12-01

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

  17. 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

    PubMed Central

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

    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™, 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 PGE2 synthases, leukotriene (LT) A4 hydrolase and LTC4 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. PMID:20840853

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

    SciTech Connect

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

    1995-12-01

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

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

    PubMed

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

    2015-09-01

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

  20. Pathogenesis of Acute and Delayed Corneal Lesions after Ocular Exposure to Sulfur Mustard Vapor

    DTIC Science & Technology

    2012-01-01

    2000) Nanoscale topography of the basement membrane underlying the corneal epithelium of the rhesus macaque. Cell Tissue Res 299: 39–46. 28. Pal-Ghosh...DATES COVERED (From - To) 4. TITLE AND SUBTITLE Pathogenesis of acute and delayed corneal lesions after ocular exposure to 5a. CONTRACT NUMBER sulfur...involves a progressive corneal degeneration resulting in chronic ocular discomfort and impaired vision for which clinical interventions have typically

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

    PubMed

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

    2014-10-15

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

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

    PubMed

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

    2014-06-15

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Lomash, Vinay; Pant, Satish C

    2014-01-01

    Sulfur mustard (SM)-induced dermatotoxicity can be prevented by an immediate use of decontamination agents. However, practically due to the time lapse between decontamination and exposure, there is always a possibility of wound formation. In view of this, a hydrophilic decontamination formulation of CC-2 (DRDE/WH-03) was fortified with Aloe vera gel and betaine (DRDE/WH-01) for improving its wound healing ability. Swiss albino mice were exposed to SM percutaneously (5 mg/kg) once, and after 24 hours, DRDE/WH-01, DRDE/WH-03, framycetin, and aloe gel were applied topically, daily for 7 days. Skin sections were subjected to histopathology, histomorphologic grading, tissue leukocytosis, and immunohistochemistry of inflammatory-reparative biomarkers on 3 and 7 days, respectively. DRDE/WH-01, framycetin, and aloe gel showed better reepithelialization, angiogenesis, and fibroplasia compared with DRDE/WH-03 and SM control. On the basis of histomorphologic scale, DRDE/WH-01, framycetin, and aloe gel were found to be equally efficacious. Up-regulation of interleukin-6 and infiltrating leukocytes, endothelial nitric oxide synthase and angiogenesis, fibroblast growth factor, and transforming growth factor-alpha with fibroplasia and reepithelialization were well correlated at various stages of the healing process. DRDE/WH-01 was equally effective as framycetin and has shown improved wound healing efficacy compared with DRDE/WH-03. Thus, DRDE/WH-01 can be recommended as a universal decontaminant and wound healant against vesicant-induced skin injury. © 2014 by the Wound Healing Society.

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

    PubMed

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

    2015-01-01

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

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

    SciTech Connect

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

    1995-12-31

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

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

    SciTech Connect

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

    2009-01-15

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

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

    PubMed

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

    2015-10-15

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

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

    PubMed

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

    2012-01-01

    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 (p<0.05) reversal in CEES-induced decrease in cell viability, apoptotic and necrotic cell death, DNA damage, and an increase in oxidative stress. Silibinin (1 mg) applied topically to mouse skin 30 min post-CEES exposure (2 mg), was effective in reversing CEES-induced increases in skin bi-fold (62%) and epidermal thickness (85%), apoptotic cell death (70%), myeloperoxidase activity (complete reversal), induction of iNOS, COX-2, and MMP-9 protein levels (>90%), 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.

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

    SciTech Connect

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

    2012-01-01

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

  12. Effect of Nebulized Morphine on Dyspnea of Mustard Gas-Exposed Patients: A Double-Blind Randomized Clinical Trial Study

    PubMed Central

    Shohrati, Majid; Ghanei, Mostafa; Harandi, Asghar Amini; Foroghi, Soniya; Harandi, Ali Amini

    2012-01-01

    Background. Dyspnea is one of the main complaints in a group of COPD patients due to exposure to sulfur mustard (SM) and is refractory to conventional therapies. We designed this study to evaluate effectiveness of nebulized morphine in such patients. Materials and Methods. In a double-blind clinical trial study, 40 patients with documented history of exposure to SM were allocated to two groups: group 1 who received 1 mg morphine sulfate diluted by 4 cc normal saline 0.5% using nebulizer once daily for 5 days and group 2 serving as control who received normal saline as placebo. They were visited by pulmonologist 7 times per day to check symptoms and signs and adverse events. Different parameters including patient-scored peak expiratory flow using pick flow meter, visual analogue scale (VAS) for dyspnea, global quality of life and cough, and number of respiratory rate, night time awaking for dyspnea and cough have been assessed. Results. The scores of VAS for dyspnea, cough and quality of life and also respiratory rate, heart rate, and night time awaking due to dyspnea and night time awaking due to cough improved significantly after morphine nebulization without any major adverse events. Also pick expiratory flow has been improved significantly after nebulization in each day. Conclusion. Our results showed the clinical benefit of nebulized morphine on respiratory complaints of patients due to exposure to SM without significant side effects. PMID:22530119

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

    PubMed

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

    2016-05-01

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

  14. 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

    DTIC Science & Technology

    2004-12-01

    Separation voltage was 20 kV. The running buffer consisted of 100 mM Boric acid adjusted to pH 9.3 with sodium hydroxide. A concentration of 3 nM was easily...i.e., the most abundant amino acid adducts formed after exposure to sulfur mustard), a work-up procedure was developed in the first two years of the...cooperative agreement for isolation of these adducts from amino acid mixtures resulting from acidic hydrolysis of globin or albumin (part B). This

  15. Longitudinal study of children exposed to sulfur oxides

    SciTech Connect

    Dodge, R.; Solomon, P.; Moyers, J.; Hayes, C.

    1985-05-01

    This study is a longitudinal comparison of the health of children exposed to markedly different concentrations of sulfur dioxide and moderately different concentrations of particulate sulfate. The four groups of subjects lived in two areas of one smelter town and in two other towns, one of which was also a smelter town. In the area of highest pollution, children were intermittently exposed to high SO/sub 2/ levels (peak three-hour average concentration exceeded 2,500 micrograms/m3) and moderate particulate SO/sub 4/= levels (average concentration was 10.1 micrograms/m3). When the children were grouped by the four gradients of pollution observed, the prevalence of cough (measured by questionnaire) correlated significantly with pollution levels (trend chi-square = 5.6, p = 0.02). No significant differences in the incidence of cough or other symptoms occurred among the groups of subjects over three years, and pulmonary function and lung function growth over the study were roughly equal among all the groups. These results suggest that intermittent elevations in SO/sub 2/ concentration, in the presence of moderate particulate SO/sub 4/= concentration, produced evidence of bronchial irritation in the subjects, but no chronic effect on lung function or lung function growth was detected.

  16. Use of Immunohistochemistry Techniques in Patients Exposed to Sulphur Mustard Gas

    PubMed Central

    Ghanei, Mostafa; Chilosi, Marco; Mohammad Hosseini Akbari, Hassan; Motiei-Langroudi, Rouzbeh; Harandi, Ali Amini; Shamsaei, Hassan; Bahadori, Moslem; Tazelaar, Henry D.

    2011-01-01

    We performed a pathologic study with further using an immunohistochemical technique (using anti-p63 and anti-CK5) on tissues obtained by open lung biopsy from 18 patients with previous exposure to sulphur mustard (SM) as case group and 8 unexposed patients (control group). The most frequent pathologic diagnosis was constrictive bronchiolitis (44.4%), followed by respiratory (22.2%) and chronic cellular bronchiolitis (16.7%) in the case group, and hypersensitivity bronchiolitis (50%) in the control group. The pathologic diagnoses were significantly different in the case and control groups (P = 0.042). In slides stained by anti-p63 and anti-CK5, the percent of stained cells and the mean number of epithelial cells were lower in the case group in comparison to the control group. This difference was significant for the mean number of cells stained by anti-CK5 (P = 0.042). Furthermore, there was a significant correlation between pathologic diagnosis and total number of cells and mean number of cells stained with anti-p63 and anti-CK5 (P  value = 0.002, <0.001, 0.044). These results suggest that constrictive bronchiolitis may be the major pathologic consequence of exposure to SM. Moreover, decrease of p63 in respiratory tissues affected by SM may suggest the lack of regenerative capacity in these patients. PMID:21776342

  17. The effect of vitamin E on pathological changes in kidney and liver of sulphur mustard-exposed guinea pigs.

    PubMed

    Boskabady, Mohammad Hossein; Tabatabayee, Abbas; Amiri, Sediqa; Vahedi, Nasim

    2012-04-01

    Sulphur mustard (SM) gas is a poisonous chemical agent causing various systemic action in laboratory animals. There is no definite treatment for disorders induced by SM. In this study, the effect of vitamin E alone and in combination with dexamethasone on the pathological changes in the kidney and liver of SM-exposed (SME) guinea pigs was examined. Guinea pigs were divided into five groups (n = 5 in each). These groups were exposed to ethanol (control group), 100 mg/m(3) inhaled SM (SME group), SME treated with vitamin E, 600 mg/kg (SME + E), SME treated with dexamethasone, 5 mg/kg (SME + D), and SME treated with both drugs (SME + E + D), respectively. Pathological evaluation of the kidneys and livers was done 14 days post exposure. There were statistically significant pathological changes in the liver and kidney of SME group compared to control animals (p < 0.05 to p < 0.001). Treatment of SME animals with vitamin E, dexamethasone and their combination caused statistically significant improvement in the pathological changes in the livers and kidneys (p < 0.05 to p < 0.001). These results showed a preventive effect of vitamin E on pathological changes in the liver and more prominently in the kidneys of SME guinea pigs.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-10-01

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

  1. Unique pioneer microbial communities exposed to volcanic sulfur dioxide

    PubMed Central

    Fujimura, Reiko; Kim, Seok-Won; Sato, Yoshinori; Oshima, Kenshiro; Hattori, Masahira; Kamijo, Takashi; Ohta, Hiroyuki

    2016-01-01

    Newly exposed volcanic substrates contain negligible amounts of organic materials. Heterotrophic organisms in newly formed ecosystems require bioavailable carbon and nitrogen that are provided from CO2 and N2 fixation by pioneer microbes. However, the knowledge of initial ecosystem developmental mechanisms, especially the association between microbial succession and environmental change, is still limited. This study reports the unique process of microbial succession in fresh basaltic ash, which was affected by long-term exposure to volcanic sulfur dioxide (SO2). Here we compared the microbial ecosystems among deposits affected by SO2 exposure at different levels. The results of metagenomic analysis suggested the importance of autotrophic iron-oxidizing bacteria, particularly those involved in CO2 and N2 fixation, in the heavily SO2 affected site. Changes in the chemical properties of the deposits after the decline of the SO2 impact led to an apparent decrease in the iron-oxidizer abundance and a possible shift in the microbial community structure. Furthermore, the community structure of the deposits that had experienced lower SO2 gas levels showed higher similarity with that of the control forest soil. Our results implied that the effect of SO2 exposure exerted a selective pressure on the pioneer community structure by changing the surrounding environment of the microbes. PMID:26791101

  2. Unique pioneer microbial communities exposed to volcanic sulfur dioxide.

    PubMed

    Fujimura, Reiko; Kim, Seok-Won; Sato, Yoshinori; Oshima, Kenshiro; Hattori, Masahira; Kamijo, Takashi; Ohta, Hiroyuki

    2016-01-21

    Newly exposed volcanic substrates contain negligible amounts of organic materials. Heterotrophic organisms in newly formed ecosystems require bioavailable carbon and nitrogen that are provided from CO2 and N2 fixation by pioneer microbes. However, the knowledge of initial ecosystem developmental mechanisms, especially the association between microbial succession and environmental change, is still limited. This study reports the unique process of microbial succession in fresh basaltic ash, which was affected by long-term exposure to volcanic sulfur dioxide (SO2). Here we compared the microbial ecosystems among deposits affected by SO2 exposure at different levels. The results of metagenomic analysis suggested the importance of autotrophic iron-oxidizing bacteria, particularly those involved in CO2 and N2 fixation, in the heavily SO2 affected site. Changes in the chemical properties of the deposits after the decline of the SO2 impact led to an apparent decrease in the iron-oxidizer abundance and a possible shift in the microbial community structure. Furthermore, the community structure of the deposits that had experienced lower SO2 gas levels showed higher similarity with that of the control forest soil. Our results implied that the effect of SO2 exposure exerted a selective pressure on the pioneer community structure by changing the surrounding environment of the microbes.

  3. Unique pioneer microbial communities exposed to volcanic sulfur dioxide

    NASA Astrophysics Data System (ADS)

    Fujimura, Reiko; Kim, Seok-Won; Sato, Yoshinori; Oshima, Kenshiro; Hattori, Masahira; Kamijo, Takashi; Ohta, Hiroyuki

    2016-01-01

    Newly exposed volcanic substrates contain negligible amounts of organic materials. Heterotrophic organisms in newly formed ecosystems require bioavailable carbon and nitrogen that are provided from CO2 and N2 fixation by pioneer microbes. However, the knowledge of initial ecosystem developmental mechanisms, especially the association between microbial succession and environmental change, is still limited. This study reports the unique process of microbial succession in fresh basaltic ash, which was affected by long-term exposure to volcanic sulfur dioxide (SO2). Here we compared the microbial ecosystems among deposits affected by SO2 exposure at different levels. The results of metagenomic analysis suggested the importance of autotrophic iron-oxidizing bacteria, particularly those involved in CO2 and N2 fixation, in the heavily SO2 affected site. Changes in the chemical properties of the deposits after the decline of the SO2 impact led to an apparent decrease in the iron-oxidizer abundance and a possible shift in the microbial community structure. Furthermore, the community structure of the deposits that had experienced lower SO2 gas levels showed higher similarity with that of the control forest soil. Our results implied that the effect of SO2 exposure exerted a selective pressure on the pioneer community structure by changing the surrounding environment of the microbes.

  4. Effect of recombinant human IFNγ in the treatment of chronic pulmonary complications due to sulfur mustard intoxication.

    PubMed

    Panahi, Yunes; Ghanei, Mostafa; Vahedi, Ensieh; Ghazvini, Ali; Parvin, Shahram; Madanchi, Nima; Bagheri, Mahsa; Sahebkar, Amirhossein

    2014-01-01

    Pulmonary problems are among the most common chronic complications of sulfur mustard (SM) intoxication and adversely affect patients' quality-of-life. The present trial investigated the impact of immunotherapy with interferon (IFN)-γ on quality-of-life, respiratory symptoms, and circulating immunologic and oxidative parameters in patients suffering from chronic SM-induced complications. Patients (n = 15) were administered IFNγ (100 μg) every other day for a period of 6 months. Assessment of quality-of-life [using St. George respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) indices], the severity and frequency of respiratory symptoms, and serum levels of immunologic [including interleukin (IL)-2, IL-4, IL-6, IL-10, IFNγ, calcitonin gene related peptide (CGRP), matrix metallopeptidase (MMP)-9, and tumor necrosis factor (TNF)-α], oxidative stress [malondialdehyde (MDA) as well as total and reduced glutathione, and catalase and superoxide dismutase (SOD) activity], and fibrogenic [transforming growth factor (TGF)-β] parameters were performed at baseline and at trial end. The results indicated that IFNγ therapy is associated with improvements in SGRQ (p < 0.001) and CAT (p < 0.001) scores, decreased severity of cough (p = 0.001), dyspnea (p < 0.001), and morning dyspnea (p < 0.001), reduced frequency of sputum production (p < 0.001) and hemoptysis (p < 0.001), and elevated FEV1 (p = 0.065). Serum levels of IL-4 (p < 0.001), IL-6 (p < 0.001), IL-10 (p < 0.001), CGRP (p < 0.001), MMP-9 (p = 0.001), TNFα (p < 0.001), TGFβ (p < 0.001) and MDA (p = 0.001) were decreased while those of IL-2 (p < 0.001), IFNγ (p < 0.001), and both total (p = 0.005) and reduced glutathione (p = 0.061) increased by the end of the trial. It was concluded that IFNγ has favorable effects on the quality-of-life and alleviates respiratory symptoms in patients suffering from chronic SM

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

    PubMed

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

    2015-12-01

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

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

    DTIC Science & Technology

    2014-05-01

    NAME(S) AND ADDRESS(ES) Director, ECBC, ATTN: RDCB-DPO- ML APG, MD 21010-5424 8. PERFORMING ORGANIZATION REPORT NUMBER ECBC-TR-1235 9...placed in the EDS .................................................................1 2. Task 1 coupons spiked with 2 mL of HD for storage...exploded pieces of UMSCs and approximately 1–2 g in mass, were placed in 40 mL volatile organic analysis (VOA) vials and weighed. Each coupon was

  7. Macrolide Antibiotics Improve Phagocytic Capacity and Reduce Inflammation In Sulfur Mustard-Exposed Monocytes

    DTIC Science & Technology

    2008-12-01

    improving SM inhalation injuries. In this study, the effects of four FDA- approved macrolide antibiotics, i.e., azithromycin , clarithromycin , erythromycin...from Sigma (St. Louis, MO). Azithromycin and clarithromycin were kindly provided by William Ellis of the Department of Chemical Information, WRAIR...0.001). Treatment with 10 µM of azithromycin , clarithromycin , erythromycin, or roxithromycin increased phagocytotic cells to 64.5%, 63.4%, 62.0

  8. Changes in Intracellular Free Calcium Levels of Cultured Human Epidermal Keratinocytes Exposed to Sulfur Mustard

    DTIC Science & Technology

    1993-05-13

    pH 7.3), 278 containing in mM: NaCl 110; MgSO4 1; KCl 5.4; KH PO 0.44; NaH PO 0.35; glucose 5; glutamine 2; Hepes 55; CaCl 2 0.i•. To facilitate dye ...uptake, 0.03% Pluronic F-127 was added. Unincorporated fluorescent dye was removed by washing the HEK with buffer. Subsequently, the cells were held for...constant (220 nM at 37 0 C). R is tie ratio of the sample, R,1n and RT are the ratios obtained with cells containing very ’ow and very high Ca

  9. A Molecular Approach to Promote Wound Healing in the Sulfur Mustard-Exposed Human Keratinocyte Model

    DTIC Science & Technology

    2006-11-01

    three NOS Isoforms It has been reported that all major NOS isoforms, that is, NOS1, NOS2 (iNOS), and NOS3 , are present in the human skin, but...The level of NO produced by NOS1 or NOS3 is very low and considered to only have a role in the maintenance of normal skin function (in barrier...All three major NOSs, nNOS (NOS1), iNOS (NOS2), and eNOS ( NOS3 ) are found in the skin. The amount of NO produced by the constitutive nNOS and eNOS

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

    PubMed

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

    2017-02-01

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

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

    PubMed

    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

  12. Is sulfur accumulation in sulfur dioxide-exposed plants related to biomass reduction

    SciTech Connect

    Lorenzini, G.; Panicucci, A. )

    1994-06-01

    Sulfur (S) is an abundant element in the Earth's crust. It is a major plant nutrient,necessary in plant metabolism. Normally, S is taken up from soil in the sulphate form and assimilated into various compounds. Sulfur dioxide (SO[sub 2]) absorbed from the air can also supply S for nutrition. Of all plant organs, the leaves have the highest S content. SO[sub 2] is an air contaminant, especially a consequence of burning fossil fuels, as well as having significant natural sources. Plants exposed to excessive SO[sub 2] levels may be associated with visible injury and biomass production perturbation. Two questions may be raised: is S accumulation correlated with other responses, such as resistance or tolerance to SO[sub 2] and can S accumulation be a useful tool for diagnostic purposes when SO[sub 2] is suspected of being responsible for altered plants Unfortunately, these questions are not easily answered. It takes a substantial build-up before any increase is significant. Accumulation may also be influenced by the level of S nutrition. Experiments under controlled conditions are essential. Many experiments performed in the past used rather high SO[sub 2] concentrations and short duration, but the extrapolation to [open quote]natural[close quote] situations is difficult. Results here reported refer to experiments carried out in order to get more information on some aspects of sulphur accumulation in plants under realistic, nonmarking, SO[sub 2] pollution conditions, in connection with biomass production. 18 refs., 1 fig., 3 tabs.

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

    PubMed

    Magnusson, R; Nordlander, T; Östin, A

    2016-01-15

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

  14. Stomatal Conductance and Sulfur Uptake of Five Clones of Populus tremuloides Exposed to Sulfur Dioxide 1

    PubMed Central

    Kimmerer, Thomas W.; Kozlowski, T. T.

    1981-01-01

    Plants of five clones of Populus tremuloides Michx. were exposed to 0, 0.2 or 0.5 microliter per liter SO2 for 8 hours in controlled environment chambers. In the absence of the pollutant, two pollution-resistant clones maintained consistently lower daytime diffusive conductance (LDC) than did a highly susceptible clone or two moderately resistant clones. Differences in LDC among the latter three clones were not significant. At 0.2 microliter per liter SO2, LDC decreased in the susceptible clone after 8 hours fumigation while the LDC of the other clones was not affected. Fumigation with 0.5 microliter per liter SO2 decreased LDC of all five clones during the fumigation. Rates of recovery following fumigation varied with the clone, but the LDC of all clones had returned to control values by the beginning of the night following fumigation. Night LDC was higher in the susceptible clone than in the other clones. Fumigation for 16 hours (14 hours day + 2 hours night) with 0.4 microliter per liter SO2 decreased night LDC by half. Sulfur uptake studies generally confirmed the results of the conductance measurements. The results show that stomatal conductance is important in determining relative susceptibility of the clones to pollution stress. PMID:16661807

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

    PubMed

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

    2011-01-01

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

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

    SciTech Connect

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

    1992-12-31

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

  17. Evaluation of bronchial hypersensitivity in veterans with sulfur mustard gas-induced skin or eye manifestations without respiratory symptoms: 15 years after exposure.

    PubMed

    Assadsangabi, Arash; Emad, Ali

    2006-01-01

    The authors evaluated the prevalence of bronchial hypersensitivity in subjects who had confirmed exposure to sulfur mustard gas (SMG) but no overt respiratory manifestations. They chose 30 patients who had proven skin or eye manifestations secondary to SMG, and performed baseline and provocative pulmonary function testing with cold air and methacholine. The authors performed the same procedure on 30 control volunteers. After challenge testing with cold air and methacholine, bronchial hypersensitivity was detected in 7 (23.3%) and 9 (30%) of cases, respectively. Only 1 control subject showed hypersensitivity after provocation testing with cold air (p = approximately .05); the same control subject showed a positive challenge testing result with 10 mg/ml of methacholine (p < .02). The kappa coefficient for evaluating the effectiveness of the cold air, as a provocative agent for challenge testing, was 93.3%.

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

    SciTech Connect

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

    1992-12-31

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

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

    SciTech Connect

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

    2011-02-01

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

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

    NASA Astrophysics Data System (ADS)

    Werrlein, Robert J.; Braue, Catherine R.

    2004-06-01

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

  1. Mustards and Vesicants

    SciTech Connect

    Young, Robert A; Bast, Cheryl B

    2009-01-01

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

  2. The Toxicity of Inhaled Sulphur Mustard

    DTIC Science & Technology

    2012-03-01

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

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

    PubMed Central

    Panahi, Yunes; Sahebkar, Amirhossein; Davoudi, Seyyed Masoud; Amiri, Mojtaba; Beiraghdar, Fatemeh

    2012-01-01

    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. PMID:22536131

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

    PubMed

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

    2011-03-15

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

  5. Proteomic features of delayed ocular symptoms caused by exposure to sulfur mustard: As studied by protein profiling of corneal epithelium.

    PubMed

    Pajoohesh, Maryam; Naderi, Mostafa; Naderi-Manesh, Hossein

    2017-11-01

    Exposure to mustard gas can lead to variations in the proteome of corneal epithelium cells and after a latency period produces delayed symptoms in the eyes of chemical victims. Hence, a comparative proteome analysis was conducted between the corneal epithelial cells of chemical victims from Iran-Iraq war (1980-1988) and healthy donors. To this end, corneal epithelium samples from victims and healthy individuals were collected, and the proteome of these samples were prepared for two-dimensional electrophoresis and the analysis of spots by statistical software. Selected spots were further analyzed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. Twenty four proteins were identified of which eighteen proteins showed downregulation while six proteins were upregulated in the victims in comparison to the normal individuals. Also, six protein spots were confirmed by western-blot analysis. In conclusion, all the twenty-four identified proteins are involved in pathways which their up- or down-regulation leads to the accumulation of undesired substrates, cell death and apoptosis. Bioinformatics' tools indicated that these identified proteins were involved in various metabolic processes, DNA damage response, immune response and etc. The present study provides a suitable platform for further clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Investigating Prevalence and Pattern of Long-term Cardiovascular Disorders in Sulphur Mustard-exposed Victims and Determining Proper Biomarkers for Early Defining, Monitoring and Analysis of Patients' Feedback on Therapy.

    PubMed

    Darvishi, Behrad; Panahi, Yunes; Ghanei, Mostafa; Farahmand, Leila

    2017-02-01

    Among the most readily existing chemical warfare agents, sulphur mustard (SM), also known as mustard gas, is the most commonly used agent owing to its ease of synthesis and stockpiling. Unprotected exposure mostly results in debilitation rather than lethal injuries, leaving an exposed victim incapacitated for days to even months. Although acute toxicity of sulphur mustard has been fairly established, the long-term post-exposure effects either chronic or short-term but significant are still evolving. A total of 30,000 Iranian victims of the Iran-Iraq imposed war have now - after 30 years - formed the key population demonstrating long-term effects from sulphur mustard exposure. Recent studies have shown that the prevalence of several long-term cardiovascular disorders (CVDs) has significantly increased among SM-exposed victims including coronary artery disorders (CAD), coronary artery ectasia (CAE), congestive heart failure (CHF) and myocardium abnormalities. The more important point is the lack of a determinant biomarker for early screening, recognizing, treating, monitoring and estimating exposed victims' response to applied therapy. Additionally, unidentified risk factors significantly decrease the chance of a successful therapy and result in undesired failure of a comprehensive therapeutic strategy. In this MiniReview, we examined the literature in detail to evaluate relevant reports considering long-term cardiovascular complications of SM, detecting possible risk factors and determining possible preventing events.

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

    PubMed

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

    2013-06-01

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

  8. Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize Functional Mechanisms of Sulfur Mustard Injury to Human Skin

    DTIC Science & Technology

    2005-03-01

    AD Award Number: DAMD17-01-1-0688 TITLE: Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize Functional Mechanisms of Sulfur...2005 Final 1 May 2001 -28 Feb 2005 4. TITLE AND SUBTITLE 5a, CONTRACT NUMBER Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize... Epidermolysis Bullosa (JEB) patients (#552), that lack a functional y2 chain of laminin 5 and do not adhere to BM, were transduced with retroviral vectors (TASK

  9. Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize Functional Mechanisms of Sulfur Mustard Injury to Human Skin

    DTIC Science & Technology

    2004-05-01

    AD Award Number: DAMD17-01-1-0688 TITLE: Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize Functional Mechanisms of Sulfur...30 Apr 2004) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Novel Tissue Models of Junctional Epidermolysis Bullosa DAMD17-01-1-0688 to Characterize...further explore the role of BM in decreased SM susceptibility, primary keratinocytes harvested from Junctional Epidermolysis Bullosa (JEB) patients (#552

  10. Sulfur mustard analog, 2-chloroethyl ethyl sulfide-induced skin injury involves DNA damage and induction of inflammatory mediators, in part via oxidative stress, in SKH-1 hairless mouse skin.

    PubMed

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

    2011-09-10

    Bifunctional alkyalating agent, sulfur mustard (SM)-induced cutaneous injury is characterized by inflammation and delayed blistering. Our recent studies demonstrated that 2-chloroethyl ethyl sulfide (CEES), a monofunctional analog of SM that can be used in laboratory settings, induces oxidative stress. This could be the major cause of the activation of Akt/MAP kinase and AP1/NF-κB pathways that are linked to the inflammation and microvesication, and histopathological alterations in SKH-1 hairless mouse skin. To further establish a link between CEES-induced DNA damage and signaling pathways and inflammatory responses, skin samples from mice exposed to 2 mg or 4 mg CEES for 9-48 h were subjected to molecular analysis. Our results show a strong CEES-induced phosphorylation of H2A.X and an increase in cyclooxygenase-2 (COX-2), inducible NOS (iNOS), and matrix metalloproteinase-9 (MMP-9) levels, indicating the involvement of DNA damage and inflammation in CEES-induced skin injury in male and female mice. Since, our recent studies showed reduction in CEES-induced inflammatory responses by glutathione (GSH), we further assessed the role of oxidative stress in CEES-related DNA damage and the induction of inflammatory molecules. Oral GSH (300 mg/kg) administration 1h before CEES exposure attenuated the increase in both CEES-induced H2A.X phosphorylation (59%) as well as expression of COX-2 (68%), iNOS (53%) and MMP-9 (54%). Collectively, our results indicate that CEES-induced skin injury involves DNA damage and an induction of inflammatory mediators, at least in part via oxidative stress. This study could help in identifying countermeasures that alone or in combination, can target the unveiled pathways for reducing skin injury in humans by SM. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  11. 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.

    PubMed

    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.

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2014-08-01

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

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

    SciTech Connect

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

    2011-06-01

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

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

    PubMed Central

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

    2012-01-01

    Dermal exposure to the vesicant sulfur mustard causes marked inflammation and tissue damage. Basal keratinocytes appear to be a major target of sulfur mustard. In the present studies, mechanisms mediating skin toxicity were examined using a mouse skin construct model and a full-thickness human skin equivalent (EpiDerm-FTTM). In both systems, administration of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide (CEES, 100–1000 µM) at the air surface induced mRNA and protein expression of heat shock proteins 27 and 70 (Hsp27 and Hsp70). CEES treatment also resulted in increased expression of caveolin-1, the major structural component of caveolae. Immunohistochemistry revealed that Hsp27, Hsp70 and caveolin-1 were localized in basal and suprabasal layers of the epidermis. Caveolin-1 was also detected in fibroblasts in the dermal component of the full thickness human skin equivalent. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that Hsp27 and Hsp70 were localized in caveolae. Treatment of mouse keratinocytes with filipin III or methyl-β-cyclodextrin, which disrupt caveolar structure, markedly suppressed CEES-induced Hsp27 and Hsp70 mRNA and protein expression. CEES treatment is known to activate JNK and p38 MAP kinases; in mouse keratinocytes, inhibition of these enzymes suppressed CEES-induced expression of Hsp27 and Hsp70. These data suggest that MAP kinases regulate Hsp 27 and Hsp70; moreover, caveolae-mediated regulation of heat shock protein expression may be important in the pathophysiology of vesicant-induced skin toxicity. PMID:21457723

  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.

    PubMed

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

    2011-06-01

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

  17. Use of EPR Spin-Trapping Techniques to Detect Radicals from Rat Lung Lavage Fluid Following Sulfur Mustard Vapor Exposure

    DTIC Science & Technology

    1993-05-13

    mechanism which produces rembrane and other tissue damage. 94-07926 113 lvailable Copy CG9POFENT PART NOTICE THIS PAPER IS A CUVONENT PART OF THE...gross pathology in HD-exposed rats include multifocal hemorrhages on the lung surface beginning at 6 hrs, and atelectasis and edema of the post-caval...dermal separation) reported for hairless guinea pig skin after HD (Mershon et al., 1990), which may suggest similar mechanisms of HD damage. Respiratory

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    1989-05-31

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

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

    PubMed

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

    2016-12-01

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

  1. Changes in pulmonary lavage fluid of guinea pigs exposed to ultrafine zinc oxide with adsorbed sulfuric acid

    SciTech Connect

    Conner, M.W.; Flood, W.H.; Rogers, A.E.; Amdur, M.O.

    1989-01-01

    Ultrafine metal oxide particles (diameters less than 0.1 microns) and sulfur dioxide are important products of coal combustion. Interaction of these products in the effluent stream results in formation of ultrafine particles with adsorbed sulfur compounds, including sulfuric acid. The toxicity of ultrafine zinc oxide particles with adsorbed sulfuric acid was evaluated by comparing pulmonary lavage fluid from guinea pigs exposed for 1, 2, 3, 4, or 5 consecutive daily 3-h periods to ultrafine zinc oxide generated in the presence of sulfur dioxide (ZnO + SO/sub 2/) to pulmonary lavage fluid from guinea pigs exposed to an equivalent concentration of ultrafine ZnO. Two groups of guinea pigs exposed either to SO/sub 2/ or to particle-free furnace gas served as additional controls. Cells, protein, and activities of lactate dehydrogenase, acid phosphatase, and alkaline phosphatase were increased in lavage fluid obtained from guinea pigs exposed to ZnO + SO/sub 2/ as compared to guinea pigs exposed to ZnO. These results demonstrate the potential importance of ultrafine metal oxides as carries of sulfuric acid derived from fossil fuel combustion.

  2. Sulfur

    USGS Publications Warehouse

    Apodaca, L.E.

    2012-01-01

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

  3. Evaluation of injury to expanded and expanding leaves of peas exposed to sulfur dioxide and ozone

    SciTech Connect

    Olszyk, D.M.; Tibbitts, T.W.

    1982-03-01

    Necrosis, chlorophyll concentration, dry weight and surface area measurements were made to evaluate injury to leaves of Pisum sativum L. cv Alsweet grown under controlled environments and exposed to sulfur dioxide, ozone and combinations of sulfur dioxide plus ozone. Injury evaluations were made at low pollutant levels causing slight necrotic injury and high levels causing severe necrotic injury. At low levels, expanded leaves with a trace of necrotic injury had a 10% reduction in chlorophyll concentration but no reductions in dry weight or surface area, while expanding leaves, also with a trace of necrotic injury, had a reduction in chlorophyll concentration accompanied by reductions in dry weight and surface area. At high pollutant levels, expanded leaves with severe necrotic injury had a 70% reduction in chlorophyll concentration and significant reductions in dry weight and surface area, while expanding leaves had a smaller amount of necrotic injury and a smaller reduction in chlorophyll concentration, but reductions in dry weight and surface area similar to those in expanded leaves. Thus, the following measurements are proposed as reliable indicators of injury at pollutant concentrations just above the threshold for injury: chlorophyll concentration for expanded leaves and surface area for expanding leaves. Reliable indicators of injury at higher concentrations causing serious injury to leaves are: necrosis for expanded leaves and chlorophyll concentration, dry weight, and surface area for expanding leaves. 19 references, 4 figures, 3 tables.

  4. Domestic Preparedness Program: Phase 2 Sarin (GB) and Distilled Sulfur Mustard (HD) Vapor Challenge Testing of Commercial Self-Contained Breathing Apparatus Facepieces

    DTIC Science & Technology

    2005-03-01

    GB Mustard HD Self-Contained Breathing Apparatus Sarin Chemical Agent Breakthrough SCBA Agent Challenge Testing ...emergency escape breathing apparatus. 3. CHEMICAL AGENT TESTING 3.1 Chemical Agent Testing Equipment. 3.1.1 Vapor Generator. The GB and HD vapors were... agent seeped inside the other two within 4 min. For all three tests , the North Model 821 resisted HD for 60 min and GB for 25, 28, and 32 min.

  5. Lung-cancer mortality in workers exposed to sulfuric acid mist and other acid mists in steel-pickling operations

    SciTech Connect

    Beaumont, J.J.; Leveton, J.; Knox, K.; Bloom, T.; McQuiston, T.

    1986-01-01

    A total of 1165 steel workers who had been exposed to sulfuric acid and other acid mists during steel-pickling operations were studied to determine whether there was any evidence of respiratory cancer which could be linked to these exposures. These workers had been employed at three large midwestern steel-manufacturing operations where acid was used to remove oxides from newly produced steel. Cancer of the trachea, bronchus, and lung showed increased mortality in this study. Deaths from buccal cavity, pharynx, and larynx cancers were at normal levels. Deaths from nonmalignant respiratory diseases were lower than normal rates. The excess lung-cancer cases occurred both in workers who had been exposed only to sulfuric-acid mists and in those exposed only to other acids. The authors conclude that there was an increased risk of lung cancer in workers exposed to sulfuric acid and in workers exposed to other acids. Continued monitoring of lung-cancer rates is recommended by the authors, since other acids have replaced sulfuric acid to a great degree.

  6. Enhanced histamine release from lung mast cells of guinea pigs exposed to sulfuric acid aerosols

    SciTech Connect

    Fujimaki, Hidekazu ); Katayama, Noboru; Wakamori, Kazuo )

    1992-06-01

    To clarify the relationship between air pollution and mast cell response, the effects of sulfuric acid aerosols on histamine release from lung mast cells of guinea pigs were investigated. Guinea pigs were exposed to 0.3, 1.0 and 3.2 mg/m{sup 3} sulfuric acid (H{sub 2}SO{sub 4}) aerosols or 4 ppm nitrogen dioxide (NO{sub 2}) for 2 and 4 weeks. After the exposure, lung mast cell suspensions were isolated by collagenase treatment and antigen- or A23187-induced histamine release was measured. Antigen-induced histamine release from mast cells was significantly enhanced by the exposure to 1.0 and 3.2 mg/m{sup 3} H{sub 2}SO{sub 4} for 2 weeks, but exposure to H{sub 2}SO{sub 4} for 4 weeks did not show the enhancement of antigen-induced histamine release. A23187-induced histamine release was significantly enhanced by the exposure to 1.0 mg/m{sup 3} H{sub 2}SO{sub 4} or 4 ppm NO{sub 2} for 2 weeks, but suppression of histamine release from lung mast cells stimulated with A23187 was observed by the exposure to 3.2 mg/m{sup 3} H{sub 2}So{sub 4} for 4 weeks. The exposure to 0.3 mg/m{sup 3} H{sub 2}So{sub 4} showed no changes in antigen- and A23187-induced histamine release. The combination of 1.0 mg/m{sup 3} H{sub 2}So{sub 4} with 4 ppm NO{sub 2} for 2 weeks resulted in no changes in antigen- and A23187-induced histamine release. These results suggested that functional properties of lung mast cells may be altered by a low concentration of H{sub 2}So{sub 4} aerosol exposure.

  7. Sulfur metabolism: different tolerances of two aquatic macrophytes exposed to arsenic.

    PubMed

    Leão, G A; Oliveira, J A; Farnese, F S; Gusman, G S; Felipe, R T A

    2014-07-01

    The toxicity of arsenic (As) and the mechanisms of response to this pollutant were analyzed in two aquatic plant species, one sensitive and one tolerant to the pollutant, Salvinia minima and Lemna gibba, respectively. The plants, grown in nutrient solution at pH 6.5, were exposed to As concentrations of 0.0 and 1.0mgL(-1) for 3 days. Both species accumulated As in their tissues, which resulted in increases in H2O2 production. L. gibba accumulated eleven times more As than S. minima. However, L. gibba was more tolerant, as shown by the absence of cell membrane damage and, despite greater accumulation, smaller growth reduction than S. minima. Indeed, the index of tolerance to As was twenty percent higher in L. gibba than in S. minima, which most likely results from the presence of a more efficient defense system. This defense system in L. gibba is most likely based on sulfate absorption, assimilation and metabolism. L. gibba showed an increase in sulfate absorption and adenosine-5'-triphosphate (ATP) sulfurylase activity (the first enzyme of the inorganic sulfate assimilation pathway) following exposure to As. Consequently, the plant produced greater concentrations of sulfur-containing compounds that are involved in cellular detoxification, such as glutathione and non-protein thiols, and demonstrated greater enzymatic activity of γ-glutamylcysteine synthetase, glutathione S-transferase and glutathione reductase. Therefore, the plant׳s ability to increase absorption, assimilation and metabolism of sulfur are key steps for tolerance to oxidative stress triggered by metals. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    PubMed

    Emad, Ali; Emad, Yasaman

    2007-01-01

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

  9. In Vitro Evaluation of Candidate Pretreatment and Treatment Compounds Against sulfur Mustard (HD) -Induced Human Mononuclear Leukocyte Toxicity Using a Dye Exclusion Cell Viability Assay

    DTIC Science & Technology

    1993-05-13

    concentration of candidate compound required to provide 50 percent protection against the fixed HD concentration) for niacinamide (NM). Various...mustard, HD) is a powerful alkylating agent that causes incapacitating injuries to the eyes, respiratory tract and skin . HD is known to irreversibly...FIGURE 3. CONTROL CHARTING OF NIACINAMIDE EC5 0 ESTIMATES 100’ gSo- 8 0- o70- S60- SSo- a÷ oC 40- X 30- .~20- 04/06/92 05 /26 /9’ 07/1𔃿/02 09 / 10~A

  10. Large Cellular Inclusions Accumulate in Arabidopsis Roots Exposed to Low-Sulfur Conditions1[OPEN

    PubMed Central

    Popov, Vladimir A.; Mathur, Jaideep; Benfey, Philip N.

    2015-01-01

    Sulfur is vital for primary and secondary metabolism in plant roots. To understand the molecular and morphogenetic changes associated with loss of this key macronutrient, we grew Arabidopsis (Arabidopsis thaliana) seedlings in low-sulfur conditions. These conditions induced a cascade of cellular events that converged to produce a profound intracellular phenotype defined by large cytoplasmic inclusions. The inclusions, termed low-sulfur Pox, show cell type- and developmental zone-specific localization. Transcriptome analysis suggested that low sulfur causes dysfunction of the glutathione/ascorbate cycle, which reduces flavonoids. Genetic and biochemical evidence indicated that low-sulfur Pox are the result of peroxidase-catalyzed oxidation of quercetin in roots grown under sulfur-depleted conditions. PMID:26099270

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

    PubMed

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

    2010-11-01

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

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

    PubMed

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

    2009-05-13

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

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

    PubMed

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

    2013-02-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2011-02-01

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

  16. Epigenetic perturbations in the pathogenesis of mustard toxicity; hypothesis and preliminary results

    PubMed Central

    Korkmaz, Ahmet; Yaren, Hakan; Kunak, Z. Ilker; Uysal, Bulent; Kurt, Bulent; Topal, Turgut; Kenar, Levent; Ucar, Ergun; Oter, Sukru

    2008-01-01

    Among the most readily available chemical warfare agents, sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. SM causes debilitating effects that can leave an exposed individual incapacitated for days to months; therefore delayed SM toxicity is of much greater importance than its ability to cause lethality. Although not fully understood, acute toxicity of SM is related to reactive oxygen and nitrogen species, oxidative stress, DNA damage, poly(ADP-ribose) polymerase (PARP) activation and energy depletion within the affected cell. Therefore several antioxidants and PARP inhibitors show beneficial effects against acute SM toxicity. The delayed toxicity of SM however, currently has no clear mechanistic explanation. One third of the 100,000 Iranian casualties are still suffering from the detrimental effects of SM in spite of the extensive treatment. We, therefore, made an attempt whether epigenetic aberrations may contribute to pathogenesis of mustard poisoning. Preliminary evidence reveals that mechlorethamine (a nitrogen mustard derivative) exposure may not only cause oxidative stress, DNA damage, but epigenetic perturbations as well. Epigenetic refers to the study of changes that influence the phenotype without causing alteration of the genotype. It involves changes in the properties of a cell that are inherited but do not involve a change in DNA sequence. It is now known that in addition to mutations, epimutations contribute to a variety of human diseases. Under light of preliminary results, the current hypothesis will focus on epigenetic regulations to clarify mustard toxicity and the use of drugs to correct possible epigenetic defects. PMID:21218122

  17. 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.

    PubMed

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

    2017-03-03

    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 (H2O2) 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.

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

    SciTech Connect

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

    1993-01-01

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

  19. ADAM17 Inhibitors Attenuate Corneal Epithelial Detachment Induced by Mustard Exposure.

    PubMed

    DeSantis-Rodrigues, Andrea; Chang, Yoke-Chen; Hahn, Rita A; Po, Iris P; Zhou, Peihong; Lacey, C Jeffrey; Pillai, Abhilash; C Young, Sherri; Flowers, Robert A; Gallo, Michael A; Laskin, Jeffrey D; Gerecke, Donald R; Svoboda, Kathy K H; Heindel, Ned D; Gordon, Marion K

    2016-04-01

    Sulfur mustard, nitrogen mustard (NM), and 2-chloroethyl ethyl sulfide all cause corneal injury with epithelial-stromal separation, differing only by degree. Injury can resolve in a few weeks or develop into chronic corneal problems. These vesicants induce microbullae at the epithelial-stromal junction, which is partially caused by cleavage of transmembranous hemidesmosomal collagen XVII, a component anchoring the epithelium to the stroma. ADAM17 is an enzyme involved in wound healing and is able to cleave collagen XVII. The activity of ADAM17 was inhibited in vesicant-exposed corneas by four different hydroxamates, to evaluate their therapeutic potential when applied 2 hours after exposure, thereby allowing ADAM17 to perform its early steps in wound healing. Rabbit corneal organ cultures exposed to NM for 2 hours were washed, then incubated at 37°C for 22 hours, with or without one of the four hydroxamates (dose range, 0.3-100 nmol in 20 μL, applied four times). Corneas were analyzed by light and immunofluorescence microscopy, and ADAM17 activity assays. Nitrogen mustard-induced corneal injury showed significant activation of ADAM17 levels accompanying epithelial-stromal detachment. Corneas treated with hydroxamates starting 2 hours post exposure showed a dose-dependent ADAM17 activity inhibition up to concentrations of 3 nmol. Of the four hydroxamates, NDH4417 (N-octyl-N-hydroxy-2-[4-hydroxy-3-methoxyphenyl] acetamide) was most effective for inhibiting ADAM17 and retaining epithelial-stromal attachment. Mustard exposure leads to corneal epithelial sloughing caused, in part, by the activation of ADAM17 at the epithelial-stromal junction. Select hydroxamate compounds applied 2 hours after NM exposure mitigated epithelial-stromal separation.

  20. Dental erosion in workers exposed to sulfuric acid in lead storage battery manufacturing facility.

    PubMed

    Suyama, Yuji; Takaku, Satoru; Okawa, Yoshikazu; Matsukubo, Takashi

    2010-01-01

    Dental erosion, and specifically its symptoms, has long been studied in Japan as an occupational dental disease. However, in recent years, few studies have investigated the development of this disease or labor hygiene management aimed at its prevention. As a result, interest in dental erosion is comparatively low, even among dental professionals. Our investigation at a lead storage battery factory in 1991 found that the work environmental sulfuric acid density was above the tolerable range (1.0mg/m(3)) and that longterm workers had dental erosion. Therefore, workers handling sulfuric acid were given an oral examination and rates of dental erosion by tooth type, rates of erosion by number of working years and rates of erosion by sulfuric acid density in the work environment investigated. Where dental erosion was diagnosed, degree of erosion was identified according to a diagnostic criterion. No development of dental erosion was detected in the maxillary teeth, and erosion was concentrated in the anterior mandibular teeth. Its prevalence was as high as 20%. Rates of dental erosion rose precipitously after 10 working years. The percentages of workers with dental erosion were 42.9% for 10-14 years, 57.1% for 15-19 years and 66.7% for over 20 years with 22.5% for total number of workers. The percentages of workers with dental erosion rose in proportion to work environmental sulfuric acid density: 17.9% at 0.5-1.0, 25.0% at 1.0-4.0 and 50.0% at 4.0-8.0mg/m(3). This suggests that it is necessary to evaluate not only years of exposure to sulfuric acid but also sulfuric acid density in the air in factory workers.

  1. The Toxicity of Inhaled Sulphur Mustard

    DTIC Science & Technology

    2012-10-01

    model. The thiol compound, N- acetyl -L- cysteine ( NAC - Mucomyst™) was chosen due to its anti-oxidant and mucolytic effects, administered via the inhaled...other beneficial therapies. Sulfur mustard, pig, inhalation, toxicology, pathology, physiology, N- acetyl -L- cysteine ( NAC ) 347 bjjugg@dstl.gov.uk 4...Finally, the efficacy of the commercial off the shelf (COTS) drug, N- acetyl -L- cysteine (Mucomyst™; NAC ), in ameliorating inhaled HD-induced lung

  2. Garlic Mustard (Pest Alert)

    Treesearch

    USDA Forest Service

    1999-01-01

    Garlic mustard was used as an edible green in Europe and may have been brought to North America by European settlers. The coarsely toothed leaves give off a garlic-like odor when crushed, accounting for its common name and use in cooking. It is a member of the mustard family.

  3. Sulfur Mustard Induces Apoptosis in Cultured Normal Human Airway Epithelial Cells: Evidence of a Dominant Caspase-8-Mediated Pathway and Differential Cellular Responses

    DTIC Science & Technology

    2008-01-01

    ELEMENT NUMBER 6. AUTHOR(S) Ray, R., Keyser, B., Benton, B., Daher , A., Simbulan-Rosenthal, C.M., Rosenthal, D. 5d. PROJECT NUMBER 5e. TASK...Responses “SM Induces Caspase-8-Dependent Apoptosis”Ray et al. Radharaman Ray,1 Brian Keyser,1 Betty Benton,1 Ahmad Daher ,2 Cynthia M. Simbulan-Rosenthal,2...5. Simbulan-Rosenthal, C., Ray, R., Benton, B., Soeda, E., Daher , A., Anderson, D., Smith, W., Rosenthal, D. (2006). Calmodulin mediates sulfur

  4. The protective effects of N-Acetl-cysteine, oxo-thiazolidine-carboxylate, acetaminophen and their combinations against sulfur mustard cytotoxicity on human skin fibroblast cell line (HF2FF).

    PubMed

    Saberi, Mehdi; Zaree Mahmodabady, Ali

    2009-10-01

    Using human skin-fibroblast cell line HF2FF, the efficacy of some drugs was evaluated against sulfur mustard (SM) cytotoxicity. The drugs were the sulfhydryl containing molecule including N-acetylcysteine (NAC), 2-oxo-thiazolidine-4-carboxylate (OTC) and acetaminophen as glutathione (GSH) stimulator pathway. The protective effects of NAC (0.1 mM), OTC (1.8 mM), and acetaminophen (25 mM) alone or in combination with each other were evaluated on SM (180 M)-induced cytotoxicity. NAC and OTC were applied with SM simultaneously and acetaminophen 30 min before SM exposure, incubated for 1 h and then were rinsed and incubated with fresh medium. The efficacy was evaluated by determination of cells viability, intracellular GSH level and catalase activity 1 and 24 h post SM exposure or co-treatments. The cells viability was decreased 21.8% and 55.2%, respectively for 1 and 24 h post SM (1 h exposure) incubation. So, the 1-h SM exposure and 24-h treatment incubation were selected for evaluation. While, NAC alone treatment increased the cells viability (25%), GSH level (320%) and catalase activity (18%), the most effective combination was NAC plus OTC and acetaminophen which increased more significantly the cells viability (about 40%), GSH level (470%) and catalase activity (100%). The most effective combination was NAC (0.1 mM) plus OTC (1.8 mM) and acetaminophen (25 mM) which should be used before or concomitant with SM exposure. These drugs may reduce SM toxicity possibly by increment of GSH level and catalase activity. This efficacy needs to be confirmed by in vivo study.

  5. Evidence of Sulfur Mustard Exposure in Human Plasma by LC-ESI-MS-MS Detection of the Albumin-Derived Alkylated HETE-CP Dipeptide and Chromatographic Investigation of Its Cis/Trans Isomerism.

    PubMed

    Gandor, Felix; Gawlik, Michael; Thiermann, Horst; John, Harald

    2015-05-01

    Sulfur mustard (SM) is a chemical warfare agent that causes painful blisters and chemically modifies endogenous biomacromolecules by alkylation to hydroxyethylthioethyl (HETE) adducts representing valuable long-term markers for post-exposure analysis. The albumin adduct formed in human plasma in vitro (HETE bound to the side chain of cysteine 34) was isolated and cleaved by current lots of pronase primarily generating the internal modified dipeptide (HETE-cysteine-proline, HETE-CP) instead of the formerly reported HETE-CPF tripeptide. The analyte was detected by liquid chromatography-electrospray ionization tandem-mass spectrometry (LC-ESI-MS-MS). In principle, HETE-CP undergoes a dynamic on-column equilibrium of cis-trans isomerism thus requiring separation at 50°C to obtain one narrow peak. Accordingly, we developed both a novel longer lasting but more sensitive microbore (1 mm i.d., flow 30 µL/min, cycle time 60 min, LOD 50 nM) and a faster, less sensitive narrowbore (2.1 mm i.d., 200 µL/min, cycle time 16 min, LOD 100 nM, both on Atlantis T3 material at 50°C) LC-ESI-MS-MS method suitable for verification analysis. The corresponding tri- and tetrapeptide, Q(HETE)-CPF were monitored simultaneously. HETE-CP peak areas were directly proportional to SM concentrations added to plasma in vitro (0.05-100 µM). Albumin adducts formed by deuterated SM (d8-SM) served as internal standard.

  6. Effects of Curcuminoids-Piperine Combination on Systemic Oxidative Stress, Clinical Symptoms and Quality of Life in Subjects with Chronic Pulmonary Complications Due to Sulfur Mustard: A Randomized Controlled Trial.

    PubMed

    Panahi, Yunes; Ghanei, Mostafa; Hajhashemi, Ali; Sahebkar, Amirhossein

    2016-01-01

    Oxidative stress plays a key role in the development of chronic pulmonary complications of sulfur mustard (SM). Curcuminoids are polyphenols with documented safety and antioxidant activity. The present study aimed to investigate the efficacy of short-term supplementation with curcuminoids (co-administered with piperine to enhance the bioavailability of curcuminoids) in alleviating systemic oxidative stress and clinical symptoms, and improvement of health-related quality of life (HRQoL) in subjects suffering from chronic pulmonary complications due to SM exposure who are receiving standard respiratory treatments. Eighty-nine subjects were recruited to this randomized double-blind placebo-controlled trial, being randomly allocated to either curcuminoids (1500 mg/day) + piperine (15 mg/day) combination (n = 45) or placebo (n = 44) for a period of 4 weeks. High-resolution computed tomography suggested the diagnosis of bronchiolitis obliterans in all subjects. Efficacy measures were changes in serum levels of reduced glutathione (GSH) and malonedialdehyde (MDA). The severity and frequency of respiratory symptoms and HRQoL were also assessed using St. George respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) indices. Serum levels of GSH were increased whilst those of MDA decreased by the end of trial in both groups. Likewise, there were significant improvements in the total as well as subscale (symptoms, activity and impact) SGRQ and CAT scores in both groups. However, comparison of magnitude of changes revealed a greater effect of curcuminoids-piperine combination compared to placebo in elevating GSH, reducing MDA and improving CAT and SGRQ (total and subscale) scores (p < 0.001). Regarding the promising effects of curcuminoids on the measures of systemic oxidative stress, clinical symptoms and HRQoL, these phytochemicals may be used as safe adjuvants in patients suffering from chronic SM-induced pulmonary complications who are receiving standard treatments.

  7. Electrophoresis pattern of serum from mice exposed to different concentrations of sulfur dioxide

    NASA Technical Reports Server (NTRS)

    Singh, J.

    1977-01-01

    Three day old mice were continuously exposed to sulphur dioxide concentrations at 0ppm, 0.05ppm, 0.15ppm and 1ppm for eight weeks. At the end of the experiment, blood samples were collected and centrifuged for electrophoresis studies of the serum in 5 percent acrylamide gel. The length of bands of different serum proteins from the SO2 exposed mice was at a variance as compared with the length of bands from the control exposed mice and alpha-1 band seems to be missing from the serum of SO2 exposed mice.

  8. Sulfur Mustard Induced Cytokine Production and Cell Death: Investigating the Potential Roles of the p38, p53, and NF-kappaB Signaling Pathways with RNA Interference

    DTIC Science & Technology

    2010-01-01

    vation pathway in cytokine production in SM-exposed NHEK. Although there are some exceptions, the clas- sical NF-κB activation pathway with the p50–p65...military campaigns since the First World War. Skin is a major target tissue, and clin- ical presentations of SM cutaneous injuries are char- acterized by...3,5]. Both p38 and NF-κB are activated in SM-exposed cells [7,9–11], but it is NF-κB that has long been im- plicated as playing a primary role in SM

  9. In Anticipation of a Noninvasive Immunodiagnostic Strategy for Confirmation of Sulfur Mustard Skin Exposure: The Technique for Skin Tape-Stripping

    DTIC Science & Technology

    2006-09-01

    to exploring the potential of stratum corneum tape-stripping to eventually visualize HD-induced keratin adducts on the tape before the onset of the...Rev. 8-98) Prescribed by ANSI Std. Z39.18 1 INTRODUCTION: Keratin is an abundant structural resident protein of the stratum corneum of...superficial skin cells of the stratum corneum of animal skin, human skin explants and human skin exposed to vesicating doses of HD vapor in vivo and in

  10. Test of Surfactant-Based Dermal Wound Cleansers on Sulfur Mustard-Exposed Human Keratinocytes in an In Vitro Wound Healing Model

    DTIC Science & Technology

    2008-11-01

    might promote wound healing. Very low dosages of Pluronic F-68 in cell culture media stimulated an increase in the attachment of human gingival ...of hGFs.19 The addition of Pluronic F-68 to cell culture media protected periodontal cells from the harmful effects of alcohol. Human gingival ...TE. Pluronic polyol effects on human gingival fibroblast attachment and growth. J Periodontol 2000; 71:803-809. 20. Chuang AH, McPherson III, JC

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

    DTIC Science & Technology

    2005-05-01

    identified in patients with junctional epidermolysis bullosa (Nakano et al., 2002). Ln-5 mediates adhesion of the epidermal cells to the underlying dermal...Tuderman L, Pfendner E, Uitto J. (2002) Laminin 5 mutations in junctional epidermolysis bullosa : molecular basis of Herlitz vs. non- Herlitz

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

    DTIC Science & Technology

    2006-11-01

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

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

    DTIC Science & Technology

    2004-01-01

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

  14. ADAM17 Inhibitors Attenuate Corneal Epithelial Detachment Induced by Mustard Exposure

    PubMed Central

    DeSantis-Rodrigues, Andrea; Chang, Yoke-Chen; A. Hahn, Rita; P. Po, Iris; Zhou, Peihong; Lacey, C. Jeffrey; Pillai, Abhilash; C. Young, Sherri; A. Flowers II, Robert; A. Gallo, Michael; D. Laskin, Jeffrey; R. Gerecke, Donald; K. H. Svoboda, Kathy; D. Heindel, Ned; Gordon, Marion K.

    2016-01-01

    Purpose Sulfur mustard, nitrogen mustard (NM), and 2-chloroethyl ethyl sulfide all cause corneal injury with epithelial–stromal separation, differing only by degree. Injury can resolve in a few weeks or develop into chronic corneal problems. These vesicants induce microbullae at the epithelial–stromal junction, which is partially caused by cleavage of transmembranous hemidesmosomal collagen XVII, a component anchoring the epithelium to the stroma. ADAM17 is an enzyme involved in wound healing and is able to cleave collagen XVII. The activity of ADAM17 was inhibited in vesicant-exposed corneas by four different hydroxamates, to evaluate their therapeutic potential when applied 2 hours after exposure, thereby allowing ADAM17 to perform its early steps in wound healing. Methods Rabbit corneal organ cultures exposed to NM for 2 hours were washed, then incubated at 37°C for 22 hours, with or without one of the four hydroxamates (dose range, 0.3–100 nmol in 20 μL, applied four times). Corneas were analyzed by light and immunofluorescence microscopy, and ADAM17 activity assays. Results Nitrogen mustard–induced corneal injury showed significant activation of ADAM17 levels accompanying epithelial–stromal detachment. Corneas treated with hydroxamates starting 2 hours post exposure showed a dose-dependent ADAM17 activity inhibition up to concentrations of 3 nmol. Of the four hydroxamates, NDH4417 (N-octyl-N-hydroxy-2-[4-hydroxy-3-methoxyphenyl] acetamide) was most effective for inhibiting ADAM17 and retaining epithelial–stromal attachment. Conclusions Mustard exposure leads to corneal epithelial sloughing caused, in part, by the activation of ADAM17 at the epithelial–stromal junction. Select hydroxamate compounds applied 2 hours after NM exposure mitigated epithelial–stromal separation. PMID:27058125

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

    PubMed

    Wendlinger, Christine; Hammann, Simon; Vetter, Walter

    2014-06-15

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

  16. 38 CFR 3.316 - Claims based on chronic effects of exposure to mustard gas and Lewisite.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  17. 38 CFR 3.316 - Claims based on chronic effects of exposure to mustard gas and Lewisite.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  18. 38 CFR 3.316 - Claims based on chronic effects of exposure to mustard gas and Lewisite.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

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

    PubMed Central

    Nokhodian, Zary; ZareFarashbandi, Firoozeh; Shoaei, Parisa

    2015-01-01

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

  20. Molecular Strategies Against Sulfur Mustard Toxicity

    DTIC Science & Technology

    2010-04-01

    for the treatment of cancer [2]. 1.1 Proposed Mechanism of Acute Toxicity SM is absorbed by inhalation or through the skin following exposure...typically affects 3 major organ systems: skin , lungs, and eyes. When absorbed in large amounts it can also damage rapidly proliferating cells of the...occur and, PARP transfers ADP-ribose units from the respiratory coenzyme nicotinamide adenine dinucleotide (NAD + ) to various nuclear proteins

  1. Medical Management of Cutaneous Sulfur Mustard Injuries

    DTIC Science & Technology

    2009-01-01

    staples. 2. Promogran* Matrix Wound Dressing (Johnson & Johnson Wound Management, Somerville, NJ) is a freeze dried composite of 45% oxidized...COTS) products were examined for their efficacy in improving wound healing of these injuries. Clinical evaluations and a variety of non-invasive...bioengineering meth- ods were used at 7 and 14 days post-surgery to follow the progress of wound healing and evaluate various cosmetic and functional

  2. Mustard meal in dairy rations.

    PubMed

    Moss, B R

    1975-11-01

    Consumption of 0% mustard meal and 15% soybean meal, 7.5% mustard meal and 7.5% soybean meal, or 15% mustard meal and 0% soybean meal rations did not differ in palatability studies with 10 group-fed lactating cows when the mustard meal was treated with 3% caustic soda. Order of preference was for 0, 7.5, and 15% mustard meal rations when mustard meal was untreated. Twelve lactating cows were in each of two lactation trials to compare the three rations of untreated mustard meal. Milk, milk fat, and solids-not-fat, and milk protein did not differ for either trial. Protein-bound iodine of plasma for all cows were within the normal range. Three cows were placed on each of the three rations and received a minimum of 9 kg per day for 6 mo preparturition to determine goitrogenic effects. All cows gave birth to normal, vigorous calves. Limited organoleptic evaluations of milk indicated that untreated mustard meal may impart a detrimental flavor to milk, but a taste panel could not differentiate between milk from cows on the three rations of treated mustard meal. Twenty-one male and 43 female Holstein claves received either 0, 10, or 20% mustard meal starter rations from birth to 3 mo of age. Growth, feed consumption, or plasma protein-bound iodine did not differ.

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2015-05-15

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

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

    SciTech Connect

    Brimfield, A.A.

    1995-12-31

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

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

    PubMed

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

    1987-10-01

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

  7. Nitrogen mustard-induced corneal injury involves DNA damage and pathways related to inflammation, epithelial-stromal separation and neovascularization

    PubMed Central

    Goswami, Dinesh G; Tewari-Singh, Neera; Dhar, Deepanshi; Kumar, Dileep; Agarwal, Chapla; Ammar, David A; Kant, Rama; Enzenauer, Robert W; Petrash, J Mark; Agarwal, Rajesh

    2015-01-01

    Purpose To evaluate the toxic effects and associated mechanisms in corneal tissue exposed to vesicating agent, nitrogen mustard (NM), a bi-functional alkylating analog of chemical warfare agent sulfur mustard (SM). Methods Toxic effects and associated mechanisms were examined in maximal affected corneal tissue employing corneal cultures and human corneal epithelial (HCE) cells exposed to nitrogen mustard (NM). Results Analysis of ex vivo rabbit corneas showed that NM exposure increased apoptotic cell death, epithelial thickness, epithelial-stromal separation and levels of VEGF, COX-2 and MMP-9. In HCE cells, NM exposure resulted in a dose-dependent decrease in cell viability and proliferation, which was associated with DNA damage in terms of an increase in p53 ser15, total p53 and H2A.X ser139 levels. NM exposure also induced caspase-3 and PARP cleavage, suggesting their involvement in NM-induced apoptotic death in rabbit cornea and HCE cells. Similar to rabbit cornea, NM exposure caused an increase in COX-2, MMP-9 and VEGF levels in HCE cells, indicating a role of these molecules and related pathways in NM-induced corneal inflammation, epithelial-stromal separation and neovascularization. NM exposure also induced activation of AP-1 transcription factor proteins and upstream signaling pathways including MAPKs and Akt, suggesting that these could be key factors involved in NM-induced corneal injury. Conclusion Results from this study provide insight into the molecular targets and pathways that could be involved in NM-induced corneal injuries laying the background for further investigation of these pathways in vesicant–induced ocular injuries, which could be helpful in the development of targeted therapies. PMID:26555588

  8. The effect of the use of NP305 masks in improving respiratory symptoms in workers exposed to sulfuric acid mists in plating and pickling units

    PubMed Central

    Rafieepour, Athena; Dolatshahi, Narges Gholamzadeh Taj; Ghasemkhan, Alireza Haj; Asghari, Mehdi; Sadeghian, Marzieh; Asadi, Ali

    2013-01-01

    Background: Plating and pickling processes are the most effective ways for increasing the strength of metal structures, and workers in these units are exposed to various contaminants, including acid mists. The aim of this study was to investigate the effect of protective masks in decreasing the respiratory symptoms and the aerobic capacity of workers that are exposed sulfuric acid mist. Methods: This interventional study was based on National Institute for Occupational Safety and Health (NIOSH) standard 7903 in which silica gel tubes are used for sampling the air in plating and pickling units for eight hours. After the samples were acquired and prepared, they were analyzed by ion chromatography and were compared with the American Conference of Governmental Industrial Hygienists (ACGIH) exposure limits. Respiratory symptoms were evaluated among two sets of test subjects, i.e., those who used NP305 masks in the workplace and those who did not use the mask. Results: The results showed that the concentration of sulfuric acid mist in the plating units was greater than the exposure limits, and concentrations at this level can cause an increase in symptoms related to irritation of the airway and a slight decrease in respiratory capacity. In this study, smoking had no significant effect on the severity of pulmonary dysfunction. Conclusion: The results indicated that the use of an NP305 mask is effective for decreasing symptoms resulting from exposure to sulfuric acid mist and improving respiratory capacity. PMID:26120392

  9. Iron and Sulfur Geochemistry in Class H Wellbore Cements Exposed to CO2 and H2S

    NASA Astrophysics Data System (ADS)

    Lopano, C. L.; Webb, S. M.; Kutchko, B. G.; Strazisar, B. R.; Hawthorne, S. B.; Miller, D. J.; Guthrie, G.; Hakala, A.

    2013-12-01

    The effects of CO2 & co-constituents (such as H2S) sequestration on cement seal integrity are not well understood in the context of wellbore integrity for CO2 storage. This study evaluates the redox effects that co-contaminants such as H2S present to the CO2-cement reaction system via synchrotron X-ray XANES mapping specific to the iron and sulfur edge energies. Portland Class H cement was exposed to various proportions of H2S:CO2 in 1% NaCl saturated brine (1%, 21 mol%, and 40% H2S) under supercritical conditions (50°C and 15MPa). The reaction of cement with H2S-CO2 results in the formation of pyrite associated with the Fe-rich cement clinker phase, brownmillerite (also termed ferrite). Ferrite has not reacted in previous exposures to CO2 alone, which was confirmed by synchrotron spectroscopic analysis of cement exposed to supercritical CO2 alone. Thus it is hypothesized that the reaction is a result of redox conditions introduced by H2S. The synchrotron X-ray microprobe fluorescence (μXRF) imaging and spectroscopy capabilities at beamlines 2-3 and 14-3 at SSRL were used to collect multiple energy (ME) maps for both Fe and S in order to evaluate reaction fronts in the cement matrix and to monitor the chemical changes in the cement associated with exposure to CO2 (and H2S) at sequestration conditions. The use of this micro-spectroscopy technique allows for in-situ identification of any reaction intermediates (including amorphous materials) for the Fe and S phases in the cement. The coupled μXANES and μXRF data were used to generate iron and S speciation maps of the cement cores. Synchrotron microprobe capabilities at 2-3 were used to collected ME maps of Fe, and show differences in Fe oxidation between the rims (Fe2+) and cores (Fe3+) of the cement thin section. Analysis of Fe XANES indicates that there are potentially 4+ distinct coordination environments for the Fe in the cement cores studied: pyrite, ferrihydrite, brownmillerite (Fe3+, and/or Fe2+) and

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

    PubMed

    Hales, B F

    1989-07-01

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

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

    DTIC Science & Technology

    1987-09-21

    was performed in the afternoon of the day designated as Odg. Bucks to be used as semen donors were trained to service an AV during a 2- to 3- week...sperm concentration and the presence of urine, bacteria, erythrocytes and leukocytes. Semen samples of sat- isfactory quality were pooled and diluted...observed in two of the three animals that died from stress . Treatment-related effects , such as gastric lesions or intestinal and respiratory infections

  12. Enhancing effects of mustard oil on preneoplastic hepatic foci development in Wistar rats.

    PubMed

    Shukla, Yogeshwer; Arora, Annu

    2003-02-01

    Dietary habits are known to be the major contributory factor in the development of cancer. Mustard oil, which is extensively used in India and elsewhere as a flying and cooking medium, is reported to induce an inflammatory response. The development of altered hepatic foci is an early carcinogenic change in rat liver in diethylnitrosamine (DEN)-induced hepatocarcinogenesis. In the present study, the development of preneoplastic lesions was observed following administration of mustard oil (0.5 mL/day for 8 weeks) in DEN-initiated and partially hepatomized Wistar rats. A significant decrease in the relative and absolute liver weight of mustard oil-exposed rats was recorded. The results revealed a significant increase in the number and area of placental glutathione-S-transferase (GST-P) and gamma-glutamyl transpeptidase (GGT)-positive foci in mustard oil-administered animals. The GST-P- and GGT-positive foci were more prominent in the animals given boiled (up to 300 degrees C for 3 hours) mustard oil in comparison to the animals given fresh mustard oil. These results indicate the possible tumourigenic risk associated with mustard oil consumption.

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

    PubMed

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

    2015-05-15

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

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

    PubMed Central

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

    2015-01-01

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

  15. Pulmonary function in normal and elastase-treated hamsters exposed to a complex mixture of olefin-ozone-sulfur dioxide reaction products

    SciTech Connect

    Raub, J.A.; Miller, F.J.; Graham, J.A.; Gardner, D.E.; O'Neil, J.J.

    1983-01-01

    An elastase-induced emphysema model was utilized to determine if hamsters with preexisting lung disease were more susceptible to lung damage from air-pollutant exposure. Male golden hamsters, divided into two treatment groups, were given a single intratracheal injection of either 6 units of porcine pancreatic elastase (EMP) or buffer (CNT). After a 4-week recovery period, equal numbers of each group were exposed 23 hr/day x 28 day to filtered air (AIR) or to the complex by-products from a dark-phase-reaction mixture of trans-2-butene, ozone, and sulfur dioxide (MIX). Lung-function measurements on the elastase-treated groups showed changes consistent with mild emphysema. There were no significant differences in lung volumes or lung compliance between the AIR- and MIX-exposed animals. However, the nitrogen washout slope decreased and the diffusing capacity for carbon monoxide increased in both the CNT and EMP hamsters exposed to the MIX. The change in diffusing capacity was greater in normal hamsters than in hamsters with emphysema, and it is hypothesized that animals with impaired lung function had a decreased ability to respond to a pulmonary insult from the mix.

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

    PubMed

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

    2009-07-30

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

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

    DTIC Science & Technology

    1991-12-01

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

  18. Mustard Vesicant-induced Lung Injury: Advances in Therapy

    PubMed Central

    Weinberger, Barry; Malaviya, Rama; Sunil, Vasanthi; 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. PMID:27212445

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

    PubMed

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

    2016-08-15

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

  20. Corrosion resistance and behavior of construction materials exposed to dilute sulfuric acid at elevated temperatures under static conditions

    SciTech Connect

    Nguyen, D.T.

    1994-10-01

    Laboratory investigation has been undertaken to determine the electrochemical behavior and corrosion resistance of various construction materials in a simulated hydrolysis environment (5 wt % sulfuric acid) at temperatures ranging from 90 to 220C. Tests were performed in an autoclave-type electrochemical cell. The corrosion behavior of the test materials was determined using computer-controlled DC potentiodynamic polarization. Corrosion rates of the test materials were determined using AC impedance techniques. Among the stainless steels tested, only alloy N08026 (Carpenter 20Mo-6) performed satisfactory up to a temperature of 100C. The alloy passivated spontaneously in the environment and corroded at a rate of less than 2 mpy. None of the stainless steels tested could be used at 120{degrees}C or above. A number of nickel-based alloys tested had good corrosion resistance up to 100C, but their corrosion rate exceeded 2 mpy at higher temperatures. Zirconium alloys were satisfactory up to 180C. Only tantalum and a tantalum-niobium alloy were satisfactory up to 220C.

  1. Element accumulation in boreal bryophytes, lichens and vascular plants exposed to heavy metal and sulfur deposition in Finland.

    PubMed

    Salemaa, Maija; Derome, John; Helmisaari, Heljä-Sisko; Nieminen, Tiina; Vanha-Majamaa, Ilkka

    2004-05-25

    Macronutrient (N, P, K, Mg, S, Ca), heavy metal (Fe, Zn, Mn, Cu, Ni, Cd, Pb) and Al concentrations in understorey bryophytes, lichens and vascular plant species growing in Scots pine forests at four distances from the Harjavalta Cu-Ni smelter (0.5, 2, 4 and 8 km) were compared to those at two background sites in Finland. The aim was to study the relationship between element accumulation and the distribution of the species along a pollution gradient. Elevated sulfur, nitrogen and heavy metal concentrations were found in all species groups near the pollution source. Macronutrient concentrations tended to decrease in the order: vascular plants>bryophytes>lichens, when all the species groups grew on the same plot. Heavy metal concentrations (except Mn) were the highest in bryophytes, followed by lichens, and were the lowest in vascular plants. In general, vascular plants, being capable of restricting the uptake of toxic elements, grew closer to the smelter than lichens, while bryophytes began to increase in the understorey vegetation at further distances from the smelter. A pioneer moss (Pohlia nutans) was an exception, because it accumulated considerably higher amounts of Cu and Ni than the other species and still survived close to the smelter. The abundance of most of the species decreased with increasing Cu and Ni concentrations in their tissues. Cetraria islandica, instead, showed a positive relationship between the abundance and Cu, Ni and S concentrations of the thallus. It is probable that, in addition to heavy metals, sporadically high SO(2) emissions have also affected the distribution of the plant species.

  2. Risk of Asthmatic Episodes in Children Exposed to Sulfur Dioxide Stack Emissions from a Refinery Point Source in Montreal, Canada

    PubMed Central

    Smargiassi, Audrey; Kosatsky, Tom; Hicks, John; Plante, Céline; Armstrong, Ben; Villeneuve, Paul J.; Goudreau, Sophie

    2009-01-01

    Background Little is known about the respiratory effects of short-term exposures to petroleum refinery emissions in young children. This study is an extension of an ecologic study that found an increased rate of hospitalizations for respiratory conditions among children living near petroleum refineries in Montreal (Canada). Methods We used a time-stratified case–crossover design to assess the risk of asthma episodes in relation to short-term variations in sulfur dioxide levels among children 2–4 years of age living within 0.5–7.5 km of the refinery stacks. Health data used to measure asthma episodes included emergency department (ED) visits and hospital admissions from 1996 to 2004. We estimated daily levels of SO2 at the residence of children using a) two fixed-site SO2 monitors located near the refineries and b) the AERMOD (American Meteorological Society/Environmental Protection Agency Regulatory Model) atmospheric dispersion model. We used conditional logistic regression to estimate odds ratios associated with an increase in the interquartile range of daily SO2 mean and peak exposures (31.2 ppb for AERMOD peaks). We adjusted for temperature, relative humidity, and regional/urban background air pollutant levels. Results The risks of asthma ED visits and hospitalizations were more pronounced for same-day (lag 0) SO2 peak levels than for mean levels on the same day, or for other lags: the adjusted odds ratios estimated for same-day SO2 peak levels from AERMOD were 1.10 [95% confidence interval (CI), 1.00–1.22] and 1.42 (95% CI, 1.10–1.82), over the interquartile range, for ED visits and hospital admissions, respectively. Conclusions Short-term episodes of increased SO2 exposures from refinery stack emissions were associated with a higher number of asthma episodes in nearby children. PMID:19440507

  3. Experimental study of interactions between purple and green sulfur bacteria in sandy sediments exposed to illumination deprived of near-infrared wavelengths.

    PubMed

    Massé, Astrid; Pringault, Olivier; De Wit, Rutger

    2002-06-01

    Sedimentary biofilms of the green sulfur bacterium Prosthecochloris aestuarii strain CE 2404, the purple sulfur bacterium Thiocapsa roseopersicina strain 5811, and a mixed culture of both were cultured in fine sand (100- to 300-microm grain size) within counter gradients of oxygen and sulfide. The artificial sediments were exposed to illumination deprived of near-infrared light (NIR) by filtering out the wavelengths longer than 700 nm to simulate the critical light conditions in submerged aquatic sediments. A 16 h of visible light-8 h of dark regimen was used. We studied the effects of these light conditions on the metabolisms of and interactions between both species by comparing the single species biofilms with the mixed biofilm. The photosynthesis rates of P. aestuarii were shown to be highly limited by the imposed light conditions, because the sulfide photooxidation rates were strongly stimulated when NIR was added. T. roseopersicina performed both aerobic chemosynthesis and photosynthesis, but the photosynthesis rates were low and poorly stimulated by the addition of NIR. This species decreased the penetration depth of oxygen in the sediment by about 1 mm by actively respiring oxygen. This way, the strict anaerobe P. aestuarii was able to grow closer to the surface in the mixed culture. As a result, P. aestuarii benefited from the presence of T. roseopersicina in the mixed culture, which was reflected by an increase in the biomass. In contrast, the density of the latter species was almost completely unaffected by the interaction. Both species coexisted in a layer of the same depth in the mixed culture, and the ecological and evolutionary implications of coexistence are discussed.

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

    DTIC Science & Technology

    2009-01-01

    radicals when reduced electrochemically . Therefore, we hypothesized that the onium ions of sulfur or nitrogen mustards might produce carbon free...solutions of mustards (Kang and Spears, 1987; Ross, 1962; Bartlett et al., 1949). Electrochemical studies have shown that the one electron reduction...homepage: www.e lsev ie r.com/ locate /ytaap Author’s personal copy electrochemical reduction of sulfonium ions in aqueous systems (Chambers, 1978

  5. Effects of simulated sulfuric acid rain on yield, growth, and foliar injury of several crops

    SciTech Connect

    Lee, J.J.; Neely, G.E.; Perrigan, S.C.; Grothaus, L.C.

    1980-10-01

    This study was designed to reveal patterns of response of major United States crops to sulfuric acid rain. Potted plants were grown in field chambers and exposed to simulated sulfuric acid rain (pH 3.0, 3.5 or 4.0) or to a control rain (pH 5.6). At harvest, the weights of the marketable portion, total aboveground portion and roots were determined for 28 crops. Of these, marketable yield production was inhibited for 5 crops (radish, beet, carrot, mustard greens, broccoli), stimulated for 6 crops (tomato, green pepper, strawberry, alfalfa, orchardgrass, timothy), and ambiguously affected for 1 crop (potato). In addition, stem and leaf production of sweet corn was stimulated. Visible injury of tomatoes might have decreased their marketability. No statistically significant effects on yield were observed for the other 15 crops. The results suggest that the likelihood of yield being affected by acid rain depends on the part of the plant utilized, as well as on species. Effects on the aboveground portions of crops and on roots are also presented. Plants were regularly examined for foliar injury associated with acid rain. Of the 35 cultivars examined, the foliage of 31 was injured at pH 3.0, 28 at pH 3.5, and 5 at pH 4.0. Foliar injury was not generally related to effects on yield. However, foilar injury of swiss chard, mustard greens and spinach was severe enough to adversely affect marketability.

  6. A Medical Research and Evaluation Facility and Studies Supporting the Medical Chemical Defense Program. Task 92-29: Efficacy Assessment of Topical Skin Protectants against Sulfur Mustard Vapors in Hairless Guinea Pigs.

    DTIC Science & Technology

    1997-09-01

    hairless guinea pigs ( HGPs ) and the incidence of microblisters observed histologically. The dose-response curve was compared to results of similar work...performed at the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD). The effects of ketamine hydrochloride anesthesia on HGP skin...reflectance were also examined. The exposure time needed to produce a 50 percent incidence of microblisters in HGP skin exposed to saturated HD vapors was

  7. Growth response of four species of Eastern hardwood tree seedlings exposed to ozone, acidic precipitation, and sulfur dioxide. [Prunus serotina, Acer rubrum, Quercus rubra, Liriodendron tulipifera

    SciTech Connect

    Davis, D.D. Skelly, J.M. )

    1992-03-01

    In 1987 a study was conducted in controlled environment chambers to determine the foliar sensitivity of tree seedlings of eight species to ozone and acidic precipitation, and to determine the influence of leaf position on symptom severity. Jensen and Dochinger conducted concurrent similar studies in Continuously Stirred Tank Reactor (CSTR) chambers with ten species of forest trees. Based on the results of these initial studies, four species representing a range in foliar sensitivity to ozone were chosen: black cherry (Prunus serotina Ehrh.), red maple (Acer rubrum L.), northern red oak (Quercus rubra L.) and yellow-poplar (Liriodendron tulipifera L.). These species were also chosen because of their ecological and/or commercial importance in Pennsylvania. Seedlings were exposed in growth chambers simulated acid rain. In addition acute exposures to sulfur dioxide were conducted in a regime based on unpublished monitoring data collected near coal-fired power plants. The objective of this study was to determine if the pollutant treatments influenced the growth and productivity of seedlings of these four species. This information will help researchers and foresters understand the role of air pollution in productivity of eastern forests.

  8. Characteristics of Mustard (Blister) Agents

    DTIC Science & Technology

    2007-10-01

    aerosol drops won’t touch skin or clothing, but the fragrance is still detectable. That fragrance is the vapor. What are the signs of exposure? Symptoms...lung tissue and blisters the skin . In amounts approaching the lethal dose, injury to bone marrow, lymph nodes and spleen may occur. Mustard agent is...colorless liquid with an odor similar to Geraniums. Exposure causes irritation to eyes, skin , respiratory tract and circulatory system and the

  9. Nitrogen and sulfur co-doped TiO2 nanosheets with exposed {001} facets: synthesis, characterization and visible-light photocatalytic activity.

    PubMed

    Xiang, Quanjun; Yu, Jiaguo; Jaroniec, Mietek

    2011-03-21

    Nitrogen and sulfur co-doped TiO(2) nanosheets with exposed {001} facets (N-S-TiO(2)) were prepared by a simple mixing-calcination method using the hydrothermally prepared TiO(2) nanosheets powder as a precursor and thiourea as a dopant. The resulting samples were characterized by transmission electron microscope, X-ray diffraction, N(2) adsorption-desorption isotherms, X-ray photoelectron spectroscopy, and UV-Vis absorption spectroscopy. The electronic properties of N,S co-doped TiO(2) were studied using the first-principle density functional theory (DFT). The photocatalytic activity of N-S-TiO(2) was evaluated by degradation of 4-chlorophenol (4-CP) aqueous solution under visible light irradiation. The production of hydroxyl radicals (˙OH) on the surface of visible-light-irradiated samples was detected by photoluminescence technique using terephthalic acid as a probe molecule. The results show that nitrogen and sulfur atoms were successfully incorporated into the lattice of TiO(2), which resulted in N-S-TiO(2) samples exhibiting stronger absorption in the UV-visible range with a red shift in the band gap transition. The first-principle DFT calculations further confirm that N and S co-dopants can induce the formation of new energy levels in the band gap, which is associated with the response of N-S-TiO(2) nanosheets to visible light irradiation. Surprisingly, pure TiO(2) nanosheets show the visible-light photocatalytic activity for the degradation of 4-CP mainly due to the substrate-surface complexation of TiO(2) and 4-CP, which results in extending absorption of titania to visible light region through ligand-to-titanium charge transfer. The N-S-TiO(2) samples studied exhibited an enhanced visible-light photocatalytic activity than pure TiO(2). Especially, the doped TiO(2) sample at the nominal weight ratio of thiourea to TiO(2) powder of 2 showed the highest photocatalytic activity, which was about twice greater than that of Degussa P25. The enhanced activity of

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

    PubMed

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

    2013-09-15

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

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

    PubMed Central

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

    2013-01-01

    Bifunctional alkylating agent sulfur mustard (SM) and its analog nitrogen mustard (NM) cause DNA damage leading to cell death, and potentially activating inflammation. Transcription factor p53 plays a critical role in DNA damage by regulating cell cycle progression and apoptosis. Earlier studies by our laboratory demonstrated phosphorylation of p53 at Ser15 and an increase in total p53 in epidermal cells both in vitro and in vivo following NM exposure. To elucidate the role of p53 in NM-induced skin toxicity, we employed SKH-1 hairless mice harboring wild type (WT) or heterozygous p53 (p53+/−). Exposure to NM (3.2 mg) caused a more profound increase in epidermal thickness and apoptotic cell death in WT relative to p53+/− mice at 24 h. However, by 72 h after exposure, there was a comparable increase in NM-induced epidermal cell death in both WT and p53+/− mice. Myeloperoxidase activity data showed that neutrophil infiltration was strongly enhanced in NM-exposed WT mice at 24 h persisting through 72 h of exposure. Conversely, robust NM-induced neutrophil infiltration (comparable to WT mice) was seen only at 72 h after exposure in p53+/− mice. Similarly, NM-exposure strongly induced macrophage and mast cell infiltration in WT, but not p53+/− mice. Together, these data indicate that early apoptosis and inflammation induced by NM in mouse skin are p53-dependent. Thus, targeting this pathway could be a novel strategy for developing countermeasures against vesicants-induced skin injury. PMID:23845566

  12. Role of MAP kinases in regulating expression of antioxidants and inflammatory mediators in mouse keratinocytes following exposure to the half mustard, 2-chloroethyl ethyl sulfide

    SciTech Connect

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

    2010-06-15

    Dermal exposure to sulfur mustard causes inflammation and tissue injury. This is associated with changes in expression of antioxidants and eicosanoids which contribute to oxidative stress and toxicity. In the present studies we analyzed mechanisms regulating expression of these mediators using an in vitro skin construct model in which mouse keratinocytes were grown at an air-liquid interface and exposed directly to 2-chloroethyl ethyl sulfide (CEES), a model sulfur mustard vesicant. CEES (100-1000 {mu}M) was found to cause marked increases in keratinocyte protein carbonyls, a marker of oxidative stress. This was correlated with increases in expression of Cu,Zn superoxide dismutase, catalase, thioredoxin reductase and the glutathione S-transferases, GSTA1-2, GSTP1 and mGST2. CEES also upregulated several enzymes important in the synthesis of prostaglandins and leukotrienes including cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-2 (mPGES-2), prostaglandin D synthase (PGDS), 5-lipoxygenase (5-LOX), leukotriene A{sub 4} (LTA{sub 4}) hydrolase and leukotriene C{sub 4} (LTC{sub 4}) synthase. CEES readily activated keratinocyte JNK and p38 MAP kinases, signaling pathways which are known to regulate expression of antioxidants, as well as prostaglandin and leukotriene synthases. Inhibition of p38 MAP kinase suppressed CEES-induced expression of GSTA1-2, COX-2, mPGES-2, PGDS, 5-LOX, LTA{sub 4} hydrolase and LTC{sub 4} synthase, while JNK inhibition blocked PGDS and GSTP1. These data indicate that CEES modulates expression of antioxidants and enzymes producing inflammatory mediators by distinct mechanisms. Increases in antioxidants may be an adaptive process to limit tissue damage. Inhibiting the capacity of keratinocytes to generate eicosanoids may be important in limiting inflammation and protecting the skin from vesicant-induced oxidative stress and injury.

  13. 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

    PubMed Central

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

    2012-01-01

    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 A4 (LTA4) hydrolase and leukotriene C4 (LTC4) 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, LTA4 hydrolase and LTC4 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. PMID:20382172

  14. The role of pro-/anti-inflammation imbalance in Aβ42 accumulation of rat brain co-exposed to fine particle matter and sulfur dioxide.

    PubMed

    Yang, Zhenhua; Chen, Yunzhu; Zhang, Yuexia; Li, Ruijin; Dong, Chuan

    2017-10-01

    Taiyuan is a center of coal-based electricity production and many chemicals industries, where mixtures of sulfur dioxide (SO2) and particulate matter may be more prominent. The focus of the present study was to determine if there is a link between adverse effects in the brain and the combined-exposure to SO2 and fine particulate matter (PM2.5). Rats were exposed alternately to PM2.5 with different dosages (1.5, 6.0 and 24.0 mg/kg body weight) and SO2 at the level of 5.6 mg/m(3). The results showed that the combined exposure to PM2.5 and SO2 enhanced the mRNA expression and protein level of TNF-α and IL-6 in rat cortex and hippocampus relative to the control, SO2 and PM2.5 alone. Instead, TGF-β1 mRNA and protein level were down-regulated in the brain. Additionally, PM2.5 at medium and/or high dose caused marked increase in Aβ42 level and PM2.5 + SO2 induced further increase of Aβ42 level in the cortex and hippocampus. It suggests that SO2 and PM2.5 can synergistically exert inflammation responses and induce Aβ42 accumulation in the brain. Also, it is notable that the Aβ42 accumulation of rat cortex and hippocampus were closely associated with pro-/anti-inflammatory cytokines ratio. These results clearly demonstrated that the combined exposure to PM2.5 and SO2 can induce the imbalance of pro-/anti-inflammatory cytokine, resulting in Aβ42 accumulation of rat brain cortex and hippocampus.

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

    PubMed

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

    2015-02-01

    Vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) are reported to be easily absorbed by skin upon exposure causing severe cutaneous injury and blistering. Our studies show that topical exposure of NM (3.2mg) onto SKH-1 hairless mouse skin, not only caused skin injury, but also led to significant body weight loss and 40-80% mortality (120 h post-exposure), suggesting its systemic effects. Accordingly, further studies herein show that NM exposure initiated an increase in circulating white blood cells by 24h (neutrophils, eosinophils and basophils) and thereafter a decrease (neutrophils, lymphocytes and monocytes). NM exposure also reduced both white and red pulp areas of the spleen. In the small intestine, NM exposure caused loss of membrane integrity of the surface epithelium, abnormal structure of glands and degeneration of villi. NM exposure also resulted in the dilation of glomerular capillaries of kidneys, and an increase in blood urea nitrogen/creatinine ratio. Our results here with NM are consistent with earlier reports that exposure to higher SM levels can cause damage to the hematopoietic system, and kidney, spleen and gastrointestinal tract toxicity. These outcomes will add to our understanding of the toxic effects of topical vesicant exposure, which might be helpful towards developing effective countermeasures against injuries from acute topical exposures. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

    PubMed Central

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

    2014-01-01

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

  17. Natural occurrence of bisphenol F in mustard

    PubMed Central

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

    2016-01-01

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

  18. Natural occurrence of bisphenol F in mustard.

    PubMed

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Garrett, Benjamin

    1999-10-01

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

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

    PubMed

    Tewari-Singh, Neera; Agarwal, Rajesh

    2016-06-01

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

  1. Free radical production from the interaction of 2-chloroethyl vesicants (mustard gas) with pyridine nucleotide-driven flavoprotein electron transport systems

    SciTech Connect

    Brimfield, A.A. Mancebo, A.M.; Mason, R.P.; Jiang, J.J.; Siraki, A.G.; Novak, M.J.

    2009-01-01

    The biochemical sequelae to chloroethyl mustard exposure correspond very well to toxic processes initiated by free radicals. Additionally, mustard solutions contain spontaneously formed cyclic onium ions which produce carbon free radicals when reduced electrochemically. Therefore, we hypothesized that the onium ions of sulfur or nitrogen mustards might produce carbon free radicals upon being reduced enzymatically, and that these radicals might constitute a metabolic activation. We set out to document radical production using an in vitro metabolic system and electron paramagnetic resonance (EPR). Our system consisted of NADPH, one of several pyridine nucleotide-driven flavoprotein reductases, cytochrome c as a terminal electron acceptor, various sulfur or nitrogen mustards and the spin trap {alpha}-[4-pyridyl-1-oxide]-N-tert-butylnitrone in buffer. Reactions were started by adding the reductase to the other materials, vortexing and immediately transferring the mixture to a 10 mm EPR flat cell. Repeated scans on a Bruker ESP 300E EPR spectrometer produced a triplet of doublets with hyperfine splitting constants of a{sub N} = 15.483 G and a{sub H} = 2.512 G. The outcome supported our hypothesis that carbon-centered free radicals are produced when mustard-related onium ions are enzymatically reduced. The EPR results varied little with the chloroethyl compound used or with porcine or human cytochrome P450 reductase, the reductase domain of rat brain neuronal nitric oxide synthase or rat liver thioredoxin reductase. Our results offer new insight into the basis for mustard-induced vesication and the outcome of exposure to different mustards. The free radical model provides an explanation for similarities in the lesions arising from mustard exposure and energy-based lesions such as those from heat, ultraviolet and nuclear radiation as well as damage across tissue types such as skin, eyes or airway epithelium.

  2. Ultrastructural pathology and immunohistochemistry of mustard gas lesion

    SciTech Connect

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

    1993-05-13

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

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

    PubMed

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

    2014-08-01

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

  4. Sulfur Mustard-Induced Increase in Intracellular Calcium: A Mechanism of Mustard Toxicity

    DTIC Science & Technology

    1993-05-13

    mitochondria and endoplasmic reticula , in the cytosol, and in particular in the euchromatin regions of the nucleus beginning at 6 hr after 0.3 mM SM exposure...CCMI’F•ENT PART NOTICE THIS PAPER IS A CCtPOENT PART OF THE FOLLOWING CCMPILATIOI REPORT: TITLE: Procf-edinms of the Medical Defense Bioscience Review...1993) Held in Baltimore, Maryland on 10-13 May 1993. Volume 1. To ORDER THE Ca*LETE COMILATION REPORi, USE AD-A275 667 THE C"tWONENT PART IS PROVII.ED

  5. Surface Decontamination of Blister Agents Lewisite, Sulfur ...

    EPA Pesticide Factsheets

    Journal Article 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 coupons (wood, metal and glass) after application of various decontaminants (household bleach, full strength and dilute; hydrogen peroxide 3 % solution; and EasyDECON® DF200).

  6. Surface Decontamination of Blister Agents Lewisite, Sulfur ...

    EPA Pesticide Factsheets

    Journal Article 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 coupons (wood, metal and glass) after application of various decontaminants (household bleach, full strength and dilute; hydrogen peroxide 3 % solution; and EasyDECON® DF200).

  7. Signaling Molecules in Sulfur Mustard-Induced Cutaneous Injury

    DTIC Science & Technology

    2007-11-27

    effect on skin , mucous membranes, eyes, and the respiratory tract.1 Several investigators have reported the signs and symptoms of the clini- cal and...rapidly after latency, and is then followed by varying degrees of blistering and necrosis depending on dose. Histological observations of skin lesions show...keratinocytes.3–6 As the injury progresses, degenerative changes occur throughout the layers of the skin , but these changes are more prevalent in the

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

    DTIC Science & Technology

    2006-05-01

    and Dangerfield, P. H. (2003). Platelet calmodulin levels in adolescent idiopathic scoliosis . Do the levels correlate with curve progression and...2002). Platelet calmodulin levels in adolescent idiopathic scoliosis : do the levels correlate with curve progression and severity? Spine 27, 768-775

  9. The Role of Energy Metabolism in Cutaneous Sulfur Mustard Injury

    DTIC Science & Technology

    2006-11-01

    et. al. (1985), is that HD penetrates the outer layers of skin to the basal cells at the dermal-epidermal junction resulting in a cascade of...cellular mechanisms of HD injury. Bioenergetic integrity is vital to cell viability and function as well as to the repair of cell/tissue damage...viability) and intracellular ATP at 100 and 500 µM HD. Our data are consistent with the findings of Mol et. al. (1989, 1992) in skin and HEK and

  10. Therapeutic Options to Treat Sulfur Mustard Poisoning - The Road Ahead

    DTIC Science & Technology

    2009-01-01

    formation. In addition to the work on a medical countermeasures, significant research has been conducted on the development of topical skin protec...cytotoxic, mutagenic and vesicating properties. ts use on the battlefield results in debilitating injuries to skin , eyes nd the respiratory system...activation PARP inhibitors Niacinamide Disruption of calcium Calcium modulators BAPTAa Proteolytic activation Protease inhibitors AEBSFa Inflammation

  11. Mechanisms of Sulfur Mustard-Induced Metabolic Injury

    DTIC Science & Technology

    1993-05-13

    1,3-5,7]. In addition, niacinamide has been shown to prevent the loss of NAD÷ in both fresh human skin (8] and in the in vivo hairless guinea pig [9...shown that partial protection against HD-induced NAD’ depletion by I mM niacinamide did not protect against the inhibition of glycolysis. In...after exposure, but not at 4 or 8 hours. As seen for glucose metabolism, 1 mM niacinamide did not prevent the loss of this high-energy intermediate

  12. Cytometric Analysis of DNA Changes Induced by Sulfur Mustard

    DTIC Science & Technology

    1993-05-13

    disfiguring injuries. The principal incapacitating injuries following cutaneous exposure to HD come from its vesicating capacity, i.e., production of skin ...somewhat different response to HD in both cytotoxicity and depletion of cellular NAD+. Since the dividing basal epidermal cell in skin appears to be the...major target of HD, proliferating epithelial cells were used as in vdQ models of HD-induced skin injury to determine the direct effects of HD on call

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

    DTIC Science & Technology

    2000-06-01

    p53 may negatively regulate p53-mediated transcriptional activation of genes important in the cell cycle and apoptosis ( Malanga and Althaus, 1997...differentiation in vitro. J. Cell. Physiol. 163, 105-114. Malanga , M., and Althaus, F. (1997). Poly(ADP-ribose): a negative regulator of p53 functions. In The 12th...Aggarwal, B. (1996) J. Interferon ribosylation Reactions, Cancun, Mexico Cytokine Res. 16, 259-267 59. Malanga , M., and Althaus, F. (1997) in The

  14. Storage studies on mustard oil blends.

    PubMed

    Chugh, Bhawna; Dhawan, Kamal

    2014-04-01

    Mustard oil blends were investigated for fatty acid composition and oxidative stability during storage for 3 months at room temperature (15 °C to 35 °C). The blends were prepared using raw mustard oil with selected refined vegetable oils namely; palm, safflower, soybean, rice bran, sunflower and sesame oil (raw). The fatty acid compositions of all these blends were studied using GLC. The developed blends were found to obey the ideal fatty acid ratio as laid down by health agencies i.e. 1:2:1:: SFA:MUFA:PUFA. The oxidative stability of blends was studied by measuring peroxide value (PV), Kries and Thiobarbituric acid (TBA) test. Blends MPSu (mustard oil, palm oil and sunflower oil), MPT (mustard oil, palm oil and sesame oil) and MPGr (mustard oil, palm oil and groundnut oil) were more stable than other blends during storage. The presence of mustard oil in all blends might make them a healthier option for many consumers as it is a rich source of ω-3 fatty acids and has anti-carcinogenic properties.

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

    SciTech Connect

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

    2013-02-01

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

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

    PubMed

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

    2013-02-01

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

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

    PubMed

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

    2013-05-01

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

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

    DTIC Science & Technology

    1989-05-31

    19P5; Tokuda and Bodell , 1987). HD is a known clastogen which produces all of the types of chromatid aberrations commonly seen with ionizing...1980; Tokuda and Bodell , 1987). HD has been reported to induce a linear increase in Lhe mutation of L5178Y cells as determined by reversion from...with cross-linking agents ( Bodell et al., 1935; Tokuda and Bodell ; 1987). The saturation at the highest dose in experiment C probably reflects the

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

    DTIC Science & Technology

    1989-07-31

    diguanine-7- ethylmethylamine. DNA cross-links are implicated in the production of chromosomal aberrations and chromosomal rearrangements ( Bodell et al...1985; Tokuda and Bodell , 1987). HD is a known clastogen which produced all of the types of chromatid aberrations commonly seen with ionizing radiation...carcinogenesis, and re-examination of the somatic cell mutation theory of cancer. Brit. J. Cancer 3: 109-118. Bodell , W.J., T. Aida and J. Rasmussen. 1985

  20. Mediation of Sulfur Mustard Cellular Toxicity by ATP: A Possible Mechanism of Action of Sulfur Mustard Toxicity

    DTIC Science & Technology

    2000-12-01

    receptor subtypes were identified and the specific P2X(sub 7) inhibitor, oxidized ATP, was found effective in reducing HD induced DNA fragmentation and...keratinocytes, although this rise did not seem causally related to HD induced cell death. However, very recent evidence indicates that HD induced DNA ... fragmentation may not he directly related to cytotoxicity. HD also activated caspase-3 in CHO-K1 cells, but neither specific nor general caspase

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

    ERIC Educational Resources Information Center

    Duchovic, Ronald J.; Vilensky, Joel A.

    2007-01-01

    The Meyer-Clarke synthetic method was used in the German process for large scale production of mustard gas during World War I, which clearly shows the historical connection of synthesis of mustard gas.

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

    ERIC Educational Resources Information Center

    Duchovic, Ronald J.; Vilensky, Joel A.

    2007-01-01

    The Meyer-Clarke synthetic method was used in the German process for large scale production of mustard gas during World War I, which clearly shows the historical connection of synthesis of mustard gas.

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

    PubMed

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

    2015-02-13

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

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

    PubMed Central

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

    2015-01-01

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

  5. Myeloperoxidase deficiency attenuates nitrogen mustard-induced skin injuries

    PubMed Central

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

    2014-01-01

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

  6. Myeloperoxidase deficiency attenuates nitrogen mustard-induced skin injuries.

    PubMed

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

    2014-06-05

    The pathologic mechanisms of skin injuries, following the acute inflammatory response induced by vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) exposure, are poorly understood. Neutrophils which accumulate at the site of injury, abundantly express myeloperoxidase (MPO), a heme protein that is implicated in oxidant-related antimicrobial and cytotoxic responses. Our previous studies have shown that exposure to SM analog 2-chloroethyl ethyl sulfide (CEES) or NM results in an inflammatory response including increased neutrophilic infiltration and MPO activity. To further define the role of neutrophil-derived MPO in NM-induced skin injury, here we used a genetic approach and examined the effect of NM exposure (12h and 24h) on previously established injury endpoints in C57BL/6J wild type (WT) and B6.129X1-MPOtm1Lus/J mice (MPO KO), homozygous null for MPO gene. NM exposure caused a significant increase in skin bi-fold thickness, epidermal thickness, microvesication, DNA damage and apoptosis in WT mice compared to MPO KO mice. MPO KO mice showed relatively insignificant effect. Similarly, NM induced increases in the expression of inflammatory and proteolytic mediators, including COX-2, iNOS and MMP-9 in WT mice, while having a significantly lower effect in MPO KO mice. Collectively, these results show that MPO, which generates microbicidal oxidants, plays an important role in NM-induced skin injuries. This suggests the development of mechanism-based treatments against NM- and SM-induced skin injuries that inhibit MPO activity and attenuate MPO-derived oxidants. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    SciTech Connect

    Young, R.J.

    1994-07-01

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

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

    PubMed

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

    2006-01-01

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

  9. Myocardial perfusion abnormalities in chemical warfare patients intoxicated with mustard gas.

    PubMed

    Gholamrezanezhad, Ali; Saghari, Mohsen; Vakili, Arsalan; Mirpour, Sahar; Farahani, Mohammad Hossein

    2007-04-01

    Mustard agents are of the major chemical agents used during Iran-Iraq war. There are no reports concerning long-term cardiac effects. The aim was to assess the scintigraphic pattern of myocardial perfusion in patients intoxicated with blistering gases. We analyzed myocardial perfusion scans of 22 consecutive intoxicated patients (21 male and 1 female, all < 44 years) and compared results with 14 controls. Only those patients and controls were entered whose 10-year risk of coronary artery disease (Framingham criteria) was <5%. Also only those patients were experimented upon that had currently other confirmed complications of intoxication (respiratory, cutaneous and ocular complications). All patients underwent a 1-day stress and rest protocol using (99m)Tc-MIBI. Images were assessed visually and quantitatively using Cedars Sinai program. The prevalence of nonhomogeneity of uptake and left and right ventricular enlargement in both visual and quantitative analyses were higher in the mustard exposed patients than unexposed controls. The prevalence of ischemia was higher in the exposed patients (P < 0.05). Cavity to myocardium ratio, as an established and validated measure of ejection fraction, was also significantly lower in the warfare patients than the controls. In so far it lies in our knowledge, this is the first report concerning the scintigraphic pattern of myocardial perfusion in mustard intoxicated patients. Based on the results, the pattern of myocardial perfusion in these patients is significantly different from normal controls, which could resemble either coronary artery disease or mild cardiomyopathic changes.

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

    SciTech Connect

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

    1984-09-17

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

  11. Sulfur Nanowires

    NASA Astrophysics Data System (ADS)

    Carvajal, Eliel; Santiago, Patricia; Escudero, Roberto; Mendoza, Doroteo

    2000-03-01

    We have synthetized sulfur nanowires by a template approach using nanoporous anodic alumina. High resolution electron microscopy shows that isolated sulfur nanowires (15 nanometers of diameter) present crystalline structure different to that observed in the stable bulk allotrope (orthorhombic alfa-sulfur). Melting behavior of the sulfur nanowires embedded into the nanoporous alumina matrix was studied by differential scanning calorimetry, showing again very different behavior of the nanowires compared to that of the bulk sulfur. On the other hand, in order to study the bonding configuration of the sulfur atoms in the nanowires, we will present infrared spectroscopy characterization of the nanowires confined into the nanoporous alumina. Finally, on the base of the experimental observations, we will present a structural model for the sulfur nanowires.

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

    PubMed Central

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

    1995-01-01

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

  13. Effect of Greens and Soil Type, Sulfur Addition and Lithium Level on Leaf Constituents

    USDA-ARS?s Scientific Manuscript database

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

  14. Comparative uptake of sulfur in sulfur dioxide and acid rain by corn (Zea mays L. )

    SciTech Connect

    Simon, J.E.

    1984-01-01

    This study has compared and evaluated the absorption and accumulation of sulfur from the two major forms of sulfur pollution (sulfur dioxide and sulfur containing acid rain), by seedlings of corn (Zea mays L.). Plants were exposed to matched treatments containing equivalent ..mu..moles S/treatment in sulfur dioxide or simulated acid rain containing sulfuric acid. Pollution levels were chosen to represent low, medium and high ambient pollutant concentrations (0.13, 1.3 and 130.0 ..mu..moles S/treatment). The uptake and distribution of sulfur by plants was followed by using radioactively labelled sulfur (35-S) in both pollutants. Plants were exposed to the pollutants via a single injection of sulfur dioxide or by rainfall simulators with acid rain treatments. From the sulfur dioxide concentrations evaluated (0.67; 1.00; 2.60; 6.70; and 16 ppm), maximum absorption occurred at the highest concentration while sulfur was more efficiently absorbed at lower concentrations. Absorption of sulfur by plants exposed to acid rain (pH 5.4; 4.4; 3.4; and 2.6) was higher with high sulfur/low pH treatments. pH per se, was not responsible for increased sulfur absorption at low pH treatments. Of the total sulfur associated with the plant following exposure to sulfur dioxide and acid rain, 55% and 97%, respectively was not absorbed, and could be released after one minute of a foliar wash. At each equivalent concentration of sulfur, corn seedlings absorbed significantly greater amounts of sulfur from sulfur dioxide than from acid rain.

  15. Putting Some Mustard into Economic Growth

    PubMed Central

    Evans, Robert G.

    2012-01-01

    On September 27, 2012, the University of Toronto launched the Fraser Mustard Institute for Human Development – an appropriate recognition of an extraordinary individual. Fraser was a keen student of the science of human development and, most particularly, of early child development (ECD). He was also a powerful and tireless advocate for translating science into action. His institute must do both. Action is needed also because 25% of Canadians lack the competencies to function effectively in a modern economy. Other countries do much better. Facing a low-growth future, we cannot afford to waste this untapped potential. Although Prime Minister Harper's personal ideology has no place for ECD, the Mustard Institute can help keep the flame alive. PMID:23968611

  16. Putting some mustard into economic growth.

    PubMed

    Evans, Robert G

    2012-11-01

    On September 27, 2012, the University of Toronto launched the Fraser Mustard Institute for Human Development - an appropriate recognition of an extraordinary individual. Fraser was a keen student of the science of human development and, most particularly, of early child development (ECD). He was also a powerful and tireless advocate for translating science into action. His institute must do both. Action is needed also because 25% of Canadians lack the competencies to function effectively in a modern economy. Other countries do much better. Facing a low-growth future, we cannot afford to waste this untapped potential. Although Prime Minister Harper's personal ideology has no place for ECD, the Mustard Institute can help keep the flame alive.

  17. Sulfur revisited.

    PubMed

    Lin, A N; Reimer, R J; Carter, D M

    1988-03-01

    Sulfur is a time-honored therapeutic agent useful in a variety of dermatologic disorders. Its keratolytic action is due to formation of hydrogen sulfide through a reaction that depends upon direct interaction between sulfur particles and keratinocytes. The smaller the particle size, the greater the degree of such interaction and the greater the therapeutic efficacy. When applied topically, sulfur induces various histologic changes, including hyperkeratosis, acanthosis, and dilatation of dermal vasculature. One study showed that sulfur was comedogenic when applied onto human and rabbit skin, findings that were not reproduced in other studies. About 1% of topically applied sulfur is systemically absorbed. Adverse effects from topically applied sulfur are uncommon and are mainly limited to the skin. In infants, however, fatal outcome after extensive application has been reported.

  18. Sulfur Cycle

    NASA Technical Reports Server (NTRS)

    Hariss, R.; Niki, H.

    1985-01-01

    Among the general categories of tropospheric sulfur sources, anthropogenic sources have been quantified the most accurately. Research on fluxes of sulfur compounds from volcanic sources is now in progress. Natural sources of reduced sulfur compounds are highly variable in both space and time. Variables, such as soil temperature, hydrology (tidal and water table), and organic flux into the soil, all interact to determine microbial production and subsequent emissions of reduced sulfur compounds from anaerobic soils and sediments. Available information on sources of COS, CS2, DMS, and H2S to the troposphere in the following paragraphs are summarized; these are the major biogenic sulfur species with a clearly identified role in tropospheric chemistry. The oxidation of SO2 to H2SO4 can often have a significant impact on the acidity of precipitation. A schematic representation of some important transformations and sinks for selected sulfur species is illustrated.

  19. Sealing Mustard Jars with Plastic Linerless Closures

    DTIC Science & Technology

    1985-10-01

    above. 2. Enclosed for your information and retention is copy of Rutgers University Report on Polyithylene Linerless Closures. 1 End as CF: C...TECHNICAL REPORT NATICK/TR-86/003 az-ALING MUSTARD JARS WITH PLASTIC LINERLESS r^ EY G. ICAPEIELIAN, J. HERNE, G. JAMBOE, J. KALICK, AND N...MASSACHUSETTS 01760-5000 FOOD ENGINEERING LABORATORY Disc laImers The findings contained in this report are not to be construed as an official

  20. 7 CFR 201.56-3 - Mustard family, Brassicaceae (Cruciferae).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  1. Harmful Effects of Mustard Bio-fumigants on Entomopathogenic Nematodes

    USDA-ARS?s Scientific Manuscript database

    Green manures, particularly mustards tilled into the soil preceding potato crops act as bio-fumigants that are toxic to plant parasitic nematodes, providing an alternative to synthetic soil fumigants. It is not known if mustard green manures also kill beneficial entomopathogenic nematodes (EPNs) tha...

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

    DTIC Science & Technology

    1988-10-01

    Life or Health JSA Job Safety Analysis MSDS Material Safety Data Sheet OSHA Occupational Safety and Health Act PC&E Protective Clothing and Equipment PEL...Chronic exposures (10-20 years) to mustard agent are considered to be a health hazard; therefore, certain health minimums must be met if workers are...exposed. Monitoring of work areas and medical surveillance must be carefully controlled and adequate records maintained. To protect the health and welfare

  3. Lunar sulfur

    NASA Technical Reports Server (NTRS)

    Kuck, David L.

    1991-01-01

    Ideas introduced by Vaniman, Pettit and Heiken in their 1988 Uses of Lunar Sulfur are expanded. Particular attention is given to uses of SO2 as a mineral-dressing fluid. Also introduced is the concept of using sulfide-based concrete as an alternative to the sulfur-based concretes proposed by Leonard and Johnson. Sulfur is abundant in high-Ti mare basalts, which range from 0.16 to 0.27 pct. by weight. Terrestrial basalts with 0.15 pct. S are rare. For oxygen recovery, sulfur must be driven off with other volatiles from ilmenite concentrates, before reduction. Troilite (FeS) may be oxidized to magnetite (Fe3O4) and SO2 gas, by burning concentrates in oxygen within a magnetic field, to further oxidize ilmenite before regrinding the magnetic reconcentration. SO2 is liquid at -20 C, the mean temperature underground on the Moon, at a minimum of 0.6 atm pressure. By using liquid SO2 as a mineral dressing fluid, all the techniques of terrestrial mineral separation become available for lunar ores and concentrates. Combination of sulfur and iron in an exothermic reaction, to form iron sulfides, may be used to cement grains of other minerals into an anhydrous iron-sulfide concrete. A sulfur-iron-aggregate mixture may be heated to the ignition temperature of iron with sulfur to make a concrete shape. The best iron, sulfur, and aggregate ratios need to be experimentally established. The iron and sulfur will be by-products of oxygen production from lunar minerals.

  4. Lunar sulfur

    NASA Astrophysics Data System (ADS)

    Kuck, David L.

    Ideas introduced by Vaniman, Pettit and Heiken in their 1988 Uses of Lunar Sulfur are expanded. Particular attention is given to uses of SO2 as a mineral-dressing fluid. Also introduced is the concept of using sulfide-based concrete as an alternative to the sulfur-based concretes proposed by Leonard and Johnson. Sulfur is abundant in high-Ti mare basalts, which range from 0.16 to 0.27 pct. by weight. Terrestrial basalts with 0.15 pct. S are rare. For oxygen recovery, sulfur must be driven off with other volatiles from ilmenite concentrates, before reduction. Troilite (FeS) may be oxidized to magnetite (Fe3O4) and SO2 gas, by burning concentrates in oxygen within a magnetic field, to further oxidize ilmenite before regrinding the magnetic reconcentration. SO2 is liquid at -20 C, the mean temperature underground on the Moon, at a minimum of 0.6 atm pressure. By using liquid SO2 as a mineral dressing fluid, all the techniques of terrestrial mineral separation become available for lunar ores and concentrates. Combination of sulfur and iron in an exothermic reaction, to form iron sulfides, may be used to cement grains of other minerals into an anhydrous iron-sulfide concrete. A sulfur-iron-aggregate mixture may be heated to the ignition temperature of iron with sulfur to make a concrete shape. The best iron, sulfur, and aggregate ratios need to be experimentally established. The iron and sulfur will be by-products of oxygen production from lunar minerals.

  5. Multi-inhibitor prodrug constructs for simultaneous delivery of anti-inflammatory agents to mustard-induced skin injury

    PubMed Central

    Lacey, C. Jeffrey; Wohlman, Irene; Guillon, Christophe; Saxena, Jaya; Fianu-Velgus, Cynthia; Aponte, Erik; Young, Sherri C.; Heck, Diane E.; Joseph, Laurie B.; Laskin, Jeffrey D.; Heindel, Ned D.

    2016-01-01

    The molecular pathology of a sulfur mustard injury is complex, with at least nine inflammation-related enzymes and receptors upregulated in the zone of the insult. A new approach wherein inhibitors of these targets have been linked by hydrolyzable bonds, either one to one or via separate pre-attachment to a carrier molecule, has been shown to significantly enhance the therapeutic response compared with the individual agents. This article reviews the published work of the authors in this drug development domain over the last 8 years. PMID:27505078

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

    PubMed

    Gasic, Ksenija; Korban, Schuyler S

    2006-01-01

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

  7. DNA cross-linking and single-strand breaks induced by teratogenic concentrations of 4-hydroperoxycyclophosphamide and phosphoramide mustard in postimplantation rat embryos.

    PubMed

    Little, S A; Mirkes, P E

    1987-10-15

    Postimplantation rat embryos (Day 10) were exposed in vitro to teratogenic concentrations of 4-hydroperoxycyclophosphamide, an activated form of cyclophosphamide, and phosphoramide mustard, the major teratogenic metabolite of cyclophosphamide. Following a 5-h exposure to these agents, drug-induced DNA damage was assessed by alkaline elution. Both drugs induced detectable DNA cross-linking at teratogenic concentrations. Alkaline elution combined with proteinase K digestion indicated that approximately half of the DNA cross-linking was DNA-DNA cross-linking and the other half was DNA-protein cross-linking. In addition to DNA cross-linking, phosphoramide mustard produced DNA strand breaks and/or alkaline labile sites. However, 4-hydroperoxycyclophosphamide did not produce detectable DNA strand breaks or alkaline labile sites. Our data also indicate that the induction of abnormal morphogenesis by 4-hydroperoxycyclophosphamide and phosphoramide mustard is correlated with drug-induced DNA cross-linking.

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

    NASA Astrophysics Data System (ADS)

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

    2009-07-01

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

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

    PubMed

    Sharma, Manoj; Vijayaraghavan, R; Ganesan, K

    2008-12-01

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

  10. Mustard vesicants alter expression of the endocannabinoid system in mouse skin.

    PubMed

    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

    2016-07-15

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2005-01-01

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

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

    PubMed Central

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

    1948-01-01

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

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

    PubMed

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

    2017-03-30

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

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

    USGS Publications Warehouse

    Berry, Kristin H.; Gowan, Timothy A.; Miller, David M.; Brooks, Matthew L.

    2015-01-01

    Introduced exotic plants can drive ecosystem change. We studied invasion and establishment ofBrassica tournefortii (African mustard), a noxious weed, in the Chemehuevi Valley, western Sonoran Desert, California. We used long-term data sets of photographs, transects for biomass of annual plants, and densities of African mustard collected at irregular intervals between 1979 and 2009. We suggest that African mustard may have been present in low numbers along the main route of travel, a highway, in the late 1970s; invaded the valley along a major axial valley ephemeral stream channel and the highway; and by 2009, colonized 22 km into the eastern part of the valley. We developed predictive models for invasibility and establishment of African mustard. Both during the initial invasion and after establishment, significant predictor variables of African mustard densities were surficial geology, proximity to the highway and axial valley ephemeral stream channel, and number of small ephemeral stream channels. The axial valley ephemeral stream channel was the most vulnerable of the variables to invasions. Overall, African mustard rapidly colonized and quickly became established in naturally disturbed areas, such as stream channels, where geological surfaces were young and soils were weakly developed. Older geological surfaces (e.g., desert pavements with soils 140,000 to 300,000 years old) were less vulnerable. Microhabitats also influenced densities of African mustard, with densities higher under shrubs than in the interspaces. As African mustard became established, the proportional biomass of native winter annual plants declined. Early control is important because African mustard can colonize and become well established across a valley in 20 yr.

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

    PubMed

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

    2008-01-01

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

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

    PubMed

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

    2013-08-01

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

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

    SciTech Connect

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

    2010-02-01

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

  18. Sulfur Earth

    NASA Astrophysics Data System (ADS)

    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

  19. Differential sensitivity of transcription factors to mustard-damaged DNA.

    PubMed

    Chen, X M; Gray, P J; Cullinane, C; Phillips, D R

    1999-03-01

    Nitrogen mustard (bis(2-chloroethyl) methylamine, HN2) inhibited the binding of upstream factors Sp1 and AP2 to their consensus sequences. At concentrations where 50% of the consensus sequence DNA contained at least one lesion, HN2 inhibited formation of the Sp1 complex by 37% (40 microM HN2) and the AP2 complex by 40% (50 microM HN2). The binding of the TATA binding protein (TBP) to the TATA element was also inhibited by HN2, whereas sulphur mustard and the monofunctional sulphur mustard 2-chloroethyl ethyl sulphide (CEES) resulted in a disproportional extent of inhibition with respect to the level of alkylation. The level of alkylation of the TBP oligonucleotide varied significantly at 100 microM drug, with 80, 42 and 15% of HN2, sulphur mustard and CEES, respectively. However, this level of alkylation inhibited formation of the TBP-DNA complex by 70, 70 and 45%, respectively. This differential sensitivity of transcription factors to mustard-induced DNA damage therefore appears to reside dominantly in the stereochemical differences between the specific mustard lesions.

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

    PubMed

    Dai, Ruyan; Lim, Loong-Tak

    2014-01-01

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

  1. Ionic dependence of sulphur mustard cytotoxicity

    SciTech Connect

    Sawyer, Thomas W. Nelson, Peggy; Bjarnason, Stephen; Vair, Cory; Shei Yimin; Tenn, Catherine; Lecavalier, Pierre; Burczyk, Andrew

    2010-09-15

    The effect of ionic environment on sulphur mustard (bis 2-chloroethyl sulphide; HD) toxicity was examined in CHO-K1 cells. Cultures were treated with HD in different ionic environments at constant osmolar conditions (320 mOsM, pH 7.4). The cultures were refed with fresh culture medium 1 h after HD exposure, and viability was assessed. Little toxicity was apparent when HD exposures were carried out in ion-free sucrose buffer compared to LC{sub 50} values of {approx} 100-150 {mu}M when the cultures were treated with HD in culture medium. Addition of NaCl to the buffer increased HD toxicity in a salt concentration-dependent manner to values similar to those obtained in culture medium. HD toxicity was dependent on both cationic and anionic species with anionic environment playing a much larger role in determining toxicity. Substitution of NaI for NaCl in the treatment buffers increased HD toxicity by over 1000%. The activity of the sodium hydrogen exchanger (NHE) in recovering from cytosolic acidification in salt-free and in different chloride salts did not correlate with the HD-induced toxicity in these buffers. However, the inhibition by HD of intracellular pH regulation correlated with its toxicity in NaCl, NaI and sucrose buffers. Analytical chemical studies and the toxicity of the iodine mustard derivative ruled out the role of chemical reactions yielding differentially toxic species as being responsible for the differences in HD toxicity observed. This work demonstrates that the early events that HD sets into motion to cause toxicity are dependent on ionic environment, possibly due to intracellular pH deregulation.

  2. Comparison of cake compositions, pepsin digestibility and amino acids concentration of proteins isolated from black mustard and yellow mustard cakes.

    PubMed

    Sarker, Ashish Kumar; Saha, Dipti; Begum, Hasina; Zaman, Asaduz; Rahman, Md Mashiar

    2015-01-01

    As a byproduct of oil production, black and yellow mustard cakes protein are considered as potential source of plant protein for feed applications to poultry, fish and swine industries. The protein contents in black and yellow mustard cakes were 38.17% and 28.80% and their pepsin digestibility was 80.33% and 77.43%, respectively. The proteins were extracted at different pH and maximum proteins (89.13% of 38.17% and 87.76% of 28.80% respectively) isolated from black and yellow mustard cakes at pH 12. The purity of isolated proteins of black and yellow mustard cakes was 89.83% and 91.12% respectively and their pepsin digestibility was 89.67% and 90.17% respectively which assigned the absence of antinutritional compounds. It was found that essential amino acids isoleucine, lysine, methionine, threonine and tryptophan and non essential amino acids arginine and tyrosine were present in greater concentration in black mustard cake protein whereas other amino acids were higher in yellow mustard cake protein.

  3. DNA damage in internal organs after cutaneous exposure to sulphur mustard

    SciTech Connect

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

    2014-07-01

    Sulphur mustard (SM) is a chemical warfare agent that attacks mainly skin, eye and lungs. Due to its lipophilic properties, SM is also able to diffuse through the skin and reach internal organs. DNA represents one of the most critical molecular targets of this powerful alkylating agent which modifies DNA structure by forming monoadducts and biadducts. These DNA lesions are involved in the acute toxicity of SM as well as its long-term carcinogenicity. In the present work we studied the formation and persistence of guanine and adenine monoadducts and guanine biadducts in the DNA of brain, lungs, kidneys, spleen, and liver of SKH-1 mice cutaneously exposed to 2, 6 and 60 mg/kg of SM. SM-DNA adducts were detected in all studied organs, except in liver at the two lowest doses. Brain and lungs were the organs with the highest level of SM-DNA adducts, followed by kidney, spleen and liver. Monitoring the level of adducts for three weeks after cutaneous exposure showed that the lifetime of adducts were not the same in all organs, lungs being the organ with the longest persistence. Diffusion from skin to internal organs was much more efficient at the highest compared to the lowest dose investigated as the result of the loss of the skin barrier function. These data provide novel information on the distribution of SM in tissues following cutaneous exposures and indicate that brain is an important target. - Highlights: • Sulphur mustard reaches internal organs after skin exposure • Adducts are detected in the DNA of internal organs • Brain is the organ with the highest level of DNA damage • The barrier function of skin is lost at high dose of sulphur mustard • DNA adducts persist in organs for 2 or 3 weeks.

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

    PubMed

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

    2013-01-01

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

  5. Pacific Northwest Condiment Yellow Mustard (Sinapis alba L.) Grower Guide: 2000-2002

    SciTech Connect

    Brown, J.; Davis, J. B.; Esser, A.

    2005-07-01

    This report is a grower guide for yellow mustard. Yellow mustard (Sinapis alba L.), synonymous with white mustard, is a spring annual crop and well adapted to hot, dry growing conditions. It has shown potential as an alternative crop in rotations with small grain cereals and has fewer limitations compared to other traditional alternative crops.

  6. Mustard seed meal for management of root-knot nematode and weeds in tomato production

    USDA-ARS?s Scientific Manuscript database

    Mustard seed meals of indian mustard [InM (Brassica juncea)] and yellow mustard [YeM (Sinapis alba)], alone and combined, were tested for effects on tomato (Solanum lycopersicum) plants and for suppression of southern root-knot nematode [RKN (Meloidogyne incognita)] and weed populations. In the gree...

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

    PubMed

    Kristinsson, Jakop; Jóhannesson, Thorkell

    2009-05-01

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

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

    PubMed

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

    1990-04-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2009-02-01

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

  11. Uses of lunar sulfur

    NASA Technical Reports Server (NTRS)

    Vaniman, D.; Pettit, D.; Heiken, G.

    1992-01-01

    Sulfur and sulfur compounds have a wide range of applications for their fluid, electrical, chemical, and biochemical properties. Although known abundances on the Moon are limited (approximately 0.1 percent in mare soils), sulfur is relatively extractable by heating. Coproduction of sulfur during oxygen extraction from ilmenite-rich mare soils could yield sulfur in masses up to 10 percent of the mass of oxygen produced. Sulfur deserves serious consideration as a lunar resource.

  12. Uses of lunar sulfur

    SciTech Connect

    Vaniman, D.T.; Pettit, D.R.; Heiken, G.

    1988-01-01

    Sulfur and sulfur compounds have a wide range of applications for their fluid, electrical, chemical and biochemical properties. Although low in abundance on the Moon (/approximately/0.1% in mare soils), sulfur is surface-correlated and relatively extractable. Co-production of sulfur during oxygen extraction from ilmenite-rich soils could yield sulfur in masses up to 10% of the mass of oxygen produced. Sulfur deserves serious consideration as a lunar resource. 29 refs., 3 figs.

  13. Sulfur to nitrogen ratios in Ponderosa pine as bioindicators of foliar sulfur loading from air pollution

    SciTech Connect

    Johns, C.

    1984-01-01

    The objective of the research was to investigate the potential of foliar S:N ratios in Ponderosa pine as bioindicators of foliar sulfur loading in areas of long-term exposure to low levels of sulfurous air pollutants. First it was necessary to document seasonal variation in S:N ratios in trees not exposed to air pollution. Fifteen Ponderosa pines were selected at a site remote from urban and industrial sources of air pollution and the trees sampled at 18 intervals over a 15 month study period. Significant differences in sulfur and nitrogen concentrations occurred among the five needle age groups within most collections. One-year-old needles contained significantly more sulfur than other needles. Current-year needles contained more nitrogen than the three and four-year-old needles. Within each foliar age class significant differences in total sulfur content and S:N ratios occurred throughout the season. Sulfur concentrations and S:N r

  14. Methyl Jasmonate Alleviates Cadmium-Induced Photosynthetic Damages through Increased S-Assimilation and Glutathione Production in Mustard

    PubMed Central

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

    2016-01-01

    The effect of methyl jasmonate (MeJA) in mitigation of 50 μM cadmium (Cd) toxicity on structure and function of photosynthetic apparatus in presence or absence of 1.0 mM SO42– was investigated in mustard (Brassica juncea L. cv. Ro Agro 4001) at 30 days after sowing. Plants exhibited increased oxidative stress, impaired photosynthetic function when grown with Cd, but MeJA in presence of sulfur (S) more prominently ameliorated Cd effects through increased S-assimilation and production of reduced glutathione (GSH) and promoted photosynthetic functions. The transmission electron microscopy showed that MeJA protected chloroplast structure against Cd-toxicity. The use of GSH biosynthetic inhibitor, buthionine sulfoximine (BSO) substantiated the findings that ameliorating effect of MeJA was through GSH production. MeJA could not alleviate Cd effects when BSO was used due to unavailability of GSH even with the input of S. The study shows that MeJA regulates S-assimilation and GSH production for protection of structure and function of photosynthetic apparatus in mustard plants under Cd stress. PMID:28066485

  15. Methyl Jasmonate Alleviates Cadmium-Induced Photosynthetic Damages through Increased S-Assimilation and Glutathione Production in Mustard.

    PubMed

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

    2016-01-01

    The effect of methyl jasmonate (MeJA) in mitigation of 50 μM cadmium (Cd) toxicity on structure and function of photosynthetic apparatus in presence or absence of 1.0 mM [Formula: see text] was investigated in mustard (Brassica juncea L. cv. Ro Agro 4001) at 30 days after sowing. Plants exhibited increased oxidative stress, impaired photosynthetic function when grown with Cd, but MeJA in presence of sulfur (S) more prominently ameliorated Cd effects through increased S-assimilation and production of reduced glutathione (GSH) and promoted photosynthetic functions. The transmission electron microscopy showed that MeJA protected chloroplast structure against Cd-toxicity. The use of GSH biosynthetic inhibitor, buthionine sulfoximine (BSO) substantiated the findings that ameliorating effect of MeJA was through GSH production. MeJA could not alleviate Cd effects when BSO was used due to unavailability of GSH even with the input of S. The study shows that MeJA regulates S-assimilation and GSH production for protection of structure and function of photosynthetic apparatus in mustard plants under Cd stress.

  16. Sulfuric acid-sulfur heat storage cycle

    DOEpatents

    Norman, John H.

    1983-12-20

    A method of storing heat is provided utilizing a chemical cycle which interconverts sulfuric acid and sulfur. The method can be used to levelize the energy obtained from intermittent heat sources, such as solar collectors. Dilute sulfuric acid is concentrated by evaporation of water, and the concentrated sulfuric acid is boiled and decomposed using intense heat from the heat source, forming sulfur dioxide and oxygen. The sulfur dioxide is reacted with water in a disproportionation reaction yielding dilute sulfuric acid, which is recycled, and elemental sulfur. The sulfur has substantial potential chemical energy and represents the storage of a significant portion of the energy obtained from the heat source. The sulfur is burned whenever required to release the stored energy. A particularly advantageous use of the heat storage method is in conjunction with a solar-powered facility which uses the Bunsen reaction in a water-splitting process. The energy storage method is used to levelize the availability of solar energy while some of the sulfur dioxide produced in the heat storage reactions is converted to sulfuric acid in the Bunsen reaction.

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

    PubMed

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

    2016-02-15

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

  18. 14. SOUTH PLANT MUSTARD FILLING BUILDING (BUILDING 728) AND WAREHOUSE ...

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

    14. SOUTH PLANT MUSTARD FILLING BUILDING (BUILDING 728) AND WAREHOUSE (BUILDING 729) FROM CHEMICAL STORAGE TANK. VIEW TO NORTHEAST. - Rocky Mountain Arsenal, Bounded by Ninety-sixth Avenue & Fifty-sixth Avenue, Buckley Road, Quebec Street & Colorado Highway 2, Commerce City, Adams County, CO

  19. 87. EAST SECTION OF SOUTH PLANT, SHOWING MUSTARD FILLING BUILDING ...

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

    87. EAST SECTION OF SOUTH PLANT, SHOWING MUSTARD FILLING BUILDING (BUILDING 728) AT LEFT AND INCINERATOR/PRECIPITATOR (BUILDING 724) AT CENTER, FROM CHEMICAL STORAGE TANK. VIEW TO SOUTHWEST. - Rocky Mountain Arsenal, Bounded by Ninety-sixth Avenue & Fifty-sixth Avenue, Buckley Road, Quebec Street & Colorado Highway 2, Commerce City, Adams County, CO

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

    SciTech Connect

    Luman, F.M.

    1983-10-18

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

  1. Mustard Seed Meal suppresses Weeds in Potato and Peppermint

    USDA-ARS?s Scientific Manuscript database

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

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

    PubMed

    Jancsó, G; Pierau, F K; Sann, H

    1993-05-01

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

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

    USDA-ARS?s Scientific Manuscript database

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

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

    USDA-ARS?s Scientific Manuscript database

    Weed control in organic onion production is often difficult and expensive, requiring numerous cultivations and extensive hand-weeding. Onion safety and weed control with mustard seed meal (MSM) derived from Sinapis alba was evaluated in greenhouse and field trials. MSM applied at 110, 220, and 440 g...

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

    NASA Astrophysics Data System (ADS)

    Duchovic, Ronald J.; Vilensky, Joel A.

    2007-06-01

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

  6. Emerging technology for increasing glucosinolates in arugula and mustard greens.

    PubMed

    Antonious, George F; Turley, Eric; Antonious, Alexander; Trivette, Thomas

    2017-07-03

    Two plant species, arugula (Eruca sativa) and mustard (Brassica juncea) were field-grown under four soil management practices: soil mixed with municipal sewage sludge (SS), soil mixed with horse manure (HM), soil mixed with chicken manure (CM), and no-mulch bare soil (NM) to investigate the impact of soil amendments on the concentration of glucosinolates (GSLs) in their shoots. GSLs, hydrophilic plant secondary metabolites in arugula and mustard were extracted using boiling methanol and separated by adsorption on sephadex ion exchange disposable pipette tips filled with DEAE, a weak base, with a net positive charge that exchange anions such as GSLs. Quantification of GSLs was based on inactivation of arugula and mustard myrosinase and liberation of the glucose moiety from the GSLs molecule by addition of standardized myrosinase (thioglucosidase) and spectrophotometric quantification of the liberated glucose moiety. Overall, GSLs concentrations were significantly greater (1287 µg g(-1) fresh shoots) in plants grown in SS compared to 929, 890, and 981 µg g(-1) fresh shoots in plants grown in CM, HM, and NM soil, respectively. Results also revealed that mustard shoots contained greater concentrations of GSLs (974 µg g(-1) fresh shoots) compared to arugula (651 µg g(-1) fresh shoots).

  7. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... harvested. Mustard. A crop of the family Cruciferae. Planted acreage. In addition to the definition... processor contracts with varying base contract prices within the same unit, we will value your production to...) 13,000 pounds × $0.15 base contract price = $1,950 value of guarantee; (3) $1,950 total value of...

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

    USGS Publications Warehouse

    Phillips-Mao, Laura; Larson, Diane L.; Jordan, Nicholas R.

    2014-01-01

    The degree to which invasive species drive or respond to environmental change has important implications for conservation and invasion management. Often characterized as a driver of change in North American woodlands, the invasive herb garlic mustard may instead respond to declines in native plant cover and diversity. We tested effects of native herb cover, richness, and light availability on garlic mustard invasion in a Minnesota oak woodland. We planted 50 garlic mustard seeds into plots previously planted with 0 to 10 native herb species. We measured garlic mustard seedling establishment, survival to rosette and adult stages, and average (per plant) and total (per plot) biomass and silique production. With the use of structural equation models, we analyzed direct, indirect, and net effects of native cover, richness, and light on successive garlic mustard life stages. Native plant cover had a significant negative effect on all life stages. Species richness had a significant positive effect on native cover, resulting in indirect negative effects on all garlic mustard stages, and net negative effects on adult numbers, total biomass, and silique production. Light had a strong negative effect on garlic mustard seedling establishment and a positive effect on native herb cover, resulting in significant negative net effects on garlic mustard rosette and adult numbers. However, light's net effect on total garlic mustard biomass and silique production was positive; reproductive output was high even in low-light/high-cover conditions. Combined effects of cover, richness, and light suggest that native herbs provide biotic resistance to invasion by responding to increased light availability and suppressing garlic mustard responses, although this resistance may be overwhelmed by high propagule pressure. Garlic mustard invasion may occur, in part, in response to native plant decline. Restoring native herbs and controlling garlic mustard seed production may effectively reduce

  9. pH-dependent toxicity of sulphur mustard in vitro

    SciTech Connect

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

    2007-06-15

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

  10. Properties of Sulfur Concrete.

    DTIC Science & Technology

    1979-07-06

    This report summarizes the state of the art of sulfur concrete . Sulfur concrete is created by mixing molten sulfur with aggregate and allowing the...and many organic compounds. It works well as a rapid runway repair material. Sulfur concrete also has unfavorable properties. It has poor durability

  11. Shrubby Reed-Mustard Habitat: Parent Material, Soil, and Landscape Characteristics

    NASA Astrophysics Data System (ADS)

    Kelly, L. S.; Boettinger, J. L.

    2012-12-01

    Shrubby reed-mustard (Glaucocarpum suffrutescens, a.k.a. Schoenocrambe suffrutescens, Glaucocarpum suffrutescens, or Hesperidanthus suffrutescens) is an endangered perennial shrub endemic to the southern Uinta Basin in northeast Utah. Only seven populations of shrubby reed-mustard have been identified. The arid area where the plant grows is rich in natural gas and oil deposits, as well as oil shale. Oil wells already dot the landscape, and there is significant concern that further development of these resources will threaten the continued existence of shrubby reed-mustard. Determination of the parent material, soil and landscape characteristics associated with shrubby reed-mustard habitat is imperative to facilitate conservation management. Shrubby reed-mustard grows where little else does and, based on field observations and remotely sensed spectral data, appears to occur in a particular type of strata. Our objective is to identify the physical and chemical characteristics of shrubby reed-mustard's environment. Site characteristics such as parent material and associated vegetation have been identified and documented. Soil properties such as water-soluble and total leachable elements, particle-size distribution, organic carbon, cation exchange capacity, total nitrogen, and available phosphorus and potassium are being determined. During the course of this investigation, soils within four shrubby reed-mustard habitat areas were sampled. Soils from non-shrubby reed-mustard areas adjacent to the four shrubby reed-mustard populations were also sampled. Soil samples were collected from a total of twenty-five shrubby reed-mustard soil pits and twenty-four non-shrubby reed-mustard soil pits. The soil horizons of each pedon were delineated, and samples were collected from each horizon. Field data indicate that shrubby reed-mustard occurs exclusively in shale-derived, shallow soils on bedrock-controlled uplands. Although there is some overlap of plant species on both types

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

    PubMed

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

    2014-06-01

    Chemical warfare agents (CWA) are highly toxic compounds which have been produced to kill or hurt people during conflicts or terrorist attacks. Despite the fact that their use is strictly prohibited according to international convention,