Sample records for agents sulfur mustard

  1. [Acute poisoning by chemical warfare agent: sulfur mustard].

    PubMed

    Mérat, S; Perez, J P; Rüttimann, M; Bordier, E; Lienhard, A; Lenoir, B; Pats, B

    2003-02-01

    To review story, mechanism of action, clinical and therapeutic bases of a sulfur mustard poisoning, by accidental, terrorism or war exposure. References were obtained from computerised bibliographic research (Medline), from personnel data (academic memoir, documents under approbation of the National Defense Office) and from the Library of Military Medical Service. Sulfur mustard is a chemical warfare agent with peace time results: leak, accidental handling, acts of terrorism. Sulfur mustard is a vesicant agent, an organochlorine agent, who alkylate DNA. Under liquid or gas form its main target are skin and lungs. Clinical effects are like burns with loss of immunity, with respiratory failure, ophthalmic, gastrointestinal and haematological signs. The last studies have improved knowledge about the mechanism of action, detection, protection and treatment. Methods for determination of sulfur mustard are based on gas chromatographic method and mass spectrometry. During sulfur mustard contamination the first priorities of treatment are to remove victims from the contaminated place and to initiate decontamination. Emergency workers and materials must take protection to avoid secondary contamination of emergency unit. With treatment of vital functions and respiratory failure, the new ways of treatment are about N-acetyl cysteine for lung injury, poly (ADP-ribose) polymerase inhibitors, calmodulin antagonists and Ca(++) chelators. Interactions between sulfur mustard and anaesthetic agents are not well known and are based on clinical observations. Emergency care unit can be confronted with sulfur mustard during accidental contamination or acts of terrorism. First and most efficacy priorities of treatment are to remove and to decontaminate victims. New means of detection and treatment are studied since several years but are not still appropriate to human victims or mass treatment.

  2. 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.

  3. Neutralization and Biodegradation of Sulfur Mustard.

    DTIC Science & Technology

    1997-02-01

    public release; distribution is unlimited. 13. ABSTRACT (Maximum 200 words) The chemical warfare agent sulfur mustard was hydrolyzed to products that...scale bioreactors processing hydrolyzed munitions-grade sulfur mustard obtained directly from the U.S. Chemical Stockpile. The bioreactor effluent was...Hydrolysis has been previously utili ed for the detoxification of Canadian HD stockpiles (Reichert, 1975). Biodegradation has widespread application in

  4. Toxicology and pharmacology of the chemical warfare agent sulfur mustard.

    PubMed

    Dacre, J C; Goldman, M

    1996-06-01

    There have been reports of chemical attacks in which sulfur mustard might have been used (a) on Iranian soldiers and civilians during the Gulf War in 1984 and 1985 and (b) in an Iraqi chemical attack on the Iranian-occupied village of Halbja in 1988, resulting in many civilian casualties. Heavy use of chemical warfare in Afghanistan by the Soviet military is a recent innovation in military tactics that has been highly successful and may ensure further use of chemical agents in future military conflicts and terrorist attacks as a profitable adjunct to conventional military arms. Mustard is a poisonous chemical agent that exerts a local action on the eyes, skin, and respiratory tissue, with subsequent systemic action on the nervous, cardiac, and digestive systems in humans and laboratory animals, causing lacrimation, malaise, anorexia, salivation, respiratory distress, vomiting, hyperexcitability, and cardiac distress. Under extreme circumstances, dependent upon the dose and length of exposure to the agent, necrosis of the skin and mucous membranes of the respiratory system, bronchitis, bronchopneumonia, intestinal lesions, hemoconcentration, leucopenia, convulsions with systemic distress, and death occur. Severe mustard poisoning in humans is associated with systemic injury, which is manifested as headache, epigastric distresses, anorexia, diarrhea, and cachexia and is usually observed at mustard doses of 1000 mg/min/m3 with damage to hematopoietic tissues and progressive leucopenia. Sulfur mustard is a cell poison that causes disruption and impairment of a variety of cellular activities that 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

  5. 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

  6. 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

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

    PubMed

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

    2003-12-01

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

  8. 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…

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 cellmore » 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.« less

  10. 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.

  11. 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

  12. Therapeutic options to treat sulfur mustard poisoning--the road ahead.

    PubMed

    Smith, William J

    2009-09-01

    For the past 15 years the international research community has conducted a basic and applied research program aimed at identifying a medical countermeasure against chemical threat vesicant, or blistering, agents. The primary emphasis of this program has been the development of therapeutic protection against sulfur mustard and its cutaneous pathology-blister formation. In addition to the work on a medical countermeasures, significant research has been conducted on the development of topical skin protectants and medical strategies for wound healing. This review will focus on the pharmacological strategies investigated, novel therapeutic targets currently under investigation and therapeutic approaches being considered for transition to advanced development. Additionally, we will review the expansion of our understanding of the pathophysiological mechanisms of mustard injury that has come from this research. While great strides have been made through these investigations, the complexity of the mustard insult demands that further studies extend the inroads made and point the way toward better understanding of cellular and tissue disruptions caused by sulfur mustard.

  13. Notes from the field: Exposures to discarded sulfur mustard munitions - Mid-Atlantic and New England States 2004-2012.

    PubMed

    2013-04-26

    Before the 1970s, the United States sometimes disposed of at sea excess, obsolete, or unserviceable munitions, including chemical munitions. Chemical munitions known to have been disposed of at sea included munitions filled with sulfur mustard, a vesicant (i.e., an agent that causes chemical burns or blisters of the skin and mucous membranes). Signs and symptoms of exposure to a mustard agent can include redness and blistering of the skin, eye irritation, rhinorrhea, hoarseness, shortness of breath, and (rarely) diarrhea and abdominal discomfort. Since 2004, CDC has received notification of three separate incidents of exposure to sulfur mustard munitions. In one incident, a munition was found with ocean-dredged marine shells used to pave a driveway. The other two incidents involved commercial clam fishing operations. This report highlights the importance of considering exposure to sulfur mustard in the differential diagnosis of signs and symptoms compatible with exposure to a vesicant agent, especially among persons involved with clam fishing or sea dredging operations.

  14. Subchronic toxicity evaluation of sulfur mustard in rats.

    PubMed

    Sasser, L B; Miller, R A; Kalkwarf, D R; Cushing, J A; Dacre, J C

    1996-01-01

    Occupational exposure criteria have not been established for sulfur mustard (bis(2-chlorethyl) sulfide), a strong alkylating agent with known mutagenic properties. Seventy-two Sprague-Dawley rats of each sex, 6-7 weeks old, were divided into six groups (12 of each sex per group) and gavaged with 0, 0.003, 0.01, 0.03, 0.1 or 0.3 mg kg-1 sulfur mustard in sesame oil for 5 days a 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-1 group. Hematological evaluations and clinical chemistry measurements found non consistent treatment-related effects at the doses studied. The only treatment-related lesion associated with gavage exposure upon histopathological evaluation was epithelial hyperplasia of the forestomach of both sexes at 0.3 mg kg-1 and of males at 0.1 mg kg-1. The hyperplastic change was minimal and characterized by cellular disorganization of the basilar layer, 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 no-observed-effect level (NOEL) for sulfur mustard in this 90-day study was 0.1 mg kg-1 day-1 when administered orally.

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

    PubMed

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

    2011-05-01

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

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

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

    DTIC Science & Technology

    1993-05-13

    i O : DUTiC-TID INTRODUCTION Sulfur mustard ( 2,2’-dichlorodiethyl sulfide or HD) is a bifunctional alkylating agent which reacts with a wide variety...of biological molecules. It is a strong alkylating agent of purine bases in DNA (Kohn 1983). Early studies strongly implicate DNA as a principal...cells have previously demonstrated stimulation of PADPRP activity following exposure to a monofunctional alkylating agent , methylnitrosourea (MNU

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

    PubMed

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

    2009-08-01

    Skin lesions are among the most common complications of contact with sulfur mustard. This study was aimed to measure skin water content and transepidermal water loss (TEWL) in patients with a history of sulfur mustard contact. Three hundred ten male participants were included in this study: 87 (28.1%) sulfur mustard-exposed patients with current skin lesions (group 1), 71 (22.9%) sulfur mustard-exposed patients without skin lesions (group 2), 78 (25.2%) patients with dermatitis (group 3) and 74 (23.8%) normal controls (group 4) The water content and TEWL of skin was measured at four different locations of the body: forehead, suprasternal, palm and dorsum of hand. Nonparametric statistical tests (Kruskal-Wallis) were used to compare the four groups, and P < 0.05 was considered statistically significant. The mean age of participants were 44.0 +/- 6.7, 41.9 +/- 5.9, 43.8 +/- 9.3 and 44.8 +/- 8.9 years in groups 1 to 4, respectively (P = 0.146). Xerosis, post-lesional hyperpigmentation and lichenification were significantly more common in either sulfur mustard-exposed participants or non-exposed participants with dermatitis (P < 0.05). Skin hydration was higher in subjects with sulfur mustard contact than in non-injured participants (P < 0.05) in the dorsum and palm of hands and forehead. TEWL was significantly higher in participants only in suprasternal area and dorsum of hand. Contact with sulfur mustard agent can alter biophysical properties of the skin--especially the function of stratum corneum as a barrier to water loss-several years after exposure.

  19. DFT and TD-DFT study of the adsorption and detection of sulfur mustard chemical warfare agent by the C24, C12Si12, Al12N12, Al12P12, Be12O12, B12N12 and Mg12O12 nanocages

    NASA Astrophysics Data System (ADS)

    Jouypazadeh, Hamidreza; Farrokhpour, Hossein

    2018-07-01

    In the present research, the interaction of sulfur mustard, a chemical warfare agent, with the surface of C24, C12Si12, Al12N12, Al12P12, Be12O12, B12N12 and Mg12O12 nanocages was studied using the dispersion corrected density function theory (DFT-D3) method. The calculated adsorption energies of sulfur mustard on the surface of the nanocages showed that the Al12N12, C12Si12 and Mg12O12 are useful for the adsorption of the sulfur mustard. The quantum theory atom in molecule (QTAIM) analysis was used to study the nature of interactions of sulfur mustard with the surface of the selected nanocages. Based on QTAIM analysis, the majority of interactions of sulfur and chlorine atoms of sulfur mustard with the surface of the considered nanocages are covalent and quasi covalent whereas the interactions of hydrogen atoms of sulfur mustard with the surface of the nanocages are generally non-covalent. The charge transfer between sulfur mustard and the nanocages as well as chemical quantum descriptors of complexes were calculated using natural bond orbital (NBO) method. The most electron charge transfers from the sulfur mustard to B12N12 nanocage where the S atom of sulfur mustard donor a chemical bond to B atom of the nanocage. The ability of the considered nanocages for detecting sulfur mustard was studied using time-dependent density function theory (TD-DFT) and density of state (DOS) diagram. It is found that the C24, Al12P12, Be12O12 and B12N12 nanocages are useful sensors for this chemical agent.

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

    PubMed

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

    2018-09-01

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

  1. 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.

  2. 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

  3. 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

  4. 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.

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

    PubMed

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

    2013-12-05

    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

  6. 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.

  7. Accidental sulfur mustard exposure: A case report.

    PubMed

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

    2018-09-01

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

  8. Nucleophilic substitution by grignard reagents on sulfur mustards.

    PubMed

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

    2004-10-15

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

  9. Sulfur mustard-induced poikiloderma: a case report.

    PubMed

    Emadi, Seyed Naser; Kaffashi, Mohammad; Poursaleh, Zohreh; Akhavan-Moghaddam, Jamal; Soroush, Mohammad Reza; Emadi, Seyed Emad; Taghavi, Nez'hat-o-Sadat

    2011-06-01

    Sulfur mustard (SM) is a potent chemical warfare agent that was widely used during the First World War and the Iran-Iraq conflict. This vesicant agent causes several acute and chronic effects on the skin, eye, and respiratory system. We report the case of a 41-year-old man who was injured with SM in Iraq chemical attack in 1988. After exposure, he developed severe skin blisters on his upper trunk, dorsum of hands, and genitalia. Based on several clinical observations, such as atrophy, pigmentation, and vascular changes on genitalia with relevant findings in histopathological studies, persistent pigmentation, and damaged skin appendix in hand lesions, a diagnosis of "SM-induced poikiloderma" was postulated. The absence of any complication on the palmar aspect of hands is another remarkable finding in presented case, which suggests a plausible role of the palms as a vector for transporting SM to other sites of the skin.

  10. 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%. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. 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

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

    NASA Astrophysics Data System (ADS)

    Sadeghi, Meysam; Yekta, Sina; Ghaedi, Hamed

    2016-07-01

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

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    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.

  14. 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. © 2016 New York Academy of Sciences.

  15. Metabolic Activation of Sulfur Mustard Leads to Oxygen Free Radical Formation

    DTIC Science & Technology

    2012-01-01

    spin trapping results that demonstrated the enzymatic reduction of sulfur mustard sulfonium ions to carbon-based free radicals using an in vitro system ...BMPO EPR signals were reduced or eliminated when mustard carbon radical production was impeded by systematically removing system components, indicating...referred to as complete incubation mixture. EPR spectrometry Mustard-related carbon or oxygen free radical production was recorded using a Bruker EMX Plus

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

    DTIC Science & Technology

    2000-01-01

    4. TITLE AND SUBTITLE Alterations in Inflammatory Cytokine Gene Expression in Sulfur Mustard-exposed Mouse Skin 6. AUTHOR(S) Sabourin , C.L.K...in Inflammatory Cytokine Gene Expression in Sulfur Mustard-Exposed Mouse Skin Carol L. K. Sabourin ,1 John P. Petrali,2 and Robert P. Casillas2...inflammatory response following HD exposure by measuring ear swelling. Further studies using the 291 292 SABOURIN , PETRALI, AND CASILLAS Volume 14

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hackett, P. L.; Rommereim, R. L.; Burton, F. G.

    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 (0.5more » 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.« less

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

    PubMed

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

    2013-04-24

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

  19. Signaling Molecules in Sulfur Mustard-Induced Cutaneous Injury

    DTIC Science & Technology

    2007-11-27

    vesicant vapors into human skin. J Gen Physiol. 1946;29:441–69. 11. Sabourin CL, Petrali JP, Casillas RP. Alterations in inflammatory cytokine gene...expression in sulfur mustard-exposed mouse skin. J Biochem Mol Toxicol. 2000;14(6):291–302. 12. Sabourin CL, Danne MM, Buxton KL, Casillas RP, Schlager

  20. Cross-Linking Interferes With Assessing Sulfur Mustard-Induced DNA Damage in Human Peripheral Blood Lymphocytes Using the Comet Assay

    DTIC Science & Technology

    2004-01-01

    of SM to impede the migration of H,0 2 -damaged mal ian cell lethality with bifunctional alkylating agents . Chemr. Biol. Iriterui. 38:75-86.DNA is an...3100 Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010-5400 N-3 position of adenine, and alkylation leads to depurination of Sulfur...mustard (SM) is a blistering agent that produces DNA DNA strands. Subsequent breakage of phosphodiester bonds at strand breaks. To detect SM-induced DNA

  1. Doxepin cream vs betamethasone cream for treatment of chronic skin lesions due to sulfur mustard.

    PubMed

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

    2011-01-01

    Oral doxepin was shown to reduce chronic pruritus due to sulfur mustard. The present study compared the effects of topical doxepin 5% with betamethasone 1% for the treatment of pruritus in veterans exposed to sulfur mustard. This investigator-blinded, randomized, clinical trial was conducted in an outpatient dermatology clinic. Seventy-five men who were exposed to sulfur mustard 23 to 28 years ago during the Iran-Iraq war who complained of pruritus were randomized to receive doxepin cream 5% (n = 40) or betamethasone cream 0.1% (n = 35) twice a day for 6 weeks. Pruritus severity and Dermatology Life Quality Index (DLQI) were evaluated before and after each treatment. Both groups showed significant improvement regarding pruritus (P < .05), burning sensation, skin dryness (P < .001), and skin scaling (P < 0.05). The lesions of all regions significantly reduced after treatments (P < .05), except those on the head, face, and genitalia. Pruritus, visual analog scores, and DLQI significantly decreased (P < .01, P < .01, and P < .001, respectively) in doxepin- and betamethasone-treated groups, and there was no difference between groups. All DLQI subscores decreased after both type of treatments (P < .01). Equal efficacy of doxepin cream and betamethasone suggest that doxepin is a potential alternative to control pruritus caused by sulfur mustard in exposed veterans.

  2. 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.

  3. 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).

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

  5. 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.

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

    PubMed

    Jiang, Austin; Maibach, Howard

    2018-01-01

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

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

    PubMed

    Jung, Hyunsook; Choi, Seungki

    2017-10-15

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

  8. 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.

  9. Protection against the Acute and Delayed Toxicity of Mustards and Mustard-Like Compounds.

    DTIC Science & Technology

    1983-09-01

    Edition, A. G. Gilman, L. S. Goodman, and A. Gilman (eds.), Macmillan, New York, 1980, pp. 1256-1313. * 2. Ludlum, D. B., Alkylating Agents and the...chemical warfare agents . They are acutely toxic to the skin, respiratory tract, eyes, bone marrow, and, in large doses, to other organs as well...related to the alkylating activity of sulfur mustards and, specifically, to alkylation of DNA (1). Investigations of related compounds have led to the

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

    PubMed

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

    2013-10-01

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

  11. 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.

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

    PubMed

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

    2018-09-01

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

  13. 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.

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

    PubMed Central

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

    2015-01-01

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

  15. Regulation of 1-alpha, 25-dihydroxyvitamin D3 on interleukin-6 and interleukin-8 induced by sulfur mustard (HD) on human skin cells.

    PubMed

    Arroyo, Carmen M; Kan, Robert K; Burman, Damon L; Kahler, David W; Nelson, Marian R; Corun, Charlene M; Guzman, Juanita J; Broomfield, Clarence A

    2003-05-01

    The regulatory effects of the active form of vitamin D, 1-alpha, 25-dihydroxyvitamin D3 (1-alpha, 25 (OH)2D3) were assessed on the cytokine and chemokine secretion induced by sulfur mustard on human skin fibroblasts and human epidermal keratinocytes. Stimulation of human skin fibroblasts with sulfur mustard (10(-4) M for 24 hr at 37 degrees ) resulted in approximately a 5 times increase in the secretion of interleukin-6 and over a 10 times increase for interleukin-8, which was inhibited by 1-alpha, 25 (OH)2D3, at sulfur mustard-stimulated human epidermal keratinocytes at concentrations sulfur mustard on human skin fibroblasts/human epidermal keratinocytes, apparent at nanomolar concentrations. Our results indicate that the suppression of these inflammatory mediators by 1-alpha, 25 (OH)2D3 is dependent on the source of the primary cultures, cell densities, and kinetics of pretreatments. In contrast to the inhibition of cytokine/chemokine production, cell proliferation was enhanced by almost 1.7 times on treated human epidermal keratinocytes with 1-alpha, 25 (OH)2D3 (1 x 10(-9) M) after sulfur mustard-stimulation (10(-4) M for 24 hr at 37 degrees C). The observed enhancement diversified based on cell density, and kinetics of pretreatment with a maximal synergism (s) observed at 1 x 10(-9) M. Photomicrographs show typical signs of cellular degeneration caused by sulfur mustard such as chromatin condensation. The observed cellular degeneration was lessened when human epidermal keratinocytes were treated with 1-alpha, 25 (OH)2D3 (2 x 10(-9) M). 1-alpha, 25(OH)2D3 could be an alternative treatment for cutaneous inflammation disorders caused by sulfur mustard because we have demonstrated its ability to suppress inflammatory

  16. 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.

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

    PubMed

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

    2018-04-25

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

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

    PubMed Central

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

    2016-01-01

    In mouse skin, sulfur mustard is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of sulfur mustard and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and progrowth/pro–wound healing mediators, including cyclooxygenase-2 (COX-2), which generates prostanoids, inducible nitric oxide synthase (iNOS), which generates nitric oxide, fibroblast growth factor receptor 2 (FGFR2), and galectin-3. Characterization of the mediators regulating structural changes in the skin during sulfur mustard–induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes. PMID:27371823

  19. Biochemical changes in mouse lung after subcutaneous injection of the sulfur mustard 2-chloroethyl 4-chlorobutyl sulfide.

    PubMed

    Elsayed, Nabil M; Omaye, Stanley T

    2004-07-01

    Sulfur mustard (HD) is a vesicant-type chemical warfare agent (CWA) introduced in World War I which continues to be produced, stockpiled, and occasionally deployed by some countries, and could be used potentially by terrorists. Exposure to HD can cause erythema, blisters, corneal opacity, and airway damage. We have reported previously that subcutaneous (SC) injection of immunodeficient athymic nude mice with the half mustard butyl 2-chloroethyl sulfide (BCS) causes systemic biochemical changes in several organs distal to the exposure site. In the present study, we examined the response of non-immunodeficient Swiss Webster mice to the mustard, 2-chloroethyl 4-chlorobutyl sulfide (CECBS). In a pilot study, we found that a single SC injection of 20-25 microl/mouse causes death within 24h. Consequently, we used 5 microl/mouse (approx. 0.017 mg/kg body weight) of neat CECBS or an equal volume of saline as control. We examined the lungs after 1, 24, and 48 h for biochemical changes including total and oxidized glutathione, protein, DNA, and lipid peroxidation contents in tissue homogenate, and superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, and glutathione S-transferases activities in the cytosol. After 1h and/or 24h, we found statistically significant changes that were resolved by 48 h. These changes mimicked those of HD and BCS and were generally consistent with free radical-mediated oxidative stress. The implications of these observations are two-fold. First, dermal exposure to low-dose mustard gas could elicit systemic changes impacting distal organs such as the lungs. It also suggests that antioxidants could potentially modulate the response and reduce the damage. Second, although the use of known CWAs such as HD is prohibited, analogs that are not recognized as agents are as toxic and could be dangerous if acquired and used by potential terrorists.

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

    PubMed

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

    2017-10-01

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

  1. A highly selective and sensitive "turn-on" fluorescence chemodosimeter for the detection of mustard gas.

    PubMed

    Raghavender Goud, D; Purohit, Ajay Kumar; Tak, Vijay; Dubey, Devendra Kumar; Kumar, Pravin; Pardasani, Deepak

    2014-10-21

    A new chemodosimetric protocol based on a tandem S-alkylation followed by desulfurisation reaction of rhodamine-thioamide with mustard gas is reported. The chemodosimeter is highly selective for potential DNA alkylating agents like sulfur mustard, over other simple alkyl halides with the limit of detection of 4.75 μM.

  2. Therapeutic journery of nitrogen mustard as alkylating anticancer agents: Historic to future perspectives.

    PubMed

    Singh, Rajesh K; Kumar, Sahil; Prasad, D N; Bhardwaj, T R

    2018-05-10

    Cancer is considered as one of the most serious health problems today. The discovery of nitrogen mustard as an alkylating agent in 1942, opened a new era in the cancer chemotherapy. This valuable class of alkylating agent exerts its biological activity by binding to DNA, cross linking two strands, preventing DNA replication and ultimate cell death. At the molecular level, nitrogen lone pairs of nitrogen mustard generate a strained intermediate "aziridinium ion" which is very reactive towards DNA of tumor cell as well as normal cell resulting in various adverse side effects alogwith therapeutic implications. Over the last 75 years, due to its high reactivity and peripheral cytotoxicity, numerous modifications have been made in the area of nitrogen mustard to improve its efficacy as well as enhancing drug delivery specifically to tumor cells. This review mainly discusses the medicinal chemistry aspects in the development of various classes of nitrogen mustards (mechlorethamine, chlorambucil, melphalan, cyclophosphamide and steroidal based nitrogen mustards). The literature collection includes the historical and the latest developments in these areas. This comprehensive review also attempted to showcase the recent progress in the targeted delivery of nitrogen mustards that includes DNA directed nitrogen mustards, antibody directed enzyme prodrug therapy (ADEPT), gene directed enzyme prodrug therapy (GDEPT), nitrogen mustard activated by glutathione transferase, peptide based nitrogen mustards and CNS targeted nitrogen mustards. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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

    PubMed Central

    2012-01-01

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

  4. 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...

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

    PubMed

    Khaheshi, Isa; Keshavarz, Saeed; Imani Fooladi, Abbas Ali; Ebrahimi, Majid; Yazdani, Samaneh; Panahi, Yunes; Shohrati, Majid; Nourani, Mohammad Reza

    2011-01-14

    Sulfur mustard (SM) is a blister-forming agent that has been used as a chemical weapon. Sulfur mustard can cause damage in various organs, especially the skin, respiratory system, and eyes. Generally, the multiple complications of mustard gas result from its alkalizing potency; it reacts with cellular components like DNA, RNA, proteins, and lipid membranes.TGF-β is a multi-functional cytokine with multiple biological effects ranging from cell differentiation and growth inhibition to extracellular matrix stimulation, immunosuppression, and immunomodulation. TGF-β has 3 isoforms (TGF-β 1, 2, 3) and its signaling is mediated by its receptors: R1, R2 and intracellular Smads molecules.TGF-β has been shown to have anti-inflammatory effects. TGF-βs and their receptors also have an important role in modulation of skin inflammation, proliferation of epidermal cells, and wound healing, and they have been implicated in different types of skin inflammatory disorders. Seventeen exposed SM individuals (48.47 ± 9.3 years), 17 chronic dermatitis patients (46.52 ± 14.6 years), and 5 normal controls (44.00 ± 14.6 years) were enrolled in this study.Evaluation of TGF-βs and their receptors expressions was performed by semiquantitative RT-PCR. Only TGF1 was analyzed immunohistochemically. Our results showed significant decreases in the expression percentages of TGF-β 1, 2 and R1, R2 in chemical victims in comparison with chronic dermatitis and normal subjects and significant decreases in the intensity of R1 and R2 expressions in chemical victims in comparison with chronic dermatitis and normal controls. (P value < 0.05) TGF-βs and their receptors appear to have a noticeable role in chronic inflammatory skin lesions caused by sulfur mustard.

  6. Delayed complications of sulfur mustard poisoning in the skin and the immune system of Iranian veterans 16-20 years after exposure.

    PubMed

    Hefazi, Mehrdad; Maleki, Masoud; Mahmoudi, Mahmoud; Tabatabaee, Abbas; Balali-Mood, Mahdi

    2006-09-01

    Extensive cutaneous burns caused by alkylating chemical warfare agent sulfur mustard (SM) have been associated with the severe suppression of the immune system in humans. We aimed to study the association between late cutaneous and immunological complications of SM poisoning. Skin examination was performed on all SM-poisoned Iranian veterans in the province of Khorasan, Iran, who had significant clinical complications, and their SM intoxication was confirmed by toxicological analysis. Light microscopy was performed on eight skin biopsies. Blood cell counts, serum immunoglobulin and complement factor, as well as flow cytometric, analyses were performed on all the patients. The severity of cutaneous complications were classified into four grades and compared with hematological and immunological parameters, using Spearman's rank correlation test. Forty male subjects, confirmed with SM poisoning 16-20 years earlier, were studied. The main objective findings were hyperpigmentation (55%), dry skin (40%), multiple cherry angiomas (37.5%), atrophy (27.5%), and hypopigmentation (25%). Histopathologic findings were nonspecific and compatible with hyperpigmented old atrophic scars. Except for the hematocrit and C4 levels, hematological and immunological parameters revealed no significant correlation with the severity grades of cutaneous complications. Sulfur mustard is an alkylating agent with prolonged adverse effects on both the skin and the immune system. Although skin is a major transporting system for SM's systemic absorption, there is probably no correlation between the severity of late cutaneous and immunological complications of SM poisoning.

  7. Kinetics of degradation of sulfur mustard and sarin simulants on HKUST-1 metal organic framework.

    PubMed

    Roy, Anuradha; Srivastava, Avanish K; Singh, Beer; Shah, Dilip; Mahato, Timir Haran; Srivastava, Anchal

    2012-10-28

    The applicability of HKUST-1 for the degradation of sulfur mustard and sarin simulants was studied with and without coadsorbed water. Degradation was found to be via hydrolysis and dependent on the nucleophilic substitution reaction, vapour pressure and molecular diameter of the toxicants.

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

    DTIC Science & Technology

    2009-07-01

    evaluations using cells harvested at lower degrees of confluence. REFERENCES Arroyo CM, Schafer RJ, Kurt EM, Broomfield CA, Carmichael AJ...Broomfield CA, Carmichael AJ. (1999) Response of normal human keratinocytes to sulfur mustard (HD): cytokine release using a non-enzymatic...Westchester Hall SUNY, NY 11794-8702 Voice: (n/a) Kertinocyte Spray, Jan30_2009Patient: USex: N/AAge: ?DOB: 30- Jan -09Biopsy Taken: 02-Feb-09Biopsy Received

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

    PubMed Central

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

    1999-01-01

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

  10. Efficacy of anti-inflammatory, antibiotic and pleiotropic agents in reversing nitrogen mustard-induced injury in ex vivo cultured rabbit cornea.

    PubMed

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

    2018-09-01

    Vesicating agent, Sulfur mustard (SM), causes devastating eye injury; however, there are no effective antidotes available. Using nitrogen mustard (NM), a bi-functional analog of SM, we have earlier reported that NM-induced corneal injury in ex vivo rabbit cornea organ culture model parallels corneal injury reported with SM. Using this model, we have demonstrated the therapeutic efficacy of dexamethasone (DEX), doxycycline (DOX) and silibinin (SB) in reversing NM (2h exposure)-induced corneal injuries when added immediately after washing NM. In the present study, we further examined the efficacy of similar/higher doses of these agents when added immediately, 2, or 4h after washing NM following its 2h exposure. All three treatment agents caused a reversal in established NM-induced injury biomarkers when added immediately or 2h after washing NM following its 2h exposure; however, when treatments were carried out 4h after washing NM, there was no significant effect. Together, our results further show the beneficial effect of these agents in reversing NM-induced corneal injury and indicate the time window for effective treatment. This could be useful towards future development of targeted therapeutics against vesicant-induced ocular injury. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2010-12-01

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

  12. Toxicokinetics of Sulfur Mustard and its DNA-Adducts in the Hairless Guinea Pig - DNA-Adducts as a Measure for Epithelial Damage.

    DTIC Science & Technology

    1996-03-01

    guinea pigs for the intravenous (i.v.), respiratory and percutaneous routes. A highly sensitive method for bioanalysis of the intact agent in blood and tissues was developed, involving gas chromatography with mass-spectrometric detection. Deuterated sulfur mustard (D8-SM) is used as the internal standard. 7-SM-guanine is measured with an immuno-slot-blot assay. In this midterm report the first results on the i.v. toxicokinetics of SM and 7-SM-guanine in hairless guinea pigs are presented. The 96-h i.v. LD50 appeared to be 8.2 mg/kg (95% confidence

  13. Reversed-phase high-performance liquid chromatography of sulfur mustard in water

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Raghuveeran, C.D.; Malhotra, R.C.; Dangi, R.S.

    1993-01-01

    A reversed-phase high-performance liquid chromatography method for the detection and quantitation of sulfur mustard (HD) in water is described with detection at 200 nm. The detection based on the solubility of HD in water revealed that extremely low quantities of HD (4 to 5 mg/L) only are soluble. Experience shows that water is still the medium of choice for the analysis of HD in water and aqueous effluents in spite of the minor handicap of its half-life of ca. 4 minutes, which only calls for speedy analysis.

  14. 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

    First World War. It was Sabourin et al., 2000). Skin injuries caused by called Hun Stoffe by the Allies and given the HD are complex and involve... Sabourin et al., 2000, Kan et al., 2003) sup- port the involvement of TNF-cx in animal models such as mouse skin and hairless guinea References pigs... Sabourin CLK. Petrali JP. Casillas RP. Alteration in inflamma- Pharmacol Toxicol. 2003:92:20 4 -13. tory cytokine gene expression in sulfur mustard exposed

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

    PubMed Central

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

    2014-01-01

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

  16. 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.

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

    DTIC Science & Technology

    2008-12-01

    phagocytotic function and on inflammatory cytokines/mediators production in vitro using SM-exposed monocyte THP - 1 cells. Using flow cytometry we found...in vitro using SM-exposed monocyte THP - 1 cells. 2. MATERIALS AND METHODS 2.1 Reagents Sulfur mustard (2,2’-dichlorodiethyl sulfide; 4 mM) was...monocyte THP - 1 cells were obtained from ATCC (Manassas, VA). Cells were grown as suspension in the optimized media as formulated by the manufacturer and

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

    PubMed

    Nokhodian, Zary; ZareFarashbandi, Firoozeh; Shoaei, Parisa

    2015-01-01

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

  19. 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

  20. 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

  1. Sulfur mustard-induced epigenetic modifications over time - a pilot study.

    PubMed

    Simons, Thilo; Steinritz, Dirk; Bölck, Birgit; Schmidt, Annette; Popp, Tanja; Thiermann, Horst; Gudermann, Thomas; Bloch, Wilhelm; Kehe, Kai

    2018-09-01

    The chemical warfare agent sulfur mustard (SM) can cause long-term health effects that may occur even years after a single exposure. The underlying pathophysiology is unknown, but epigenetic mechanisms are discussed as feasible explanation. "Epigenetics" depicts regulation of gene function without affecting the DNA sequence itself. DNA-methylation and covalent histone modifications (methylation or acetylation) are regarded as important processes. In the present in vitro study using early endothelial cells (EEC), we analyzed SM-induced DNA methylation over time and compared results to an in vivo skin sample that was obtained approx. one year after an accidental SM exposure. EEC were exposed to low SM concentrations (0.5 and 1.0μM). DNA methylation and histone acetylation (H3-K9, H3-K27, H4-K8) or histone di-methylation (H3-K9, H3-K27, H3-K36) were investigated 24h after exposure, and after 2 or 4 additional cell passages. The human skin sample was assessed in parallel. SM had only some minor effects on histone modifications. However, a significant and pronounced increase of DNA methylation was detected in the late cell passages as well as in the skin sample. Our results indicate that SM does indeed cause epigenetic modifications that appear to persist over time. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 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

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

    PubMed Central

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

    2014-01-01

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

  4. Catalytic antioxidant AEOL 10150 treatment ameliorates sulfur mustard analog 2-chloroethyl ethyl sulfide-associated cutaneous toxic effects.

    PubMed

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

    2014-07-01

    Our previous studies and other published reports on the chemical warfare agent sulfur mustard (SM) and its analog 2-chloroethyl ethyl sulfide (CEES) have indicated a role of oxidative stress in skin injuries caused by these vesicating agents. We examined the effects of the catalytic antioxidant AEOL 10150 in the attenuation of CEES-induced toxicity using our established skin injury models (skin epidermal cells and SKH-1 hairless mice) to validate the role of oxidative stress in the pathophysiology of mustard vesicating agents. Treatment of mouse epidermal JB6 and human HaCaT cells with AEOL 10150 (50μM) 1h post-CEES exposure resulted in significant (p < 0.05) reversal of CEES-induced decreases in both cell viability and DNA synthesis. Similarly, AEOL 10150 treatment 1h after CEES exposure attenuated CEES-induced DNA damage in these cells. Similar AEOL 10150 treatments also caused significant (p < 0.05) reversal of CEES-induced decreases in cell viability in normal human epidermal keratinocytes. Cytoplasmic and mitochondrial reactive oxygen species measurements showed that AEOL 10150 treatment drastically ameliorated the CEES-induced oxidative stress in both JB6 and HaCaT cells. Based on AEOL 10150 pharmacokinetic studies in SKH-1 mouse skin, mice were treated with a topical formulation plus subcutaneous injection (5mg/kg) of AEOL 10150 1h after CEES (4mg/mouse) exposure and every 4h thereafter for 12h. This AEOL 10150 treatment regimen resulted in over 50% (p < 0.05) reversal of CEES-induced skin bi-fold and epidermal thickness, myeloperoxidase activity, and DNA oxidation in mouse skin. Results from this study demonstrate the potential therapeutic efficacy of AEOL 10150 against CEES-mediated cutaneous lesions, supporting AEOL 10150 as a medical countermeasure against SM-induced skin injuries. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure: analysis of 197 cases.

    PubMed

    Emad, A; Rezaian, G R

    1997-09-01

    To find out the late pulmonary sequelae of sulfur mustard gas inhalation in 197 veterans, 10 years after their exposure. Cross-sectional clinical study. University hospital. One hundred ninety-seven veterans with a single, heavy exposure to sulfur mustard gas in 1986 and 86 nonexposed veterans as their control group. Pulmonary function tests, carbon monoxide diffusion capacity, bronchoscopy, and high-resolution CT of the chest were performed in all patients. Transbronchial lung biopsy was done in 24 suspected cases of pulmonary fibrosis. Asthma was diagnosed in 21 (10.65%), chronic bronchitis in 116 (58.88%), bronchiectasis in 17 (8.62%), airway narrowing due to searing or granulation tissue in 19 (9.64%), and pulmonary fibrosis in 24 (12.18%) cases. None of these were found among the control group except for a single case of chronic bronchitis. Although the respiratory symptoms of an acute sulfur mustard gas inhalation are usually transient and nonspecific, it can lead to the development of a series of chronic destructive pulmonary sequelae in such cases.

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

    PubMed

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

    2009-09-01

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

  7. 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

  8. Sulfur mustard and respiratory diseases.

    PubMed

    Tang, Feng Ru; Loke, Weng Keong

    2012-09-01

    Victims exposed to sulfur mustard (HD) in World War I and Iran-Iraq war, and those suffered occupational or accidental exposure have endured discomfort in the respiratory system at early stages after exposure, and marked general physical deterioration at late stages due to pulmonary fibrosis, bronchiolitis obliterans or lung cancer. At molecule levels, significant changes of cytokines and chemokines in bronchoalveolar lavage and serum, and of selectins (in particular sE-selectin) and soluble Fas ligand in the serum have been reported in recent studies of patients exposed to HD in Iran-Iraq war, suggesting that these molecules may be associated with the pathophysiological development of pulmonary diseases. Experimental studies in rodents have revealed that reactive oxygen and nitrogen species, their product peroxynitrite (ONOO(-)), nitric oxide synthase, glutathione, poly (adenosine diphosphate-ribose) polymerase, activating protein-1 signaling pathway are promising drug targets for preventing HD-induced toxicity, whereas N-acetyl cysteine, tocopherols, melatonin, aprotinin and many other molecules have been proved to be effective in prevention of HD-induced damage to the respiratory system in different animal models. In this paper, we will systemically review clinical and pathophysiological changes of respiratory system in victims exposed to HD in the last century, update clinicians and researchers on the mechanism of HD-induced acute and chronic lung damages, and on the relevant drug targets for future development of antidotes for HD. Further research directions will also be proposed.

  9. 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.

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

    PubMed

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

    2011-04-15

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

  11. [Long-term complications of sulfur mustard exposure: a therapeutic update].

    PubMed

    Shiyovich, Arthur; Rosman, Yossi; Krivoy, Amir; Statlender, Liran; Kassirer, Michael; Shrot, Shai

    2014-01-01

    Sulfur mustard (SM) is an alkylating chemical warfare agent with high military significance due to its high toxicity, resistance and availability. SM was widely used in military conflicts, the last being the Iran-Iraq war with more than 100,000 Iranians exposed, one-third of whom are still suffering from late effects. The intensity of the delayed complications correlates to the extent, the area and the route of exposure. The clinical manifestations most commonly involve respiratory, ocular and dermal effects. Respiratory complications include dyspnea, cough and expectorations and various obstructive and restrictive lung diseases. Dermal complications are itching, burning sensation, blisters, dry skin, dermatitis and pigmentary changes. Ocular complications include photophobia, red eye, tearing, corneal ulcers and blindness. Although the picture remains incomplete the major mechanisms responsible for the clinical and pathological effects of SM are: DNA alkylation and cross-linking, protein modification and membrane damage in addition to induction of inflammatory mediators in the target tissues causing extensive necrosis, apoptosis and loss of tissue structure. The current report reviews long-term complications of SM exposure, focusing on new treatments tested in clinical trials conducted on humans. Such treatments include: N-acetyl cysteine, bronchodilators, corticosteroids, Interferon-gamma, furosemide and morphine for the respiratory complications. Ocular complications may entail: Invasive procedures treating corneal complication, limbal ischemia and stem cell deficiency. Treatment for dermatological complications include: anti-depressants, pimercrolimus, Unna's boot, capsaicin, phenol and menthol, Aloe vera and olive oil, curcumin and Interferon-gamma.

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

    PubMed Central

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

    2014-01-01

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

  13. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Mustard vesicating agents–induced toxicity in the skin tissue and silibinin as a potential countermeasure

    PubMed Central

    Tewari-Singh, Neera; Agarwal, Rajesh

    2016-01-01

    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, 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. PMID:27326543

  15. Mechanisms of sulfur mustard analog 2-chloroethyl ethyl sulfide-induced DNA damage in skin epidermal cells and fibroblasts.

    PubMed

    Inturi, Swetha; Tewari-Singh, Neera; Gu, Mallikarjuna; Shrotriya, Sangeeta; Gomez, Joe; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2011-12-15

    Employing mouse skin epidermal JB6 cells and dermal fibroblasts, here we examined the mechanisms of DNA damage by 2-chloroethyl ethyl sulfide (CEES), a monofunctional analog of sulfur mustard (SM). CEES exposure caused H2A.X and p53 phosphorylation as well as p53 accumulation in both cell types, starting at 1h, that was sustained for 24h, indicating a DNA-damaging effect of CEES, which was also confirmed and quantified by alkaline comet assay. CEES exposure also induced oxidative stress and oxidative DNA damage in both cell types, measured by an increase in mitochondrial and cellular reactive oxygen species and 8-hydroxydeoxyguanosine levels, respectively. In the studies distinguishing between oxidative and direct DNA damage, 1h pretreatment with glutathione (GSH) or the antioxidant Trolox showed a decrease in CEES-induced oxidative stress and oxidative DNA damage. However, only GSH pretreatment decreased CEES-induced total DNA damage measured by comet assay, H2A.X and p53 phosphorylation, and total p53 levels. This was possibly due to the formation of GSH-CEES conjugates detected by LC-MS analysis. Together, our results show that CEES causes both direct and oxidative DNA damage, suggesting that to rescue SM-caused skin injuries, pleiotropic agents (or cocktails) are needed that could target multiple pathways of mustard skin toxicities. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    Garrett, Benjamin

    1999-10-01

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

  17. Surface-enhanced Raman spectroscopy of half-mustard agent.

    PubMed

    Stuart, Douglas A; Biggs, Kevin B; Van Duyne, Richard P

    2006-04-01

    The detection and identification of chemical warfare agents is an important analytical goal. Herein, it is demonstrated that 2-chloroethyl ethyl sulfide (half-mustard, CEES) can be successfully analysed using surface-enhanced Raman spectroscopy (SERS). A critical component in this detection system is the fabrication of a robust, yet highly enhancing, sensor surface. Recent advances in substrate fabrication and in the fundamental understanding of the SERS phenomenon enable the development of improved substrates for practical SERS applications.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 methylenemore » 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.« less

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

    PubMed Central

    Watson, A P; Griffin, G D

    1992-01-01

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

  20. 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

    activity ca. 40 units/mg protein) from Boehringer (Mannheim, Germany); RNase A, and Tween 20 from Sigma Chemical Co. (St. Louis, MO, USA); and skimmed milk ...al. 1997). This hypothesis is still awaiting falsification . Measurement of the concentration-time course of the adduct of sulfur mustard to hemoglobin

  1. EPA Science Matters Newsletter: Chemical Warfare Agent Analytical Standards Facilitate Lab Testing (Published November 2013)

    EPA Pesticide Factsheets

    Learn about the EPA chemists' efforts to develop methods for detecting extremely low concentrations of nerve agents, such as sarin, VX, soman and cyclohexyl sarin, and the blister agent sulfur mustard.

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

    PubMed

    Zubel, Tabea; Bürkle, Alexander; Mangerich, Aswin

    2018-09-01

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

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

    PubMed

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

    2016-01-01

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

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

    DTIC Science & Technology

    2015-06-01

    J (2008) Health effects of exposure to vesicant agents. In: Chemical Warfare Agents – Chemistry , Pharmacology, Toxicology, and Therapeutics. Eds...sulfphide and the protective effect of flavonoids . Toxicology 69: 35-42. Wada S, Nishimoto Y, Miyanishi M, Kambe S, Miller R W(1968) Mustard gas as

  5. Mustard vesicants alter expression of the endocannabinoid system in mouse skin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wohlman, Irene M.; Composto, Gabriella M.

    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 andmore » dermal appendages. Topical administration of NM or SM, at concentrations that induce tissue injury, resulted in upregulation of FAAH, CB1, CB2 and PPARα, a response that persisted throughout the wound healing process. Inhibitors of FAAH including a novel class of vanillyl alcohol carbamates were found to be highly effective in suppressing vesicant-induced inflammation in mouse skin. Taken together, these data indicate that the endocannabinoid system is important in regulating skin homeostasis and that inhibitors of FAAH may be useful as medical countermeasures against vesicants. - Highlights: • Sulfur mustard and nitrogen mustard are potent skin vesicants. • The endocannabinoid system regulates keratinocyte growth and differentiation. • Vesicants are potent inducers of the endocannabinoid system in mouse skin. • Endocannabinoid proteins upregulated are FAAH, CB1, CB2 and PPARα. • FAAH inhibitors suppress vesicant-induced inflammation in mouse skin.« less

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

    PubMed

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

    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 6h 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. © 2013.

  7. 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

  8. Chemical warfare agents: their past and continuing threat and evolving therapies. Part I of II.

    PubMed

    Smith, Kathleen J; Skelton, Henry

    2003-01-01

    Chemical warfare agents are potentially accessible to even underdeveloped nations because they are easily and inexpensively produced. This means that they are ideal for use by terrorists and in military operations against civilian populations and troops. In terms of cutaneous injury, vesicants-mainly sulfur mustard-are the most significant chemical warfare agents. Advances in understanding the pathophysiology of the lesions produced by sulfur mustard have led to the research and development of barrier creams as well as pre- and post-exposure therapies to moderate the damage and accelerate healing. Part I of this paper will discuss the history and classification of chemical agents; Part II, which will appear in the September/October 2003 issue of SKINmed, will discuss characteristic manifestations of exposure to chemical agents, as well as prevention and therapy.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rancourt, Raymond C., E-mail: raymond.rancourt@ucdenver.edu; Veress, Livia A., E-mail: livia.veress@ucdenver.edu; Ahmad, Aftab, E-mail: aftab.ahmad@ucdenver.edu

    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 activatormore » 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

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

    DTIC Science & Technology

    1988-12-01

    Page No. 1. Light Microscopy of Human Skin Grafted onto Congenitally Athymic Nude Mice .................. 4 2. Ultrastructural Changes Produced by HD...laboratory published a report on the ultrastructure of the pathogenesis of blister formation following exposure to sulfur mustard of human- skin grafted to...candidate prophylactic compounds such as niacirnamide. By way of review, hD-induced pathology of human skin grafted onto congenitally athymic nude mice was

  11. 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

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

  12. 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

  13. Key Facts about Tularemia

    MedlinePlus

    ... Methyl isocyanate Case Definition: Methyl Isocyanate Poisoning Mustard gas (H) (sulfur mustard) Facts About Sulfur Mustard Case ... choking/lung agents Ricin Riot control agents/tear gas Facts About Riot Control Agents Case Definition: Riot ...

  14. 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

    crucial signals in the development of appropriate defenses. However, exaggerated or prolonged release can lead to pathological conditions ( Sabourin ...gene expression of the inflammatory cytokines ( Sabourin et al., 2000). In this study we examined the expression of four major inflammatory...Med., 117, 2S-4S. Sabourin C. L., Petrali, J. P., and Casillas, R. P., 2000: Alterations in inflammatory cytokine gene expression in sulfur mustard

  15. Chemical Agents

    MedlinePlus

    ... E Ethylene glycol F Fentanyls and other opioids H Hydrazine Hydrofluoric acid (hydrogen fluoride) Hydrogen chloride Hydrogen ... M Mercury Methyl bromide Methyl isocyanate Mustard gas (H) (sulfur mustard) N Nicotine Nitrogen mustard (HN-1, ...

  16. Evaluation of plasma, erythrocytes, and bronchoalveolar lavage fluid antioxidant defense system in sulfur mustard-injured patients.

    PubMed

    Jafari, Mahvash; Ghanei, Mostafa

    2010-03-01

    Sulfur mustard (SM) is a strong alkylating agent that causes acute and chronic effects on different organs following exposure. Main late respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, asthma, and bronchiolitis obliterans. It seems that oxidative stress plays a major role in pathogenesis of diseases. This study was undertaken to evaluate the long-term effect of SM on plasma, erythrocytes, and brochoalveolar lavage fluid antioxidant defense system in SM-injured patients. Brochoalveolar lavage fluid, plasma, and erythrocyte samples were taken from 54 patients in the case group exposed to SM and 25 controls with chronic respiratory disease without a history of exposure to SM. Superoxide dismutase, catalase, and glutathione peroxidase activities in lavage fluid, plasma, and erythrocytes were significantly higher in case group. The increased glutathione S-transferase activity in lavage fluid was associated with a depletion of glutathione and an increase of malondialdehyde levels. There was no significant change observed in glutathione reductase activity. The data suggest that oxidative damage might have an important role for patients exposed to SM. SM may induce an oxidative stress response by depleting the antioxidant defense systems and increasing lipid peroxidation in lung cells.

  17. 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

    Received 21 May 2009; revised 6 July 2009; accepted 12 July 2009 ABSTRACT: Cutaneous and ocular injuries caused by sulfur mustard (SM; bis-( 2 ...nal transduction events in lung injury induced by 2 - chloroethyl ethyl sulfide, a mustard analog. J Biochem Mol Toxicol 2003;17( 2 ):114–121. 13. Das SK...Mukherjee S, Smith MG, Chatterjee D. Pro- phylactic protection by N-acetylcysteine against the pul- monary injury induced by 2 -chloroethyl ethyl

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

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Weinberger, Barry, E-mail: bweinberger@northwell.e

    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,more » 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.« less

  1. 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.

  2. H5PV2Mo10O40 encapsulated in MIL-101(Cr): facile synthesis and characterization of rationally designed composite materials for efficient decontamination of sulfur mustard.

    PubMed

    Li, Yanqin; Gao, Qi; Zhang, Lijuan; Zhou, Yunshan; Zhong, Yuxu; Ying, Ying; Zhang, Mingcai; Huang, Chunqian; Wang, Yong'an

    2018-05-08

    Currently extensive effort is compulsively expended to decontaminate efficiently banned chemical war agents. In this work, H5PV2Mo10O40 molecules have been encapsulated in mesoporous MIL-101(Cr), which features two types of mesoporous cages (internal diameters of 29 Å and 34 Å) and microporous windows (diameters of 12 Å and 16 Å), leading to the formation of a new composite H5PV2Mo10O40@MIL-101(Cr) through a simple impregnation method. The composite was characterized thoroughly by elemental analysis, FT-IR spectroscopy, powder X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, TG/DTA, and textural analysis thereby confirming the encapsulation of the H5PV2Mo10O40 into MIL-101(Cr). The decontamination efficiency of sulfur mustard (4 μL HD in 40 μL of petroleum ether) by 20 mg of the composite is found to be 97.39% in 120 min under ambient conditions. GC-MS analysis on the decontaminated products using 2-chloroethyl ethyl sulfide (CEES), which has been widely used as a simulant of sulfur mustard, showed that MIL-101(Cr) just decontaminates CEES by adsorption, while CEES can be decontaminated under ambient conditions by a synergetic combination of adsorption of MIL-101(Cr) and subsequent chemical oxidation degradation to nontoxic 2-chloroethyl ethyl sulfoxide (CEESO) due to the presence of highly dispersed H5PV2Mo10O40 within the composites.

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

    PubMed

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

    2015-03-01

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

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

    PubMed

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

    2017-06-01

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

  5. 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.

  6. History and perspectives of bioanalytical methods for chemical warfare agent detection.

    PubMed

    Black, Robin M

    2010-05-15

    This paper provides a short historical overview of the development of bioanalytical methods for chemical warfare (CW) agents and their biological markers of exposure, with a more detailed overview of methods for organophosphorus nerve agents. Bioanalytical methods for unchanged CW agents are used primarily for toxicokinetic/toxicodynamic studies. An important aspect of nerve agent toxicokinetics is the different biological activity and detoxification pathways for enantiomers. CW agents have a relatively short lifetime in the human body, and are hydrolysed, metabolised, or adducted to nucleophilic sites on macromolecules such as proteins and DNA. These provide biological markers of exposure. In the past two decades, metabolites, protein adducts of nerve agents, vesicants and phosgene, and DNA adducts of sulfur and nitrogen mustards, have been identified and characterized. Sensitive analytical methods have been developed for their detection, based mainly on mass spectrometry combined with gas or liquid chromatography. Biological markers for sarin, VX and sulfur mustard have been validated in cases of accidental and deliberate human exposures. The concern for terrorist use of CW agents has stimulated the development of higher throughput analytical methods in support of homeland security. Copyright (c) 2010. Published by Elsevier B.V.

  7. μ-PADs for detection of chemical warfare agents.

    PubMed

    Pardasani, Deepak; Tak, Vijay; Purohit, Ajay K; Dubey, D K

    2012-12-07

    Conventional methods of detection of chemical warfare agents (CWAs) based on chromogenic reactions are time and solvent intensive. The development of cost, time and solvent effective microfluidic paper based analytical devices (μ-PADs) for the detection of nerve and vesicant agents is described. The detection of analytes was based upon their reactions with rhodamine hydroxamate and para-nitrobenzyl pyridine, producing red and blue colours respectively. Reactions were optimized on the μ-PADs to produce the limits of detection (LODs) as low as 100 μM for sulfur mustard in aqueous samples. Results were quantified with the help of a simple desktop scanner and Photoshop software. Sarin achieved a linear response in the two concentration ranges of 20-100 mM and 100-500 mM, whereas the response of sulfur mustard was found to be linear in the concentration range of 10-75 mM. Results were precise enough to establish the μ-PADs as a valuable tool for security personnel fighting against chemical terrorism.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.

    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 themore » 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

  9. 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

  10. Sulfur mustard-induced apoptosis in hairless guinea pig skin.

    PubMed

    Kan, Robert K; Pleva, Christina M; Hamilton, Tracey A; Anderson, Dana R; Petrali, John P

    2003-01-01

    The present study was aimed to examine whether apoptosis is involved in the pathogenesis of sulfur mustard (SM)-induced basal cell death. Skin sites of the hairless guinea pig exposed to SM vapor for 8 minutes were harvested at 3, 6, 12, 24, and 48 hours postexposure. Immunohistochemical detection of basal cell apoptosis was performed using the ApopTag in situ apoptosis labeling kit. Only occasional apoptotic basal cells (BC)were observed in nonexposed and perilesional control sites. At lesional sites, apoptosis of BC was not detected at 3 hours postexposure. However, at 6 hours and 12 hours postexposure, 18% and 59% of BC were apoptotic, respectively. At 24 and 48 hours postexposure, individual apoptotic basal cells were not clearly recognizable due to necrosis. At the ultrastructural level, degenerating BC exhibited typical apoptotic morphology including nuclear condensation and chromatin margination. The results suggest that apoptotic cell death is a cytotoxic mechanism with the number of BC undergoing apoptosis significantly increasing from 6 to 12 hours postexposure. In addition, because necrosis is preferential at 24 hours postexposure, we believe that SM-induced cell death involves early apoptosis and late necrosis, which temporally overlap to produce a single cell death pathway along an apoptotic-necrotic continuum.

  11. Comparison of topical capsaicin and betamethasone in the treatment of chronic skin lesions due to sulfur mustard exposure.

    PubMed

    Panahi, Yunes; Davoudi, Seyyed Masoud; Moharamzad, Yashar; Beiraghdar, Fatemeh; Naghizadeh, Mohammad Mehdi

    2008-01-01

    Chronic pruritic skin lesions are considered to be one of the late complications of sulfur mustard exposure. The purpose of this study was to compare the efficacy of topical capsaicin with that of betamethasone in the treatment of these lesions. In this investigator-blinded, randomized clinical trial, patients applied capsaicin cream 0.025% (n=32) or betamethasone cream 0.1% (n=32) 2 times a day for 6 weeks. Efficacy was based on a dermatologist assessment. The severity of the pruritus was assessed by pruritic score questionnaire and a visual analog scale before and after treatment. All patients complained of pruritus. Both groups showed a significant decrease in pruritus, scaling, and skin dryness (p<0.05), but burning sensation was not improved significantly in the capsaicin group. The mean (+/- standard deviation [SD]) baseline pruritic scores in the capsaicin and betamethasone groups were 29.4 (13.1) and 33.6 (7.2), respectively (p=0.1). The mean (SD) pruritus score change from baseline to after the treatment was significantly higher (p<0.001) in the betamethasone group than in the capsaicin group, 12.7 (6.4) vs. 6.9 (5.6). Fourteen (35%) patients in the capsaicin group reported a burning sensation and intolerable odor, but these effects were not serious enough to necessitate discontinuing the treatment. Topical capsaicin cream 0.025% was much less well tolerated than betamethasone and inferior to betamethasone in reducing chronic skin lesions and symptoms from sulfur mustard exposure.

  12. 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.

  13. 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.

  14. Glucocorticoids inhibit sulfur mustard-induced airway muscle hyperresponsiveness to substance P.

    PubMed

    Calvet, J H; D'Ortho, M P; Jarreau, P H; Levame, M; Harf, A; Macquin-Mavier, I

    1994-11-01

    To explore the mechanisms of airway hyperreactivity to aerosolized substance P observed in guinea pigs 14 days after intratracheal injection of sulfur mustard (SM), we studied the effects of epithelium removal and inhibition of neutral endopeptidase (NEP) activity on airway muscle responsiveness. Tracheal rings from SM-intoxicated guinea pigs expressed a greater contractile response to substance P than rings from nonintoxicated guinea pigs. After epithelium removal or incubation with the NEP inhibitor phosphoramidon, the contractile responses of tracheal rings to substance P did not differ in guinea pigs injected with SM or ethanol (SM solvent). Treatment of the guinea pigs with betamethasone for 7 days before measurement abolished the airway muscle hyperresponsiveness observed in untreated SM-intoxicated guinea pigs and partially restored tracheal epithelium NEP activity. In addition, the tracheal epithelium height and cell density of SM-intoxicated guinea pigs treated with betamethasone were significantly greater than in those without betamethasone. These results demonstrate that SM intoxication induces airway muscle hyperresponsiveness to substance P by reducing tracheal epithelial NEP activity and that glucocorticoids might inhibit this hyperresponsiveness by increasing this activity.

  15. Pro-inflammatory cytokines among individuals with skin findings long-term after sulfur mustard exposure: Sardasht-Iran Cohort Study.

    PubMed

    Moin, Athar; Khamesipour, Ali; Hassan, Zuhair Mohammad; Ebtekar, Massoumeh; Davoudi, Seyyed-Masoud; Vaez-Mahdavi, Mohammad-Reza; Soroush, Mohammad-Reza; Faghihzadeh, Soghrat; Naghizadeh, Mohammad-Mehdi; Ghazanfari, Tooba

    2013-11-01

    Sulfur mustard (SM) is a potent alkylating vesicant warfare chemical agent which causes severe damages to the interface organs, skin, lungs and eyes. The most common chronic skin lesions are mustard scars, xerosis, eczema, seborrheic dermatitis, cherry angioma and hyperpigmentation. This study is part of Sardasht-Iran Cohort Study (SICS) which was performed to compare the serum levels of inflammatory cytokines in SM-exposed individuals (n=372) with long-term relevant skin findings versus unexposed controls (n=128). Serum levels of pro-inflammatory cytokines including IL-1α, IL-1β, IL-1Ra, IL-6, and TNF (tumor necrosis factor) were titrated using ELISA method, 79.9% (n=290) of the exposed group and 60.5% (n=98) of the control group showed skin findings. In the exposed group, 52.1% (n=189) had only skin findings (OSFE) and in the control group, 32% (n=41) had no problem (NC, normal). Median serum levels of cytokines IL-1α, IL-1β, IL-1Ra, IL-6 and TNF-α in the OSFE group were: 1.077, 1.745, 25.640, 0.602 and 12.768 pg/ml, respectively. These values in normal controls were 1.889, 1.896, 32.190, 1.022 and 23.786 pg/ml, respectively which are higher than the corresponding values in the OSFE group, the differences were statistically significant only for IL-1α and TNF-α. This may be due to a damage incurred upon precursors of cytokine producing cells or failure of their functions, increase in suppressive mediators or other mechanisms which are not well known. More studies are needed in molecular dimensions of the immune and cytokine responses in the SM-exposed patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Veterans at Risk: The Health Effects of Mustard Gas and Lewisite

    DTIC Science & Technology

    1993-01-01

    to Mustard Gas During WWII Testing Programs 370 F. Summary of the Department of the Army Report: Use of Volunteers in Chemical Agent Research 378 Key...concentrations of mustard agents or Lewisite in gas chambers or in field exercises over contaminated ground areas. The human subjects had experienced a...wide range of exposures to mustard agents or Lewisite, from mild (a drop of agent on the arm in "patch" tests) to quite severe (repeated gas chamber

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

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

    2010-01-01

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

  18. Determination of mustard and lewisite related compounds in abandoned chemical weapons (Yellow shells) from sources in China and Japan.

    PubMed

    Hanaoka, Shigeyuki; Nomura, Koji; Wada, Takeharu

    2006-01-06

    Knowledge of the states of the contents in chemical munitions that Japanese Imperial Forces abandoned at the end of World War II in Japan and China is gravely lacking. To unearth and recover these chemical weapons and detoxify the contents safely, it is essential to establish analytical procedures to definitely determine the CWA contents. We established such a procedure and applied it to the analysis of chemicals in the abandoned shells. Yellow shells are known to contain sulfur mustard, lewisite, or a mixture of both. Lewisite was analyzed without thiol derivatization, because it and its decomposition products yield the same substances in the derivatization. Analysis using our new procedure showed that both mustard and lewisite remained as the major components after the long abandonment of nearly 60 years. The content of mustard was 43% and that of lewisite 55%. The viscous material found was suggested to be mostly oligomers of mustard. Comparison of the components in the Yellow agents with mustard recovered in both Japan and China showed a difference in the impurities between the CWAs produced by the former Imperial navy and those by the former Imperial army.

  19. Long-term neurological and neuropsychological complications of sulfur mustard and Lewisite mixture poisoning in Chinese victims exposed to chemical warfare agents abandoned at the end of WWII.

    PubMed

    Isono, O; Kituda, A; Fujii, M; Yoshinaka, T; Nakagawa, G; Suzuki, Y

    2018-09-01

    In August 2003, 44 victims were poisoned by chemical warfare agents (CWAs) leaked from five drums that were excavated at a construction site in Qiqihar, Northeast China. The drums were abandoned by the former Japanese imperial army during World War II and contained a mixture of Sulfur mustard (SM) and Lewisite. We carried out a total of six regular check-ups between 2006 and 2014, and from 2008 we added neurological evaluations including neuropsychological test and autonomic nervous function test in parallel with medical follow-up as much as was possible. Severe autonomic failure, such as hyperhidrosis, pollakiuria, diarrhoea, diminished libido, and asthenia appeared in almost all victims. Polyneuropathy occurred in 35% of the victims and constricted vision occurred in 20% of them. The rates of abnormal response on cold pressor test (CPT), active standing test (AST), Heart rate variability (CV R-R ), performed in 2014, were 63.1%, 31.6%, and 15.9%, respectively. On neuropsychological testing evaluated in 2010, a generalized cognitive decline was observed in 42% of the victims. Memories and visuospatial abilities were affected in the remaining victims. Finally, a 17-item PTSD questionnaire and the Beck Depression Inventory evaluated in 2014 revealed long-lasting severe PTSD symptoms and depression of the victims. Our findings suggest that an SM/Lewisite compound have significant adverse consequences directly in cognitive and emotional network and autonomic nervous systems in the brain. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2016-01-01

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

  1. 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.

  2. Delayed Complications and Long-term Management of Sulfur Mustard Poisoning: Recent Advances by Iranian Researchers (Part I of II)

    PubMed Central

    Darchini-Maragheh, Emadodin; Balali-Mood, Mahdi

    2018-01-01

    Chemical warfare agents are the most brutal weapons among the weapons of mass destruction. Sulfur mustard (SM) is a potent toxic alkylating agent known as “the King of the Battle Gases”. SM has been the most widely used chemical weapon during the wars. It was widely used in World War I. Thereafter, it was extensively employed by the Iraqi troops against the Iranian military personnel and even civilians in the border cities of Iran and Iraq in the period between 1983 and 1988. Long-term incapacitating properties, significant environmental persistence, lack of an effective antidote, and relative ease of manufacturing have kept SM a potential agent for both terrorist and military uses. Even 3 decades after SM exposure, numerous delayed complications among Iranian victims are still being reported by researchers. The most common delayed complications have been observed in the respiratory tracts of chemically injured Iranian war veterans. Also, skin lesions and eye disorders have been observed in most Iranian SM-exposed war veterans in the delayed phase of SM intoxication. Thus, extensive research has been conducted on Iranian war veterans during the past decades. Nevertheless, major gaps still continue to exist in the SM literature. Part I of this paper will discuss the delayed complications and manifestations of exposure to SM among Iranian victims of the Iran–Iraq conflict. Part II, which will appear in the next issue of Iran J Med Sci, will discuss the long-term management and therapy of SM-exposed patients. PMID:29749980

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

    PubMed

    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. Rats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5mg/kg) in vehicle, or vehicle alone, was 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 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. 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. Intratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Epigenetic modulations in early endothelial cells and DNA hypermethylation in human skin after sulfur mustard exposure.

    PubMed

    Steinritz, Dirk; Schmidt, Annette; Balszuweit, Frank; Thiermann, Horst; Simons, Thilo; Striepling, Enno; Bölck, Birgit; Bloch, Wilhelm

    2016-02-26

    Victims that were exposed to the chemical warfare agent sulfur mustard (SM) suffer from chronic dermal and ocular lesions, severe pulmonary problems and cancer development. It has been proposed that epigenetic perturbations might be involved in that process but this has not been investigated so far. In this study, we investigated epigenetic modulations in vitro using early endothelial cells (EEC) that were exposed to different SM concentrations (0.5, 1.0, 23.5 and 50μM). A comprehensive analysis of 78 genes related to epigenetic pathways (i.e., DNA-methylation and post-translational histone modifications) was performed. Moreover, we analyzed global DNA methylation in vitro in EEC after SM exposure as a maker for epigenetic modulations and in vivo using human skin samples that were obtained from a patient 1 year after an accidently exposure to pure SM. SM exposure resulted in a complex regulation pattern of epigenetic modulators which was accompanied by a global increase of DNA methylation in vitro. Examination of the SM exposed human skin samples also revealed a significant increase of global DNA methylation in vivo, underlining the biological relevance of our findings. Thus, we demonstrated for the first time that SM affects epigenetic pathways and causes epigenetic modulations both in vivo and in vitro. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Highly Efficient and Selective Photooxidation of Sulfur Mustard Simulant by a Triazolobenzothiadiazole-Moiety-Functionalized Metal-Organic Framework in Air.

    PubMed

    Zhang, Wen-Qiang; Cheng, Ke; Zhang, He; Li, Qiu-Yan; Ma, Zheng; Wang, Zixuan; Sheng, Jialing; Li, Yinwei; Zhao, Xinsheng; Wang, Xiao-Jun

    2018-04-16

    A photoactive triazolobenzothiadiazole (TBTD)-conjugated terphenyldicarboxylate (TPDC) linker was introduced into a porous and robust UiO-68 isoreticular zirconium metal-organic framework (denoted as UiO-68-TBTD) by the de novo synthetic approach of mixed TPDC struts. Under blue-light-emitting-diode irradiation, UiO-68-TBTD can serve as a heterogeneous photocatalyst for the highly efficient and selective oxidation of a sulfur mustard simulant (2-chloroethyl ethyl sulfide) to the corresponding much less toxic sulfoxide product, with a half-life of only 3 min in the open air atmosphere.

  6. 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

  7. Transcriptional responses associated with sulfur mustard and thermal burns in porcine skin.

    PubMed

    Rogers, James V; McDougal, James N; Price, Jennifer A; Reid, Frances M; Graham, John S

    2008-01-01

    In military and civilian environments, serious cutaneous damage can result from thermal burns or exposure to the blistering agent sulfur mustard [bis (2-chloroethyl) sulfide; HD]. Similar therapies have historically been used to treat cutaneous thermal and HD injuries; however, the underlying molecular mechanisms of tissue damage and wound healing may differ between the types of burns. Using microarray analysis, this study assessed the transcriptional responses to cutaneous HD and thermal injury at 48 hours post-exposure to identify molecular networks and genes associated with each type of skin injury. Ventral abdominal sites on each of 4 weanling swine were exposed to 400 mul of undiluted HD or a heated brass rod (70 degrees C) for 8 minutes and 45-60 seconds, respectively. At 48 hours post-exposure, total RNA was isolated from excised skin samples and hybridized to Affymetrix GeneChip Porcine Genome Arrays (containing 20,201 genes). Both HD and thermal exposure promoted significant transcriptional changes where 290 and 267 transcripts were increased and 197 and 707 transcripts were decreased with HD and thermal exposure, respectively. HD- and thermal-injured skin expressed 149 increased and 148 decreased common transcripts. Comparison of the 10 most significantly changed biological functions for HD and thermal exposures identified 7 overlapping functional groups. Canonical pathways analysis revealed 15 separate signaling pathways containing transcripts associated with both HD and thermal exposure. Within these pathways, 5 transcripts (CXCR4, FGFR2, HMOX1, IL1R1, and TLR4) were identified as known targets for existing phase II/III clinical trial or Food and Drug Administration (FDA)-approved drugs. This study is the first to directly assess transcriptional changes in porcine skin subjected to HD or thermal injury over the same time period.

  8. Postexposure Application of Fas Receptor Small-Interfering RNA to Suppress Sulfur Mustard-Induced Apoptosis in Human Airway Epithelial Cells: Implication for a Therapeutic Approach

    DTIC Science & Technology

    2013-01-01

    bronchiolitis, bronchopneumo- nia, chronic obstructive pulmonary disease, bronchiectasis, asthma, large airway narrowing, and pulmonary fibrosis ... pulmonary fibrosis , acute lung injury [ALI], acute respiratory distress syndrome, etc.) (Beheshti et al., 2006; Emmler et al., 2007; Kuwano, 2008...cytokine in bronchoalveolar lavage (BAL) fluid in patients with pulmonary fibrosis due to sulfur mustard gas inhalation. J In- terferon Cytokine Res 27:38

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

    PubMed

    Thiermann, Horst; Worek, Franz; Kehe, Kai

    2013-12-05

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

  10. Rapid simultaneous determination of apoptosis, necrosis, and viability in sulfur mustard exposed HaCaT cell cultures.

    PubMed

    Heinrich, A; Balszuweit, F; Thiermann, H; Kehe, K

    2009-12-15

    Sulfur mustard (SM; bis(2-chloroethyl)sulphide; HD) is a blister inducing agent causing DNA damage and subsequently, cell death, mostly by apoptosis in basal keratinocytes. Despite intensive investigations on the cellular mechanism, there are, as of now, no causal therapeutics to prevent or antagonize SM-related damage to cells and tissues. In order to develop treatment strategies against vesication, it is important to distinguish apoptosis from necrosis in SM treated human keratinocytes. DNA fragmentation is a hallmark of apoptosis and regulated by a cascade of enzymes (endonucleases, DNase I, NUC 18), which finally cut the chromatin into specific formations of 180-200 base pairs, the nucleosomes. A feasible way to monitor apoptosis is the detection of nucleosomes by means of the Cell Death Detection ELISA(plus) (CDDE). In contrast, during necrosis DNA fragmentation is at random and delivers larger fragments, which therefore are significantly less in number and predominantly occur in cell culture supernatant. To monitor necrosis, we measured the release of intracellular adenylate kinase (AK) into cell culture supernatant by means of the ToxiLight Bioluminescence Assay (TL). With combination of the Cell Death Detection ELISA(plus) and the ToxiLight Bioluminescence Assay, we acquired more comprehensive information on cell survival and mechanisms of cell death, following an SM exposure. To validate the assay we tested common apoptosis- and necrosis-inducing agents like SM 300 microM for 30 min, Lewisite (L) 60 microM for 5 min and Triton X-100 0.1%. The results show that it is possible to differentiate between the two modes of cell death and to quantify their extent. This assay is highly effective in quantifying apoptosis and necrosis caused by cytotoxic agents and in estimating protective effects of potential active pharmaceutical ingredients.

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

    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

  12. 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

    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™, 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. Copyright © 2010 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2016-01-01

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

  14. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Medical management of cutaneous sulfur mustard injuries.

    PubMed

    Graham, John S; Stevenson, Robert S; Mitcheltree, Larry W; Hamilton, Tracey A; Deckert, Robin R; Lee, Robyn B; Schiavetta, Ann M

    2009-09-01

    Sulfur mustard (2,2'-dichlorodiethyl sulfide; HD) is a potent vesicating chemical warfare agent that poses a continuing threat to both military and civilian populations. Significant cutaneous HD injuries can take several months to heal, necessitate lengthy hospitalizations, and result in long-term complications. There are currently no standardized or optimized methods of casualty management. New strategies are needed to provide for optimal and rapid wound healing. The primary aim of this research was to develop improved clinical strategies (treatment guidelines) for optimal treatment of superficial dermal (second degree) cutaneous HD injuries, with the goal of returning damaged skin to optimal appearance and normal function in the shortest period of time. Superficial dermal HD injuries were created on the ventral abdominal surface of weanling pigs. At 48h post-exposure, lesions were laser debrided and a treatment adjunct applied. Cultured epithelial allografts and 11 commercial off-the-shelf (COTS) products were examined for their efficacy in improving wound healing of these injuries. Clinical evaluations and a variety of non-invasive bioengineering methods were used at 7 and 14 days post-surgery to follow the progress of wound healing and evaluate various cosmetic and functional properties of the wounds. Measurements included reflectance colorimetry to measure erythema; evaporimetry to examine transepidermal water loss as a method of evaluating barrier function; torsional ballistometry to evaluate the mechanical properties of skin firmness and elasticity; and two-dimensional high frequency ultrasonography (HFU) to monitor skin thickness (e.g., edema, scar tissue). Histopathology and immunohistochemistry were performed 14 days following surgery to examine structural integrity and quality of healing. Logical Decisions((R)) for Windows was used to rank the 12 treatment adjuncts that were studied. The most efficacious treatment adjuncts included (1) Vacuum Assisted

  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 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

  17. Sulfur mustard skin lesions: A systematic review on pathomechanisms, treatment options and future research directions.

    PubMed

    Rose, Dorothee; Schmidt, Annette; Brandenburger, Matthias; Sturmheit, Tabea; Zille, Marietta; Boltze, Johannes

    2018-09-01

    Sulfur mustard (SM) is a chemical warfare, which has been used for one hundred years. However, its exact pathomechanisms are still incompletely understood and there is no specific therapy available so far. In this systematic review, studies published between January 2000 and July 2017 involving pathomechanisms and experimental treatments of SM-induced skin lesions were analyzed to summarize current knowledge on SM pathology, to provide an overview on novel treatment options, and to identify promising targets for future research to more effectively counter SM effects. We suggest that future studies should focus on (I) systemic effects of SM intoxication due to its distribution throughout the body, (II) removal of SM depots that continuously release active compound contributing to chronic skin damage, and (III) therapeutic options that counteract the pleiotropic effects of SM. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.

    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 revealedmore » 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.« less

  19. 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. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Exposure to a First World War blistering agent.

    PubMed

    Le, H Q; Knudsen, S J

    2006-04-01

    Sulfur mustards act as vesicants and alkylating agents. They have been used as chemical warfare since 1917 during the first world war. This brief report illustrates the progression of injury on a primary exposed patient to a first world war blistering agent. This case documents the rapid timeline and progression of symptoms. It emphasises the importance of appropriate personal protective equipment and immediate medical response plan with rapid decontamination and proper action from military and civilian medical treatment facilities. This case reports the first US active duty military exposure to a blistering agent in the age of global terrorism.

  1. Prediction of acute mammalian toxicity using QSAR methods: a case study of sulfur mustard and its breakdown products.

    PubMed

    Ruiz, Patricia; Begluitti, Gino; Tincher, Terry; Wheeler, John; Mumtaz, Moiz

    2012-07-27

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

  2. Inflammatory biomarkers of sulfur mustard analog 2-chloroethyl ethyl sulfide-induced skin injury in SKH-1 hairless mice.

    PubMed

    Tewari-Singh, Neera; Rana, Sumeet; Gu, Mallikarjuna; Pal, Arttatrana; Orlicky, David J; White, Carl W; Agarwal, Rajesh

    2009-03-01

    Sulfur mustard (HD) is an alkylating and cytotoxic chemical warfare agent, which inflicts severe skin toxicity and an inflammatory response. Effective medical countermeasures against HD-caused skin toxicity are lacking due to limited knowledge of related mechanisms, which is mainly attributed to the requirement of more applicable and efficient animal skin toxicity models. Using a less toxic analog of HD, chloroethyl ethyl sulfide (CEES), we identified quantifiable inflammatory biomarkers of CEES-induced skin injury in dose- (0.05-2 mg) and time- (3-168 h) response experiments, and developed a CEES-induced skin toxicity SKH-1 hairless mouse model. Topical CEES treatment at high doses caused a significant dose-dependent increase in skin bi-fold thickness indicating edema. Histopathological evaluation of CEES-treated skin sections revealed increases in epidermal and dermal thickness, number of pyknotic basal keratinocytes, dermal capillaries, neutrophils, macrophages, mast cells, and desquamation of epidermis. CEES-induced dose-dependent increases in epidermal cell apoptosis and basal cell proliferation were demonstrated by the terminal deoxynucleotidyl transferase (tdt)-mediated dUTP-biotin nick end labeling and proliferative cell nuclear antigen stainings, respectively. Following an increase in the mast cells, myeloperoxidase activity in the inflamed skin peaked at 24 h after CEES exposure coinciding with neutrophil infiltration. F4/80 staining of skin integuments revealed an increase in the number of macrophages after 24 h of CEES exposure. In conclusion, these results establish CEES-induced quantifiable inflammatory biomarkers in a more applicable and efficient SKH-1 hairless mouse model, which could be valuable for agent efficacy studies to develop potential prophylactic and therapeutic interventions for HD-induced skin toxicity.

  3. 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.

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

    PubMed

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

    2012-01-01

    Sulfur mustard induces severe acute and prolonged damage to the skin and only partially effective treatments are available. We have previously validated the use of hairless guinea pigs as an experimental model for skin lesions. The present study aimed to characterize a model of a deep dermal lesion and to compare it with the previously described superficial lesion. Clinical evaluation of the lesions was conducted using reflectance colorimetry, trans-epidermal water loss and wound area measurements. Prostaglandin E(2) content, matrix metalloproteinase-2 and 9 activity, and histopathology were conducted up to 4 weeks post-exposure. Sulfur mustard skin injury, including erythema and edema, impairment of skin barrier and wounds developed in a dose-dependent manner. Prostaglandin E(2) content and matrix metalloproteinase-2 and 9 activities were elevated during the wound development and the healing process. Histological evaluation revealed severe damage to the epidermis and deep dermis and vesications. At 4 weeks postexposure, healing was not completed: significantly impaired stratum corneum, absence of hair follicles, and epidermal hyperplasia were observed. These results confirm the use of the superficial and deep dermal skin injuries in the hairless guinea pigs as suitable models that can be utilized for the investigation of the pathological processes of acute as well as long-term injuries. These models will be further used to develop treatments to improve the healing process and prevent skin damage and long-term effects. © 2012 by the Wound Healing Society.

  5. Iron-montmorillonite clays as active sorbents for the decontamination of hazardous chemical warfare agents.

    PubMed

    Carniato, F; Bisio, C; Evangelisti, C; Psaro, R; Dal Santo, V; Costenaro, D; Marchese, L; Guidotti, M

    2018-02-27

    A class of heterogeneous catalysts based on commercial bentonite from natural origin, containing at least 80 wt% of montmorillonite clay, was designed to transform selectively and under mild conditions toxic organosulfur and organophosphorus chemical warfare agents into non-noxious products with a reduced impact on health and environment. The bentonite from the natural origin was modified by introducing iron species and acid sites in the interlayer space, aiming to obtain a sorbent with strong catalytic oxidising and hydrolytic properties. The catalytic performance of these materials was evaluated in the oxidative abatement of (2-chloroethyl)ethyl sulfide (CEES), a simulant of sulfur mustard, in the presence of aqueous hydrogen peroxide as an oxidant. A new decontamination formulation was, moreover, proposed and obtained by mixing sodium perborate, as a solid oxidant, to iron-bentonite catalysts. Solid-phase decontamination tests, performed on a cotton textile support contaminated with organosulfide and organophosphonate simulant agents revealed the good activity of the solid formulation, especially in the in situ detoxification of blistering agents. Tests carried out on the real blistering warfare agent, sulfur mustard (HD agent), showed that, thanks to the co-presence of the iron-based clay together with the solid oxidant component, a good decontamination of the test surface from the real warfare agent could be achieved (80% contaminant degradation, under ambient conditions, in 24 h).

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

    DTIC Science & Technology

    2014-11-19

    C. A. S.; Sumpter, K. B.; Wagner, G. W.; Rice, J. S. Degradation of the Blister Agent Sulfur Mustard, Bis(2-chloroethyl) Sulfide, on Concrete . J...SECURITY CLASSIFICATION OF: This work investigates the fundamental nature of sulfur mustard surface adsorption by characterizing interfacial hydrogen...nature of sulfur mustard surface adsorption by characterizing interfacial hydrogen bonding and other intermolecular forces for the surrogate molecule

  7. Effect of Melatonin Administration on Sleep Quality in Sulfur Mustard Exposed Patients with Sleep Disorders

    PubMed Central

    Mousavi, Seyyedeh Soghra; Shohrati, Majid; Vahedi, Ensieh; Abdollahpour-Alitappeh, Meghdad; Panahi, Yunes

    2018-01-01

    Sulfur mustard (SM) is a toxic agent that targets several tissues. It is the leading cause of persistent lung disease, progressive deterioration in lung function, and mortality among injured patients. Disturbed sleep and poor quality of sleep are common in SM-exposed patients with chronic respiratory problems. Melatonin is an alternative medication that has been widely used to treat poor sleep quality caused by several specific conditions. This study aimed to evaluate the efficacy of melatonin administration in improvement of sleep quality in SM-injured patients. In this randomized, double-blind and placebo-controlled trial study a total of 30 SM-exposed male patients were recruited. Patients received 3 mg melatonin (N = 15) or placebo (N = 15), orally in a single dose, 1 h before bedtime for 56 consecutive days. Sleep quality was evaluated by Pittsburgh Sleep Quality Index (PSQI); daytime sleepiness was measured by Epworth Sleepiness Scale (ESS), and the risk of obstructive sleep apnea was determined by STOP-Bang questionnaire. Compared with placebo, melatonin administration significantly improved global PSQI score, particularly sleep latency (P = 0.03) and subjective sleep quality (P = 0.004). Mean of global PSQI score was declined significantly (P = 0.01) from 10.13 ± 3.44 to 6.66 ± 3.08 in melatonin group. No differences in ESS and STOP-Bang scores were observed between two groups. Melatonin was effective in improving global PSQI score and sleep latency, but not daytime sleepiness and obstructive sleep apnea in SM-exposed patients. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.

  8. 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.

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

    PubMed

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

    2016-08-01

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

  10. 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. © The Author(s) 2015.

  11. Sulfur mustard analog induces oxidative stress and activates signaling cascades in the skin of SKH-1 hairless mice.

    PubMed

    Pal, Arttatrana; Tewari-Singh, Neera; Gu, Mallikarjuna; Agarwal, Chapla; Huang, Jie; Day, Brian J; White, Carl W; Agarwal, Rajesh

    2009-12-01

    A monofunctional analog of the chemical warfare agent sulfur mustard (HD), 2-chloroethyl ethyl sulfide (CEES), induces tissue damage similar to HD. Herein we studied the molecular mechanisms associated with CEES-induced skin inflammation and toxicity in SKH-1 hairless mice. Topical CEES exposure caused an increase in oxidative stress as observed by enhanced 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid)-1-pyrroline N-oxide protein adduct formation and an increase in protein oxidation. The CEES-induced increase in the formation of 8-oxo-2-deoxyguanosine indicated DNA oxidation. CEES exposure instigated an increase in the phosphorylation of mitogen-activated protein kinases (MAPKs; ERK1/2, JNK, and p38). After CEES exposure, a significant increase in the phosphorylation of Akt at Ser473 and Thr308 was observed as well as upregulation of its upstream effector, PDK1, in mouse skin tissue. Subsequently, CEES exposure caused activation of AP-1 family proteins and the NF-kappaB pathway, including phosphorylation and degradation of IkappaBalpha in addition to phosphorylation of the NF-kappaB essential modulator. Collectively, our results indicate that CEES induces oxidative stress and the activation of the transcription factors AP-1 and NF-kappaB via upstream signaling pathways including MAPKs and Akt in SKH-1 hairless mouse skin. These novel molecular targets could be supportive in the development of prophylactic and therapeutic interventions against HD-related skin injury.

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

    PubMed

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

    2014-06-01

    Sulfur mustard (SM) is a bifunctional alkylating agent causing skin inflammation, edema and blistering. A hallmark of SM-induced toxicity is follicular and interfollicular epithelial damage. In the present studies we determined if SM-induced structural alterations in hair follicles and sebaceous glands were correlated with cell damage, inflammation and wound healing. The dorsal skin of hairless mice was treated with saturated SM vapor. One to seven days later, epithelial cell karyolysis within the hair root sheath, infundibulum and isthmus was apparent, along with reduced numbers of sebocytes. Increased numbers of utriculi, some with connections to the skin surface, and engorged dermal cysts were also evident. This was associated with marked changes in expression of markers of DNA damage (phospho-H2A.X), apoptosis (cleaved caspase-3), and wound healing (FGFR2 and galectin-3) throughout pilosebaceous units. Conversely, fatty acid synthase and galectin-3 were down-regulated in sebocytes after SM. Decreased numbers of hair follicles and increased numbers of inflammatory cells surrounding the utriculi and follicular cysts were noted within the wound 3-7 days post-SM exposure. Expression of phospho-H2A.X, cleaved caspase-3, FGFR2 and galectin-3 was decreased in dysplastic follicular epidermis. Fourteen days after SM, engorged follicular cysts which expressed galectin-3 were noted within hyperplastic epidermis. Galectin-3 was also expressed in basal keratinocytes and in the first few layers of suprabasal keratinocytes in neoepidermis formed during wound healing indicating that this lectin is important in the early stages of keratinocyte differentiation. These data indicate that hair follicles and sebaceous glands are targets for SM in the skin. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. N-acetylcysteine and endothelial cell injury by sulfur mustard.

    PubMed

    Atkins, K B; Lodhi, I J; Hurley, L L; Hinshaw, D B

    2000-12-01

    Understanding the underlying mechanisms of cell injury and death induced by the chemical warfare vesicant sulfur mustard (HD) will be extremely helpful in the development of effective countermeasures to this weapon of terror. We have found recently that HD induces both apoptosis and necrosis in endothelial cells (Toxicol. Appl. Pharmacol. 1996; 141: 568-583). Pretreatment of the endothelial cells for 20 h with the redox-active agent N-acetyl-L-cysteine (NAC) selectively prevented apoptotic death induced by HD. In this study, we tested the hypotheses that pretreatment with NAC acts through two different pathways to minimize endothelial injury by HD: NAC pretreatment acts via a glutathione (GSH)-dependent pathway; and NAC pretreatment acts to suppress HD-induced activation of the nuclear transcription factor NFkappaB. We used a fluorescence microscopic assay of apoptotic nuclear features to assess viability and electrophoretic mobility shift assays (EMSAs) to assess the activity of NFkappaB following exposure to HD. The cells were treated with 0-10 mM GSH for 1 h prior to and during exposure to 0 or 500 microM HD for 5-6 h. Cells were also treated with 50 mM NAC or 200 microM buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, alone or in combination overnight prior to exposure to 0 or 500 microM HD for 5-6 h. Externally applied GSH up to a concentration of 5 mM had no toxic effect on the cells. Mild toxicity was associated with 10 mM GSH alone. There was a dose-related enhancement of viability when 2.5 and 5 mM GSH were present during the HD exposure. Pretreatment with BSO alone had no discernible toxicity. However, pretreatment with this inhibitor of GSH synthesis potentiated the toxicity of HD. Pretreatment with 50 mM NAC, as previously reported, provided substantial protection. Combining pretreatment with both BSO and NAC eliminated the protective effect of NAC pretreatment alone on HD injury. These observations are highly suggestive that NAC enhances

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

    PubMed Central

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

    2015-01-01

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

  15. 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

    radioactivity. Mustard gas appeared to be a very effective alkylating agent for. bases in DNA. Even in blood, with a variety of reactive sites, 1 out of 124...single-stranded material is required for effective competition in the ELISA test. although it contained at least as many adducts as the single-stranded DNA...DNA isolated from human white blood cells as competitor. 203 Figure 92: The effect of the concentration of mustard gas to which single-stranded calf

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

    PubMed

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

    2014-08-18

    We synthesized a series of phenyl N-mustard-4-anilinoquinoline conjugates to study their antitumorigenic effects. These agents were prepared by the condensation of 4-[N,N-bis(2-chloroethyl)amino]phenyl isocyanate with 6-amino-4-methylamino or 4-anilinoquinolines. The structure-activity relationship (SAR) studies revealed that the C2-methylquinoline derivatives (18a-o) were generally more cytotoxic than the C2-phenylquinoline conjugates (23a-d) in inhibiting the cell growth of various human tumor cell lines in vitro. However, the methylamino or aniline substituents at C4 of quinoline did not influence the cytotoxic effects. The title conjugates were capable of inducing DNA cross-linking and promoting cell-cycle arrest at the G2/M phase. This study demonstrates that phenyl N-mustard-4-anilinoquinoline conjugates are generally more potent than phenyl N-mustard-4-anilinoquinazoline conjugates against the cell growth of various tumor cell-lines. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

    PubMed Central

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

    2016-01-01

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

  18. Silibinin Attenuates Sulfur Mustard Analog-Induced Skin Injury by Targeting Multiple Pathways Connecting Oxidative Stress and Inflammation

    PubMed Central

    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. PMID:23029417

  19. 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.

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

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., 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 Lewisite...

  2. 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 Lewisite...

  3. 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 Lewisite...

  4. 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 Lewisite...

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., 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 Lewisite...

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

    DTIC Science & Technology

    2006-05-01

    Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT: See next page. 15. SUBJECT TERMS Mustard, Chemical Defense 16...points after SM exposure, cells were harvested for further analyses. Chemicals . SM (bis-(2-chloroethyl) sulfide; >98% purity) was obtained from the...US Army Edgewood Research, Development and Engineering Center. The CaM antagonist W-13 (N- (4-Aminobutyl)-5-chloro-2-naphthalenesulfonamide, HCl

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

    PubMed

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

    2018-09-01

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

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

    PubMed

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

    2017-12-01

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

  9. Biological effects of adipocytes in sulfur mustard induced toxicity.

    PubMed

    Xu, Hua; Gao, Zhongcai; Wang, Peng; Xu, Bin; Zhang, Yajiao; Long, Long; Zong, Cheng; Guo, Lei; Jiang, Weijian; Ye, Qinong; Wang, Lili; Xie, Jianwei

    2018-01-15

    Sulphur mustard (2,2'-dichloroethyl sulfide; SM) is a vesicant chemical warfare agent whose mechanism of acute or chronic action is not known with any certainty and to date there is no effective antidote. SM accumulation in adipose tissue (AT) has been originally verified in our previous study. To evaluate the biological effect caused by the presence of abundant SM in adipocyte and assess the biological role of AT in SM poisoning, in vitro and in vivo experiments were performed. High content analysis revealed multi-cytotoxicity in SM exposed cells in a time and dose dependent manner, and adipocytes showed a relative moderate damage compared with non-adipocytes. Cell co-culture model was established and revealed the adverse effect of SM-exposed adipocyte supernatant on the growth of co-cultured cells. The pathological changes in AT from 10mg/kg SM percutaneously exposed rats were checked and inflammation phenomena were observed. The mRNA and protein levels of inflammation-related adipokines secreted from AT in rats exposed to 1, 3 and 10mg/kg doses of SM were determined by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assays. The expressions of proinflammatory and anti-inflammatory adipokines together promoted the inflammation development in the body. The positive correlations between AT and serum adipokine levels were explored, which demonstrated a substantial role of AT in systemic inflammation responding to SM exposure. Thus, AT is not only a target of SM but also a modulator in the SM toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. 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.

  11. Acute and long-term transcriptional responses in sulfur mustard-exposed SKH-1 hairless mouse skin.

    PubMed

    Vallet, V; Poyot, T; Cléry-Barraud, C; Coulon, D; Sentenac, C; Peinnequin, A; Boudry, I

    2012-03-01

    Sulfur mustard (HD) ranks among the alkylating chemical warfare agents. Skin contact with HD produces an inflammatory response that evolves into separation at the epidermal-dermal junction conducting to blistering and epidermis necrosis. Up to now, current treatment strategies of HD burns have solely consisted in symptomatic management of skin damage. Therapeutic efficacy studies are still being conducted; classically using appropriate animal skin toxicity models. In order to substantiate the use of SKH-1 hairless mouse as an appropriate model for HD-induced skin lesions, we investigate the time-dependent quantitative gene expression of various selected transcripts associated to the dorsal skin exposure to HD saturated vapors. Using quantitative real time polymerase chain reaction (RT-qPCR), the expression of interleukins (IL-1β and IL-6), tumor necrosis factor (TNF)-α, macrophage inflammatory proteins (MIP)-2α (also called Cxcl2) and MIP-1αR (also called Ccr1), matrix metalloproteases (MMP-9 and MMP-2), laminin γ2 monomer (Lamc2) and keratin (K)1 was determined up to 21 days after HD challenge in order to allow enough time for wound repair to begin. Specific transcript RT-qPCR analysis demonstrated that IL-6, IL-1β, Ccr1, Cxcl2 mRNA levels increased as early as 6 h in HD-exposed skins and remained up-regulated over a 14-day period. Topical application of HD also significantly up-regulated MMP-9, TNF-α, and Lamc2 expression at specific time points. In contrast, MMP-2 mRNA levels remained unaffected by HD over the time-period considered, whereas that long-term study revealed that K1 mRNA level significantly increased only 21 days after HD challenge. Our study hereby provides first-hand evidence to substantiate a long period variation expression in the inflammatory cytokine, MMPs and structural components following cutaneous HD exposure in hairless mouse SKH-1. Our data credit the use of SKH-1 for investigating mechanisms of HD-induced skin toxicity and for

  12. A cutaneous full-thickness liquid sulfur mustard burn model in weanling swine: clinical pathology and urinary excretion of thiodiglycol.

    PubMed

    Graham, J S; Reid, F M; Smith, J R; Stotts, R R; Tucker, E S; Shumaker, S M; Niemuth, N A; Janny, S J

    2000-12-01

    Sulfur mustard (bis(2-chloroethyl)sulfide, HD) is a well-known blistering chemical warfare agent. We have developed a cutaneous full-thickness HD burn model in weanling pigs for efficacy testing of candidate treatment regimens. This report addresses clinical pathology findings and the urinary excretion profile of a major HD metabolite (thiodiglycol, TDG) in this model. Six female Yorkshire pigs were exposed to HD liquid on the ventral surface for 2 h, generating six 3-cm diameter full-thickness dermal lesions per pig. Blood samples were collected throughout a 7-day observation period for hematology and serum chemistry examinations. Urine was collected in metabolism cages. Routine urinalysis was performed and the urine analyzed for TDG using gas chromatography/mass spectrometry. Examination of clinical pathology parameters revealed subtle HD-related changes that are suggestive of a mild hemolytic episode. No other signs of clinically significant systemic toxicities were noted, including bone marrow suppression. Thiodiglycol was detected at the earliest time point tested (6-8 h post-exposure) at levels ranging from 0.66 to 4.98 microg ml(-1) with a mean of 2.14 microg ml(-1). Thiodiglycol concentrations were the highest for half of the animals at this earliest time point and at 24-48 h for the others. By the evening of day 3, the mean level had reached 50 ng ml(-1). Mean levels remained 10-40 ng ml(-1) for the remainder of the 7-day observation period, with the highest individual concentration noted during this period of 132 ng ml(-1). Our results are in general agreement with the TDG excretion profiles previously described for rodent models and humans. Urinary excretion of absorbed HD in our weanling pig wound healing model appears to follow the same pattern as is seen in other laboratory animals models. In general, urinary excretion of TDG appears to peak within the first 1-4 days following exposure, with detectable levels after 1 week. Relatively high urinary TDG

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

    PubMed

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

    2017-05-01

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

  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. 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

  16. Wide Area Recovery and Resiliency Program (WARRP) Integrated Program Plan

    DTIC Science & Technology

    2011-06-01

    Agent YELLOW, which is a mixture of the chemical warfare agents Sulfur Mustard and Lewisite, is a liquid with a garlic-like odor. Sulfur mustard...Radioisotope Background Cesium -137 (137Cs) is a radioactive isotope of cesium . The half-life of cesium -137 is 30.17 years. Because of the chemical...nature of cesium , it moves easily through the environment. This makes the cleanup of cesium - 137 difficult. People may ingest cesium -137 with food

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

    PubMed

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

    2006-06-15

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

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hartmann, H.; Environmental Assessment

    2002-06-01

    The U.S. Army has estimated acute lethality guideline levels for inhalation of the chemical warfare agents mustard, GB, and VX. These levels are expressed as dosages measured in milligram-minutes per cubic meter (mg-min/m3). The National Advisory Council has also proposed acute emergency guideline levels (AEGLs) for the agents. The AEGLs are threshold exposure limits for the general public for mild effects, serious adverse effects, and lethality. They are expressed as air concentrations (in units of mg/m3) and are applicable to emergency exposure periods ranging from 10 min to 8 h. The report discusses strengths and deficiencies in the levels, importantmore » parameters (i.e., exposure time, breathing rate) that need to be explicitly addressed in deriving the guideline levels, and possible impacts that could result from using AEGLs instead of guideline dosages in future assessments.« less

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

    PubMed

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

    2016-07-01

    The role of gibberellic acid (GA) or sulfur (S) in stimulation of photosynthesis is known. However, information on the involvement of ethylene in GA-induced photosynthetic responses and cadmium (Cd) tolerance is lacking. This work shows that ethylene is involved in S-assimilation, photosynthetic responses and alleviation of Cd stress by GA in mustard (Brassica juncea L.). Plants grown with 200 mg Cd kg(-1) soil were less responsive to ethylene despite high ethylene evolution and showed photosynthetic inhibition. Plants receiving 10 μM GA spraying plus 100 mg S kg(-1) soil supplementation exhibited increased S-assimilation and photosynthetic responses under Cd stress. Application of GA plus S decreased oxidative stress of plants grown with Cd and limited stress ethylene formation to the range suitable for promoting sulfur use efficiency (SUE), glutathione (GSH) production and photosynthesis. The role of ethylene in GA-induced S-assimilation and reversal of photosynthetic inhibition by Cd was substantiated by inhibiting ethylene biosynthesis with the use of aminoethoxyvinylglycine (AVG). The suppression of S-assimilation and photosynthetic responses by inhibiting ethylene in GA plus S treated plants under Cd stress indicated the involvement of ethylene in GA-induced S-assimilation and Cd stress alleviation. The outcome of the study is important to unravel the interaction between GA and ethylene and their role in Cd tolerance in plants. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Structural Changes in the Skin of Hairless Mice Following Exposure to Sulfur Mustard Correlate with Inflammation and DNA Damage

    PubMed Central

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

    2011-01-01

    Sulfur mustard (SM, bis(2-chloroethyl)sulfide) is a bifunctional alkylating agent that causes dermal inflammation, edema and blistering. To investigate the pathogenesis of SM-induced injury, we used a vapor cup model which provides an occlusive environment in which SM is in constant contact with the skin. The dorsal skin of SKH-1 hairless mice was exposed to saturated SM vapor or air control. Histopathological changes, inflammatory markers and DNA damage were analyzed 1–14 days later. After 1 day, SM caused epidermal thinning, stratum corneum shedding, basal cell karyolysis, hemorrhage and macrophage and neutrophil accumulation in the dermis. Cleaved caspase-3 and phosphorylated histone 2A.X (phospho-H2A.X), markers of apoptosis and DNA damage, respectively, were increased whereas proliferating cell nuclear antigen (PCNA) was down-regulated after SM exposure. By 3 days, epithelial cell hypertrophy, edema, parakeratosis and loss of epidermal structures were noted. Enzymes generating pro-inflammatory mediators including myeloperoxidase and cyclooxygenase-2 were upregulated. After 7 days, keratin-10, a differentiation marker, was evident in the stratum corneum. This was associated with an underlying eschar, as neoepidermis began to migrate at the wound edges. Trichrome staining revealed increased collagen deposition in the dermis. PCNA expression in the epidermis was correlated with hyperplasia, hyperkeratosis, and parakeratosis. By 14 days, there was epidermal regeneration with extensive hyperplasia, and reduced expression of cleaved caspase-3, cyclooxygenase-2 and phospho-H2A.X. These findings are consistent with the pathophysiology of SM-induced skin injury in humans suggesting that the hairless mouse can be used to investigate the dermatoxicity of vesicants and the potential efficacy of countermeasures. PMID:21672537

  1. A guanine-ethylthioethyl-glutathione adduct as a major DNA lesion in the skin and in organs of mice exposed to sulfur mustard.

    PubMed

    Batal, Mohamed; Rebelo-Moreira, Silvestre; Hamon, Nadège; Bayle, Pierre-Alain; Mouret, Stéphane; Cléry-Barraud, Cécile; Boudry, Isabelle; Douki, Thierry

    2015-02-17

    Sulfur mustard (SM) is an old chemical warfare but it remains a threat to both militaries and civilians. SM mainly targets skin, eyes and lungs and diffuses to internal organs. At the molecular level, SM is able to damage DNA through the formation of monoadducts and biadduct. Glutathione (GSH) is another critical target of SM in cells since it is part of the detoxification mechanism against alkylating agents. In the present work, we investigated whether SM could form covalent bonds simultaneously with a DNA base and the sulfhydryl group of GSH. The expected guanine adduct, S-[2-(N7-guanyl)-ethylthioethyl]-glutathione (N7Gua-ETE-GSH), was synthesized and detected in several tissues of SKH-1 mice exposed to 60mg/kg of SM in the dorsal-lumbar region. N7Gua-ETE-GSH was detected in all organs studied, except in the liver. The tissue exhibiting the highest levels of N7Gua-ETE-GSH was skin, followed by brain, lungs, kidneys and spleen. N7Gua-ETE-GSH was detected in skin, brain and lungs as long as two weeks after exposure. The persistence was less in other organs. The observation of the formation of N7Gua-ETE-GSH in vivo confirms the variety of damages induced by SM in DNA. It also provides another example of the formation of DNA adducts involving glutathione following in vivo exposure to bifunctional alkylating compounds. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

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

    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 significantlymore » 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

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

    PubMed

    Sharma, Manoj; Vijayaraghavan, R; Gautam, Anshoo

    2009-08-10

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

  4. Paper-based electrochemical sensor for on-site detection of the sulphur mustard.

    PubMed

    Colozza, Noemi; Kehe, Kai; Popp, Tanja; Steinritz, Dirk; Moscone, Danila; Arduini, Fabiana

    2018-06-22

    Herein, we report a novel paper-based electrochemical sensor for on-site detection of sulphur mustards. This sensor was conceived combining office paper-based electrochemical sensor with choline oxidase enzyme to deliver a sustainable sensing tool. The mustard agent detection relies on the evaluation of inhibition degree of choline oxidase, which is reversibly inhibited by sulphur mustards, by measuring the enzymatic by-product H 2 O 2 in chronoamperometric mode. A nanocomposite constituted of Prussian Blue nanoparticles and Carbon Black was used as working electrode modifier to improve the electroanalytical performances. This bioassay was successfully applied for the measurement of a sulphur mustard, Yprite, obtaining a detection limit in the millimolar range (LOD = 0.9 mM). The developed sensor, combined with a portable and easy-to-use instrumentation, can be applied for a fast and cost-effective detection of sulphur mustards.

  5. Miniaturized low-cost ion mobility spectrometer for fast detection of chemical warfare agents.

    PubMed

    Zimmermann, Stefan; Barth, Sebastian; Baether, Wolfgang K M; Ringer, Joachim

    2008-09-01

    Ion mobility spectrometry (IMS) is a well-known method for detecting hazardous compounds in air. Typical applications are the detection of chemical warfare agents, highly toxic industrial compounds, explosives, and drugs of abuse. Detection limits in the low part per billion range, fast response times, and simple instrumentation make this technique more and more popular. In particular, there is an increasing demand for miniaturized low-cost IMS for hand-held devices and air monitoring of public areas by sensor networks. In this paper, we present a miniaturized aspiration condenser type ion mobility spectrometer for fast detection of chemical warfare agents. The device is easy to manufacture and allows single substance identification down to low part per billion-level concentrations within seconds. The improved separation power results from ion focusing by means of geometric constraints and fluid dynamics. A simple pattern recognition algorithm is used for the identification of trained substances in air. The device was tested at the German Armed Forces Scientific Institute for Protection Technologies-NBC-Protection. Different chemical warfare agents, such as sarin, tabun, soman, US-VX, sulfur mustard, nitrogen mustard, and lewisite were tested. The results are presented here.

  6. 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.

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

    DTIC Science & Technology

    1990-09-01

    90% of all radioactivity. Mustard gas appeared to be a very effective alkylating agent for bases in DNA. Even in blood, with a variety of reactive...stranded than of the single-stranded material is required for effective competition in the ELISA test, probably as a result of interstrand crosslinks...first noticed by their effects on casualties. If a total ban on the use, possession and production of chemical agents will eventually materialize, the

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

    PubMed

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

    2011-10-01

    Sulfur mustard (SM, bis(2-chloroethyl)sulfide) is a bifunctional alkylating agent that causes dermal inflammation, edema and blistering. To investigate the pathogenesis of SM-induced injury, we used a vapor cup model which provides an occlusive environment in which SM is in constant contact with the skin. The dorsal skin of SKH-1 hairless mice was exposed to saturated SM vapor or air control. Histopathological changes, inflammatory markers and DNA damage were analyzed 1-14 days later. After 1 day, SM caused epidermal thinning, stratum corneum shedding, basal cell karyolysis, hemorrhage and macrophage and neutrophil accumulation in the dermis. Cleaved caspase-3 and phosphorylated histone 2A.X (phospho-H2A.X), markers of apoptosis and DNA damage, respectively, were increased whereas proliferating cell nuclear antigen (PCNA) was down-regulated after SM exposure. By 3 days, epithelial cell hypertrophy, edema, parakeratosis and loss of epidermal structures were noted. Enzymes generating pro-inflammatory mediators including myeloperoxidase and cyclooxygenase-2 were upregulated. After 7 days, keratin-10, a differentiation marker, was evident in the stratum corneum. This was associated with an underlying eschar, as neoepidermis began to migrate at the wound edges. Trichrome staining revealed increased collagen deposition in the dermis. PCNA expression in the epidermis was correlated with hyperplasia, hyperkeratosis, and parakeratosis. By 14 days, there was epidermal regeneration with extensive hyperplasia, and reduced expression of cleaved caspase-3, cyclooxygenase-2 and phospho-H2A.X. These findings are consistent with the pathophysiology of SM-induced skin injury in humans suggesting that the hairless mouse can be used to investigate the dermatoxicity of vesicants and the potential efficacy of countermeasures. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Toward Hypoxia-Selective DNA-Alkylating Agents Built by Grafting Nitrogen Mustards onto the Bioreductively Activated, Hypoxia-Selective DNA-Oxidizing Agent 3-Amino-1,2,4-benzotriazine 1,4-Dioxide (Tirapazamine)

    PubMed Central

    2015-01-01

    Tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide) is a heterocyclic di-N-oxide that undergoes enzymatic deoxygenation selectively in the oxygen-poor (hypoxic) cells found in solid tumors to generate a mono-N-oxide metabolite. This work explored the idea that the electronic changes resulting from the metabolic deoxygenation of tirapazamine analogues might be exploited to activate a DNA-alkylating species selectively in hypoxic tissue. Toward this end, tirapazamine analogues bearing nitrogen mustard units were prepared. In the case of the tirapazamine analogue 18a bearing a nitrogen mustard unit at the 6-position, it was found that removal of the 4-oxide from the parent di-N-oxide to generate the mono-N-oxide analogue 17a did indeed cause a substantial increase in reactivity of the mustard unit, as measured by hydrolysis rates and DNA-alkylation yields. Hammett sigma values were measured to quantitatively assess the magnitude of the electronic changes induced by metabolic deoxygenation of the 3-amino-1,2,4-benzotriazine 1,4-dioxide heterocycle. The results provide evidence that the 1,2,4-benzotiazine 1,4-dioxide unit can serve as an oxygen-sensing prodrug platform for the selective unmasking of bioactive agents in hypoxic cells. PMID:25029663

  10. Toward hypoxia-selective DNA-alkylating agents built by grafting nitrogen mustards onto the bioreductively activated, hypoxia-selective DNA-oxidizing agent 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine).

    PubMed

    Johnson, Kevin M; Parsons, Zachary D; Barnes, Charles L; Gates, Kent S

    2014-08-15

    Tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide) is a heterocyclic di-N-oxide that undergoes enzymatic deoxygenation selectively in the oxygen-poor (hypoxic) cells found in solid tumors to generate a mono-N-oxide metabolite. This work explored the idea that the electronic changes resulting from the metabolic deoxygenation of tirapazamine analogues might be exploited to activate a DNA-alkylating species selectively in hypoxic tissue. Toward this end, tirapazamine analogues bearing nitrogen mustard units were prepared. In the case of the tirapazamine analogue 18a bearing a nitrogen mustard unit at the 6-position, it was found that removal of the 4-oxide from the parent di-N-oxide to generate the mono-N-oxide analogue 17a did indeed cause a substantial increase in reactivity of the mustard unit, as measured by hydrolysis rates and DNA-alkylation yields. Hammett sigma values were measured to quantitatively assess the magnitude of the electronic changes induced by metabolic deoxygenation of the 3-amino-1,2,4-benzotriazine 1,4-dioxide heterocycle. The results provide evidence that the 1,2,4-benzotiazine 1,4-dioxide unit can serve as an oxygen-sensing prodrug platform for the selective unmasking of bioactive agents in hypoxic cells.

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

    PubMed

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

    2017-12-01

    Sulfur mustard (SM) exposure causes respiratory disorders, progressive deterioration in lung function and mortality in injured victims and poor sleep quality is one of the most common problems among SM-exposed patients. Since melatonin has a critical role in regulation of sleep and awareness, this study aimed to evaluate the serum melatonin levels in SM-injured subjects. A total of 30 SM-exposed male patients and 10 controls was evaluated. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI); daytime sleepiness was measured by the Epworth Sleepiness Scale (ESS), and the risk of obstructive sleep apnoea was determined by the STOP-Bang questionnaire. Polysomnography (PSG) and pulmonary function tests (PFTs) were also available. Nocturnal serum melatonin levels were measured using an ELISA kit. The mean of PSQI, ESS and STOP-Bang scores in patients (11.76±3.56, 12.6±3.03 and 5.03±1.09, respectively) were significantly (p<0.01) higher than those in the controls (2.78±0.83, 4.69±1.15 and 1.18±0.82, respectively). PFTs also showed declined respiratory quality in SM-patients. There was a significant difference regarding the PSG results between patients and controls (p<0.01). The mean of nocturnal serum melatonin levels in patients (29.78±19.31 pg/mL) was significantly (p=0.005) lower than that in the controls (78.53±34.41 pg/mL). Reduced nocturnal serum melatonin and respiratory disorders can be the reasons for poor sleep quality among these patients. IRCT2015092924267N1, Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Foye, W.O.

    1992-09-01

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

  13. Methyl salicylate: a reactive chemical warfare agent surrogate to detect reaction with hypochlorite.

    PubMed

    Salter, W Bruce; Owens, Jeffery R; Wander, Joseph D

    2011-11-01

    Methyl salicylate (MeS) has a rich history as an inert physical simulant for the chemical warfare agents sulfur mustard and soman, where it is used extensively for liquid- and vapor-permeation testing. Here we demonstrate possible utility of MeS as a reactivity simulant for chlorine-based decontaminants. In these experiments MeS was reacted with sodium hypochlorite varying stoichiometry, temperature, reaction time, and pH. No colored oxidation products were observed; however, chlorination of the aromatic ring occurred ortho (methyl 3-chlorosalicylate) and para (methyl 5-chlorosalicylate) to the position bearing the -OH group in both the mono- and disubstituted forms. The monosubstituted para product accumulated initially, and the ortho and 3,5-dichloro products formed over the next several hours. Yields from reactions conducted below pH 11 declined rapidly with decreasing pH. Reactions run at 40 °C produced predominantly para substitution, while those run at 0 °C produced lower yields of ortho- and para-substituted products. Reactions were also carried out on textile substrates of cotton, 50/50 nylon-cotton, and a meta aramid. The textile data broadly reproduced reaction times and stoichiometry observed in the liquid phase, but are complicated by physical and possibly chemical interactions with the fabric. These data indicate that, for hypochlorite-containing neutralizing agents operating at strongly alkaline pH, one can expect MeS to react stoichiometrically with the hypochlorite it encounters. This suggests utility of MeS in lieu of such highly hazardous surrogates as monochloroalkyl sulfides as a simulant for threat scenarios involving the stoichiometric decomposition of sulfur mustard. Specifically, the extent of coverage of the simulant on a fabric by the neutralizing agent can be directly measured. Similar reactivity toward other halogen oxidizing agents is likely but remains to be demonstrated.

  14. Biodegradation of Mustard

    DTIC Science & Technology

    1994-07-01

    hydrolyzed during incubation in the aqueous medium used for growth of the microorganism. Microorganisms possessing an enzyme system functional against mustard...indicated. Acidophilic Thiobacillus appear to have limited use for mustard breakdown except for the halotolerant T. DrosDerus, originally isolated from a...microorganisms for mustard breakdown is a viable alternative. Enzymes of halophilic and thermophilic microorganisms are able to function in the presence organic

  15. Degradation of Toxic Chemicals by Zero-Valent Metal Nanoparticles - A Literature Review

    DTIC Science & Technology

    2005-11-01

    oxidative reactions. Oxidative reactions are of primary interest to us as they have the potential to degrade organophosphorous nerve agents as well...a) mustard and b) nerve agent (general structure). To decontaminate mustard there are two approaches, dechlorination or oxidation of the sulfur, the...later of which is preferable due to the reversibility of the former. To decontaminate the nerve agents oxidation is required to replace X2, X3 and

  16. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Delayed head and neck complications of sulphur mustard poisoning in Iranian veterans.

    PubMed

    Zojaji, R; Balali-Mood, M; Mirzadeh, M; Saffari, A; Maleki, M

    2009-10-01

    Sulphur mustard is a chemical warfare agent which was used against Iranian combatants and civilians between 1983 and 1988. The purpose of this study was to document the delayed toxic effects of sulphur mustard in Iranian veterans, focussing on head and neck complications. This was a two-year, prospective, descriptive study of 43 male Iranian veterans aged 34 to 48 years (mean 41.8 years) who were moderately disabled or worse due to sulphur mustard poisoning. Investigations were performed with consent, including haematological, biochemical and immunological tests, spirometry, chest X-ray, high resolution computed tomography of the lungs, and skin biopsies. Further investigations and interventions were performed as clinically indicated. The most affected sites were the lungs (95 per cent), peripheral nerves (77 per cent), skin (73 per cent), eyes (68 per cent), and head and neck (16.2 per cent). Of seven patients with mostly head and neck complications, four had a skin disorder (hyperpigmentation in all four, an erythematous, papular rash in two, and dry skin in one). Two patients had thyroid cancer (undifferentiated thyroid carcinoma in one and papillary carcinoma of a thyroglossal cyst in the other, 12 and 14 years after sulphur mustard exposure, respectively). One patient had nasopharyngeal carcinoma, 12 years after sulphur mustard exposure. Carcinomas of the thyroid and nasopharynx in three patients with sulphur mustard exposure are reported for the first time.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 amore » 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.« less

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

    PubMed

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

    2014-09-15

    A Nb(V)-containing saponite clay was designed to selectively transform toxic organosulfur chemical warfare agents (CWAs) under extremely mild conditions into nontoxic products with reduced environmental impact. Thanks to the insertion of Nb(V) sites within the saponite framework, a bifunctional catalyst with strong oxidizing and acid properties was obtained. Remarkable activity and high selectivity were observed for the oxidative abatement of (2-chloroethyl)ethyl sulfide (CEES), a simulant of sulfur mustard, at room temperature with aqueous hydrogen peroxide. This performance was significantly better compared to a conventional commercial decontamination powder. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. 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.

  1. Treatment of skin injuries induced by sulfur mustard with calmodulin antagonists, using the pig model.

    PubMed

    Kadar, T; Fishbeine, E; Meshulam, Y; Sahar, R; Chapman, S; Liani, H; Barness, I; Amir, A

    2000-12-01

    Sulfur mustard (HD) is a potent cutaneous vesicant that penetrates rapidly through the skin, causing prolonged injuries and leading to severe incapacitation. Although there has been long and intensive efforts to find a treatment for HD skin lesions, no effective treatment is available for HD-induced skin injuries. Recently, ointments containing calmodulin antagonists were found to be effective in preventing skin injuries induced by HD in hairless mice. The present study was designed to investigate the beneficial effects of topical treatments with calmodulin antagonists against HD skin lesions in the pig model. The pig is used as a preferred animal model for human skin in many studies, including vesicants. Neat HD, either in liquid form (0.2-1 microl droplets) or as vapour, was applied to the back skin of female pigs (a cross Large White & Landrace, 10-12 kg) for various exposure durations. Evaluation was based on quantitative analysis of the degree of erythema and area of the lesions, as well as histological evaluation. Calmodulin antagonists (10% pentamide, 1% trifluoperazine, 2% thioridazine) and anaesthetics (20% lidocaine and 3% benoxinate) were dissolved in pluronic F-127 base according to Kim et al. (Eur. J. Pharmacol. 1996; 313: 107-114) or in saline, and were applied either topically as ointments or by intradermal injection, as early as 5 min post-exposure (twice a day for at least 3 days). The results demonstrated that topically applied pluronic base ointments containing lidocaine or pentamide produce beneficial effects when applied immediately after short-term HD exposure to pig skin.

  2. Efficacy of Glutathione in Ameliorating Sulfur Mustard Analog-Induced Toxicity in Cultured Skin Epidermal Cells and in SKH-1 Mouse Skin In Vivo

    PubMed Central

    Tewari-Singh, Neera; Agarwal, Chapla; Huang, Jie; Day, Brian J.; White, Carl W.

    2011-01-01

    Exposure to chemical warfare agent sulfur mustard (HD) is reported to cause GSH depletion, which plays an important role in HD-linked oxidative stress and skin injury. Using the HD analog 2-chloroethyl ethyl sulfide (CEES), we evaluated the role of GSH and its efficacy in ameliorating CEES-caused skin injury. Using mouse JB6 and human HaCaT epidermal keratinocytes, we observed both protective and therapeutic effects of exogenous GSH (1 or 10 mM) in attenuating a CEES-caused decrease in cell viability and DNA synthesis, as well as S and G2M phase arrest in cell cycle progression. However, the protective effect of GSH was stronger than its ability to reverse CEES-induced cytotoxic effect. The observed effect of GSH could be associated with an increase in intracellular GSH levels after its treatment before or after CEES exposure, which strongly depleted cellular GSH levels. N-Acetyl cysteine, a GSH precursor, also showed both protective and therapeutic effects against CEES-caused cytotoxicity. Buthionine sulfoximine, which reduces cellular GSH levels, caused an increased CEES cytotoxicity in both JB6 and HaCaT cells. In further studies translating GSH effects in cell culture, pretreatment of mice with 300 mg/kg GSH via oral gavage 1 h before topical application of CEES resulted in significant protection against CEES-caused increase in skin bifold and epidermal thickness, apoptotic cell death, and myeloperoxidase activity, which could be associated with increased skin GSH levels. Together, these results highlight GSH efficacy in ameliorating CEES-caused skin injury and further support the need for effective antioxidant countermeasures against skin injury by HD exposure. PMID:20974699

  3. Efficacy of glutathione in ameliorating sulfur mustard analog-induced toxicity in cultured skin epidermal cells and in SKH-1 mouse skin in vivo.

    PubMed

    Tewari-Singh, Neera; Agarwal, Chapla; Huang, Jie; Day, Brian J; White, Carl W; Agarwal, Rajesh

    2011-02-01

    Exposure to chemical warfare agent sulfur mustard (HD) is reported to cause GSH depletion, which plays an important role in HD-linked oxidative stress and skin injury. Using the HD analog 2-chloroethyl ethyl sulfide (CEES), we evaluated the role of GSH and its efficacy in ameliorating CEES-caused skin injury. Using mouse JB6 and human HaCaT epidermal keratinocytes, we observed both protective and therapeutic effects of exogenous GSH (1 or 10 mM) in attenuating a CEES-caused decrease in cell viability and DNA synthesis, as well as S and G(2)M phase arrest in cell cycle progression. However, the protective effect of GSH was stronger than its ability to reverse CEES-induced cytotoxic effect. The observed effect of GSH could be associated with an increase in intracellular GSH levels after its treatment before or after CEES exposure, which strongly depleted cellular GSH levels. N-Acetyl cysteine, a GSH precursor, also showed both protective and therapeutic effects against CEES-caused cytotoxicity. Buthionine sulfoximine, which reduces cellular GSH levels, caused an increased CEES cytotoxicity in both JB6 and HaCaT cells. In further studies translating GSH effects in cell culture, pretreatment of mice with 300 mg/kg GSH via oral gavage 1 h before topical application of CEES resulted in significant protection against CEES-caused increase in skin bifold and epidermal thickness, apoptotic cell death, and myeloperoxidase activity, which could be associated with increased skin GSH levels. Together, these results highlight GSH efficacy in ameliorating CEES-caused skin injury and further support the need for effective antioxidant countermeasures against skin injury by HD exposure.

  4. Metal-organic frameworks for the removal of toxic industrial chemicals and chemical warfare agents.

    PubMed

    Bobbitt, N Scott; Mendonca, Matthew L; Howarth, Ashlee J; Islamoglu, Timur; Hupp, Joseph T; Farha, Omar K; Snurr, Randall Q

    2017-06-06

    Owing to the vast diversity of linkers, nodes, and topologies, metal-organic frameworks can be tailored for specific tasks, such as chemical separations or catalysis. Accordingly, these materials have attracted significant interest for capture and/or detoxification of toxic industrial chemicals and chemical warfare agents. In this paper, we review recent experimental and computational work pertaining to the capture of several industrially-relevant toxic chemicals, including NH 3 , SO 2 , NO 2 , H 2 S, and some volatile organic compounds, with particular emphasis on the challenging issue of designing materials that selectively adsorb these chemicals in the presence of water. We also examine recent research on the capture and catalytic degradation of chemical warfare agents such as sarin and sulfur mustard using metal-organic frameworks.

  5. 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.

  6. Hypothermia as an Adjunct Therapy to Vesicant-induced Skin Injury

    PubMed Central

    Sawyer, Thomas W; Nelson, Peggy

    2008-01-01

    Objective: The notion that cooling vesicant-exposed tissue may ameliorate or prevent resultant injury is not a novel concept. During both World Wars, studies were conducted that investigated this potential mode of therapy with sulfur mustard and seemed to conclude that there might be merit in pursuing this research direction. However, it does not appear that these studies were followed up vigorously, and the literature that describes this work is not readily accessible. In this report, we compare the toxicities of lewisite and sulfur mustard in vitro and in vivo and also provide an overview of historical and recent work on the effect of temperature on the toxicity of these vesicating chemical warfare agents.Methods: Tissue culture and animal studies were utilized to examine the effects of hypothermia on vesicant-induced toxicity. Results: Cytotoxicity was either significantly delayed (lewisite) or prevented (sulfur mustard) when cultures were maintained at 25°C. However, the effects of hypothermia on sulfur mustard–induced cell death were reversible when the cells were returned to 37°C. Despite these in vitro results, animal studies demonstrated that the therapeutic cooling of both mustard sulfur–exposed and lewisite-exposed skin resulted in dramatic and permanent protection against injury. Cooling also increased the therapeutic window in which drugs were effective against vesicant agents in tissue culture and lewisite-induced skin injury. Conclusions: The simple and noninvasive application of cooling measures may not only provide significant therapeutic relief to vesicant-exposed skin but also increase the therapeutic window in which medical countermeasures against vesicant agents are useful. PMID:18516227

  7. Fate of chemical warfare agents and toxic industrial chemicals in landfills.

    PubMed

    Bartelt-Hunt, Shannon L; Barlaz, Morton A; Knappe, Detlef R U; Kjeldsen, Peter

    2006-07-01

    One component of preparedness for a chemical attack is planning for the disposal of contaminated debris. To assess the feasibility of contaminated debris disposal in municipal solid waste (MSW) landfills, the fate of selected chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) in MSW landfills was predicted with a mathematical model. Five blister agents [sulfur mustard (HD), nitrogen mustard (HN-2), lewisite (L), ethyldichloroarsine (ED), and phosgene oxime (CX)], eight nerve agents [tabun (GA), sarin (GB), soman (GD), GE, GF, VX, VG, and VM], one riot-control agent [CS], and two TICs [furan and carbon disulfide] were studied. The effects of both infiltration (climate) and contaminant biodegradability on fate predictions were assessed. Model results showed that hydrolysis and gas-phase advection were the principal fate pathways for CWAs and TICs, respectively. Apart from CX and the TICs, none of the investigated compounds was predicted to persist in a landfill for more than 5 years. Climate had little impact on CWA/TIC fate, and biodegradability was only important for compounds with long hydrolysis half-lives. Monte Carlo simulations were performed to assess the influence of uncertainty in model input parameters on CWA/TIC fate predictions. Correlation analyses showed that uncertainty in hydrolysis rate constants was the primary contributor to variance of CWA fate predictions, while uncertainty in the Henry's Law constant and landfill gas-production rate accounted for most of the variance of TIC fate predictions. CWA hydrolysates were more persistent than the parent CWAs, but limited information is available on abiotic or biotic transformation rates for these chemicals.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chang, Yoke-Chen; Wang, James D.; Svoboda, Kathy K.

    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 frommore » 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.« less

  9. Decontamination of adsorbed chemical warfare agents on activated carbon using hydrogen peroxide solutions.

    PubMed

    Osovsky, Ruth; Kaplan, Doron; Nir, Ido; Rotter, Hadar; Elisha, Shmuel; Columbus, Ishay

    2014-09-16

    Mild treatment with hydrogen peroxide solutions (3-30%) efficiently decomposes adsorbed chemical warfare agents (CWAs) on microporous activated carbons used in protective garments and air filters. Better than 95% decomposition of adsorbed sulfur mustard (HD), sarin, and VX was achieved at ambient temperatures within 1-24 h, depending on the H2O2 concentration. HD was oxidized to the nontoxic HD-sulfoxide. The nerve agents were perhydrolyzed to the respective nontoxic methylphosphonic acids. The relative rapidity of the oxidation and perhydrolysis under these conditions is attributed to the microenvironment of the micropores. Apparently, the reactions are favored due to basic sites on the carbon surface. Our findings suggest a potential environmentally friendly route for decontamination of adsorbed CWAs, using H2O2 without the need of cosolvents or activators.

  10. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tewari-Singh, Neera, E-mail: Neera.Tewari-Singh@ucdenver.edu; Jain, Anil K., E-mail: Anil.Jain@ucdenver.edu; Inturi, Swetha, E-mail: Swetha.Inturi@ucdenver.edu

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and everymore » 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost

  11. 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.

  12. Transcriptional changes in porcine skin at 7 days following sulfur mustard and thermal burn injury.

    PubMed

    Price, Jennifer A; Rogers, James V; McDougal, James N; Shaw, Morgan Q; Reid, Frances M; Graham, John S

    2009-01-01

    Severe cutaneous injuries continue to result from exposure to sulfur mustard [bis(2-chloroethyl)sulfide; HD] and thermal burns. Microarray analysis was utilized in this study to evaluate transcriptional changes in porcine skin assessing the underlying repair mechanisms of HD and thermal injury involved in wound healing. Four ventral abdominal sites on each of 4 weanling swine were exposed to 400 microL undiluted HD or a heated brass rod (70 degrees C) for 8 minutes and 45-60 seconds, respectively. At 7 days postexposure, skin samples were excised and total RNA was isolated, labeled, and hybridized to Affymetrix GeneChip (Santa Clara, CA, USA) Porcine Genome Arrays (containing 20,201 genes). Based on the gene expression patterns in HD- and thermal-exposed skin at 7 days, the transcriptional profiles do not differ greatly. HD and thermal exposures promoted similar changes in transcription, where 270 and 283 transcripts were increased with HD and thermal exposures, respectively. Both exposures promoted decreases in 317 and 414 transcripts, respectively. Of the significantly increased transcripts, at least 77% were commonly expressed in both HD- and thermal-exposed skin, whereas at least 67% of decreased transcripts were common between both exposure types. Six of the top 10 biological functions were common to HD and thermal injury in which 9 canonical pathways were shared. The present study illustrates the similarities found between HD and thermal injury with respect to transcriptional response and wound healing and identifies specific genes (CXCL2, CXCR4, FGFR2, HMOX1, IGF1, PF4, PLAU, PLAUR, S100A8, SPP1, and TNC) that may be useful as potential therapeutic targets to promote improved wound healing.

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

    PubMed

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

    2014-06-01

    Chemical warfare agents (CWA) are highly toxic compounds which have been produced to kill or hurt people during conflicts or terrorist attacks. Despite the fact that their use is strictly prohibited according to international convention, populations' exposure still recently occurred. Development of markers of exposure to CWA is necessary to distinguish exposed victims from unexposed ones. We present the first study of hair usage as passive sampler to assess contamination by chemicals in vapour form. This work presents more particularly the hair adsorption capacity for methyl salicylate used as a surrogate of the vesicant sulphur mustard. Chemical vapours toxicity through the respiratory route has historically been defined through Haber's law's concentration-time (Ct) product, and vapour exposure of hair to methyl salicylate was conducted with various times or doses of exposure in the range of incapacitating and lethal Ct products corresponding to sulphur mustard. Following exposure, extraction of methyl salicylate from hair was conducted by simple soaking in dichloromethane. Methyl salicylate could be detected on hair for vapour concentration corresponding to about one fifth of the sulphur mustard concentration that would kill 50% of exposed individuals (LCt50). The amount of methyl salicylate recovered from hair increased with time or dose of exposure. It showed a good correlation with the concentration-time product, suggesting that hair could be used like a passive sampler to assess vapour exposure to chemical compounds. It introduces great perspectives concerning the use of hair as a marker of exposure to CWA. Copyright © 2014 John Wiley & Sons, Ltd.

  14. Chlorambucil (nitrogen mustard) induced impairment of early vascular endothelial cell migration - effects of α-linolenic acid and N-acetylcysteine.

    PubMed

    Steinritz, Dirk; Schmidt, Annette; Simons, Thilo; Ibrahim, Marwa; Morguet, Christian; Balszuweit, Frank; Thiermann, Horst; Kehe, Kai; Bloch, Wilhelm; Bölck, Birgit

    2014-08-05

    Alkylating agents (e.g. sulfur and nitrogen mustards) cause a variety of cell and tissue damage including wound healing disorder. Migration of endothelial cells is of utmost importance for effective wound healing. In this study we investigated the effects of chlorambucil (a nitrogen mustard) on early endothelial cells (EEC) with special focus on cell migration. Chlorambucil significantly inhibited migration of EEC in Boyden chamber and wound healing experiments. Cell migration is linked to cytoskeletal organization. We therefore investigated the distribution pattern of the Golgi apparatus as a marker of cell polarity. Cells are polarized under control conditions, whereas chlorambucil caused an encircling perinuclear position of the Golgi apparatus, indicating non-polarized cells. ROS are discussed to be involved in the pathophysiology of alkylating substances and are linked to cell migration and cell polarity. Therefore we investigated the influence of ROS-scavengers (α-linolenic acid (ALA) and N-acetylcysteine (NAC)) on the impaired EEC migration. Both substances, in particular ALA, improved EEC migration. Notably ALA restored cell polarity. Remarkably, investigations of ROS and RNS biomarkers (8-isoprostane and nitrotyrosine) did not reveal a significant increase after chlorambucil exposure when assessed 24h post exposure. A distinct breakdown of mitochondrial membrane potential (measured by TMRM) that recovered under ALA treatment was observed. In conclusion our results provide compelling evidence that the alkylating agent chlorambucil dramatically impairs directed cellular migration, which is accompanied by perturbations of cell polarity and mitochondrial membrane potential. ALA treatment was able to reconstitute cell polarity and to stabilize mitochondrial potential resulting in improved cell migration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2015-07-01

    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. 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. 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). Exposure to SM could decrease the function of stratum corneum and lipid production as a barrier, even after several years of its exposure.

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

    DTIC Science & Technology

    1993-07-01

    be a very effective alkylating agent for bases in DNA. Even in blood, with a variety of reactive sites, I out of 124 guanine bases was alkylated to...required for effective competition in the ELISA test, although it contained at least as many adducts as the single-stranded DNA. This difference is...competitor. 203 Figure 92: The effect of the concentration of mustard gas to which single-stranded calf-thymus DNA had been exposed on the 50% inhibition

  17. Development of an automated on-line pepsin digestion-liquid chromatography-tandem mass spectrometry configuration for the rapid analysis of protein adducts of chemical warfare agents.

    PubMed

    Carol-Visser, Jeroen; van der Schans, Marcel; Fidder, Alex; Hulst, Albert G; van Baar, Ben L M; Irth, Hubertus; Noort, Daan

    2008-07-01

    Rapid monitoring and retrospective verification are key issues in protection against and non-proliferation of chemical warfare agents (CWA). Such monitoring and verification are adequately accomplished by the analysis of persistent protein adducts of these agents. Liquid chromatography-mass spectrometry (LC-MS) is the tool of choice in the analysis of such protein adducts, but the overall experimental procedure is quite elaborate. Therefore, an automated on-line pepsin digestion-LC-MS configuration has been developed for the rapid determination of CWA protein adducts. The utility of this configuration is demonstrated by the analysis of specific adducts of sarin and sulfur mustard to human butyryl cholinesterase and human serum albumin, respectively.

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

    PubMed

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

    2014-03-01

    Sulfur mustard (SM) is a vesicant warfare agent which causes severe skin injuries. Currently, we lack effective antidotes against SM-induced skin injuries, in part due to lack of appropriate animal model(s) that can be used for efficacy studies in laboratory settings to identify effective therapies. Therefore, to develop a relevant mouse skin injury model, we examined the effects of nitrogen mustard (NM), a primary vesicant and a bifunctional alkylating agent that induces toxic effects comparable to SM. Specifically, we conducted histopathological and immunohistochemical evaluation of several applicable cutaneous pathological lesions following skin NM (3.2mg) exposure for 12-120h in SKH-1 and C57BL/6 mice. NM caused a significant increase in epidermal thickness, incidence of microvesication, cell proliferation, apoptotic cell death, inflammatory cells (neutrophils, macrophages and mast cells) and myleoperoxidase activity in the skin of both mouse strains. However, there was a more prominent NM-induced increase in epidermal thickness, and macrophages and mast cell infiltration, in SKH-1 mice relative to what was seen in C57BL/6 mice. NM also caused collagen degradation and edema at early time points (12-24h); however, at later time points (72 and 120h), dense collagen staining was observed, indicating either water loss or start of integument repair in both the mouse strains. This study provides quantitative measurement of NM-induced histopathological and immunohistochemical cutaneous lesions in both hairless and haired mouse strains that could serve as useful tools for screening and identification of effective therapies for treatment of skin injuries due to NM and SM. Copyright © 2013 Elsevier GmbH. All rights reserved.

  19. Nitrogen Mustard-Induced Corneal Injury Involves DNA Damage and Pathways Related to Inflammation, Epithelial-Stromal Separation, and Neovascularization.

    PubMed

    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

    2016-02-01

    To evaluate the toxic effects and associated mechanisms in corneal tissue exposed to the vesicating agent, nitrogen mustard (NM), a bifunctional alkylating analog of the chemical warfare agent sulfur mustard. Toxic effects and associated mechanisms were examined in maximally affected corneal tissue using corneal cultures and human corneal epithelial (HCE) cells exposed to NM. Analysis of ex vivo rabbit corneas showed that NM exposure increased apoptotic cell death, epithelial thickness, epithelial-stromal separation, and levels of vascular endothelial growth factor, cyclooxygenase 2, and matrix metalloproteinase-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 poly ADP ribose polymerase cleavage, suggesting their involvement in NM-induced apoptotic death in the rabbit cornea and HCE cells. Similar to rabbit cornea, NM exposure caused an increase in cyclooxygenase 2, matrix metalloproteinase-9, and vascular endothelial growth factor 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 activator protein 1 transcription factor proteins and upstream signaling pathways including mitogen-activated protein kinases and Akt protein kinase, suggesting that these could be key factors involved in NM-induced corneal injury. 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.

  20. Development of a co-culture of keratinocytes and immune cells for in vitro investigation of cutaneous sulfur mustard toxicity.

    PubMed

    Balszuweit, Frank; Menacher, Georg; Bloemeke, Brunhilde; Schmidt, Annette; Worek, Franz; Thiermann, Horst; Steinritz, Dirk

    2014-11-05

    Sulfur mustard (SM) is a chemical warfare agent causing skin blistering, ulceration and delayed wound healing. Inflammation and extrinsic apoptosis are known to have an important role in SM-induced cytotoxicity. As immune cells are involved in those processes, they may significantly modulate SM toxicity, but the extent of those effects is unknown. We adapted a co-culture model of immortalized keratinocytes (HaCaT) and immune cells (THP-1) and exposed this model to SM. Changes in necrosis, apoptosis and inflammation, depending on SM challenge, absence or presence and number of THP-1 cells were investigated. THP-1 were co-cultured for 24h prior to SM exposure in order to model SM effects on immune cells continuously present in the skin. Our results indicate that the presence of THP-1 strongly increased necrosis, apoptosis and inflammation. This effect was already significant when the ratio of THP-1 and HaCaT cells was similar to the ratio of Langerhans immune cells and keratinocytes in vivo. Any further increases in the number of THP-1 had only slight additional effects on SM-induced cytotoxicity. In order to assess the effects of immune cells migrating into skin areas damaged by SM, we added non-exposed THP-1 to SM-exposed HaCaT. Those THP-1 had only slight effects on SM-induced cytotoxicity. Notably, in HaCaT exposed to 300μM SM, necrosis and inflammation were slightly reduced by adding intact THP-1. This effect was dependent on the number of immune cells, steadily increasing with the number of unexposed THP-1 added. In summary, we have demonstrated that (a) the presented co-culture is a robust model to assess SM toxicity and can be used to test the efficacy of potential antidotes in vitro; (b) immune cells, damaged by SM strongly amplified cytotoxicity, (c) in contrast, unexposed THP-1 (simulating migration of immune cells into affected areas after exposure in vivo) had no pronounced adverse, but exhibited some protective effects. Thus, protecting immune cells

  1. 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.

  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. Validation of minicams for measuring concentrations of chemical agent in environmental air

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Menton, R.G.; Hayes, T.L.; Chou, Y.L.

    1993-05-13

    Environmental monitoring for chemical agents is necessary to ensure that notification and appropriate action will be taken in the, event that there is a release exceeding control limits of such agents into the workplace outside of engineering controls. Prior to implementing new analytical procedures for environmental monitoring, precision and accuracy (PA) tests are conducted to ensure that an agent monitoring system performs according to specified accuracy, precision, and sensitivity requirements. This testing not only establishes the accuracy and precision of the method, but also determines what factors can affect the method's performance. Performance measures that are particularly important in agentmore » monitoring include the Detection Limit (DL), Decision Limit (DC), Found Action Level (FAL), and the Target Action Level (TAL). PA experiments were performed at Battelle's Medical Research and Evaluation Facility (MREF) to validate the use of the miniature chemical agent monitoring system (MINICAMs) for measuring environmental air concentrations of sulfur mustard (HD). This presentation discusses the experimental and statistical approaches for characterizing the performance of MINICAMS for measuring HD in air.« less

  4. Effect of ionic strength and cationic DNA affinity binders on the DNA sequence selective alkylation of guanine N7-positions by nitrogen mustards

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hartley, J.A.; Forrow, S.M.; Souhami, R.L.

    Large variations in alkylation intensities exist among guanines in a DNA sequence following treatment with chemotherapeutic alkylating agents such as nitrogen mustards, and the substituent attached to the reactive group can impose a distinct sequence preference for reaction. In order to understand further the structural and electrostatic factors which determine the sequence selectivity of alkylation reactions, the effect of increase ionic strength, the intercalator ethidium bromide, AT-specific minor groove binders distamycin A and netropsin, and the polyamine spermine on guanine N7-alkylation by L-phenylalanine mustard (L-Pam), uracil mustard (UM), and quinacrine mustard (QM) was investigated with a modification of the guanine-specificmore » chemical cleavage technique for DNA sequencing. The result differed with both the nitrogen mustard and the cationic agent used. The effect, which resulted in both enhancement and suppression of alkylation sites, was most striking in the case of netropsin and distamycin A, which differed from each other. DNA footprinting indicated that selective binding to AT sequences in the minor groove of DNA can have long-range effects on the alkylation pattern of DNA in the major groove.« less

  5. The effects of sulfur mustard exposure and freezing on transdermal penetration of tritiated water through ex vivo pig skin.

    PubMed

    Payne, O J; Graham, S J; Dalton, C H; Spencer, P M; Mansson, R; Jenner, J; Azeke, J; Braue, E

    2013-02-01

    The percutaneous absorption of tritiated water ((3)H(2)O) through sulfur mustard (SM) exposed abdominal pig skin was measured using in vitro Franz-type static diffusion cells. The barrier function to water permeation following exposure to liquid SM for 8 min and excision 3h later did not change significantly. A small, but statistically significant difference (P<0.05) in steady state penetration (Jss), permeability coefficient (Kp) and lag time (t(L)) of (3)H(2)O was observed between fresh skin and skin stored frozen (-20 °C) for up to two weeks. Steady-state penetration and Kp values were significantly higher (P < 0.05) in skin stored frozen compared with fresh skin. Fresh naïve skin had an average Kp of 1.65 × 10(-3) cm h(-1), whereas frozen naïve skin was 2.04 × 10(-3) cm h(-1). Fresh SM exposed skin had a mean Kp of 1.72 × 10(-3) cm h(-1), whereas frozen SM exposed skin was 2.31 × 10(-3) cm h(-1). Lag times were also shorter (P<0.05) in skin that had been stored frozen. Frozen, SM-exposed porcine abdominal skin may be used for in vitro penetration studies, but effects of treatment and storage on the barrier layer should be taken into account. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. 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.

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

    PubMed Central

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

    2016-01-01

    Sulfur mustard and nitrogen mustard (mechlorethamine, HN2) are potent vesicants developed as chemical warfare agents. These electrophilic, bifunctional alkylating agents cause skin injury, including inflammation, edema, and blistering. HN2 covalently modifies macromolecules such as DNA, RNA, and proteins or is scavenged by glutathione, forming adducts that can contribute to toxicity. Multidrug resistance-associated protein 1 (Mrp1/MRP1) is a transmembrane ATPase known to efflux glutathione-conjugated electrophiles. In the present studies, we examined the effects of modulating Mrp1-mediated transport activity on the sensitivity of primary and PAM212 mouse keratinocytes to HN2. Primary keratinocytes, and to a lesser extent, PAM212 cells, express Mrp1 mRNA and protein and possess Mrp1 functional activity, as measured by calcein efflux. Sulforaphane, an activator of Nrf2, increased Mrp1 mRNA, protein, and functional activity in primary keratinocytes and PAM212 cells and decreased their sensitivity to HN2-induced growth inhibition (IC50 = 1.4 and 4.8 µM in primary keratinocytes and 1 and 13 µM in PAM212 cells, in the absence and presence of sulforaphane, respectively). The Mrp1 inhibitor, MK-571, reversed the effects of sulforaphane on HN2-induced growth inhibition in both primary keratinocytes and PAM212 cells. In primary keratinocytes from Nrf2−/− mice, sulforaphane had no impact on Mrp1 expression or activity, or on sensitivity to HN2, demonstrating that its effects depend on Nrf2. These data suggest that Mrp1-mediated efflux is important in regulating HN2-induced keratinocyte growth inhibition. Enhancing HN2 efflux from keratinocytes may represent a novel strategy for mitigating vesicant-induced cytotoxicity. PMID:26454883

  8. New Methods for Evaluating Skin Injury from Sulfur Mustard in the Hairless Guinea Pig

    DTIC Science & Technology

    1993-05-13

    MUSTARD IN THE HAIRLESS GUINEA PIG Ernest H. Braue, Jr., Catherine R. Bangledorf, and Robert G. Rieder "U.S. Army Medical Research Institute of Chemical...evaluating the skin hydration state. The skin of anesthetized hairless guinea pigs was exposed to saturated HD vapor (1.4mg/ml) at 4 sites for 3, 5, 7, or 9...assessment of skin damage following cutaneous exposure to HD vapor. EXPERIMENTAL METHODS Each hairless guinea pig (HGP) was exposed to saturated HD vapor

  9. [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.

  10. Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice.

    PubMed

    Mouret, Stéphane; Wartelle, Julien; Batal, Mohamed; Emorine, Sandy; Bertoni, Marine; Poyot, Thomas; Cléry-Barraud, Cécile; Bakdouri, Nacera El; Peinnequin, André; Douki, Thierry; Boudry, Isabelle

    2015-01-05

    Sulfur mustard (SM) is a strong bifunctional alkylating agent that produces severe tissue injuries characterized by erythema, edema, subepidermal blisters and a delayed inflammatory response after cutaneous exposure. However, despite its long history, SM remains a threat because of the lack of effective medical countermeasures as the molecular mechanisms of these events remain unclear. This limited number of therapeutic options results in part of an absence of appropriate animal models. We propose here to use SKH-1 hairless mouse as the appropriate model for the design of therapeutic strategies against SM-induced skin toxicity. In the present study particular emphasis was placed on histopathological changes associated with inflammatory responses after topical exposure of dorsal skin to three different doses of SM (0.6, 6 and 60mg/kg) corresponding to a superficial, a second-degree and a third-degree burn. Firstly, clinical evaluation of SM-induced skin lesions using non invasive bioengineering methods showed that erythema and impairment of skin barrier increased in a dose-dependent manner. Histological evaluation of skin sections exposed to SM revealed that the time to onset and the severity of symptoms including disorganization of epidermal basal cells, number of pyknotic nuclei, activation of mast cells and neutrophils dermal invasion were dose-dependent. These histopathological changes were associated with a dose- and time-dependent increase in expression of specific mRNA for inflammatory mediators such as interleukins (IL1β and IL6), tumor necrosis factor (TNF)-α, cycloxygenase-2 (COX-2), macrophage inflammatory proteins (MIP-1α, MIP-2 and MIP-1αR) and keratinocyte chemoattractant (KC also called CXCL1) as well as adhesion molecules (L-selectin and vascular cell adhesion molecule (VCAM)) and growth factor (granulocyte colony-stimulating factor (Csf3)). A dose-dependent increase was also noted after SM exposure for mRNA of matrix metalloproteinases (MMP9

  11. Brassicaceae Mustards: Traditional and Agronomic Uses in Australia and New Zealand.

    PubMed

    Rahman, Mahmudur; Khatun, Amina; Liu, Lei; Barkla, Bronwyn J

    2018-01-21

    Commonly cultivated Brassicaceae mustards, namely garlic mustard ( Alliaria petiolata ), white mustard ( Brassica alba ), Ethiopian mustard ( B. carinata ), Asian mustard ( B. juncea ), oilseed rape ( B. napus ), black mustard ( B. nigra ), rapeseed ( B. rapa ), white ball mustard ( Calepina irregularis ), ball mustard ( Neslia paniculata ), treacle mustard ( Erysimum repandum ), hedge mustard ( Sisymbrium officinale ), Asian hedge mustard ( S. orientale ), smooth mustard ( S. erysimoides ) and canola are the major economically important oilseed crops in many countries. Mustards were naturalized to Australia and New Zealand and Australia is currently the second largest exporter of Brassicaceae oilseeds to meet the global demand for a healthy plant-derived oil, high in polyunsaturated fats. Apart from providing edible oil, various parts of these plants and many of their phytochemicals have been used traditionally for both agronomic as well as medicinal purposes, with evidence of their use by early Australian and New Zealand settlers and also the indigenous population. This review provides an overview of the current knowledge of traditional and agronomic uses of Brassicaceae oilseeds and mustards with a focus on their importance in Australia and New Zealand.

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

    PubMed Central

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

    2013-01-01

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

  13. Occurrence and possible sources of arsenic in seafloor sediments surrounding sea-disposed munitions and chemical agents near O´ahu, Hawai´i

    NASA Astrophysics Data System (ADS)

    Tomlinson, Michael S.; De Carlo, Eric Heinen

    2016-06-01

    The Department of Defense disposed of conventional and chemical munitions as well as bulk containers of chemical agents in US coastal waters including those surrounding the State of Hawai´i. The Hawai´i Undersea Military Munitions Assessment has been collecting biota, water, and sediment samples from two disposal areas south of the island of O´ahu in waters 500 to 600 m deep known to have received both conventional munitions and chemical agents (specifically sulfur mustard). Unlike a number of other sea-disposed munitions investigations which used grabs or corers lowered from surface vessels, we used manned submersibles to collect the samples. Using this approach, we were able to visually identify the munitions and precisely locate our samples in relation to the munitions on the seafloor. This paper focuses on the occurrence and possible sources of arsenic found in the sediments surrounding the disposed military munitions and chemical agents. Using nonparametric multivariate statistical techniques, we looked for patterns in the chemical data obtained from these sediment samples in order to determine the possible sources of the arsenic found in these sediments. The results of the ordination technique nonmetric multidimensional scaling indicate that the arsenic is associated with terrestrial sources and not munitions. This was not altogether surprising given that: (1) the chemical agents disposed of in this area supposedly did not contain arsenic, and (2) the disposal areas studied were under terrestrial influence or served as dredge spoil disposal sites. The sediment arsenic concentrations during this investigation ranged from <1.3 to 40 mg/kg-dry weight with the lower concentrations typically found around control sites and munitions (not located in dredge disposal areas) and the higher values found at dredge disposal sites (with or without munitions). During the course of our investigation we did, however, discover that mercury appears to be loosely associated

  14. 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

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Allon, Nahum, E-mail: nahuma@iibr.gov.i; Amir, Adina; Manisterski, Eliau

    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 fewmore » 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.« less

  16. 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

  17. Poly High Internal Phase Emulsion for the Immobilization of Chemical Warfare Agents.

    PubMed

    Wright, Alexander J; Main, Marcus J; Cooper, Nicholas J; Blight, Barry A; Holder, Simon J

    2017-09-20

    We report a facile method for the absorption (characterized by the weight/weight swelling degree, Q) of a variety of chemical warfare agents (CWAs); including sulfur mustard (HD) (Q = 40) and V-series (VM, VX, i-Bu-VX, n-Bu-VX) of nerve agents (Q ≥ 45) and a simulant, methyl benzoate (Q = 55), through the use of a poly(styrene-co-vinyl benzyl chloride-co-divinylbenzene) lightly cross-linked poly high internal phase emulsion (polyHIPE). By varying the vinyl benzyl chloride (VBC) content and the volume of the internal phase of the precursor emulsion it is demonstrated that absorption is facilitated both by the swelling of the polymer and the uptake of liquid in the pores. In particular the sample prepared from a 95% internal emulsion water content showed rapid swelling (<5 min to total absorption) and the ability to swell both from a monolithic state and from a compressed state, making these systems ideal practical candidates for the rapid immobilization of CWAs.

  18. Sulfur and sulfur nanoparticles as potential antimicrobials: from traditional medicine to nanomedicine.

    PubMed

    Rai, Mahendra; Ingle, Avinash P; Paralikar, Priti

    2016-10-01

    The alarming rate of infections caused by various pathogens and development of their resistance towards a large number of antimicrobial agents has generated an essential need to search for novel and effective antimicrobial agents. Metal nanoparticles such as silver have been widely used and accepted as strong antimicrobial agents, but considering the cost effectiveness and significant bioactivities, researchers are looking to utilize sulfur nanoparticles as an effective alternative to silver nanoparticles. This review has been focused on different approaches for the synthesis of sulfur nanoparticles, their broad spectrum bioactivities and possible mechanisms involved in their bioactivities. Expert commentary: Sulfur nanoparticles are reported to possess broad spectrum antimicrobial activity, and hence can be used to treat microbial infections and potentially tackle the problem of antibiotic resistance. Thus, in the future, sulfur nanoparticles can be used as an effective, non-toxic and economically viable alternative to other precious metal nanoparticles.

  19. Reactions of sulphur mustard on impregnated carbons.

    PubMed

    Prasad, G K; Singh, Beer

    2004-12-31

    Activated carbon of surface area 1100 m2/gm is impregnated with 4% sodium hydroxide plus 3% Cr(VI) as CrO3 with and without 5% ethylene diamine (EDA), 4% magnesium nitrate and 5% ruthenium chloride by using their aqueous solutions. These carbons are characterized for surface area analysis by BET conventional method and exposed to the vapours of sulphur mustard (HD) at room temperature (30 degrees C). After 24 h, the reaction products are extracted in dichloromethane and analyzed using gas chromatography and mass spectrometry (GC-MS). Hemisulphur mustard, thiodiglycol, 1,4-oxathiane are observed to be the products of reaction between sulphur mustard and NaOH/CrO3/C system, whereas on NaOH/CrO3/EDA/C system HD reacted to give 1,4-thiazane. On Mg(NO3)2/C system it gave hemisulphur mustard and thiodiglycol. On RuCl3/C system it degraded to divinyl sulphone. Residual sulphur mustard is observed along with reaction products in all systems studied. Reaction mechanisms are also proposed for these interesting surface reactions. Above-mentioned carbons can be used in filtration systems for protection against hazardous gases such as sulphur mustard.

  20. Therapeutics effect of N-acetyl cysteine on mustard gas exposed patients: evaluating clinical aspect in patients with impaired pulmonary function test.

    PubMed

    Shohrati, Majid; Aslani, Jafar; Eshraghi, Mehdi; Alaedini, Farshid; Ghanei, Mostafa

    2008-03-01

    Long-term prescription of N-acetyl cysteine (NAC) may be effective in diseases caused by active radicals of oxygen species. The aim of this study was to determine the effect of 2- and 4-month administration of NAC (1800 mg daily) on mustard induced bronchiolitis obliterans. In a double blind clinical trial, 144 patients with bronchiolitis obliterans due to sulfur mustard in bronchiolitis obliterans syndrome (BOS) classes 1 and 2, randomly entered Group 1 (n=72, NAC) and Group 2 (n=72, placebo). Dyspnea, wake-up dyspnea, cough, and sputum were measured after 4 months. Spirometric findings were measured at the beginning of the trial, 2 months after and after 4 months of prescription of 1800 mg/day in three doses of NAC or placebo. Dyspnea, cough, sputum, and wake-up dyspnea improved after 4 months of NAC compared to the control group. After 4 months, spirometric components were significantly improved in NAC group compared to placebo group. Fourth months administration of NAC (1800 mg daily) can improve clinical conditions and spirometric findings in mustard exposed in BOS class 1 or 2.

  1. The effect of nightly nasal CPAP treatment on nocturnal hypoxemia and sleep disorders in mustard gas-injured patients.

    PubMed

    Vahedi, Ensieh; Fazeli Varzaneh, Ali Reza; Ghanei, Mostafa; Afsharpaiman, Shahla; Poursaleh, Zohre

    2014-12-01

    Sleep-related breathing disorders are associated with unusual respiratory pattern or an abnormal reduction in gas exchange during sleep that is common in sulfur mustard (SM) exposure. We compared 57 Iranian male patients injured with SM and had any complaints of sleep problems with an age-matched group of 21 Iranian male patients who had complaints of sleep problems and were not chemically injured; this group had Epworth Sleepiness Scale (ESS) above 10 and whom referred for polysomnography. Split-night studies were performed for patients with diagnostic polysomnography for obstructive sleep apnea (OSA) and respiratory events. We then studied respiratory events including episodes of OSA, apnea-hypopnea index (AHI) and respiratory disturbance index (RDI). The mean age in mustard-exposed patients was 48.14±8.04 years and in age-matched group, 48.19±8.39 years. In mustard exposed patients, there were statistical differences for the episodes of OSA (p=0.001), AHI (p=0.001), and RDI (p=0.001) between two segments of split-night studies. In the age-matched group, there were statistically differences for each parameter (episodes of OSA (p=0.001), AHI (p=0.001), and RDI (p=0.001)). There were no significant differences between two groups. This study indicated that the incidence of respiratory events and nocturnal hypoxemia during sleep in mustard-exposed patients were high and treatment with CPAP significantly reduced all these events.

  2. Harmony of computational quantum chemistry and experimental chemistry: Comprehensive DFT studies, microsynthesis, and characterization of mustard gas polysulfide analogues

    NASA Astrophysics Data System (ADS)

    Saeidian, Hamid; Faraz, Sajjad Mousavi; Mirjafary, Zohreh; Babri, Mehran

    2018-05-01

    After microsynthesis, structures of mustard gas polysulfide analogues were characterized using electron impact (EI) mass spectrometry. General EI fragmentation pathways for such compounds are proposed. The structure of sulfur mustard (HD) and its two other polysulfide analogues have been examined through B3LYP/6-311++G(2d, 2p) calculations. Geometrical analysis of HD shows that the calculated bond distances are satisfactorily comparable with experimental results. Calculated NMR chemical shifts for HD also were compared with experimental data, indicating good agreement both for 1H and 13C atoms. The vibrational frequencies of HD and polysulfide analogues have been precisely assigned. At the end, based on visual inspection of lowest unoccupied molecular orbitals and the relative difference in the total energies of their episulfonium ions, relative reactivity of HD and its polysulfide analogues were investigated.

  3. Effect of sulphur mustard on human skin cell lines with differential agent sensitivity.

    PubMed

    Simpson, Rachel; Lindsay, Christopher D

    2005-01-01

    The ability of sulphur mustard (HD) to induce DNA damage places limits on the efficacy of approaches aimed at protecting human cells from the cytotoxic effects of HD using a variety of protective agents such as thiol-containing esters and protease inhibitors. In the present study, potential alternative strategies were investigated by examining the differential effects of HD on G361, SVK14, HaCaT and NCTC 2544 human skin cells. The G361 cell line was more resistant to the cytotoxic effects of HD than the NCTC, HaCaT and SVK14 cell lines at HD doses of >3 and <100 microM HD as determined by the MTT assay. At 72 h after exposure to 60 microM HD there was up to an 8.8-fold difference (P < 0.0001) between G361 and SVK14 cell culture viability. Buthionine sulphoximine (BSO) pretreatment increased the sensitivity of all four cell lines to HD. A substantial proportion of the resistance of G361 cells to HD was attributable to BSO-mediated effects on antioxidant-mediated metabolism, although G361 cultures still retained a high degree of viability at 30 microM HD following BSO pretreatment. Cell cycle analysis confirmed that SVK14 cells were relatively more sensitive to HD, as shown by the 2.1-fold reduction (P < 0.0001) in the percentage of cells in G0/G1 phase 24 h after HD exposure compared with control cultures. This compared well with a 1.2-fold increase (P < 0.05) in the percentage of G361 cells in G0/G1 phase following HD exposure, suggesting the existence of a more efficient G0/G1 checkpoint control mechanism in this cell line. Manipulation of the cell cycle using various modulating agents did not increase the resistance of cell lines to the cytotoxic effects of HD. Crown copyright 2005

  4. Iron oxide functionalized graphene nano-composite for dispersive solid phase extraction of chemical warfare agents from aqueous samples.

    PubMed

    Chinthakindi, Sridhar; Purohit, Ajay; Singh, Varoon; Tak, Vijay; Goud, D Raghavender; Dubey, D K; Pardasani, Deepak

    2015-05-15

    Present study deals with the preparation and evaluation of graphene based magnetic nano-composite for dispersive solid phase extraction of Chemical Weapons Convention (CWC) relevant chemicals from aqueous samples. Nano-composite, Fe3O4@SiO2-G was synthesized by covalently bonding silica coated Fe3O4 onto the graphene sheets. Nerve agents (NA), Sulfur mustard (SM) and their non-toxic environmental markers were the target analytes. Extraction parameters like amount of sorbent, extraction time and desorption conditions were optimized. Dispersion of 20 milligram of sorbent in 200mL of water sample for 20min. followed by methanol/chloroform extraction produced average to good recoveries (27-94%) of targeted analytes. Recoveries of real agents exhibited great dependency upon sample pH and ionic strength. Sarin produced maximum recovery under mild acidic conditions (56% at pH 5) while VX demanded alkaline media (83% at pH 9). Salts presence in the aqueous samples was found to be advantageous, raising the recoveries to as high as 94% for SM. Excellent limits of detection (LOD) for sulphur mustard and VX (0.11ngmL(-1) and 0.19ngmL(-1) respectively) proved the utility of the developed method for the off-site analysis of CWC relevant chemicals. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Identification of chemical warfare agents from vapor samples using a field-portable capillary gas chromatography/membrane-interfaced electron ionization quadrupole mass spectrometry instrument with Tri-Bed concentrator.

    PubMed

    Nagashima, Hisayuki; Kondo, Tomohide; Nagoya, Tomoki; Ikeda, Toru; Kurimata, Naoko; Unoke, Shohei; Seto, Yasuo

    2015-08-07

    A field-portable gas chromatograph-mass spectrometer (Hapsite ER system) was evaluated for the detection of chemical warfare agents (CWAs) in the vapor phase. The system consisted of Tri-Bed concentrator gas sampler (trapping time: 3s(-1)min), a nonpolar low thermal-mass capillary gas chromatography column capable of raising temperatures up to 200°C, a hydrophobic membrane-interfaced electron ionization quadrupole mass spectrometer evacuated by a non-evaporative getter pump for data acquisition, and a personal computer for data analysis. Sample vapors containing as little as 22μg sarin (GB), 100μg soman (GD), 210μg tabun (GA), 55μg cyclohexylsarin (GF), 4.8μg sulfur mustard, 390μg nitrogen mustard 1, 140μg of nitrogen mustard 2, 130μg nitrogen mustard 3, 120μg of 2-chloroacetophenone and 990μg of chloropicrin per cubic meter could be confirmed after Tri-Bed micro-concentration (for 1min) and automated AMDIS search within 12min. Using manual deconvolution by background subtraction of neighboring regions on the extracted ion chromatograms, the above-mentioned CWAs could be confirmed at lower concentration levels. The memory effects were also examined and we found that blister agents showed significantly more carry-over than nerve agents. Gasoline vapor was found to interfere with the detection of GB and GD, raising the concentration limits for confirmation in the presence of gasoline by both AMDIS search and manual deconvolution; however, GA and GF were not subject to interference by gasoline. Lewisite 1, and o-chlorobenzylidene malononitrile could also be confirmed by gas chromatography, but it was hard to quantify them. Vapors of phosgene, chlorine, and cyanogen chloride could be confirmed by direct mass spectrometric detection at concentration levels higher than 2, 140, and 10mg/m(3) respectively, by bypassing the micro-concentration trap and gas chromatographic separation. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2016-09-01

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

  7. Mercury-induced oxidative stress in Indian mustard (Brassica juncea L.).

    PubMed

    Shiyab, Safwan; Chen, Jian; Han, Fengxiang X; Monts, David L; Matta, Fank B; Gu, Mengmeng; Su, Yi; Masad, Motasim A

    2009-10-01

    Mercury, a potent neurotoxin, is released to the environment in significant amounts by both natural processes and anthropogenic activities. No natural hyperaccumulator plant has been reported for mercury phytoremediation. Few studies have been conducted on the physiological responses of Indian mustard, a higher biomass plant with faster growth rates, to mercury pollution. This study investigated the phytotoxicity of mercury to Indian mustard (Brassica juncea L.) and mercury-induced oxidative stress in order to examine the potential application of Indian mustard to mercury phytoremediation. Two common cultivars (Florida Broadleaf and Longstanding) of Indian mustard were grown hydroponically in a mercury-spiked solution. Plant uptake, antioxidative enzymes, peroxides, and lipid peroxidation under mercury stress were investigated. Antioxidant enzymes (catalase, CAT; peroxidase, POD; and superoxide dismutase, SOD) were the most sensitive indices of mercury-induced oxidative response of Indian mustard plants. Indian mustard effectively generated an enzymatic antioxidant defense system (especially CAT) to scavenge H(2)O(2), resulting in lower H(2)O(2) in shoots with higher mercury concentrations. These two cultivars of Indian mustard demonstrated an efficient metabolic defense and adaptation system to mercury-induced oxidative stress. A majority of Hg was accumulated in the roots and low translocations of Hg from roots to shoots were found in two cultivars of Indian mustard. Thus Indian mustard might be a potential candidate plant for phytofiltration/phytostabilization of mercury contaminated waters and wastewater.

  8. 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

  9. Screening of nitrogen mustards and their degradation products in water and decontamination solution by liquid chromatography-mass spectrometry.

    PubMed

    Chua, Hoe-Chee; Lee, Hoi-Sim; Sng, Mui-Tiang

    2006-01-13

    Analysing nitrogen mustards and their degradation products in decontamination emulsions posed a significant challenge due to the different phases present in such matrices. Extensive sample preparation may be required to isolate target analytes. Furthermore, numerous reaction products are formed in the decontamination emulsion. A fast and effective qualitative screening procedure was developed for these compounds, using liquid chromatography-mass spectrometry (LC-MS). This eliminated the need for additional sample handling and derivatisation that are required for gas chromatographic-mass spectrometric (GC-MS) analysis. A liquid chromatograph with mixed mode column and isocratic elution gave good chromatography. The feasibility of applying this technique for detecting these compounds in spiked water and decontamination emulsion was demonstrated. Detailed characterisation of the degradation products in these two matrices was carried out. The results demonstrated that N-methyldiethanolamine (MDEA), N-ethyldiethanolamine (EDEA) and triethanolamine (TEA) are not the major degradation products of their respective nitrogen mustards. Degradation profiles of nitrogen mustards in water were also established. In verification analysis, it is important not only to develop methods for the identification of the actual chemical agents; the methods must also encompass degradation products of the chemical agents as well so as to exclude false negatives. This study demonstrated the increasingly pivotal role that LC-MS play in verification analysis.

  10. 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.

  11. Method for Derivatization and Detection of Chemical Weapons Convention Related Sulfur Chlorides via Electrophilic Addition with 3-Hexyne.

    PubMed

    Goud, D Raghavender; Pardasani, Deepak; Purohit, Ajay Kumar; Tak, Vijay; Dubey, Devendra Kumar

    2015-07-07

    Sulfur monochloride (S2Cl2) and sulfur dichloride (SCl2) are important precursors of the extremely toxic chemical warfare agent sulfur mustard and classified, respectively, into schedule 3.B.12 and 3.B.13 of the Chemical Weapons Convention (CWC). Hence, their detection and identification is of vital importance for verification of CWC. These chemicals are difficult to detect directly using chromatographic techniques as they decompose and do not elute. Until now, the use of gas chromatographic approaches to follow the derivatized sulfur chlorides is not reported in the literature. The electrophilic addition reaction of sulfur monochloride and sulfur dichloride toward 3-hexyne was explored for the development of a novel derivatization protocol, and the products were subjected to gas chromatography-mass spectrometric (GC-MS) analysis. Among various unsaturated reagents like alkenes and alkynes, symmetrical alkyne 3-hexyne was optimized to be the suitable derivatizing agent for these analytes. Acetonitrile was found to be the suitable solvent for the derivatization reaction. The sample preparation protocol for the identification of these analytes from hexane spiked with petrol matrix was also optimized. Liquid-liquid extraction followed by derivatization was employed for the identification of these analytes from petrol matrix. Under the established conditions, the detection and quantification limits are 2.6 μg/mL, 8.6 μg/mL for S2Cl2 and 2.3 μg/mL, 7.7 μg/mL for SCl2, respectively, in selected ion monitoring (SIM) mode. The calibration curve had a linear relationship with y = 0.022x - 0.331 and r(2) = 0.992 for the working range of 10 to 500 μg/mL for S2Cl2 and y = 0.007x - 0.064 and r(2) = 0.991 for the working range of 10 to 100 μg/mL for SCl2, respectively. The intraday RSDs were between 4.80 to 6.41%, 2.73 to 6.44% and interday RSDs were between 2.20 to 7.25% and 2.34 to 5.95% for S2Cl2 and SCl2, respectively.

  12. 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.

  13. 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 Central

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

    2011-01-01

    Bifunctional alkyalating agent, Sulfur mustard (SM)-caused 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 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 COX-2, iNOS, and MMP-9 levels, indicating the involvement of DNA damage and inflammation in CEES-caused 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-caused DNA damage and the induction of inflammatory molecules. Oral GSH (300mg/kg) administration 1 h 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 injuries involve 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 injuries in humans by SM. PMID:21722719

  14. Impairment of hypoxia-induced HIF-1α signaling in keratinocytes and fibroblasts by sulfur mustard is counteracted by a selective PHD-2 inhibitor.

    PubMed

    Deppe, Janina; Popp, Tanja; Egea, Virginia; Steinritz, Dirk; Schmidt, Annette; Thiermann, Horst; Weber, Christian; Ries, Christian

    2016-05-01

    Skin exposure to sulfur mustard (SM) provokes long-term complications in wound healing. Similar to chronic wounds, SM-induced skin lesions are associated with low levels of oxygen in the wound tissue. Normally, skin cells respond to hypoxia by stabilization of the transcription factor hypoxia-inducible factor 1 alpha (HIF-1α). HIF-1α modulates expression of genes including VEGFA, BNIP3, and MMP2 that control processes such as angiogenesis, growth, and extracellular proteolysis essential for proper wound healing. The results of our studies revealed that exposure of primary normal human epidermal keratinocytes (NHEK) and primary normal human dermal fibroblasts (NHDF) to SM significantly impaired hypoxia-induced HIF-1α stabilization and target gene expression in these cells. Addition of a selective inhibitor of the oxygen-sensitive prolyl hydroxylase domain-containing protein 2 (PHD-2), IOX2, fully recovered HIF-1α stability, nuclear translocation, and target gene expression in NHEK and NHDF. Moreover, functional studies using a scratch wound assay demonstrated that the application of IOX2 efficiently counteracted SM-mediated deficiencies in monolayer regeneration under hypoxic conditions in NHEK and NHDF. Our findings describe a pathomechanism by which SM negatively affects hypoxia-stimulated HIF-1α signaling in keratinocytes and fibroblasts and thus possibly contributes to delayed wound healing in SM-injured patients that could be treated with PHD-2 inhibitors.

  15. 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

  16. Sensory evaluation of dry-fermented sausage containing ground deodorized yellow mustard.

    PubMed

    Li, Shuliu; Aliani, Michel; Holley, Richard A

    2013-10-01

    Ground deodorized yellow mustard is used as a binder and meat protein substitute in cooked processed meat products. Recent studies have shown that it has the potential to be used in uncooked processed meat products because of its natural antimicrobial properties. In the present study, ground deodorized yellow mustard was added to uncooked dry-fermented sausage during manufacture at 1% to 4% (w/w) and analyzed for its effects on starter cultures, physico-chemical properties, and consumer acceptability. Mustard had a nondose-dependent inhibitory effect on the Staphylococcus starter culture, had no effect on water activity or instrumental texture, and tended to accelerate sausage pH reduction. At 3% and 4% mustard, consumer scores on all sensory attributes as well as overall acceptability were significantly lower. The appearance and color of 3% and 4% mustard-treated sausages were liked slightly, whereas flavor, texture, and overall acceptability scores were reduced. The control without mustard and 1% mustard-treated sausages had similar sensory properties and were the most acceptable, while 2% mustard-treated sausages were given "like moderately" and "like slightly" descriptors. Sensory results mean that at concentrations necessary for mandated regulatory control of Escherichia coli O157:H7 in dry sausages, mustard may have a negative effect on consumer acceptance. © 2013 Institute of Food Technologists®

  17. 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.

  18. 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...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...in a animal model of an HO contaminated wound. The euthymic hairless guinea pig (EHGP) has been extensrvely studied and aicepted as the model of

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

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

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

  20. Evaluation of the Effectiveness of Five Odor Reducing Agents for Sewer System Odors Using an On-Line Total Reduced Sulfur Analyzer

    PubMed Central

    Choi, Il; Lee, Hyunjoo; Shin, Joungdu; Kim, Hyunook

    2012-01-01

    Sewer odors have been a concern to citizens of the Metropolitan Seoul region, which has installed combined sewer systems (CSSs) in 86% of its area. Although a variety of odorants are released from sewers, volatile sulfur compounds (VSCs) have been recognized as major ones. A number of technologies have been proposed to monitor or control odors from sewers. One of the most popular strategies adopted for the control of sewage odor is by applying a commercial odor-reducing agent into the sewer. In this study, the effectiveness of five different commercial odor-reducing agents (i.e., an odor masking agent, an alkaline solution, two microbial agents, and a chemical oxidant) was evaluated by continuously monitoring VSCs released from the sewer with an on-line total reduced sulfur (TRS) analyzer before and after each agent was sprayed into CSSs at five different locations of the city. In short, when the effectiveness of odor treatment was tested in the sewer system using five commercial odor reducing treatments, only the chemical oxidant was good enough to reduce the odor in terms of TRS levels measured before and after the application (p < 0.01). PMID:23223148

  1. Competitive Interactions of Garlic Mustard (Alliaria petiolata) and Damesrocket (Hesperis matronalis)

    USGS Publications Warehouse

    Leicht-Young, Stacey A.; Pavlovic, Noel B.; Adams, Jean V.

    2012-01-01

    Competitive interactions between native plants and nonnative, invasive plant species have been extensively studied; however, within degraded landscapes, the effect of interspecific interactions among invasive plants is less explored. We investigated a competitive interaction between two sympatric, invasive mustard species that have similar life history strategies and growth forms: garlic mustard and damesrocket. Greenhouse experiments using a full range of reciprocal density ratios were conducted to investigate interspecific competition. Garlic mustard had a negative effect on the final biomass, number of leaves, and relative growth rate in height of damesrocket. Survival of damesrocket was not negatively affected by interspecific competition with garlic mustard; however, garlic mustard showed higher mortality because of intraspecific competition. These results indicated that although garlic mustard has been observed to be the dominant species in this landscape, it may not completely outcompete damesrocket in all situations. Studies of invasive species in competition are important in degraded landscapes because this is the common situation in many natural areas.

  2. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    .... Harvest. Combining or threshing for seed. A crop that is swathed prior to combining is not considered... contained in the Basic Provisions, mustard seed must be planted in rows. Acreage planted in any other manner... written agreement. Processor. Any business enterprise regularly engaged in buying and processing mustard...

  3. 7 CFR 457.168 - Mustard crop insurance provisions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .... Harvest. Combining or threshing for seed. A crop that is swathed prior to combining is not considered... contained in the Basic Provisions, mustard seed must be planted in rows. Acreage planted in any other manner... written agreement. Processor. Any business enterprise regularly engaged in buying and processing mustard...

  4. Toxicology Studies of Lewisite and Sulfur Mustard Agents: Genetic Toxicity of Lewisite (L) in Chinese Hamster Ovary Cells

    DTIC Science & Technology

    1989-05-31

    Density at 20°C: 1.888 g/ml State: Dark, oily liquid (stable in steel and glass ) Vapor pressure at 200C: 0.394 m Decomposition temperature: >1000C...Bradley, M.O., B. Bhuyan, M.C. Francis, R. Langenbach, A. Peterson and E. Huberman !981 Mutagenesis by chemical agents in V79 Chinese haaster ceill : a

  5. Blaptica dubia as sentinels for exposure to chemical warfare agents - a pilot study.

    PubMed

    Worek, Franz; Seeger, Thomas; Neumaier, Katharina; Wille, Timo; Thiermann, Horst

    2016-11-16

    The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e.g. lack of automated, remote warning and detection of primarily low volatile chemical warfare agents. An alternative approach is the use of animals as sentinels for exposure to toxic chemicals. To overcome disadvantages of vertebrates the present pilot study was initiated to investigate the suitability of South American cockroaches (Blaptica dubia) as warning system for exposure to chemical warfare nerve and blister agents. Initial in vitro experiments with nerve agents showed an increasing inhibitory potency in the order tabun - cyclosarin - sarin - soman - VX of cockroach cholinesterase. Exposure of cockroaches to chemical warfare agents resulted in clearly visible and reproducible reactions, the onset being dependent on the agent and dose. With nerve agents the onset was related to the volatility of the agents. The blister agent lewisite induced signs largely comparable to those of nerve agents while sulfur mustard exposed animals exhibited a different sequence of events. In conclusion, this first pilot study indicates that Blaptica dubia could serve as a warning system to exposure of chemical warfare agents. A cockroach-based system will not detect or identify a particular chemical warfare agent but could trigger further actions, e.g. specific detection and increased protective status. By designing appropriate boxes with (IR) motion sensors and remote control (IR) camera automated off-site warning systems could be realized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Characterisation of a LoVo subline resistant to a benzoyl mustard derivative of distamycin A (FCE 24517).

    PubMed Central

    Capolongo, L.; Melegaro, G.; Broggini, M.; Mongelli, N.; Grandi, M.

    1993-01-01

    Human colon adenocarcinoma cells (LoVo) resistant to the new antitumor agent FCE 24517 [benzoyl-mustard derivative of distamycin A] (LoVo/24517) are resistant to the selecting agent and related molecules as well as to vinblastine, with marginal or no resistance to other antitumour drugs. Treatment with verapamil, tamoxifen, nicergoline or cyclosporin A only partially restores the activity of FCE 24517 against LoVo/24517 cells. Such results suggest that resistance mechanisms possible specific for this class of compounds are operating. Images Figure 2 PMID:8105866

  7. Measurement of breakthrough volumes of volatile chemical warfare agents on a poly(2,6-diphenylphenylene oxide)-based adsorbent and application to thermal desorption-gas chromatography/mass spectrometric analysis.

    PubMed

    Kanamori-Kataoka, Mieko; Seto, Yasuo

    2015-09-04

    To establish adequate on-site solvent trapping of volatile chemical warfare agents (CWAs) from air samples, we measured the breakthrough volumes of CWAs on three adsorbent resins by an elution technique using direct electron ionization mass spectrometry. The trapping characteristics of Tenax(®) TA were better than those of Tenax(®) GR and Carboxen(®) 1016. The latter two adsorbents showed non-reproducible breakthrough behavior and low VX recovery. The specific breakthrough values were more than 44 (sarin) L/g Tenax(®) TA resin at 20°C. Logarithmic values of specific breakthrough volume for four nerve agents (sarin, soman, tabun, and VX) showed a nearly linear correlation with the reciprocals of their boiling points, but the data point of sulfur mustard deviated from this linear curve. Next, we developed a method to determine volatile CWAs in ambient air by thermal desorption-gas chromatography (TD-GC/MS). CWA solutions that were spiked into the Tenax TA(®) adsorbent tubes were analyzed by a two-stage TD-GC/MS using a Tenax(®) TA-packed cold trap tube. Linear calibration curves for CWAs retained in the resin tubes were obtained in the range between 0.2pL and 100pL for sarin, soman, tabun, cyclohexylsarin, and sulfur mustard; and between 2pL and 100pL for VX and Russian VX. We also examined the stability of CWAs in Tenax(®) TA tubes purged with either dry or 50% relative humidity air under storage conditions at room temperature or 4°C. More than 80% sarin, soman, tabun, cyclohexylsarin, and sulfur mustard were recovered from the tubes within 2 weeks. In contrast, the recoveries of VX and Russian VX drastically reduced with storage time at room temperature, resulting in a drop to 10-30% after 2 weeks. Moreover, we examined the trapping efficiency of Tenax TA(®) adsorbent tubes for vaporized CWA samples (100mL) prepared in a 500mL gas sampling cylinder. In the concentration range of 0.2-2.5mg/m(3), >50% of sarin, soman, tabun, cyclohexylsarin, and HD were

  8. 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).

  9. Evaporation Rates of Chemical Warfare Agents Using 5-CM Wind Tunnels I. CASARM Sulfur Mustard (HD) from Glass

    DTIC Science & Technology

    2008-10-01

    Blank CONTENTS 1. INTRODUCTION 9 2. EXPERIMENTAL PROCEDURES 9 2.1 Wind Tunnel 9 2.2 Agent 10 2.3 Gas Chromatography /Mass Spectrometry Detection 10...protective equipment. 2.3 Gas Chromatography /Mass Spectrometry Detection (GC/MSD) The GC/MSD analysis of the thermal desorption tubes was performed on a...coupled to thermal desorption tubes that were analyzed using gas chromatography /mass spectrometry detection (GC/MSD). Differences between the tunnels

  10. 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.

  11. Sulfur Mustard

    MedlinePlus

    ... Cyanogen chloride (CK) Digitalis Case Definition: Digitalis Poisoning Ethylene glycol Fentanyls and other opioids Case Definition: Opioids ( ... Thallium Toxic alcohols Case Definition: Toxic Alcohol Poisoning Ethylene glycol Trichothecene Case Definition: Trichothecene Mycotoxin Poisoning Unidentified ...

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

    PubMed Central

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

    2002-01-01

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

  13. A Polyoxoniobate-Polyoxovanadate Double-Anion Catalyst for Simultaneous Oxidative and Hydrolytic Decontamination of Chemical Warfare Agent Simulants.

    PubMed

    Dong, Jing; Hu, Jufang; Chi, Yingnan; Lin, Zhengguo; Zou, Bo; Yang, Song; Hill, Craig L; Hu, Changwen

    2017-04-10

    A novel double-anion complex, H 13 [(CH 3 ) 4 N] 12 [PNb 12 O 40 (V V O) 2 ⋅(V IV 4 O 12 ) 2 ]⋅22 H 2 O (1), based on bicapped polyoxoniobate and tetranuclear polyoxovanadate was synthesized, characterized by routine techniques and used in the catalytic decontamination of chemical warfare agents. Under mild conditions, 1 catalyzes both hydrolysis of the nerve agent simulant, diethyl cyanophosphonate (DECP) and selective oxidation of the sulfur mustard simulant, 2-chloroethyl ethyl sulfide (CEES). In the oxidative decontamination system 100 % CEES was transformed selectively to nontoxic 2-chloroethyl ethyl sulfoxide and vinyl ethyl sulfoxide using nearly stoichiometric 3 % aqueous H 2 O 2 with a turnover frequency (TOF) of 16 000 h -1 . Importantly, the catalytic activity is maintained even after ten recycles and CEES is completely decontaminated in 3 mins without formation of the highly toxic sulfone by-product. A three-step oxidative mechanism is proposed. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Efficacy of liquid and foam decontamination technologies for chemical warfare agents on indoor surfaces.

    PubMed

    Love, Adam H; Bailey, Christopher G; Hanna, M Leslie; Hok, Saphon; Vu, Alex K; Reutter, Dennis J; Raber, Ellen

    2011-11-30

    Bench-scale testing was used to evaluate the efficacy of four decontamination formulations on typical indoor surfaces following exposure to the liquid chemical warfare agents sarin (GB), soman (GD), sulfur mustard (HD), and VX. Residual surface contamination on coupons was periodically measured for up to 24h after applying one of four selected decontamination technologies [0.5% bleach solution with trisodium phosphate, Allen Vanguard Surface Decontamination Foam (SDF™), U.S. military Decon Green™, and Modec Inc. and EnviroFoam Technologies Sandia Decontamination Foam (DF-200)]. All decontamination technologies tested, except for the bleach solution, performed well on nonporous and nonpermeable glass and stainless-steel surfaces. However, chemical agent residual contamination typically remained on porous and permeable surfaces, especially for the more persistent agents, HD and VX. Solvent-based Decon Green™ performed better than aqueous-based bleach or foams on polymeric surfaces, possibly because the solvent is able to penetrate the polymer matrix. Bleach and foams out-performed Decon Green for penetrating the highly polar concrete surface. Results suggest that the different characteristics needed for an ideal and universal decontamination technology may be incompatible in a single formulation and a strategy for decontaminating a complex facility will require a range of technologies. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Identification and validation of vesicant therapeutic targets using a high, throughput siRNA screening approach

    DTIC Science & Technology

    2014-12-24

    toxlet.2011.04.007 Rogers JV, Choi YW, Kiser RC et al (2004) Microarray analysis of gene expression in murine skin exposed to sulfur mustard. J Bio...Chemotactic factors released in culture by intact developing and healing skin lesions produced in rabbits by the irritant sulfur mustard. Inflam- mation 21(2...Project ID Number CBM.CUTOC.04.10. RC 00114. ABSTRACT See reprint. 15. SUBJECT TERMS sulfur mustard, cutaneous injury, siRNA, high-throughput screening

  16. Effects of anti-inflammatory compounds on sulfur mustard injured cells: Recommendations and caveats suggested by in vitro cell culture models.

    PubMed

    Menacher, Georg; Steinritz, Dirk; Schmidt, Annette; Popp, Tanja; Worek, Franz; Gudermann, Thomas; Thiermann, Horst; Balszuweit, Frank

    2018-09-01

    Sulfur mustard (SM) is a vesicant agent who had its first military use 100 years ago, in Ypres. Since then it has been used in several conflicts like the Iran-Iraq war in the 1980s. The use of SM in Syria 2015 indicated the still existing threat. Despite decades of research no causal antidote against SM intoxication is available, so far. A SM intoxication is accompanied by necrosis, apoptosis and inflammation. To counteract the SM-induced inflammation, glucocorticoids and non-steroidal anti-inflammatory compounds (NSAIDs) are recommended. Aim of this study was to evaluate the efficacy of the anti-inflammatory compounds dexamethasone, ibuprofen and diclofenac in vitro. For that purpose, two different cell culture models were used. Firstly, a monoculture of keratinocytes (HaCaT) and secondly, an established co-culture of keratinocytes (HaCaT) and immunocompetent cells (THP-1) to identify the role of immune cells in the process and to mimic the dermal physiology more closely. Both models were challenged with different SM concentrations (100, 200 and 300μM) and treated with different anti-inflammatory compounds one hour after the SM exposure. Analytical analysis of necrosis (ToxiLight), apoptosis (CDDE) and inflammation (IL-6 and -8 ELISAs) followed 24h thereafter. Dexamethasone provided small but consistent protective effects in the monoculture. For the reduction of apoptosis, 3μM dexamethasone was sufficient. The most effective reduction regarding interleukin (IL) production was found with 6μM dexamethasone. Protective effects were less pronounced in co-culture, which implies, that the protective effects of dexamethasone are rather generic and not due to a modulation of the immune cells. Against our expectations, ibuprofen strongly amplified apoptosis and necrosis in SM exposed cells in the monoculture as well as the co-culture. Therefore, use of ibuprofen for treatment of SM intoxication should at least be considered most critically, if not even regarded as

  17. Patterns of cross-sensitivity in the responses of clonal subpopulations isolated from the RIF-1 mouse sarcoma to selected nitrosoureas and nitrogen mustards.

    PubMed Central

    Reeve, J. G.; Wright, K. A.; Workman, P.

    1984-01-01

    The response of clonal subpopulations isolated from the RIF-1 mouse sarcoma to melphalan treatment is independent of cell ploidy, whereas a clear relationship exists between ploidy and cell sensitivity to CCNU treatment. In the present study RIF-1 clones have been exposed to nitrogen mustard, aniline mustard and chlorambucil, and to nitrosoureas BCNU, MeCCNU and chlorozotocin, in order to evaluate whether or not the different physiochemical and biological activities of these agents would affect the patterns of drug sensitivity obtained for melphalan and CCNU. Irrespective of the different lipophilicities, transport properties and chemical reactivities of the nitrogen mustards, RIF-1 clones showed the same pattern of sensitivity as previously observed for melphalan. Similarly, RIF-1 clones when exposed to nitrosoureas BCNU, MeCCNU and chlorozotocin, showed the same pattern of sensitivity as that obtained for CCNU exposure. These data suggest (a) that the variation in the sensitivity of RIF-1 clones to treatment by the nitrogen mustards is unlikely to reflect differences in either membrane permeability or in drug transport and (b) that the ploidy dependent nitrosourea responses shown by RIF-1 clones similarly do not reflect differences in drug uptake. PMID:6466534

  18. Pacific Northwest Condiment Yellow Mustard (Sinapis alba L.) Grower Guide: 2000-2002

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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.

  19. Characterization of acute and long-term sulfur mustard-induced skin injuries in hairless guinea-pigs using non-invasive methods.

    PubMed

    Dachir, Shlomit; Cohen, Maayan; Fishbeine, Eliezer; Sahar, Rita; Brandies, Rachel; Horwitz, Vered; Kadar, Tamar

    2010-02-01

    Skin exposure to sulfur mustard (HD) results in erythema, edema and severe injury, which take long time to heal and might impose a heavy burden on the health system. Despite many years of research, there is no treatment that prevents the development of the cytotoxic effects of HD causing acute and prolonged damage to the skin. Therefore, it is of great importance to develop treatments that will ameliorate the extent of injury and improve as well as shorten the healing process. The aim of the present study was to establish a small animal model for a long-term HD-induced skin injury using the hairless guinea-pig (HGP) and to further test the efficacy of anti-inflammatories in ameliorating the pathology. HGPs were exposed to HD vapor on four sites for various time durations (1, 5, 10, 15 and 30 min). Clinical evaluation was conducted using reflectance colorimetry, transepidermal water loss and wound-area measurements. Biochemical [prostaglandin (PGE) content and metalloproteinase-9 (MMP-9) activity] and histopathological evaluations were conducted up to 2 weeks post-exposure. Typical symptoms of HD skin injury developed including erythema and edema and the extent of injury was closely related to the exposure duration. Histological evaluation revealed severe edema, infiltration of inflammatory cells, damage to basal cells and vesication. By 2 weeks, healing was not completed, impaired basement membrane and epithelial hyperplasia were observed. PGE content and MMP-9 activity increased at 2 h post-exposure; however, while PGE returned to baseline levels within 24 h, MMP-9 remained elevated at least up to 48 h. Furthermore, a short-term, topical, anti-inflammatory post-exposure treatment was effective in reducing the extent of the acute injury. These results indicate that the effects of HD on HGP skin are similar to previously shown effects in the pig model and in humans and therefore support the use of the HGP as an animal model for long-term effects of HD on skin injury

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

    PubMed

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

    2014-01-01

    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. 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. 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. 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.

  1. 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

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

    PubMed

    Jõul, Piia; Vaher, Merike; Kuhtinskaja, Maria

    2018-05-01

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

  3. Method for removing elemental sulfur in sour gas wells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sample, T.E. Jr.

    1975-09-30

    A process is described for removing sulfur deposits from sour gas wells. The formation, well, and surface equipment are contacted with a chemical composition whose aqueous solution will solubilize the sulfur by primary chemical reaction and contains a wetting agent to facilitate and accelerate the sulfur dissolution and removal. The wetting agent or surfactant may be any of a wide variety of surface-active substances such as soaps, sodium or ammonium salts of alkyl or alkyl-aryl sulfates and sulfonates. Nonionic surfactants are preferred, such as ethoxylated substituted phenols. The aqueous solvents are capable of chemically reacting with sulfur to form water-solublemore » sulfur derivatives and include aqueous solutions of alkalies, bases (both inorganic and organic), ammonia, sulfites, bisulfites, etc. (6 claims)« less

  4. Mid-wave infrared hyperspectral imaging of unknown chemical warfare agents

    NASA Astrophysics Data System (ADS)

    Clewes, Rhea J.; Howle, Chris R.; Guicheteau, Jason; Emge, Darren; Ruxton, Keith; Robertson, Gordon; Miller, William; Malcolm, Graeme; Maker, Gareth T.

    2013-05-01

    The ability of a stand-off chemical detector to distinguish two different chemical warfare agents is demonstrated in this paper. Using Negative Contrast Imaging, based upon IR absorption spectroscopy, we were able to detect 1 μl of VX, sulfur mustard and water on a subset of representative surfaces. These experiments were performed at a range of 1.3 metres and an angle of 45° to the surface. The technique employed utilises a Q-switched intracavity MgO:PPLN crystal that generated 1.4 - 1.8 μm (shortwave) and 2.6 - 3.6 μm (midwave) infrared radiation (SWIR and MWIR, respectively). The MgO:PPLN crystal has a fanned grating design which, via translation through a 1064 nm pump beam, enables tuning through the SWIR and MWIR wavelength ranges. The SWIR and MWIR beams are guided across a scene via a pair of raster scanned mirrors allowing detection of absorption features within these spectral regions. This investigation exploited MWIR signatures, as they provided sufficient molecular information to distinguish between toxic and benign chemicals in these proof-of-concept experiments.

  5. Review of Toxicological Data Regarding Contact Hazards of Chemical Agents

    DTIC Science & Technology

    2006-08-01

    march 6 miles full equipment and complete an assault course only with difficulty. On the 2d day marching was very uncomfortable and he was unable to...woods, painted surfaces, plastics, rubber and earth with various sulfur mustards or HT and then partially decontaminated the materials with...underpants4 socks2 short-sleeve undershirt4 leggings2 leggings2 M5 ointment shoes2 shoes5 helmet liners; webbing gas mask gas mask or eye shield

  6. Quantitation of biomarkers of exposure to nitrogen mustards in urine from rats dosed with nitrogen mustards and from an unexposed human population.

    PubMed

    Lemire, Sharon W; Barr, John R; Ashley, David L; Olson, Carl T; Hayes, Timothy L

    2004-01-01

    The nitrogen mustards bis(2-chloroethyl)ethylamine (HN1), bis(2-chloroethyl)methylamine (HN2), and tris(2-chloroethyl)amine (HN3) have the potential to be used as chemical terrorism agents because of their extreme vesicant properties. We modified a previously reported method to incorporate automated solid-phase extraction, improve chromatography, and include the urinary metabolite for HN3. The improved method was used to measure levels of the urinary metabolites N-ethyldiethanolamine (EDEA), N-methyldiethanolamine (MDEA), and triethanolamine (TEA) in rats dosed with HN1, HN2, and HN3, respectively, and to establish background levels of EDEA, MDEA, and TEA in human urine samples from a population with no known exposure to nitrogen mustards. Rat dosing experiments confirmed that EDEA, MDEA, and TEA could be detected in urine for at least 48 h after exposure to HN1, HN2, and HN3, respectively. Substantial amounts of EDEA (89 ng/mL), MDEA (170 ng/mL), and TEA (1105 ng/mL) were measured in the urine of rats exposed to 10 mg HN1, HN2, and HN3, respectively, 48 h after exposure. The background concentrations for TEA in the human population ranged from below the limit of detection (LOD 3 ng/mL) to approximately 6500 ng/mL. Neither EDEA (LOD 0.4 ng/mL) nor MDEA (LOD 0.8 ng/mL) was detected above the LOD in the human samples.

  7. Analysis of chemical warfare agents. II. Use of thiols and statistical experimental design for the trace level determination of vesicant compounds in air samples.

    PubMed

    Muir, Bob; Quick, Suzanne; Slater, Ben J; Cooper, David B; Moran, Mary C; Timperley, Christopher M; Carrick, Wendy A; Burnell, Christopher K

    2005-03-18

    Thermal desorption with gas chromatography-mass spectrometry (TD-GC-MS) remains the technique of choice for analysis of trace concentrations of analytes in air samples. This paper describes the development and application of a method for analysing the vesicant compounds sulfur mustard and Lewisites I-III. 3,4-Dimercaptotoluene and butanethiol were used to spike sorbent tubes and vesicant vapours sampled; Lewisite I and II reacted with the thiols while sulfur mustard and Lewisite III did not. Statistical experimental design was used to optimise thermal desorption parameters and the optimum method used to determine vesicant compounds in headspace samples taken from a decontamination trial. 3,4-Dimercaptotoluene reacted with Lewisites I and II to give a common derivative with a limit of detection (LOD) of 260 microg m(-3), while the butanethiol gave distinct derivatives with limits of detection around 30 microg m(-3).

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

    PubMed

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

    2011-06-01

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

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

    PubMed

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

    2014-09-01

    Direct analysis in real time (DART) is a novel technique with great potential for rapid screening analysis. The DART ionization method coupled with high-resolution time-of-flight mass spectrometry (TOF-MS) has been used for characterization of mustard seeds and table mustard. The possibility to use DART to analyse glucosinolates was confirmed on determination of sinalbin (4-hydroxybenzyl glucosinolate). The DART-TOF-MS method was optimized and validated. A set of samples of mustard seeds and mustard products was analyzed. High-performance liquid chromatography and DART-TOF-MS were used to determine glucosinolates in mustard seeds and compared. The correlation equation between these methods was DART = 0.797*HPLC + 6.987, R(2)  = 0.972. The DART technique seems to be a suitable method for evaluation of the quality of mustard seeds and mustard products. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Mustard catch crop enhances denitrification in shallow groundwater beneath a spring barley field.

    PubMed

    Jahangir, M M R; Minet, E P; Johnston, P; Premrov, A; Coxon, C E; Hackett, R; Richards, K G

    2014-05-01

    Over-winter green cover crops have been reported to increase dissolved organic carbon (DOC) concentrations in groundwater, which can be used as an energy source for denitrifiers. This study investigates the impact of a mustard catch crop on in situ denitrification and nitrous oxide (N2O) emissions from an aquifer overlain by arable land. Denitrification rates and N2O-N/(N2O-N+N2-N) mole fractions were measured in situ with a push-pull method in shallow groundwater under a spring barley system in experimental plots with and without a mustard cover crop. The results suggest that a mustard cover crop could substantially enhance reduction of groundwater nitrate NO3--N via denitrification without significantly increasing N2O emissions. Mean total denitrification (TDN) rates below mustard cover crop and no cover crop were 7.61 and 0.002 μg kg(-1) d(-1), respectively. Estimated N2O-N/(N2O-N+N2-N) ratios, being 0.001 and 1.0 below mustard cover crop and no cover crop respectively, indicate that denitrification below mustard cover crop reduces N2O to N2, unlike the plot with no cover crop. The observed enhanced denitrification under the mustard cover crop may result from the higher groundwater DOC under mustard cover crop (1.53 mg L(-1)) than no cover crop (0.90 mg L(-1)) being added by the root exudates and root masses of mustard. This study gives insights into the missing piece in agricultural nitrogen (N) balance and groundwater derived N2O emissions under arable land and thus helps minimise the uncertainty in agricultural N and N2O-N balances. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Competitive immunochromatographic assay for the detection of thiodiglycol sulfoxide, a degradation product of sulfur mustard.

    PubMed

    Sathe, Manisha; Srivastava, Shruti; Merwyn, S; Agarwal, G S; Kaushik, M P

    2014-10-21

    An immunochromatographic assay (ICA) based on the competitive antigen-coated format using colloidal gold as the label was developed for the detection of thiodiglycol sulfoxide (TDGO), an important metabolite and degradation compound of sulphur mustard (SM). The ICA test strip consisted of a membrane with a detection zone, a sample pad and an absorbent pad. The membrane was separately coated with hapten-OVA conjugate (test line) and anti-rabbit mouse IgG (control line). The visual detection limit for TDGO by ICA detection was found to be 10 μg mL(-1). For validation, the ICA results obtained for spiked water samples were in good agreement with those obtained by indirect competitive inhibition enzyme-linked immunosorbent assay (ELISA) for TDGO. The assay time for detection was less than 10 min. The developed ICA has the potential to be a useful on-site screening tool for the retrospective detection of SM in environmental samples.

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

    PubMed

    Willison, Stuart A

    2012-12-28

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

  13. Fate and Transport of Chemical Warfare Agents VX and HD ...

    EPA Pesticide Factsheets

    Report The intent of this investigation was to study the fate and transport of CWA applied to painted/sealed materials including the potential partitioning of CWA into permeable paints/sealants and subsequently into underlying porous materials. Based on the results obtained from this investigation, VX and sulfur mustard (HD) have the ability to permeate into paints and sealants, including in some cases the underlying porous materials. It is likely that other permeable materials besides paints and sealants may also show similar behavior.

  14. Efficacy of mineral cationic carrier against sulphur mustard in skin decontamination.

    PubMed

    Vucemilović, Ante; Hadzija, Mirko; Jukić, Ivan

    2008-12-01

    The aim of this study was to evaluate decontamination (absorption) efficacy of a preparation called Mineral Cationic Carrier (MCC) against skin contamination with sulphur mustard in vivo. MCC is a synthetic preparation with known ion exchange, absorption efficiency, and bioactive potential. CBA mice were applied increasing doses of sulphur mustard on their skin and MCC was administered immediately after skin contamination. The results have confirmed the decontamination efficacy of MCC preparation, corresponding to 8.4 times the LD50 of percutaneous sulphur mustard, and call for further investigation.

  15. 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...

  16. Zirconium doped nano-dispersed oxides of Fe, Al and Zn for destruction of warfare agents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stengl, Vaclav, E-mail: stengl@uach.cz; Houskova, Vendula; Bakardjieva, Snejana

    2010-11-15

    Zirconium doped nano dispersive oxides of Fe, Al and Zn were prepared by a homogeneous hydrolysis of the respective sulfate salts with urea in aqueous solutions. Synthesized metal oxide hydroxides were characterized using Brunauer-Emmett-Teller (BET) surface area and Barrett-Joiner-Halenda porosity (BJH), X-ray diffraction (XRD), infrared spectroscopy (IR), scanning electron microscopy (SEM) and energy-dispersive X-ray microanalysis (EDX). These oxides were taken for an experimental evaluation of their reactivity with sulfur mustard (HD or bis(2-chloroethyl)sulfide), soman (GD or (3,3'-Dimethylbutan-2-yl)-methylphosphonofluoridate) and VX agent (S-[2-(diisopropylamino)ethyl]-O-ethyl-methylphosphonothionate). The presence of Zr{sup 4+} dopant can increase both the surface area and the surface hydroxylation of the resultingmore » doped oxides, decreases their crystallites' sizes thereby it may contribute in enabling the substrate adsorption at the oxide surface thus it can accelerate the rate of degradation of warfare agents. Addition of Zr{sup 4+} converts the product of the reaction of ferric sulphate with urea from ferrihydrite to goethite. We found out that doped oxo-hydroxides Zr-FeO(OH) - being prepared by a homogeneous hydrolysis of ferric and zirconium oxo-sulfates mixture in aqueous solutions - exhibit a comparatively higher degradation activity towards chemical warfare agents (CWAs). Degradation of soman or VX agent on Zr-doped FeO(OH) containing ca. 8.3 wt.% of zirconium proceeded to completion within 30 min.« less

  17. Comparative study on the effect of chemicals on Alternaria blight in Indian mustard--a multi-location study in India.

    PubMed

    Meena, P D; Chattopadhyay, C; Kumar, A; Awasthi, R P; Singh, R; Kaur, S; Thomas, L; Goyal, P; Chand, P

    2011-05-01

    High severity of Altemaria blight disease is a major constraint in production of rapeseed-mustard in India. The aim of this study was to investigate the suppressive potential of chemicals viz., zinc sulphate, borax, sulphur, potash and calcium sulphate, aqueous extracts viz., Eucalyptus globosus (50 g l-1) leaf extract and garlic (Allium sativum) bulb (20 g l-1) extract, cow urine and bio-agents Trichoderma harzianum, Pseudomonas fluorescence in comparison with the recommended chemical fungicide (mancozeb), against foliar disease Alternaria blight of Indian mustard [Brassica juncea (L.) Czern. and Coss] under five different geographical locations of India. Mancozeb recorded the lowest mean severity (leaf: 33.1%; pod: 26.3%) of Alternaria blight with efficacy of garlic bulb extract alone (leaf = 34.4%; pod = 27.3%) or in combination with cow urine (leaf = 34.2%; pod = 28.6%) being statistically at par with the recommended chemical fungicide. Chemicals also proved effective in reducing Alternaria blight severity on leaves and pods of Indian mustard (leaf = 36.3-37.9%; pod = 27.5-30.1%). The effective treatments besides providing significant reduction in disease severity also enabled increase in dry seed yield of the crop (mancozeb = 2052 kg ha-1; garlic = 2006 kg ha-1; control = 1561 kg ha-1).

  18. N-Chloramide Modified Nomex(Registered) as a Regenerable Self-Decontaminating Material for Protection Against Chemical Warfare Agents (Postprint)

    DTIC Science & Technology

    2009-02-26

    weaponizable bacteria, mustard, and VX, as well as possessing antimicrobial properties against nuisance organisms that cause conditions such as athlete’s foot...were assayed for content of active oxidizing agent, and tested for efficacy against 2-chloroethyl ethyl sulfide and Demeton-S, simulants for mustard and...attached to Nomex intended for use as self-decontaminating regenerable military textiles. The materials were assayed for content of active oxidizing

  19. Ion mobility spectrometric analysis of vaporous chemical warfare agents by the instrument with corona discharge ionization ammonia dopant ambient temperature operation.

    PubMed

    Satoh, Takafumi; Kishi, Shintaro; Nagashima, Hisayuki; Tachikawa, Masumi; Kanamori-Kataoka, Mieko; Nakagawa, Takao; Kitagawa, Nobuyoshi; Tokita, Kenichi; Yamamoto, Soichiro; Seto, Yasuo

    2015-03-20

    The ion mobility behavior of nineteen chemical warfare agents (7 nerve gases, 5 blister agents, 2 lachrymators, 2 blood agents, 3 choking agents) and related compounds including simulants (8 agents) and organic solvents (39) was comparably investigated by the ion mobility spectrometry instrument utilizing weak electric field linear drift tube with corona discharge ionization, ammonia doping, purified inner air drift flow circulation operated at ambient temperature and pressure. Three alkyl methylphosphonofluoridates, tabun, and four organophosphorus simulants gave the intense characteristic positive monomer-derived ion peaks and small dimer-derived ion peaks, and the later ion peaks were increased with the vapor concentrations. VX, RVX and tabun gave both characteristic positive monomer-derived ions and degradation product ions. Nitrogen mustards gave the intense characteristic positive ion peaks, and in addition distinctive negative ion peak appeared from HN3. Mustard gas, lewisite 1, o-chlorobenzylidenemalononitrile and 2-mercaptoethanol gave the characteristic negative ion peaks. Methylphosphonyl difluoride, 2-chloroacetophenone and 1,4-thioxane gave the characteristic ion peaks both in the positive and negative ion mode. 2-Chloroethylethylsulfide and allylisothiocyanate gave weak ion peaks. The marker ion peaks derived from two blood agents and three choking agents were very close to the reactant ion peak in negative ion mode and the respective reduced ion mobility was fluctuated. The reduced ion mobility of the CWA monomer-derived peaks were positively correlated with molecular masses among structurally similar agents such as G-type nerve gases and organophosphorus simulants; V-type nerve gases and nitrogen mustards. The slope values of the calibration plots of the peak heights of the characteristic marker ions versus the vapor concentrations are related to the detection sensitivity, and within chemical warfare agents examined the slope values for sarin, soman

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

    PubMed

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

    2014-09-01

    Broccoli, a rich source of glucosinolates, is a commonly consumed vegetable of the Brassica family. Hydrolysis products of glucosinolates, isothiocyanates, have been associated with health benefits and contribute to the flavor of Brassica. However, boiling broccoli causes the myrosinase enzyme needed for hydrolysis to denature. In order to ensure hydrolysis, broccoli must either be mildly cooked or active sources of myrosinase, such as mustard seed powder, can be added postcooking. In this study, samples of broccoli were prepared in 6 different ways; standard boiling, standard boiling followed by the addition of mustard seeds, sous vide cooking at low temperature (70 °C) and sous vide cooking at higher temperature (100 °C) and sous vide cooking at higher temperature followed by the addition of mustard seeds at 2 different concentrations. The majority of consumers disliked the mildly cooked broccoli samples (70 °C, 12 min, sous vide) which had a hard and stringy texture. The highest mean consumer liking was for standard boiled samples (100 °C, 7 min). Addition of 1% mustard seed powder developed sensory attributes, such as pungency, burning sensation, mustard odor, and flavor. One cluster of consumers (32%) found mustard seeds to be a good complement to cooked broccoli; however, the majority disliked the mustard-derived sensory attributes. Where the mustard seeds were partially processed, doubling the addition to 2% led to only the same level of mustard and pungent flavors as 1% unprocessed seeds, and mean consumer liking remained unaltered. This suggests that optimization of the addition level of partially processed mustard seeds may be a route to enhance bioactivity of cooked broccoli without compromising consumer acceptability. © 2014 Institute of Food Technologists®

  1. On the use of spectra from portable Raman and ATR-IR instruments in synthesis route attribution of a chemical warfare agent by multivariate modeling.

    PubMed

    Wiktelius, Daniel; Ahlinder, Linnea; Larsson, Andreas; Höjer Holmgren, Karin; Norlin, Rikard; Andersson, Per Ola

    2018-08-15

    Collecting data under field conditions for forensic investigations of chemical warfare agents calls for the use of portable instruments. In this study, a set of aged, crude preparations of sulfur mustard were characterized spectroscopically without any sample preparation using handheld Raman and portable IR instruments. The spectral data was used to construct Random Forest multivariate models for the attribution of test set samples to the synthetic method used for their production. Colored and fluorescent samples were included in the study, which made Raman spectroscopy challenging although fluorescence was diminished by using an excitation wavelength of 1064 nm. The predictive power of models constructed with IR or Raman data alone, as well as with combined data was investigated. Both techniques gave useful data for attribution. Model performance was enhanced when Raman and IR spectra were combined, allowing correct classification of 19/23 (83%) of test set spectra. The results demonstrate that data obtained with spectroscopy instruments amenable for field deployment can be useful in forensic studies of chemical warfare agents. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2013-01-01

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

  3. 'Petite' mutagenesis and mitotic crossing-over in yeast by DNA-targeted alkylating agents.

    PubMed

    Ferguson, L R; Turner, P M; Gourdie, T A; Valu, K K; Denny, W A

    1989-12-01

    Although the biological properties (cytotoxicity, mutagenicity and carcinogenicity) of alkylating agents result from their bonding interactions with DNA, such compounds generally do not show any special binding affinity for DNA. A series of acridine-linked aniline mustards of widely-varying alkylator reactivity have been designed as DNA-directed alkylating agents. We have considered whether such DNA targeting has an effect on mutagenic properties by evaluating this series of drugs in comparison with their untargeted counterparts for toxic, recombinogenic and mutagenic properties in Saccharomyces cerevisiae strain D5. The simple untargeted aniline mustards are effective inducers of mitotic crossing-over in this strain, but resemble other reported alkylators in being rather inefficient inducers of the "petite" or mitochondrial mutation in yeast. However, the majority of the DNA-targeted mustards were very efficient petite mutagens, while showing little evidence of mitotic crossing-over or other nuclear events. The 100% conversion of cells into petites and the lack of a differential between growing and non-growing cells are similar to the effects of the well characterised mitochondrial mutagen ethidium bromide. These data suggest very different modes of action between the DNA-targeted alkylators and their non-targeted counterparts.

  4. Effect of pH and sulfur precursor concentration on electrochemically deposited CZTS thin films using glycine as the complexing agent

    NASA Astrophysics Data System (ADS)

    Paraye, Akanksha; Sani, Rabiya; Ramachandran, Manivannan; Selvam, Noyel Victoria

    2018-03-01

    Copper zinc tin sulfide (CZTS) a promising quaternary chalcogenide material was deposited using single step electrodeposition using glycine as the complexing agent. The deposition was studied at different sulfur concentrations and at different pH. The pH of the electrolyte was found to influence the stoichiometry of the deposits significantly. The deposits formed at pH 2.5 showed satisfactory stoichiometry. The thickness of the deposits was observed to decrease with increase in sulfur concentration and pH. The transmission electron spectroscopy analysis showed the formation of flower shaped core shell particles from the electrolyte that contained 80 mM sulfur precursor at pH 2.5. The band gap of the deposits was found to be in the range from 1.57 eV to 2.1 eV. X-ray diffraction analysis showed that the as synthesized particles were amorphous in nature, the crystallinity of which improved with annealing. The Mott Schottky analysis of the deposits in 0.1 M sodium perchlorate showed that the particles exhibited p-type conductivity.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bambal, Ashish S.; Guggilla, Vidya S.; Kugler, Edwin L.

    2014-04-09

    The effects of sulfur impurities on the performance of cobalt-based Fischer–Tropsch catalysts are evaluated under industrially relevant operating conditions of temperature, pressure, and impurity levels. Chelating agents (CAs) were used to modify the SiO 2 support, and the performances of the CA-modified catalysts are compared with conventional Co/SiO 2 catalysts. For both the Co/SiO 2 and CA-modified catalysts, the presence of sulfur in the inlet syngas results in a notable drop in the CO conversion, an undesired shift in the hydrocarbon selectivity toward short-chain hydrocarbons, more olefins in the products, and lower product yields. In the post-poisoning stage, i.e., aftermore » termination of sulfur introduction in the inlet syngas, the CA-modified catalysts recover activity and selectivity (to some extent at least), whereas such trends are not observed for the base-case, i.e., unmodified Co/SiO 2 catalyst. Finally, the improved performance of the CA-modified catalysts in the presence of sulfur is attributed to higher densities of active sites.« less

  6. Ultraviolet Raman scattering from persistent chemical warfare agents

    NASA Astrophysics Data System (ADS)

    Kullander, Fredrik; Wästerby, Pär.; Landström, Lars

    2016-05-01

    Laser induced Raman scattering at excitation wavelengths in the middle ultraviolet was examined using a pulsed tunable laser based spectrometer system. Droplets of chemical warfare agents, with a volume of 2 μl, were placed on a silicon surface and irradiated with sequences of laser pulses. The Raman scattering from V-series nerve agents, Tabun (GA) and Mustard gas (HD) was studied with the aim of finding the optimum parameters and the requirements for a detection system. A particular emphasis was put on V-agents that have been previously shown to yield relatively weak Raman scattering in this excitation band.

  7. Exogenous salicylic acid improves photosynthesis and growth through increase in ascorbate-glutathione metabolism and S assimilation in mustard under salt stress

    PubMed Central

    Nazar, Rahat; Umar, Shahid; Khan, Nafees A.

    2015-01-01

    Ascorbate (AsA)–glutathione (GSH) cycle metabolism has been regarded as the most important defense mechanism for the resistance of plants under stress. In this study the influence of salicylic acid (SA) was studied on ascorbate-glutathione pathway, S-assimilation, photosynthesis and growth of mustard (Brassica juncea L.) plants subjected to 100 mM NaCl. Treatment of SA (0.5 mM) alleviated the negative effects of salt stress and improved photosynthesis and growth through increase in enzymes of ascorbate-glutathione pathway which suggest that SA may participate in the redox balance under salt stress. The increase in leaf sulfur content through higher activity of ATP sulfurylase (ATPS) and serine acetyl transferase (SAT) by SA application was associated with the increased accumulation of glutathione (GSH) and lower levels of oxidative stress. These effects of SA were substantiated by the findings that application of SA-analog, 2,6, dichloro-isonicotinic acid (INA) and 1 mM GSH treatment produced similar results on rubisco, photosynthesis and growth of plants establishing that SA application alleviates the salt-induced decrease in photosynthesis mainly through inducing the enzyme activity of ascorbate-glutathione pathway and increased GSH production. Thus, SA/GSH could be a promising tool for alleviation of salt stress in mustard plants. PMID:25730495

  8. Perspective on recent developments on sulfur-containing agents and hydrogen sulfide signaling.

    PubMed

    Jacob, Claus; Anwar, Awais; Burkholz, Torsten

    2008-10-01

    The last couple of years have witnessed the coming together of several initially unconnected lines of investigation which now link natural sulfur products to hydrogen sulfide release and wide ranging cardiovascular protection. It has become apparent that sulfur compounds contained within garlic, onions, mushrooms and various edible beans and fruits may be transformed chemically or enzymatically in the human body with subsequent formation of hydrogen sulfide. The latter has emerged during the last decade from a shadowy existence as toxic gas to be recognized as the third gaseous transmitter besides nitric oxide ( (.)NO) and carbon monoxide (CO). Hydrogen sulfide is formed endogenously in the human body by enzymes such as cystathionine beta-synthase (CBS) in the brain and cystathionine gamma-lyase (CSE) in liver, vascular and non-vascular smooth muscle. Although its exact chemical and biochemical modes of action are still not fully understood, levels of hydrogen sulfide in the brain and vasculature have unambiguously been associated with human health and disease. Not surprisingly, agents releasing hydrogen sulfide, as well as inhibitors of hydrogen sulfide synthesis (CBS and CSE inhibitors) have been investigated. Apart from linking our daily diet to a healthy brain and cardiovasculature, these findings may also provide new leads for drug design. Future studies will therefore need to focus on how such compounds are formed and transformed in the relevant plants, how food processing affects their chemical constitution, and how they release hydrogen sulfide (or control its levels) in the human body. Such multidisciplinary research should ultimately answer the all-important question if a hearty diet is also good for the heart.

  9. 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.

  10. Operation of the Chemical Agent Munitions Disposal System (CAMDS) at Tooele Army Depot, Utah.

    DTIC Science & Technology

    1978-09-01

    parts furnace where the container is opened to expose the agent; the agent is boiled out and burned ; and the residual container is heat treated for...fuze booster to expose the booster pellet so it will burn instead of detonate in the Deactivation Furnace. A portion of the solution in the coolant...demilitarization equipment exposed to agent GB will be chemically decontaminated to prepare for operations with burstered mustard projectiles. The

  11. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abel, E.L.; Boulware, S.; Fields, T.

    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,more » 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.« less

  12. After Action Report for the Service Response Force Conducting Operation Safe Removal, 5 January - 3 February 1993

    DTIC Science & Technology

    1994-03-01

    proving ground operational from approximately 1917- 1919. 2. The initial response force to the site included the 67th Explosive Ordnance Disposal (EOD...conclusion determined that one round contained mustard agent (H) and two rounds contained fuming sulfuric acid, an experimental smoke mixture. 12. Throughout...Batt, subj: Assessment of Munitions Awaiting Transport to Aberdeen Proving Ground -Edgewood Area, 29 Jan 93 Note [Fax Transmittal], from TEU, to Mrs

  13. Treating exposure to chemical warfare agents: implications for health care providers and community emergency planning.

    PubMed Central

    Munro, N B; Watson, A P; Ambrose, K R; Griffin, G D

    1990-01-01

    Current treatment protocols for exposure to nerve and vesicant agents found in the U.S. stockpile of unitary chemical weapons are summarized, and the toxicities of available antidotes are evaluated. The status of the most promising of the new nerve agent antidotes is reviewed. In the U.S. atropine and pralidoxime compose the only approved antidote regimen for organophosphate nerve agent poisoning. Diazepam may also be used if necessary to control convulsions. To avoid death, administration must occur within minutes of substantial exposure together with immediate decontamination. Continuous observation and repeated administration of antidotes are necessary as symptoms warrant. Available antidotes do not necessarily prevent respiratory failure or incapacitation. The toxicity of the antidotes themselves and the individualized nature of medical care preclude recommending that autoinjectors be distributed to the general public. In addition, precautionary administration of protective drugs to the general population would not be feasible or desirable. No antidote exists for poisoning by the vesicant sulfur mustard (H, HD, HT); effective intervention can only be accomplished by rapid decontamination followed by palliative treatment of symptoms. British anti-Lewisite (BAL) (2,3-dimercapto-1-propanolol) is the antidote of choice for treatment of exposure to Lewisite, another potent vesicant. Experimental water-soluble BAL analogues have been developed that are less toxic than BAL. Treatment protocols for each antidote are summarized in tabular form for use by health care providers. PMID:2088748

  14. Parameters for the Evaluation of the Fate, Transport, and Environmental Impacts of Chemical Agents in Marine Environments

    DTIC Science & Technology

    2007-07-01

    result, estimation of the lifetime of hydrogen cyanide in deeper ocean waters is likely to be difficult. 2.4 Sulfur Mustard (HS) The principle active ...single first-order reaction rather than consecutive first-order reactions.159 A recent study determined the activation energy of 18.5 kcal mole-1for...on the chloride ion activity . Despite the relative rapidity of the hydrolysis reaction, 1,1’-thiobis[2-chloroethane] has been found to persist in

  15. Emergency management of chemical weapons injuries.

    PubMed

    Anderson, Peter D

    2012-02-01

    The potential for chemical weapons to be used in terrorism is a real possibility. Classes of chemical weapons include nerve agents, vesicants (blister agents), choking agents, incapacitating agents, riot control agents, blood agents, and toxic industrial chemicals. The nerve agents work by blocking the actions of acetylcholinesterase leading to a cholinergic syndrome. Nerve agents include sarin, tabun, VX, cyclosarin, and soman. The vesicants include sulfur mustard and lewisite. The vesicants produce blisters and also damage the upper airways. Choking agents include phosgene and chlorine gas. Choking agents cause pulmonary edema. Incapacitating agents include fentanyl and its derivatives and adamsite. Riot control agents include Mace and pepper spray. Blood agents include cyanide. The mechanism of toxicity for cyanide is blocking oxidative phosphorylation. Toxic industrial chemicals include agents such as formaldehyde, hydrofluoric acid, and ammonia.

  16. GERD related micro-aspiration in chronic mustard-induced pulmonary disorder

    PubMed Central

    Aliannejad, Rasoul; Hashemi-Bajgani, Seyed-Mehdi; Karbasi, Asharaf; Jafari, Mahvash; Aslani, Jafar; Salehi, Maryam; Ghanei, Mostafa

    2012-01-01

    Background and Aim: Bronchiolitis obliterans (BO) is the main pulmonary involvement resulting from sulfur mustard (SM) gas exposure that was used against Iranian civilians and military forces during the Iran-Iraq war. The present study aimed to investigate the prevalence of gastro-esophageal reflux (GER) and gastric micro-aspiration in SM gas injured patients with chronic pulmonary diseases and recurrent episodes of exacerbations. Materials and Methods: This cross-sectional study was done at Baqiyatallah University of Medical Sciences, Tehran, Iran. Gastric micro-aspiration and GER were assessed in the enrolled patients by assessing bile acids, pepsin and trypsin in their bronchoalveolar lavage fluid. Results: Our result showed that bile acids were found to be high in 21.4% patients, and low in 53.6% of patients. Only in 16% patients, no bile was detected in the BALF. Trypsin and pepsin were detected in BAL fluid of all patients. Conclusion: Most of BO patients after exposure to SM suffer GER, while none the etiologic factors of GER in post lung transplant BO are present. It would be hypothesized that GER per se could be considered as an aggregative factor for exacerbations in patients. Further studies will provide more advances to better understanding of pathophysiological mechanism regarding GER and BO and treatment. PMID:23798946

  17. GERD related micro-aspiration in chronic mustard-induced pulmonary disorder.

    PubMed

    Aliannejad, Rasoul; Hashemi-Bajgani, Seyed-Mehdi; Karbasi, Asharaf; Jafari, Mahvash; Aslani, Jafar; Salehi, Maryam; Ghanei, Mostafa

    2012-08-01

    Bronchiolitis obliterans (BO) is the main pulmonary involvement resulting from sulfur mustard (SM) gas exposure that was used against Iranian civilians and military forces during the Iran-Iraq war. The present study aimed to investigate the prevalence of gastro-esophageal reflux (GER) and gastric micro-aspiration in SM gas injured patients with chronic pulmonary diseases and recurrent episodes of exacerbations. This cross-sectional study was done at Baqiyatallah University of Medical Sciences, Tehran, Iran. Gastric micro-aspiration and GER were assessed in the enrolled patients by assessing bile acids, pepsin and trypsin in their bronchoalveolar lavage fluid. Our result showed that bile acids were found to be high in 21.4% patients, and low in 53.6% of patients. Only in 16% patients, no bile was detected in the BALF. Trypsin and pepsin were detected in BAL fluid of all patients. Most of BO patients after exposure to SM suffer GER, while none the etiologic factors of GER in post lung transplant BO are present. It would be hypothesized that GER per se could be considered as an aggregative factor for exacerbations in patients. Further studies will provide more advances to better understanding of pathophysiological mechanism regarding GER and BO and treatment.

  18. 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.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

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

    2012-01-01

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

  20. Development of Reactive Topical Skin Protectants against Sulfur Mustard and Nerve Agents

    DTIC Science & Technology

    1997-06-01

    Inorganic pollutants such as hydrogen cyanide, cyanogen chloride, and acid gases are not adsorbed well by activated carbon, and (3) Clean-up and...with Fe203 caused an increase in destructive adsorbent capacity of chlorocarbons, acid gases, and organophosphorus compounds. We attribute this...solution of distilled water, concentrated nitric acid , and methanol were added to methanol and neat titanium (IV) butoxide. The formed gel was aged

  1. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Batal, Mohamed; Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche; Boudry, Isabelle

    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 DNAmore » 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.« less

  2. 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.

  3. 2014 Review on the Extension of the AMedP-8(C) Methodology to New Agents, Materials, and Conditions

    DTIC Science & Technology

    2015-08-01

    chemical agents, five biological agents, seven radioisotopes , nuclear fallout, or prompt nuclear effects.1 Each year since 2009, OTSG has sponsored IDA...evaluated four agents: anthrax, botulinum toxin, sarin (GB), and distilled mustard (HD), first using the default parameters and methods in HPAC and...the IDA team then made incremental changes to the default casualty parameters and methods to control for all known data and methodological

  4. Sulfuric acid in the Venus clouds.

    NASA Technical Reports Server (NTRS)

    Sill, G. T.

    1972-01-01

    The extremely dry nature of the Venus upper atmosphere appears to demand the presence of an efficient desiccating agent as the chief constituent of the clouds of Venus. On the basis of polarization measures it is to be expected that this substance is present as spherical droplets, 1 to 2 microns in diameter, with a refractive index n of 1.46 plus or minus 0.02 at 3500A in the observed region of the atmosphere, with T about equal to 235 K. This substance must have ultraviolet, visible, and infrared reflection properties not inconsistent with the observed spectrum of Venus. Sulfuric acid, of about 86% by weight composition, roughly fulfills the first of these properties. The visible and ultraviolet transmission features of a thin layer of elemental bromine and hydrobromic acid dissolved in sulfuric acid somewhat resemble the Venus spectrum, up to 14 microns. The chemical process postulated for forming sulfuric acid involves the oxidation of sulfur and its compounds to sulfuric acid through the agency of elemental bromine produced by the photolytic decomposition of hydrogen bromide.

  5. 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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Black, Adrienne T.; Joseph, Laurie B.; Casillas, Robert P.

    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,more » 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.« less

  6. Comparison of the metabolism of inorganic and organic selenium species between two selenium accumulator plants, garlic and Indian mustard.

    PubMed

    Ogra, Yasumitsu; Ogihara, Yurie; Anan, Yasumi

    2017-01-25

    The metabolism of selenomethionine (SeMet) in two major selenium (Se) accumulator plants, garlic and Indian mustard, was compared to that of stable isotope labeled selenate. Indian mustard more efficiently transported Se from roots to leaves than garlic. In addition, Indian mustard accumulated larger amounts of Se than garlic. γ-Glutamyl-Se-methylselenocysteine (γ-GluMeSeCys) and Se-methylselenocysteine (MeSeCys) were the common metabolites of selenate and SeMet in garlic and Indian mustard. Indian mustard had a specific metabolic pathway to selenohomolanthionine (SeHLan) from both inorganic and organic Se species. SeMet was a more effective fertilizer for cultivating Se-enriched plants than selenate in terms of the production of selenoamino acids.

  7. Development of spent fuel reprocessing process based on selective sulfurization: Study on the Pu, Np and Am sulfurization

    NASA Astrophysics Data System (ADS)

    Kirishima, Akira; Amano, Yuuki; Nihei, Toshifumi; Mitsugashira, Toshiaki; Sato, Nobuaki

    2010-03-01

    For the recovery of fissile materials from spent nuclear fuel, we have proposed a novel reprocessing process based on selective sulfurization of fission products (FPs). The key concept of this process is utilization of unique chemical property of carbon disulfide (CS2), i.e., it works as a reductant for U3O8 but works as a sulfurizing agent for minor actinides and lanthanides. Sulfurized FPs and minor actinides (MA) are highly soluble to dilute nitric acid while UO2 and PuO2 are hardly soluble, therefore, FPs and MA can be removed from Uranium and Plutonium matrix by selective dissolution. As a feasibility study of this new concept, the sulfurization behaviours of U, Pu, Np, Am and Eu are investigated in this paper by the thermodynamical calculation, phase analysis of chemical analogue elements and tracer experiments.

  8. Activation of the chemosensing transient receptor potential channel A1 (TRPA1) by alkylating agents.

    PubMed

    Stenger, Bernhard; Zehfuss, Franziska; Mückter, Harald; Schmidt, Annette; Balszuweit, Frank; Schäfer, Eva; Büch, Thomas; Gudermann, Thomas; Thiermann, Horst; Steinritz, Dirk

    2015-09-01

    The transient receptor potential ankyrin 1 (TRPA1) cation channel is expressed in different tissues including skin, lung and neuronal tissue. Recent reports identified TRPA1 as a sensor for noxious substances, implicating a functional role in the molecular toxicology. TRPA1 is activated by various potentially harmful electrophilic substances. The chemical warfare agent sulfur mustard (SM) is a highly reactive alkylating agent that binds to numerous biological targets. Although SM is known for almost 200 years, detailed knowledge about the pathophysiology resulting from exposure is lacking. A specific therapy is not available. In this study, we investigated whether the alkylating agent 2-chloroethyl-ethylsulfide (CEES, a model substance for SM-promoted effects) and SM are able to activate TRPA1 channels. CEES induced a marked increase in the intracellular calcium concentration ([Ca(2+)]i) in TRPA1-expressing but not in TRPA1-negative cells. The TRP-channel blocker AP18 diminished the CEES-induced calcium influx. HEK293 cells permanently expressing TRPA1 were more sensitive toward cytotoxic effects of CEES compared with wild-type cells. At low CEES concentrations, CEES-induced cytotoxicity was prevented by AP18. Proof-of-concept experiments using SM resulted in a pronounced increase in [Ca(2+)]i in HEK293-A1-E cells. Human A549 lung epithelial cells, which express TRPA1 endogenously, reacted with a transient calcium influx in response to CEES exposure. The CEES-dependent calcium response was diminished by AP18. In summary, our results demonstrate that alkylating agents are able to activate TRPA1. Inhibition of TRPA1 counteracted cellular toxicity and could thus represent a feasible approach to mitigate SM-induced cell damage.

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

    PubMed

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

    2006-01-01

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

  10. Declines in a ground-dwelling arthropod community during an invasion by Sahara mustard (Brassica tournefortii) in aeolian sand habitats

    Treesearch

    Heather L. Hulton VanTassel; Anne M. Hansen; Cameron W. Barrows; Quresh Latif; Margaret W. Simon; Kurt E. Anderson

    2014-01-01

    Sahara Mustard (Brassica tournefortii; hereafter mustard), an exotic plant species, has invaded habitats throughout the arid southwestern United States. Mustard has reached high densities across aeolian sand habitats of southwestern deserts, including five distinct sand habitats in the eastern Coachella Valley, California. We examined trends in ground-dwelling...

  11. Synthesis and biological evaluation of sulfur-containing shikonin oxime derivatives as potential antineoplastic agents.

    PubMed

    Huang, Guang; Zhao, Hui-Ran; Meng, Qing-Qing; Zhang, Qi-Jing; Dong, Jin-Yun; Zhu, Bao-Quan; Li, Shao-Shun

    2018-01-01

    As a continuation of our research on developing potent and potentially safe antineoplastic agents, a set of forty five sulfur-containing shikonin oxime derivatives were synthesized and evaluated for their in vitro cytotoxic activity against human colon cancer (HCT-15), gastric carcinoma (MGC-803), liver (Bel7402), breast (MCF-7) cancer cells and human skin fibroblast (HSF) cells. All the synthesized compounds exhibited potent cytotoxic activity selectively towards HCT-15 cells and did not display apparent toxicity to the normal HSF cells, some of which were more or comparatively effective to the parent compound against HCT-15, MGC-803 and Bel7402 cells. The most active agent 9m displayed high potency against human cancer cells with IC 50 ranging from 0.27 ± 0.02 to 9.23 ± 0.12 μM. The structure-activity relationships (SARs) studies suggested that the nature of substituent group in the side chain is important for antitumor potency in vitro. Additionally, nitric oxide release studies revealed that the amount of nitric oxide generated from these oxime derivatives was relatively low. Furthermore, cellular mechanism investigations indicated that compound 9m could arrest cell cycle at G1 phase and induce a strong apoptotic response in HCT-15 cells. Moreover, western blot studies revealed that compound 9m induced apoptosis through the down-regulation of Bcl-2 and up-regulation of Bax, caspase 3 and 9. For all these reasons, compound 9m hold promising potential as antineoplastic agent. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Suppression of bacterial blight on mustard greens with host plant resistance and Acibenzolar-S-Methyl

    USDA-ARS?s Scientific Manuscript database

    Bacterial blight, caused by Pseudomonas cannabina pv. alisalensis, attacks the leaves of most brassica vegetables, including mustard greens (Brassica juncea). ‘Carolina Broadleaf,’ a new mustard cultivar, is resistant to bacterial blight. Acibenzolar-S-methyl (trade name Actigard) has been used to m...

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

    PubMed

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

    2011-09-30

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

  14. New thymine-based derivative of nitrogen mustards.

    PubMed

    Boëns, Benjamin; Teste, Karine; Hadj-Bouazza, Amel; Ismaili, Jihane; Zerrouki, Rachida

    2012-01-01

    This work deals with the synthesis of a new nitrogen mustard derivative based on thymine. To introduce the bis(2-chloroethyl)amine group to position 4 of the pyrimidine base, many strategies were explored and the desired compound was finally obtained, thanks to a synthetic pathway in five steps.

  15. Enhanced performance of sulfur-infiltrated bimodal mesoporous carbon foam by chemical solution deposition as cathode materials for lithium sulfur batteries

    NASA Astrophysics Data System (ADS)

    Jeong, Tae-Gyung; Chun, Jinyong; Cho, Byung-Won; Lee, Jinwoo; Kim, Yong-Tae

    2017-02-01

    The porous carbon matrix is widely recognized to be a promising sulfur reservoir to improve the cycle life by suppressing the polysulfide dissolution in lithium sulfur batteries (LSB). Herein, we synthesized mesocellular carbon foam (MSUF-C) with bimodal mesopore (4 and 30 nm) and large pore volume (1.72 cm2/g) using MSUF silica as a template and employed it as both the sulfur reservoir and the conductive agent in the sulfur cathode. Sulfur was uniformly infiltrated into MSUF-C pores by a chemical solution deposition method (MSUF-C/S CSD) and the amount of sulfur loading was achieved as high as 73% thanks to the large pore volume with the CSD approach. MSUF-C/S CSD showed a high capacity (889 mAh/g after 100 cycles at 0.2 C), an improved rate capability (879 mAh/g at 1C and 420 mAh/g at 2C), and a good capacity retention with a fade rate of 0.16% per cycle over 100 cycles.

  16. Enhanced performance of sulfur-infiltrated bimodal mesoporous carbon foam by chemical solution deposition as cathode materials for lithium sulfur batteries

    PubMed Central

    Jeong, Tae-Gyung; Chun, Jinyong; Cho, Byung-Won; Lee, Jinwoo; Kim, Yong-Tae

    2017-01-01

    The porous carbon matrix is widely recognized to be a promising sulfur reservoir to improve the cycle life by suppressing the polysulfide dissolution in lithium sulfur batteries (LSB). Herein, we synthesized mesocellular carbon foam (MSUF-C) with bimodal mesopore (4 and 30 nm) and large pore volume (1.72 cm2/g) using MSUF silica as a template and employed it as both the sulfur reservoir and the conductive agent in the sulfur cathode. Sulfur was uniformly infiltrated into MSUF-C pores by a chemical solution deposition method (MSUF-C/S CSD) and the amount of sulfur loading was achieved as high as 73% thanks to the large pore volume with the CSD approach. MSUF-C/S CSD showed a high capacity (889 mAh/g after 100 cycles at 0.2 C), an improved rate capability (879 mAh/g at 1C and 420 mAh/g at 2C), and a good capacity retention with a fade rate of 0.16% per cycle over 100 cycles. PMID:28165041

  17. IMS software developments for the detection of chemical warfare agent

    NASA Technical Reports Server (NTRS)

    Klepel, ST.; Graefenhain, U.; Lippe, R.; Stach, J.; Starrock, V.

    1995-01-01

    Interference compounds like gasoline, diesel, burning wood or fuel, etc. are presented in common battlefield situations. These compounds can cause detectors to respond as a false positive or interfere with the detector's ability to respond to target compounds such as chemical warfare agents. To ensure proper response of the ion mobility spectrometer to chemical warfare agents, two special software packages were developed and incorporated into the Bruker RAID-1. The programs suppress interferring signals caused by car exhaust or smoke gases resulting from burning materials and correct the influence of variable sample gas humidity which is important for detection and quantification of blister agents like mustard gas or lewisite.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abel, Erika L.; Bubel, Jennifer D.; Simper, Melissa S.

    2011-09-01

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

  19. Influence of organic loading rate on integrated bioreactor treating hypersaline mustard wastewater.

    PubMed

    Kang, Wei; Chai, Hongxiang; Yang, Shiwei; Du, Guojun; Zhou, Jian; He, Qiang

    2016-07-01

    Mustard tuber wastewater is characterized by high salinity and high organic content that is potentially detrimental to the biological treatment system and affects the treatment efficiency accordingly. The experiment used the integrated bioreactor to reduce much of the organics in mustard tuber wastewater, and found the influence of organic loading rate on effluent chemical oxygen demand (COD) and phosphate (PO4 (3-) -P). Results showed that under the condition of 10-15 °C, 6 mg/L of dissolved oxygen, the reduction value of COD removal rate in anaerobic and aerobic area was 14.5% and 31.7% when the organic loading rate increased from 2.0 to 4.0 kg COD/m(3) /day. Therefore, an integrated bioreactor should take 2.0 kg COD/m(3) /day organic loading rate in mustard wastewater treatment if the effluent is expected to meet the third level of "Integrated Wastewater Discharge Standard" (GB 8978-1996). © 2015 International Union of Biochemistry and Molecular Biology, Inc.

  20. 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.

  1. Study on mechanisms of different sulfuric acid leaching technologies of chromite

    NASA Astrophysics Data System (ADS)

    Shi, Pei-yang; Liu, Cheng-jun; Zhao, Qing; Shi, Hao-nan

    2017-09-01

    The extraction of chromate from chromite via the sulfuric acid leaching process has strong potential for practical use because it is a simple and environmentally friendly process. This paper aims to study the sulfuric acid leaching process using chromite as a raw material via either microwave irradiation or in the presence of an oxidizing agent. The results show that the main phases in Pakistan chromite are ferrichromspinel, chrompicotite, hortonolite, and silicate embedded around the spinel phases. Compared with the process with an oxidizing agent, the process involving microwaves has a higher leaching efficiency. When the mass fraction of sulfuric acid was 80% and the leaching time was 20 min, the efficiency could exceed 85%. In addition, the mechanisms of these two technologies fundamentally differ. When the leaching was processed in the presence of an oxidizing agent, the silicate was leached first and then expanded. By contrast, in the case of leaching under microwave irradiation, the chromite was dissolved layer by layer and numerous cracks appeared at the particle surface because of thermal shock. In addition, the silicate phase shrunk instead of expanding.

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

    PubMed

    Cipollini, Don; Gruner, Bill

    2007-01-01

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

  3. 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.

  4. Pepsin and bile acid concentrations in sputum of mustard gas exposed patients.

    PubMed

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

    2013-01-01

    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. 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. 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). 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.

  5. 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

  6. A binder-free sulfur/reduced graphene oxide aerogel as high performance electrode materials for lithium sulfur batteries

    PubMed Central

    Nitze, Florian; Agostini, Marco; Lundin, Filippa; Palmqvist, Anders E. C.; Matic, Aleksandar

    2016-01-01

    Societies’ increasing need for energy storage makes it necessary to explore new concepts beyond the traditional lithium ion battery. A promising candidate is the lithium-sulfur technology with the potential to increase the energy density of the battery by a factor of 3–5. However, so far the many problems with the lithium-sulfur system have not been solved satisfactory. Here we report on a new approach utilizing a self-standing reduced graphene oxide based aerogel directly as electrodes, i.e. without further processing and without the addition of binder or conducting agents. We can thereby disrupt the common paradigm of “no battery without binder” and can pave the way to a lithium-sulfur battery with a high practical energy density. The aerogels are synthesized via a one-pot method and consist of more than 2/3 sulfur, contained inside a porous few-layered reduced graphene oxide matrix. By combining the graphene-based aerogel cathode with an electrolyte and a lithium metal anode, we demonstrate a lithium-sulfur cell with high areal capacity (more than 3 mAh/cm2 after 75 cycles), excellent capacity retention over 200 cycles and good sulfur utilization. Based on this performance we estimate that the energy density of this concept-cell can significantly exceed the Department of Energy (DEO) 2020-target set for transport applications. PMID:28008981

  7. A binder-free sulfur/reduced graphene oxide aerogel as high performance electrode materials for lithium sulfur batteries.

    PubMed

    Nitze, Florian; Agostini, Marco; Lundin, Filippa; Palmqvist, Anders E C; Matic, Aleksandar

    2016-12-23

    Societies' increasing need for energy storage makes it necessary to explore new concepts beyond the traditional lithium ion battery. A promising candidate is the lithium-sulfur technology with the potential to increase the energy density of the battery by a factor of 3-5. However, so far the many problems with the lithium-sulfur system have not been solved satisfactory. Here we report on a new approach utilizing a self-standing reduced graphene oxide based aerogel directly as electrodes, i.e. without further processing and without the addition of binder or conducting agents. We can thereby disrupt the common paradigm of "no battery without binder" and can pave the way to a lithium-sulfur battery with a high practical energy density. The aerogels are synthesized via a one-pot method and consist of more than 2/3 sulfur, contained inside a porous few-layered reduced graphene oxide matrix. By combining the graphene-based aerogel cathode with an electrolyte and a lithium metal anode, we demonstrate a lithium-sulfur cell with high areal capacity (more than 3 mAh/cm 2 after 75 cycles), excellent capacity retention over 200 cycles and good sulfur utilization. Based on this performance we estimate that the energy density of this concept-cell can significantly exceed the Department of Energy (DEO) 2020-target set for transport applications.

  8. A binder-free sulfur/reduced graphene oxide aerogel as high performance electrode materials for lithium sulfur batteries

    NASA Astrophysics Data System (ADS)

    Nitze, Florian; Agostini, Marco; Lundin, Filippa; Palmqvist, Anders E. C.; Matic, Aleksandar

    2016-12-01

    Societies’ increasing need for energy storage makes it necessary to explore new concepts beyond the traditional lithium ion battery. A promising candidate is the lithium-sulfur technology with the potential to increase the energy density of the battery by a factor of 3-5. However, so far the many problems with the lithium-sulfur system have not been solved satisfactory. Here we report on a new approach utilizing a self-standing reduced graphene oxide based aerogel directly as electrodes, i.e. without further processing and without the addition of binder or conducting agents. We can thereby disrupt the common paradigm of “no battery without binder” and can pave the way to a lithium-sulfur battery with a high practical energy density. The aerogels are synthesized via a one-pot method and consist of more than 2/3 sulfur, contained inside a porous few-layered reduced graphene oxide matrix. By combining the graphene-based aerogel cathode with an electrolyte and a lithium metal anode, we demonstrate a lithium-sulfur cell with high areal capacity (more than 3 mAh/cm2 after 75 cycles), excellent capacity retention over 200 cycles and good sulfur utilization. Based on this performance we estimate that the energy density of this concept-cell can significantly exceed the Department of Energy (DEO) 2020-target set for transport applications.

  9. Iron phthalocyanine modified mesoporous titania nanoparticles for photocatalytic activity and CO2 capture applications.

    PubMed

    Ramacharyulu, P V R K; Muhammad, Raeesh; Praveen Kumar, J; Prasad, G K; Mohanty, Paritosh

    2015-10-21

    An iron(II)phthalocyanine (Fepc) modified mesoporous titania (Fepc-TiO2) nanocatalyst with a specific surface area of 215 m(2) g(-1) has been synthesized by a hydrothermal method. Fepc-TiO2 degrades one of the highly toxic chemical warfare agents, sulfur mustard (SM), photocatalytically under sunlight with an exposure time of as low as 70 min. Furthermore, the mesoporous Fepc-TiO2 also captured 2.1 mmol g(-1) of CO2 at 273 K and 1 atm.

  10. Simultaneous removal of nitrogen oxides and sulfur oxides from combustion gases

    DOEpatents

    Clay, David T.; Lynn, Scott

    1976-10-19

    A process for the simultaneous removal of sulfur oxides and nitrogen oxides from power plant stack gases comprising contacting the stack gases with a supported iron oxide catalyst/absorbent in the presence of sufficient reducing agent selected from the group consisting of carbon monoxide, hydrogen, and mixtures thereof, to provide a net reducing atmosphere in the SO.sub.x /NO.sub.x removal zone. The sulfur oxides are removed by absorption substantially as iron sulfide, and nitrogen oxides are removed by catalytic reduction to nitrogen and ammonia. The spent iron oxide catalyst/absorbent is regenerated by oxidation and is recycled to the contacting zone. Sulfur dioxide is also produced during regeneration and can be utilized in the production of sulfuric acid and/or sulfur.

  11. The Quality of Life of Mustard Gas Victims: A Systematic Review

    PubMed Central

    Satkin, Mojtaba; Ghanei, Mostafa; Allahverdi, Sahar; Elikaei, Mahdi

    2017-01-01

    Background: Today, a host of veterans who were exposed to mustard gas suffer from substantially poor quality of life (QoL). However, factors that influence these patients’ QoL have not been yet scrutinized. QoL is deemed as a crucial construct that demands careful attention during evaluation as well as intervention. The present study aimed to delve into the physical, mental, and social factors that affect the QoL of mustard gas victims. Materials and Methods: All the physical, mental, and social parameters that influence the QoL of mustard gas victims were scrutinized through a systematic review. We searched for Persian and English scientific databases, i.e., PubMed, Scopus, and Google Scholar, and national databanks, namely SID, IranMedex, and Magiran to identify studies related to chemical victims conducted up to the end of 2015. Next, the quality of 21 articles and studies were assessed using the checklist of the National Institute of Health (NIH), and subsequently, 13 articles were selected for the stages of data extraction and analysis. Results: Findings revealed that, among the physical factors, coexistence of several medical conditions caused by chemical injury and the severity of the chemical injury had the greatest impact on the QoL of chemically injured veterans. Besides, suffering from psychological and neurological disorders, along with educational level and employment status, were the most influential psychosocial parameters that influenced veterans’ QoL. Conclusion: The review conducted herein identified the physical and psychosocial factors affecting the QoL of mustard gas victims. In fact, it is the first to present a large collection of descriptive information on QoL contributors in a systematic and orderly fashion. PMID:29308076

  12. S - and N-alkylating agents diminish the fluorescence of fluorescent dye-stained DNA.

    PubMed

    Giesche, Robert; John, Harald; Kehe, Kai; Schmidt, Annette; Popp, Tanja; Balzuweit, Frank; Thiermann, Horst; Gudermann, Thomas; Steinritz, Dirk

    2017-01-25

    Sulfur mustard (SM), a chemical warfare agent, causes DNA alkylation, which is believed to be the main cause of its toxicity. SM DNA adducts are commonly used to verify exposure to this vesicant. However, the required analytical state-of-the-art mass-spectrometry methods are complex, use delicate instruments, are not mobile, and require laboratory infrastructure that is most likely not available in conflict zones. Attempts have thus been made to develop rapid detection methods that can be used in the field. The analysis of SM DNA adducts (HETE-G) by immunodetection is a convenient and suitable method. For a diagnostic assessment, HETE-G levels must be determined in relation to the total DNA in the sample. Total DNA can be easily visualized by the use of fluorescent DNA dyes. This study examines whether SM and related compounds affect total DNA staining, an issue that has not been investigated before. After pure DNA was extracted from human keratinocytes (HaCaT cells), DNA was exposed to different S- and N-alkylating agents. Our experiments revealed a significant, dose-dependent decrease in the fluorescence signal of fluorescent dye-stained DNA after exposure to alkylating agents. After mass spectrometry and additional fluorescence measurements ruled out covalent modifications of ethidium bromide (EthBr) by SM, we assumed that DNA crosslinks caused DNA condensation and thereby impaired access of the fluorescent dyes to the DNA. DNA digestion by restriction enzymes restored fluorescence, a fact that strengthened our hypothesis. However, monofunctional agents, which are unable to crosslink DNA, also decreased the fluorescence signal. In subsequent experiments, we demonstrated that protons produced during DNA alkylation caused a pH decrease that was found responsible for the reduction in fluorescence. The use of an appropriate buffer system eliminated the adverse effect of alkylating agents on DNA staining with fluorescent dyes. An appropriate buffer system is thus

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

    PubMed Central

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

    2015-01-01

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

  14. Chemical agent simulant release from clothing following vapor exposure.

    PubMed

    Feldman, Robert J

    2010-02-01

    Most ambulatory victims of a terrorist chemical attack will have exposure to vapor only. The study objective was to measure the duration of chemical vapor release from various types of clothing. A chemical agent was simulated using methyl salicylate (MeS), which has similar physical properties to sulfur mustard and was the agent used in the U.S. Army's Man-In-Simulant Test (MIST). Vapor concentration was measured with a Smiths Detection Advanced Portable Detector (APD)-2000 unit. The clothing items were exposed to vapor for 1 hour in a sealed cabinet; vapor concentration was measured at the start and end of each exposure. Clothing was then removed and assessed every 5 minutes with the APD-2000, using a uniform sweep pattern, until readings remained 0. Concentration and duration of vapor release from clothing varied with clothing composition and construction. Lightweight cotton shirts and jeans had the least trapped vapor; down outerwear, the most. Vapor concentration near the clothing often increased for several minutes after the clothing was removed from the contaminated environment. Compression of thick outerwear released additional vapor. Mean times to reach 0 ranged from 7 minutes for jeans to 42 minutes for down jackets. This simulation model of chemical vapor release demonstrates persistent presence of simulant vapor over time. This implies that chemical vapor may be released from the victims' clothing after they are evacuated from the site of exposure, resulting in additional exposure of victims and emergency responders. Insulated outerwear can release additional vapor when handled. If a patient has just moved to a vapor screening point, immediate assessment before additional vapor can be released from the clothing can lead to a false-negative assessment of contamination.

  15. Pyrrole as a promising electrolyte additive to trap polysulfides for lithium-sulfur batteries

    NASA Astrophysics Data System (ADS)

    Yang, Wu; Yang, Wang; Song, Ailing; Gao, Lijun; Sun, Gang; Shao, Guangjie

    2017-04-01

    Lithium-sulfur batteries are a promising energy storage devices beyond conventional lithium ion batteries. However, the "shuttle effect" of soluble polysulfides is a major barrier between electrodes, resulting in rapid capacity fading. To address above issue, pyrrole has been investigated as an electrolyte additive to trap polysulfides. When pyrrole is added into electrolyte, a surface protective layer of polypyrrole can be formed on the sulfur cathode, which not only acts as a conductive agent to provide an effective electron conduction path but also acts as an absorbing agent and barrier layer suppressing the diffusion of polysulfide intermediates. The results demonstrate that an appropriate amount of pyrrole added into the electrolyte leads to excellent cycling stability and rate capability. Apparently, pyrrole is an effective additive for the entrapment of polysulfides of lithium-sulfur batteries.

  16. Occurrence of Mycosis Fungoides in an Iranian Chemical Victim of the Iran-Iraq War with a Long-term Follow-Up: A Case Report and Review of Literature.

    PubMed

    Mortazavi, Hossein; Izadi Firouzabadi, Leila; Ghanadan, Alireza; Seirafi, Hassan; Emadi, Seyed Naser; Shakoei, Safoura

    2018-05-01

    Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma. Persistent antigenic stimulation has been claimed to play a role in the development of this malignancy. We aimed to show the role of sulfur mustard in the pathogenesis of MF. A 45-year-old man with MF is introduced herein. He was a victim of chemical exposure in 1987 during the Iran-Iraq war. He developed skin lesions 3 years after exposure to sulfur mustard gas at the age of 21. Seven years after his exposure to sulfur mustard gas, a biopsy from the posterior distal part of his calf, which was injured and had bulla, revealed MF. Later, he developed more lesions on his extremities, trunk, and abdomen. On his previous admission, his left eyebrow was involved. A punch biopsy specimen was obtained from his eyebrow lesion, which rendered diffuse infiltration of atypical lymphocyte cells with some convoluted nuclei and scant cytoplasm admixed with lymphocytes, histiocytes, and mast cells compatible with the nodular stage of MF. At his last admission, a biopsy was obtained from the plaque lesions on his left thigh, and a TCR-γ gene rearrangement of the paraffin block of the plaque lesions revealed positive monoclonality. All the findings supported the MF diagnosis. We concluded that sulfur mustard could be a risk factor for MF development.

  17. Sardasht-Iran cohort study of chemical warfare victims: design and methods.

    PubMed

    Ghazanfari, Tooba; Faghihzadeh, Soghrat; Aragizadeh, Hassan; Soroush, Mohammad-Reza; Yaraee, Roya; Mohammad Hassan, Zuhair; Foroutan, Abbas; Vaez-Mahdavi, Mohammad-Reza; Javadi, Mohammad-Ali; Moaiedmohseni, Sakine; Azizi, Fereidoun; Panahi, Yunes; Mostafaie, Ali; Ghasemi, Hassan; Shams, Jalaleddin; Pourfarzam, Shahryar; Jalali-Nadoushan, Mohammad-Reza; Fallahi, Faramarz; Ebtekar, Massoumeh; Davoudi, Seyyed-Masoud; Ghazanfari, Zeinab; Ardestani, Sussan K; Shariat-Panahi, Shamsa; Moin, Athar; Rezaei, Abbas; Kariminia, Amina; Ajdary, Soheila; Mahmoudi, Mahmoud; Roshan, Rasoul; Ghaderi, Sulayman; Babai, Mahmoud; Naghizadeh, Mohammad-Mehdi; Ghanei, Mohammad-Mostafa

    2009-01-01

    Insights into long-term clinical consequences of sulfur mustard have emerged from some investigations but less is known about the basic and molecular mechanisms of these complications. Sardasht-Iran Cohort Study is a comprehensive historical cohort study on Sardasht chemical victims' population which was designed to find out the long-term complications of sulfur mustard exposure and the basic mechanisms underlying clinical manifestations. This paper describes the design and methodology of Sardasht-Iran Cohort Study. In Sardasht-Iran Cohort Study, 500 individuals including 372 subjects from Sardasht, as the exposed group, and 128 subjects from Rabat, as the unexposed age-matched control group were evaluated. The exposed group was divided into two groups based on the severity of clinical complications at the time of exposure. Different samples including blood, sputum, saliva, tear, urine, and semen were collected for immunologic, hematologic, biochemical, and other laboratory analysis. Data were gathered from medical records, clinical examinations, laboratory tests, and questionnaires for psychological and lifestyle situations. The important distinctions setting this study apart from the previous ones are discussed. The Sardasht-Iran Cohort Study provides important information on various aspects of long-term consequences of sulfur mustard exposure. This database will provide a better position to suggest guidelines for the diagnosis, treatment, and prevention of delayed complications in the patients exposed to sulfur mustard.

  18. 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.

  19. Inspiratory and expiratory high-resolution computed tomography (HRCT) in patients with chemical warfare agents exposure.

    PubMed

    Bakhtavar, Khadijeh; Sedighi, Nahid; Moradi, Zahra

    2008-03-01

    Chemical warfare agents (CWA) including sulfur mustard (SM) were commonly used in Iran-Iraq war. Respiratory problems are the greatest cause of long-term disability among people who had combat exposure to SM. High-resolution computed tomography (HRCT) has been accepted as the imaging modality of choice in these patients. We used expiratory HRCT findings in comparison to inspiratory HRCT for demonstration of pulmonary damage in these patients. HRCT in deep inspiration as well as full expiration was performed in 473 patients with a history of chemical gas exposure during the war and the results were compared. The study was prospective during 1 yr. Of 473 patients, 366 (77.38%) showed normal HRCT in deep inspiration; however, on corresponding expiratory cuts, 263 (71.86%) had abnormalities. The most frequent abnormal finding in expiration was patchy air trapping (77.77%). We conclude that exposure to SM causes pulmonary complications resulting in disability in the affected patients; however, HRCT in inspiration is normal in most of the affected patients. Expiratory HRCT showed patchy air trapping as the most common finding, which is suggestive of small air way diseases such as bronchiolitis obliterans; therefore it is recommended to do HRCT both in deep inspiration and full expiration in patients with a history of CWA exposure.

  20. Ifosfamide metabolites CAA, 4-OH-Ifo and Ifo-mustard reduce apical phosphate transport by changing NaPi-IIa in OK cells.

    PubMed

    Patzer, L; Hernando, N; Ziegler, U; Beck-Schimmer, B; Biber, J; Murer, H

    2006-11-01

    Renal Fanconi syndrome occurs in about 1-5% of all children treated with Ifosfamide (Ifo) and impairment of renal phosphate reabsorption in about 20-30% of them. Pathophysiological mechanisms of Ifo-induced nephropathy are ill defined. The aim has been to investigate whether Ifo metabolites affect the type IIa sodium-dependent phosphate transporter (NaPi-IIa) in viable opossum kidney cells. Ifo did not influence viability of cells or NaPi-IIa-mediated transport up to 1 mM/24 h. Incubation of confluent cells with chloroacetaldehyde (CAA) and 4-hydroperoxyIfosfamide (4-OH-Ifo) led to cell death by necrosis in a concentration-dependent manner. At low concentrations (50-100 microM/24 h), cell viability was normal but apical phosphate transport, NaPi-IIa protein, and -mRNA expression were significantly reduced. Coincubation with sodium-2-mercaptoethanesulfonate (MESNA) prevented the inhibitory action of CAA but not of 4-OH-Ifo; DiMESNA had no effect. Incubation with Ifosfamide-mustard (Ifo-mustard) did alter cell viability at concentrations above 500 microM/24 h. At lower concentrations (50-100 microM/24 h), it led to significant reduction in phosphate transport, NaPi-IIa protein, and mRNA expression. MESNA did not block these effects. The effect of Ifo-mustard was due to internalization of NaPi-IIa. Cyclophosphamide-mustard (CyP-mustard) did not have any influence on cell survival up to 1000 microM, but the inhibitory effect on phosphate transport and on NaPi-IIa protein was the same as found after Ifo-mustard. In conclusion, CAA, 4-OH-Ifo, and Ifo- and CyP-mustard are able to inhibit sodium-dependent phosphate cotransport in viable opossum kidney cells. The Ifo-mustard effect took place via internalization and reduction of de novo synthesis of NaPi-IIa. Therefore, it is possible that Ifo-mustard plays an important role in pathogenesis of Ifo-induced nephropathy.

  1. Devices and methods to detect and quantify trace gases

    DOEpatents

    Allendorf, Mark D.; Robinson, Alex

    2016-05-03

    Sensing devices based on a surface acoustic wave ("SAW") device coated with an absorbent crystalline or amorphous layer for detecting at least one chemical analyte in a gaseous carrier. Methods for detecting the presence of a chemical analyte in a gaseous carrier using such devices are also disclosed. The sensing devices and methods for their use may be configured for sensing chemical analytes selected from the group consisting of water vapor, carbon dioxide, methanol, ethanol, carbon monoxide, nitric oxide, nitrous oxide, organic amines, organic compounds containing NO.sub.2 groups, halogenated hydrocarbons, acetone, hexane, toluene, isopropanol, alcohols, alkanes, alkenes, benzene, functionalized aromatics, ammonia (NH.sub.3), phosgene (COCl.sub.2), sulfur mustard, nerve agents, sulfur dioxide, tetrahydrofuran (THF) and methyltertbutyl ether (MTBE) and combinations thereof.

  2. Performance, combustion and emission analysis of mustard oil biodiesel and octanol blends in diesel engine

    NASA Astrophysics Data System (ADS)

    Devarajan, Yuvarajan; Munuswamy, Dinesh Babu; Nagappan, Beemkumar; Pandian, Amith Kishore

    2018-01-01

    Biodiesels from the mustard oil promise to be an alternative to the conventional diesel fuel due to their similarity in properties. Higher alcohols are added to neat Mustard oil biodiesel (M100) to vary the properties of biodiesel for improving its combustion, emission and performance characteristics. N-Octanol has the ability to act as an oxygen buffer during combustion which contributes to the catalytic effect and accelerates the combustion process. N-Octanol is dispersed to neat Mustard oil biodiesel in the form of emulsions at different dosage levels of 10, 20 and 30% by volume. Three emulsion fuels prepared for engine testing constitutes of 90% of biodiesel and 10% of n-Octanol (M90O10), 80% of biodiesel and 20% of n-Octanol (M80O20) and 70% of biodiesel and 30% of n-Octanol (M70O30) by volume respectively. AVL 5402 diesel engine is made to run on these fuels to study the effect of n-Octanol on combustion, emission and performance characteristics of the mustard oil biodiesel. Experimental results show that addition of n-octanol has a positive effect on performance, combustion and emission characteristics owing to its inbuilt oxygen content. N-octanol was found to be the better oxidizing catalyst as it was more effective in reducing HC and CO emissions. A significant reduction in NOx emission was found when fuelled with emulsion techniques. The blending of n-octanol to neat Mustard oil biodiesel reduces the energy and fuel consumption and a marginal increase in brake thermal efficiency. Further, n-octanol also reduces the ignition delay and aids the combustion.

  3. Performance, combustion and emission analysis of mustard oil biodiesel and octanol blends in diesel engine

    NASA Astrophysics Data System (ADS)

    Devarajan, Yuvarajan; Munuswamy, Dinesh Babu; Nagappan, Beemkumar; Pandian, Amith Kishore

    2018-06-01

    Biodiesels from the mustard oil promise to be an alternative to the conventional diesel fuel due to their similarity in properties. Higher alcohols are added to neat Mustard oil biodiesel (M100) to vary the properties of biodiesel for improving its combustion, emission and performance characteristics. N-Octanol has the ability to act as an oxygen buffer during combustion which contributes to the catalytic effect and accelerates the combustion process. N-Octanol is dispersed to neat Mustard oil biodiesel in the form of emulsions at different dosage levels of 10, 20 and 30% by volume. Three emulsion fuels prepared for engine testing constitutes of 90% of biodiesel and 10% of n-Octanol (M90O10), 80% of biodiesel and 20% of n-Octanol (M80O20) and 70% of biodiesel and 30% of n-Octanol (M70O30) by volume respectively. AVL 5402 diesel engine is made to run on these fuels to study the effect of n-Octanol on combustion, emission and performance characteristics of the mustard oil biodiesel. Experimental results show that addition of n-octanol has a positive effect on performance, combustion and emission characteristics owing to its inbuilt oxygen content. N-octanol was found to be the better oxidizing catalyst as it was more effective in reducing HC and CO emissions. A significant reduction in NOx emission was found when fuelled with emulsion techniques. The blending of n-octanol to neat Mustard oil biodiesel reduces the energy and fuel consumption and a marginal increase in brake thermal efficiency. Further, n-octanol also reduces the ignition delay and aids the combustion.

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

    PubMed

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

    2015-01-01

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

  5. Physiological and anthocyanin biosynthesis genes response induced by vanadium stress in mustard genotypes with distinct photosynthetic activity.

    PubMed

    Imtiaz, Muhammad; Mushtaq, Muhammad Adnan; Nawaz, Muhammad Amjad; Ashraf, Muhammad; Rizwan, Muhammad Shahid; Mehmood, Sajid; Aziz, Omar; Rizwan, Muhammad; Virk, Muhammad Safiullah; Shakeel, Qaiser; Ijaz, Raina; Androutsopoulos, Vasilis P; Tsatsakis, Aristides M; Coleman, Michael D

    2018-06-13

    The present study aimed to elucidate the photosynthetic performance, antioxidant enzyme activities, anthocyanin contents, anthocyanin biosynthetic gene expression, and vanadium uptake in mustard genotypes (purple and green) that differ in photosynthetic capacity under vanadium stress. The results indicated that vanadium significantly reduced photosynthetic activity in both genotypes. The activities of the antioxidant enzymes were increased significantly in response to vanadium in both genotypes, although the purple exhibited higher. The anthocyanin contents were also reduced under vanadium stress. The anthocyanin biosynthetic genes were highly expressed in the purple genotype, notably the genes TT8, F3H, and MYBL2 under vanadium stress. The results indicate that induction of TT8, F3H, and MYBL2 genes was associated with upregulation of the biosynthetic genes required for higher anthocyanin biosynthesis in purple compared with the green mustard. The roots accumulated higher vanadium than shoots in both mustard genotypes. The results indicate that the purple mustard had higher vanadium tolerance. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Sulfuric acid on Europa and the radiolytic sulfur cycle.

    PubMed

    Carlson, R W; Johnson, R E; Anderson, M S

    1999-10-01

    A comparison of laboratory spectra with Galileo data indicates that hydrated sulfuric acid is present and is a major component of Europa's surface. In addition, this moon's visually dark surface material, which spatially correlates with the sulfuric acid concentration, is identified as radiolytically altered sulfur polymers. Radiolysis of the surface by magnetospheric plasma bombardment continuously cycles sulfur between three forms: sulfuric acid, sulfur dioxide, and sulfur polymers, with sulfuric acid being about 50 times as abundant as the other forms. Enhanced sulfuric acid concentrations are found in Europa's geologically young terrains, suggesting that low-temperature, liquid sulfuric acid may influence geological processes.

  7. The skin reservoir of sulphur mustard.

    PubMed

    Hattersley, I J; Jenner, J; Dalton, C; Chilcott, R P; Graham, J S

    2008-09-01

    Studies of the percutaneous reservoir of sulphur mustard (HD) formed during absorption carried out during WWI and WWII are inconclusive. More recent studies have indicated that a significant amount of unreacted HD remains in human epidermal membranes during percutaneous penetration studies in vitro. The present study investigated the nature and persistence of the HD reservoir formed during in vitro penetration studies using dermatomed slices of human and pig skin (0.5mm thick). Amounts of (14)C-HD that (a) penetrated, (b) remained on the surface, (c) were extractable from and (d) remained in the skin after extraction were estimated by liquid scintillation counting (confirmed using GC-MS analysis). The results demonstrated that there is a reservoir of HD in human and pig skin for up to 24 h after contamination of the skin surface in vitro with liquid agent. At least some of this reservoir could be extracted with acetonitrile, and the amounts of extracted and unextracted HD exceed the amount required to produce injury in vivo by at least 20 fold. The study demonstrated the presence of a reservoir whether the skin was covered (occluded) or left open to the air (unoccluded). The study concluded that the extractable reservoir was significant in terms of the amount of HD required to induce a vesicant response in human skin. The extractable reservoir was at least 20 times the amount required per cm(2) estimated to cause a response in all of the human population, as defined by studies carried out in human volunteers during the 1940s.

  8. Sea-dumped chemical weapons: environmental risk, occupational hazard.

    PubMed

    Greenberg, M I; Sexton, K J; Vearrier, D

    2016-01-01

    Chemical weapons dumped into the ocean for disposal in the twentieth century pose a continuing environmental and human health risk. In this review we discuss locations, quantity, and types of sea-dumped chemical weapons, related environmental concerns, and human encounters with sea-dumped chemical weapons. We utilized the Ovid (http://ovidsp.tx.ovid.com) and PubMed (http://www.pubmed.org) search engines to perform MEDLINE searches for the terms 'sea-dumped chemical weapons', 'chemical warfare agents', and 'chemical munitions'. The searches returned 5863 articles. Irrelevant and non-English articles were excluded. A review of the references for these articles yielded additional relevant sources, with a total of 64 peer-reviewed articles cited in this paper. History and geography of chemical weapons dumping at sea: Hundreds of thousands of tons of chemical munitions were disposed off at sea following World War II. European, Russian, Japanese, and United States coasts are the areas most affected worldwide. Several areas in the Baltic and North Seas suffered concentrated large levels of dumping, and these appear to be the world's most studied chemical warfare agent marine dumping areas. Chemical warfare agents: Sulfur mustard, Lewisite, and the nerve agents appear to be the chemical warfare agents most frequently disposed off at sea. Multiple other type of agents including organoarsenicals, blood agents, choking agents, and lacrimators were dumped at sea, although in lesser volumes. Environmental concerns: Numerous geohydrologic variables contribute to the rate of release of chemical agents from their original casings, leading to difficult and inexact modeling of risk of release into seawater. Sulfur mustard and the organoarsenicals are the most environmentally persistent dumped chemical agents. Sulfur mustard in particular has a propensity to form a solid or semi-solid lump with a polymer coating of breakdown products, and can persist in this state on the ocean floor

  9. Quality and Consumer Acceptance of Berry Fruit Pomace-Fortified Specialty Mustard.

    PubMed

    Davis, Lissa; Jung, Jooyeoun; Colonna, Ann; Hasenbeck, Aimee; Gouw, Virginia; Zhao, Yanyun

    2018-06-15

    Blueberry pomace (BP) and cranberry pomace (CP) are good sources of dietary fiber and phenolics. This study aimed to develop berry fruit pomace (FP)-fortified specialty mustard with elevated bioactive compounds and ascertain consumer acceptance of a new product. Wet BP and CP were ground and incorporated into Dijon-style mustard at concentrations of 15%, 20%, and 25% (w/w). Total dietary fiber (TDF), total phenolic content (TPC), and radical scavenging activity (RSA) were evaluated for samples obtained from both chemical extraction (CE) and simulated gastrointestinal digestion (SGD). Physicochemical properties and consumer acceptance were also examined. Increasing concentrations of BP or CP significantly increased TDF of mustards from both CE (AOAC methods) and SGD, with the highest values from 25% fortifications. TDF from AOAC ranged from 26.86% to 40.16% for BP and from 26.86% to 38.42% for CP, while TDF from SGD ranged from 31.02% to 42.68% for BP and 31.02% to 63.65% for CP. From CE, no significant variation of TPC was found, but RSA significantly increased with increasing concentration of BP and CP. TPC from SGD was higher than that from CE, where TPC decreased with increasing concentration of BP or CP. RSA from SGD was lower than that from CE. Sensory scores of pomace-fortified samples were significantly lower than the control; however, informed panelists scored BP-fortified mustard significantly higher on appearance and color liking than uninformed panelists. This study demonstrated that with proper marketing, the utilization of FP in condiments is a viable option for potential health benefits. This research is applicable to multiple areas of the food industry. Juice manufacturers or other companies that process raw agricultural produce can use this research as another way to repurpose biowaste, and companies making specialty condiments can use this research to inform future product development. General considerations discussed regarding the use of berry

  10. Sulfur oxidation genes in diverse deep-sea viruses.

    PubMed

    Anantharaman, Karthik; Duhaime, Melissa B; Breier, John A; Wendt, Kathleen A; Toner, Brandy M; Dick, Gregory J

    2014-05-16

    Viruses are the most abundant biological entities in the oceans and a pervasive cause of mortality of microorganisms that drive biogeochemical cycles. Although the ecological and evolutionary effects of viruses on marine phototrophs are well recognized, little is known about their impact on ubiquitous marine lithotrophs. Here, we report 18 genome sequences of double-stranded DNA viruses that putatively infect widespread sulfur-oxidizing bacteria. Fifteen of these viral genomes contain auxiliary metabolic genes for the α and γ subunits of reverse dissimilatory sulfite reductase (rdsr). This enzyme oxidizes elemental sulfur, which is abundant in the hydrothermal plumes studied here. Our findings implicate viruses as a key agent in the sulfur cycle and as a reservoir of genetic diversity for bacterial enzymes that underpin chemosynthesis in the deep oceans. Copyright © 2014, American Association for the Advancement of Science.

  11. Use of Industrial Waste (Al-Dross, Red Mud, Mill Scale) as Fluxing Agents in the Sulfurization of Fe-Ni-Cu-Co Alloy by Carbothermic Reduction of Calcium Sulfate

    NASA Astrophysics Data System (ADS)

    Heo, Jung Ho; Jeong, Eui Hyuk; Nam, Chul Woo; Park, Kyung Ho; Park, Joo Hyun

    2018-06-01

    The use of industrial waste [mill scale (MS), red mud (RM), Al-dross (AD)] as fluxing agents in the sulfurization of Fe-Ni-Cu-Co alloy to matte (Fe-Ni-Cu-Co-S) by carbothermic reduction of CaSO4 was investigated at 1673 K (1400 °C). The sulfurization efficiency (SE) was 76 (± 2) pct at RM or AD single fluxing. However, SE drastically increased to approximately 89 pct at a `5AD + 5MS' combination, which was equivalent to reagent-grade chemical `5Al2O3 + 5Fe2O3' fluxing (SE = 88 pct). The present results can be used to improve the cost-effective recovery of rare metals (Ni and Co) from deep sea manganese nodules.

  12. Use of Industrial Waste (Al-Dross, Red Mud, Mill Scale) as Fluxing Agents in the Sulfurization of Fe-Ni-Cu-Co Alloy by Carbothermic Reduction of Calcium Sulfate

    NASA Astrophysics Data System (ADS)

    Heo, Jung Ho; Jeong, Eui Hyuk; Nam, Chul Woo; Park, Kyung Ho; Park, Joo Hyun

    2018-03-01

    The use of industrial waste [mill scale (MS), red mud (RM), Al-dross (AD)] as fluxing agents in the sulfurization of Fe-Ni-Cu-Co alloy to matte (Fe-Ni-Cu-Co-S) by carbothermic reduction of CaSO4 was investigated at 1673 K (1400 °C). The sulfurization efficiency (SE) was 76 (± 2) pct at RM or AD single fluxing. However, SE drastically increased to approximately 89 pct at a `5AD + 5MS' combination, which was equivalent to reagent-grade chemical `5Al2O3 + 5Fe2O3' fluxing (SE = 88 pct). The present results can be used to improve the cost-effective recovery of rare metals (Ni and Co) from deep sea manganese nodules.

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

    PubMed

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

    2014-06-15

    The paper presents a duplex real-time PCR assay for the simultaneous detection of three potentially allergenic mustard species commonly used in food: white mustard (Sinapis alba), black mustard (Brassica nigra) and brown mustard (Brassica juncea). White mustard is detected in the "green" and black/brown mustard in the "yellow" channel. The duplex real-time PCR assay does not show cross-reactivity with other Brassicaceae species including broccoli, cauliflower, radish and rapeseed. Low cross-reactivities (difference in the Ct value ⩾ 11.91 compared with the positive control) were obtained with cumin, fenugreek, ginger, rye and turmeric. When applying 500 ng DNA per PCR tube, the duplex real-time PCR assay allowed the detection of white, black and brown mustard in brewed model sausages down to a concentration of 5mg/kg in 10 out of 10 replicates. The duplex real-time PCR assay was applied to verify correct labelling of commercial foodstuffs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Mycosis fungoides two decades after exposure to sulphur mustard: a follow-up of 1100 victims.

    PubMed

    Emadi, S N; Shiri, M; Shiri, Z; Emadi, S E; Mortazavi, H; Nikoo, A; Akhavan-Moghaddam, J

    2017-03-01

    Sulphur mustard (SM) is an alkylating chemical warfare agent which causes acute and chronic injuries to the eyes, skin, lung and respiratory tract. We aimed to investigate the relationship between SM poisoning and Mycosis fungoides (MF) as a late consequence. In this retrospective study, the medical files of 1100 Iranian veterans confirmed to have exposure to SM agent during the Iraq-Iran war of the 1980s were reviewed. All 10 cases with MF were confirmed by clinical and histopathological examinations. The mean age of the studied subjects was 43.3 ± 9.8 (years). In comparison to MF incidence rate in Iranian general population (0.39/100 000 person-years), we found an incidence rate of 0.799/100 000 person-years for MF among those who had short-term exposure to SM. The most common sites for SM lesions were flexural and thin skin areas. The main limitation was the retrospective design. This study indicates that the risk of MF in those exposed to SM may increase over time. Therefore, their follow-up is recommended. © 2016 European Academy of Dermatology and Venereology.

  15. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gray, Joshua P.; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ; Mishin, Vladimir

    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 cytochromemore » 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.« less

  16. Ferrocene-Promoted Long-Cycle Lithium-Sulfur Batteries.

    PubMed

    Mi, Yingying; Liu, Wen; Yang, Ke R; Jiang, Jianbing; Fan, Qi; Weng, Zhe; Zhong, Yiren; Wu, Zishan; Brudvig, Gary W; Batista, Victor S; Zhou, Henghui; Wang, Hailiang

    2016-11-14

    Confining lithium polysulfide intermediates is one of the most effective ways to alleviate the capacity fade of sulfur-cathode materials in lithium-sulfur (Li-S) batteries. To develop long-cycle Li-S batteries, there is an urgent need for material structures with effective polysulfide binding capability and well-defined surface sites; thereby improving cycling stability and allowing study of molecular-level interactions. This challenge was addressed by introducing an organometallic molecular compound, ferrocene, as a new polysulfide-confining agent. With ferrocene molecules covalently anchored on graphene oxide, sulfur electrode materials with capacity decay as low as 0.014 % per cycle were realized, among the best of cycling stabilities reported to date. With combined spectroscopic studies and theoretical calculations, it was determined that effective polysulfide binding originates from favorable cation-π interactions between Li + of lithium polysulfides and the negatively charged cyclopentadienyl ligands of ferrocene. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. 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.

  18. Characterization of chemical agent transport in paints.

    PubMed

    Willis, Matthew P; Gordon, Wesley; Lalain, Teri; Mantooth, Brent

    2013-09-15

    A combination of vacuum-based vapor emission measurements with a mass transport model was employed to determine the interaction of chemical warfare agents with various materials, including transport parameters of agents in paints. Accurate determination of mass transport parameters enables the simulation of the chemical agent distribution in a material for decontaminant performance modeling. The evaluation was performed with the chemical warfare agents bis(2-chloroethyl) sulfide (distilled mustard, known as the chemical warfare blister agent HD) and O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX), an organophosphate nerve agent, deposited on to two different types of polyurethane paint coatings. The results demonstrated alignment between the experimentally measured vapor emission flux and the predicted vapor flux. Mass transport modeling demonstrated rapid transport of VX into the coatings; VX penetrated through the aliphatic polyurethane-based coating (100 μm) within approximately 107 min. By comparison, while HD was more soluble in the coatings, the penetration depth in the coatings was approximately 2× lower than VX. Applications of mass transport parameters include the ability to predict agent uptake, and subsequent long-term vapor emission or contact transfer where the agent could present exposure risks. Additionally, these parameters and model enable the ability to perform decontamination modeling to predict how decontaminants remove agent from these materials. Published by Elsevier B.V.

  19. DNA damage in internal organs after cutaneous exposure to sulphur mustard.

    PubMed

    Batal, Mohamed; Boudry, Isabelle; Mouret, Stéphane; Cléry-Barraud, Cécile; Wartelle, Julien; Bérard, Izabel; Douki, Thierry

    2014-07-01

    Sulphur mustard (SM) is a chemical warfare agent that attacks mainly skin, eye and lungs. Due to its lipophilic properties, SM is also able to diffuse through the skin and reach internal organs. DNA represents one of the most critical molecular targets of this powerful alkylating agent which modifies DNA structure by forming monoadducts and biadducts. These DNA lesions are involved in the acute toxicity of SM as well as its long-term carcinogenicity. In the present work we studied the formation and persistence of guanine and adenine monoadducts and guanine biadducts in the DNA of brain, lungs, kidneys, spleen, and liver of SKH-1 mice cutaneously exposed to 2, 6 and 60mg/kg of SM. SM-DNA adducts were detected in all studied organs, except in liver at the two lowest doses. Brain and lungs were the organs with the highest level of SM-DNA adducts, followed by kidney, spleen and liver. Monitoring the level of adducts for three weeks after cutaneous exposure showed that the lifetime of adducts were not the same in all organs, lungs being the organ with the longest persistence. Diffusion from skin to internal organs was much more efficient at the highest compared to the lowest dose investigated as the result of the loss of the skin barrier function. These data provide novel information on the distribution of SM in tissues following cutaneous exposures and indicate that brain is an important target. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Methods Development for the Isolation and Culture of Primary Corneal Endothelial Cells

    DTIC Science & Technology

    2017-02-01

    are collectively referred to as mustard gas keratopathy (MGK). Prevailing evidence suggests that late onset MGK may result from a deficit in corneal...and PBK is similar to that seen in mustard gas keratopathy (MGK).3,6,7 MGK can occur years after ocular sulfur mustard (SM) exposure. Treatment...component into the stage component such that the O-ring creates a liquid -tight seal. The final assembled device is shown in panel D. A primary

  1. Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse. (I) Development of a model for screening studies in skin decontamination and protection.

    PubMed

    Dorandeu, F; Taysse, L; Boudry, I; Foquin, A; Hérodin, F; Mathieu, J; Daulon, S; Cruz, C; Lallement, G

    2011-06-01

    Exposure to lethal chemical warfare agents (CWAs) is no longer only a military issue due to the terrorist threat. Among the CWAs of concern are the organophosphorus nerve agent O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX) and the vesicant sulfur mustard (SM). Although efficient means of decontamination are available, most of them lose their efficacy when decontamination is delayed after exposure of the bare skin. Alternatively, CWA skin penetration can be prevented by topical skin protectants. Active research in skin protection and decontamination is thus paramount. In vivo screening of decontaminants or skin protectants is usually time consuming and may be expensive depending on the animal species used. We were thus looking for a suitable, scientifically sound and cost-effective model, which is easy to handle. The euthymic hairless mouse Crl: SKH-1 (hr/hr) BR is widely used in some skin studies and has previously been described to be suitable for some experiments involving SM or SM analogs. To evaluate the response of this species, we studied the consequences of exposing male anaesthetized SKH-1 mice to either liquid VX or to SM, the latter being used in liquid form or as saturated vapours. Long-term effects of SM burn were also evaluated. The model was then used in the companion paper (Taysse et al.(1)).

  2. Yellow mustard bran attenuates glycaemic response of a semi-solid food in young healthy men.

    PubMed

    Lett, Aron M; Thondre, Pariyarath S; Rosenthal, Andrew J

    2013-03-01

    In a randomized, repeated-measures design, the glycaemic response and satiety ratings of a potato and leek soup were compared with and without the addition of 5 g of yellow mustard bran. Ten healthy, non-smoking, moderately active male subjects (mean age of 21.1 years and mean body mass index 23.2 kg/m(2)) were recruited to the study. Capillary blood glucose and satiety were measured at 0, 15, 30, 45, 60, 90 and 120 min, postprandial of each food. The incremental area under the blood glucose curve, blood glucose at each time point and satiety rating were calculated and compared via paired t-test. Mean blood glucose values at 15, 30 and 90 min (p < 0.0001, p < 0.0001 and p = 0.0059, respectively) were all significantly lower with the addition of 5 g of yellow mustard bran. In conclusion, this study demonstrated the attenuation of postprandial glycaemic response following the addition of 5 g of yellow mustard bran to a soup.

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

    USDA-ARS?s Scientific Manuscript database

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

  4. Graphene-sulfur nanocomposites for rechargeable lithium-sulfur battery electrodes

    DOEpatents

    Liu, Jun; Lemmon, John P; Yang, Zhenguo; Cao, Yuiliang; Li, Xiaolin

    2014-06-17

    Rechargeable lithium-sulfur batteries having a cathode that includes a graphene-sulfur nanocomposite can exhibit improved characteristics. The graphene-sulfur nanocomposite can be characterized by graphene sheets with particles of sulfur adsorbed to the graphene sheets. The sulfur particles have an average diameter less than 50 nm..

  5. 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...

  6. 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...

  7. 40 CFR 180.1167 - Allyl isothiocyanate as a component of food grade oil of mustard; exemption from the requirement...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  8. Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans

    PubMed Central

    Balali-Mood, M; Mousavi, SH; Balali-Mood, B

    2008-01-01

    The widespread use of sulphur mustard (SM) as an incapacitating chemical warfare agent in the past century has proved its long-lasting toxic effects. It may also be used as a chemical terrorist agent. Therefore, all health professionals should have sufficient knowledge and be prepared for any such chemical attack. SM exerts direct toxic effects on the eyes, skin, and respiratory tissue, with subsequent systemic action on the nervous, immunological, haematological, digestive, and reproductive systems. SM is an alkylating agent that affects DNA synthesis, and, thus, delayed complications have been seen since the First World War. Cases of malignancies in the target organs, particularly in haematopoietic, respiratory, and digestive systems, have been reported. Important delayed respiratory complications include chronic bronchitis, bronchiectasis, frequent bronchopneumonia, and pulmonary fibrosis, all of which tend to deteriorate with time. Severe dry skin, delayed keratitis, and reduction of natural killer cells with subsequent increased risk of infections and malignancies are also among the most distressing long-term consequences of SM intoxication. However, despite a lot of research over the past decades on Iranian veterans, there are still major gaps in the SM literature. Immunological and neurological dysfunction, as well as the relationship between SM exposure and mutagenicity, carcinogenicity, and teratogenicity are important fields that require further studies, particularly on Iranian veterans with chronic health effects of SM poisoning. There is also a paucity of information on the medical management of acute and delayed toxic effects of SM poisoning—a subject that greatly challenges health care specialists. PMID:22460216

  9. Correlations of sleep disorders with severity of obstructive airway disease in mustard gas-injured patients.

    PubMed

    Vahedi, Ensieh; Taheri, Saeed; Alaedini, Farshid; Poursaleh, Zohreh; Ameli, Javad; Ghanei, Mostafa

    2012-06-01

    Mustard gas has serious adverse effects on several organs and functions in humans. In this study, we analyzed potential correlations between obstructive airway disease and sleep disorders in Iranian mustard gas-injured patients. We enrolled 30 male mustard gas-injured veterans and civilians from the Chemical Warfare Exposure Clinic at Baqiyatallah Hospital, Tehran. All the subjects underwent comprehensive polysomnographic and spirometric evaluations for diagnosis of sleep disorders. Patients were categorized into three groups according to the severity of their obstructive airway disease based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria: group 1 (GOLD I and II), group 2 (GOLD III), and group 3 (GOLD IV). Patients with less severe obstructive airway disease had significantly higher rate of hypopnea (p = 0.05) and AHI (p = 0.05). The number of REM events was significantly higher in patients with less severe airway disease (p = 0.028). Stage 1 sleep among patients with higher FEV1 significantly constituted a higher proportion of sleep, and stage 4 sleep was significantly longer in patients with higher DLCO (p = 0.043, both). We found that sleep parameters in SM-exposed patients have some relations with spirometric parameters. Future studies with large patient populations are needed for confirmation of our results, and therapeutic interventions are needed to evaluate endeavors we can do to enhance health and quality of life in our mustard gas-injured population.

  10. Lipoic Acid as a Possible Pharmacological Source of Hydrogen Sulfide/Sulfane Sulfur.

    PubMed

    Bilska-Wilkosz, Anna; Iciek, Małgorzata; Kowalczyk-Pachel, Danuta; Górny, Magdalena; Sokołowska-Jeżewicz, Maria; Włodek, Lidia

    2017-03-02

    The aim of the present study was to verify whether lipoic acid (LA) itself is a source of H₂S and sulfane sulfur. It was investigated in vitro non-enzymatically and enzymatically (in the presence of rat tissue homogenate). The results indicate that both H₂S and sulfane sulfur are formed from LA non-enzymatically in the presence of environmental light. These results suggest that H₂S is the first product of non-enzymatic light-dependent decomposition of LA that is, probably, next oxidized to sulfane sulfur-containing compound(s). The study performed in the presence of rat liver and kidney homogenate revealed an increase of H₂S level in samples containing LA and its reduced form dihydrolipoic acid (DHLA). It was accompanied by a decrease in sulfane sulfur level. It seems that, in these conditions, DHLA acts as a reducing agent that releases H₂S from an endogenous pool of sulfane sulfur compounds present in tissues. Simultaneously, it means that exogenous LA cannot be a direct donor of H₂S/sulfane sulfur in animal tissues. The present study is an initial approach to the question whether LA itself is a donor of H₂S/sulfane sulfur.

  11. Combined effects of mustard flour, acetic acid, and salt against Esherichia coil O157:H7 stored at 5 and 22 degrees C.

    PubMed

    Rhee, Min-Suk; Dougherty, Richard H; Kang, Dong-Hyun

    2002-10-01

    The combined effects of acetic acid and mustard flour were investigated to ascertain their impact on Escherichia coli O157:H7 stored at 5 and 22 degrees C. Samples were prepared with various concentrations of acetic acid (0, 0.25, 0.5, 0.75, and 1% [vol/vol]) combined with 10% (wt/vol) Baltimore or Coleman mustard flour and 2% (fixed; wt/vol) sodium chloride. An acid-adapted mixture of three E. coli O157:H7 strains (10(6) to 10(7) CFU/ml) was inoculated into prepared mustard samples that were stored at 5 and 22 degrees C, and samples were assayed periodically for the survival of E. coli O157:H7. The numbers of E. coli O157:H7 were reduced much more rapidly at 22 degrees C than at 5 degrees C. E. coli O157:H7 was rapidly reduced to below the detection limit (<0.3 log10, CFU/ml) after 1 day at 22 degrees C, whereas it survived for up to 5 days at 5 degrees C. There was no synergistic or additive effect with regard to the killing of E. coli O157:H7 with the addition of small amounts of acetic acid to the mustard flour. When stored at 5 degrees C, mustard in combination with 0.25 (M-0.25), 0.5 (M-0.5), and 0.75% (M-0.75) acetic acid exerted less antimicrobial activity than the control (M-0). The order of lethality at 5 degrees C was generally M-0.25 = M-0.5 < M-0.75 = M-0 < M-1. The addition of small amounts of acetic acid (<0.75%) to mustard retards the reduction of E coli O157:H7. Statistical reduction in populations of E. coli O157:H7 (P < 0.05) was enhanced relative to that of the control (mustard alone) only with the addition of 1% acetic acid. This information may help mustard manufacturers to understand the antimicrobial activity associated with use of mustard flour in combination with acetic acid.

  12. 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.

  13. Using Metal Complex Ion-Molecule Reactions in a Miniature Rectilinear Ion Trap Mass Spectrometer to Detect Chemical Warfare Agents

    NASA Astrophysics Data System (ADS)

    Graichen, Adam M.; Vachet, Richard W.

    2013-06-01

    The gas-phase reactions of a series of coordinatively unsaturated [Ni(L)n]y+ complexes, where L is a nitrogen-containing ligand, with chemical warfare agent (CWA) simulants in a miniature rectilinear ion trap mass spectrometer were investigated as part of a new approach to detect CWAs. Results show that upon entering the vacuum system via a poly(dimethylsiloxane) (PDMS) membrane introduction, low concentrations of several CWA simulants, including dipropyl sulfide (simulant for mustard gas), acetonitrile (simulant for the nerve agent tabun), and diethyl phosphite (simulant for nerve agents sarin, soman, tabun, and VX), can react with metal complex ions generated by electrospray ionization (ESI), thereby providing a sensitive means of detecting these compounds. The [Ni(L)n]2+ complexes are found to be particularly reactive with the simulants of mustard gas and tabun, allowing their detection at low parts-per-billion (ppb) levels. These detection limits are well below reported exposure limits for these CWAs, which indicates the applicability of this new approach, and are about two orders of magnitude lower than electron ionization detection limits on the same mass spectrometer. The use of coordinatively unsaturated metal complexes as reagent ions offers the possibility of further tuning the ion-molecule chemistry so that desired compounds can be detected selectively or at even lower concentrations.

  14. Wet Chemistry Synthesis of Multidimensional Nanocarbon-Sulfur Hybrid Materials with Ultrahigh Sulfur Loading for Lithium-Sulfur Batteries.

    PubMed

    Du, Wen-Cheng; Yin, Ya-Xia; Zeng, Xian-Xiang; Shi, Ji-Lei; Zhang, Shuai-Feng; Wan, Li-Jun; Guo, Yu-Guo

    2016-02-17

    An optimized nanocarbon-sulfur cathode material with ultrahigh sulfur loading of up to 90 wt % is realized in the form of sulfur nanolayer-coated three-dimensional (3D) conducting network. This 3D nanocarbon-sulfur network combines three different nanocarbons, as follows: zero-dimensional carbon nanoparticle, one-dimensional carbon nanotube, and two-dimensional graphene. This 3D nanocarbon-sulfur network is synthesized by using a method based on soluble chemistry of elemental sulfur and three types of nanocarbons in well-chosen solvents. The resultant sulfur-carbon material shows a high specific capacity of 1115 mA h g(-1) at 0.02C and good rate performance of 551 mA h g(-1) at 1C based on the mass of sulfur-carbon composite. Good battery performance can be attributed to the homogeneous compositing of sulfur with the 3D hierarchical hybrid nanocarbon networks at nanometer scale, which provides efficient multidimensional transport pathways for electrons and ions. Wet chemical method developed here provides an easy and cost-effective way to prepare sulfur-carbon cathode materials with high sulfur loading for application in high-energy Li-S batteries.

  15. Vesicants and nerve agents in chemical warfare. Decontamination and treatment strategies for a changed world.

    PubMed

    Devereaux, Asha; Amundson, Dennis E; Parrish, J S; Lazarus, Angeline A

    2002-10-01

    Vesicants and nerve agents have been used in chemical warfare for ages. They remain a threat in today's altered political climate because they are relatively simple to produce, transport, and deploy. Vesicants, such as mustard and lewisite, can affect the skin, eyes, respiratory system, and gastrointestinal system. They leave affected persons at risk for long-term effects. Nerve agents, such as tabun, sarin, soman, and VX, hyperstimulate the muscarinic and nicotinic receptors of the nervous system. Physicians need to familiarize themselves with the clinical findings of such exposures and the decontamination and treatment strategies necessary to minimize injuries and deaths.

  16. Evaluating mustard seed meal for weed suppression in potato (Solanum tuberosum)

    USDA-ARS?s Scientific Manuscript database

    Mustard seed meal (MSM) derived from Sinapis alba controls weeds for several weeks following application to soil, but also has potential to injure the planted crop. Producers of certified organic potatoes typically utilize a combination of cover crops, soil hilling, harrowing, and cultivation for we...

  17. Potential of powdered activated mustard cake for decolorising raw sugar.

    PubMed

    Singh, Kaman; Bharose, Ram; Verma, Sudhir Kumar; Singh, Vimalesh Kumar

    2013-01-15

    Carbon decolorisation has become customary in the food processing industries; however, it is not economical. Extensive research has therefore been directed towards investigating potential substitutes for commercial activated carbons which might have the advantage of offering an effective, lower-cost replacement for existing bone char or coal-based granular activated carbon (GAC). The physical (bulk density and hardness), chemical (pH and mineral content) and adsorption characteristics (iodine test, molasses test and raw sugar decolorisation efficiency) of powdered activated mustard cake (PAMC) made from de-oiled mustard cake were determined and compared to commercial adsorbents. Although the colour removal efficiency of the PAMC is lower than that of commercial materials, it is cost effective and eco-friendly compared to the existing decolorisation/refining processes. To reduce the load on GAC/activated carbon/charcoal, PAMC could be used on an industrial scale. A decolorisation mechanism has been postulated on the basis of oxygen surface functionalities and surface charge of the PAMC and, accordingly, charge transfer interaction seems to be responsible for the decolorisation mechanism. In addition, a complex interplay of electrostatics and dispersive interaction seem to be involved during the decolorisation process. A low-cost agricultural waste product in the form of de-oiled mustard cake was converted to an efficient adsorbent, PAMC, for use in decolorising raw as well as coloured sugar solutions. The physical, chemical, adsorption characteristics and raw sugar decolorisation efficiency of PAMC were determined and compared to those of commercial adsorbents. The colour removal efficiency of the PAMC is lower than that of commercial materials but it is cost effective and eco-friendly as compared to existing decolorisation/refining processes. The availability of the raw material for the production of PAMC further demands its use on an industrial scale. Copyright

  18. Sulfur-impregnated disordered carbon nanotubes cathode for lithium-sulfur batteries.

    PubMed

    Guo, Juchen; Xu, Yunhua; Wang, Chunsheng

    2011-10-12

    The commercialization of lithium-sulfur batteries is hindered by low cycle stability and low efficiency, which are induced by sulfur active material loss and polysulfide shuttle reaction through dissolution into electrolyte. In this study, sulfur-impregnated disordered carbon nanotubes are synthesized as cathode material for the lithium-sulfur battery. The obtained sulfur-carbon tube cathodes demonstrate superior cyclability and Coulombic efficiency. More importantly, the electrochemical characterization indicates a new stabilization mechanism of sulfur in carbon induced by heat treatment.

  19. Transcriptome analysis of stem development in the tumourous stem mustard Brassica juncea var. tumida Tsen et Lee by RNA sequencing.

    PubMed

    Sun, Quan; Zhou, Guanfan; Cai, Yingfan; Fan, Yonghong; Zhu, Xiaoyan; Liu, Yihua; He, Xiaohong; Shen, Jinjuan; Jiang, Huaizhong; Hu, Daiwen; Pan, Zheng; Xiang, Liuxin; He, Guanghua; Dong, Daiwen; Yang, Jianping

    2012-04-21

    Tumourous stem mustard (Brassica juncea var. tumida Tsen et Lee) is an economically and nutritionally important vegetable crop of the Cruciferae family that also provides the raw material for Fuling mustard. The genetics breeding, physiology, biochemistry and classification of mustards have been extensively studied, but little information is available on tumourous stem mustard at the molecular level. To gain greater insight into the molecular mechanisms underlying stem swelling in this vegetable and to provide additional information for molecular research and breeding, we sequenced the transcriptome of tumourous stem mustard at various stem developmental stages and compared it with that of a mutant variety lacking swollen stems. Using Illumina short-read technology with a tag-based digital gene expression (DGE) system, we performed de novo transcriptome assembly and gene expression analysis. In our analysis, we assembled genetic information for tumourous stem mustard at various stem developmental stages. In addition, we constructed five DGE libraries, which covered the strains Yong'an and Dayejie at various development stages. Illumina sequencing identified 146,265 unigenes, including 11,245 clusters and 135,020 singletons. The unigenes were subjected to a BLAST search and annotated using the GO and KO databases. We also compared the gene expression profiles of three swollen stem samples with those of two non-swollen stem samples. A total of 1,042 genes with significantly different expression levels occurring simultaneously in the six comparison groups were screened out. Finally, the altered expression levels of a number of randomly selected genes were confirmed by quantitative real-time PCR. Our data provide comprehensive gene expression information at the transcriptional level and the first insight into the understanding of the molecular mechanisms and regulatory pathways of stem swelling and development in this plant, and will help define new mechanisms of stem

  20. Reevaluation of 1999 Health-Based Environmental Screening Levels (HBESLs) for Chemical Warfare Agents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Watson, Annetta Paule; Dolislager, Fredrick G

    2007-05-01

    This report evaluates whether new information and updated scientific models require that changes be made to previously published health-based environmental soil screening levels (HBESLs) and associated environmental fate/breakdown information for chemical warfare agents (USACHPPM 1999). Specifically, the present evaluation describes and compares changes that have been made since 1999 to U.S. Environmental Protection Agency (EPA) risk assessment models, EPA exposure assumptions, as well as to specific chemical warfare agent parameters (e.g., toxicity values). Comparison was made between screening value estimates recalculated with current assumptions and earlier health-based environmental screening levels presented in 1999. The chemical warfare agents evaluated include themore » G-series and VX nerve agents and the vesicants sulfur mustard (agent HD) and Lewisite (agent L). In addition, key degradation products of these agents were also evaluated. Study findings indicate that the combined effect of updates and/or changes to EPA risk models, EPA default exposure parameters, and certain chemical warfare agent toxicity criteria does not result in significant alteration to the USACHPPM (1999) health-based environmental screening level estimates for the G-series and VX nerve agents or the vesicant agents HD and L. Given that EPA's final position on separate Tier 1 screening levels for indoor and outdoor worker screening assessments has not yet been released as of May 2007, the study authors find that the 1999 screening level estimates (see Table ES.1) are still appropriate and protective for screening residential as well as nonresidential sites. As such, risk management decisions made on the basis of USACHPPM (1999) recommendations do not require reconsideration. While the 1999 HBESL values are appropriate for continued use as general screening criteria, the updated '2007' estimates (presented below) that follow the new EPA protocols currently under development are also

  1. Sulfur-Containing Organic-Inorganic Hybrid Gel Compositions and Aerogels

    NASA Technical Reports Server (NTRS)

    Evans, Owen R (Inventor); Deshpande, Kiranmayi (Inventor); Dong, Wenting (Inventor)

    2017-01-01

    Methods and materials are described for preparing organic-inorganic hybrid gel compositions where a sulfur-containing cross-linking agent covalently links the organic and inorganic components. The gel compositions are further dried to provide porous gel compositions and aerogels. The mechanical and thermal properties of the dried gel compositions are also disclosed.

  2. Sulfur-Containing Organic-Inorganic Hybrid Gel Compositions and Aerogels

    NASA Technical Reports Server (NTRS)

    Deshpande, Kiranmayi (Inventor); Evans, Owen R. (Inventor); Dong, Wenting (Inventor)

    2015-01-01

    Methods and materials are described for preparing organic-inorganic hybrid gel compositions where a sulfur-containing cross-linking agent covalently links the organic and inorganic components. The gel compositions are further dried to provide porous gel compositions and aerogels. The mechanical and thermal properties of the dried gel compositions are also disclosed.

  3. Effect of sulfur content in a sulfur-activated carbon composite on the electrochemical properties of a lithium/sulfur battery

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, Jin-Woo; Kim, Changhyeon; Ryu, Ho-Suk

    2015-09-15

    Highlights: • The content of sulfur in activated carbon was controlled by solution process. • The sulfur electrode with low sulfur content shows the best performance. • The Li/S battery has capacity of 1360 mAh/g at 1 C and 702 mAh/g at 10 C. - Abstract: The content of sulfur in sulfur/activated carbon composite is controlled from 32.37 wt.% to 55.33 wt.% by a one-step solution-based process. When the sulfur content is limited to 41.21 wt.%, it can be loaded into the pores of an activated carbon matrix in a highly dispersed state. On the contrary, when the sulfur contentmore » is 55.33 wt.%, crystalline sulfur can be detected on the surface of the activated carbon matrix. The best electrochemical performance can be obtained for a sulfur electrode with the lowest sulfur content. The sulfur/activated carbon composite with 32.37 wt.% sulfur afforded the highest first discharge capacity of 1360 mAh g{sup −1} at 1 C rate and a large reversible capacity of 702 mAh g{sup −1} at 10 C (16.75 A/g)« less

  4. DNA Repair Modulates The Vulnerability of The Developing Brain to Alkylating Agents

    PubMed Central

    Kisby, G.E.; Olivas, A.; Park, T.; Churchwell, M.; Doerge, D.; Samson, L. D.; Gerson, S.L.; Turker, M.S.

    2009-01-01

    Neurons of the developing brain are especially vulnerable to environmental agents that damage DNA (i.e., genotoxicants), but the mechanism is poorly understood. The focus of the present study is to demonstrate that DNA damage plays a key role in disrupting neurodevelopment. To examine this hypothesis, we compared the cytotoxic and DNA damaging properties of the methylating agents methylazoxymethanol (MAM) and dimethyl sulfate (DMS) and the mono- and bifunctional alkylating agents chloroethylamine (CEA) and nitrogen mustard (HN2), in granule cell neurons derived from the cerebellum of neonatal wild type mice and three transgenic DNA repair strains. Wild type cerebellar neurons were significantly more sensitive to the alkylating agents DMS and HN2 than neuronal cultures treated with MAM or the half-mustard CEA. Parallel studies with neuronal cultures from mice deficient in alkylguanine DNA glycosylase (Aag-/-) or O6-methylguanine methyltransferase (Mgmt-/-), revealed significant differences in the sensitivity of neurons to all four genotoxicants. Mgmt-/- neurons were more sensitive to MAM and HN2 than the other genotoxicants and wild type neurons treated with either alkylating agent. In contrast, Aag-/- neurons were for the most part significantly less sensitive than wild type or Mgmt-/- neurons to MAM and HN2. Aag-/- neurons were also significantly less sensitive than wild type neurons treated with either DMS or CEA. Granule cell development and motor function were also more severely disturbed by MAM and HN2 in Mgmt-/- mice than in comparably treated wild type mice. In contrast, cerebellar development and motor function were well preserved in MAM treated Aag-/- or MGMT overexpressing (MgmtTg+) mice, even as compared with wild type mice suggesting that AAG protein increases MAM toxicity, whereas MGMT protein decreases toxicity. Surprisingly, neuronal development and motor function were severely disturbed in MgmtTg+ mice treated with HN2. Collectively, these in vitro

  5. N-mustard analogs of S-adenosyl-L-methionine as biochemical probes of protein arginine methylation.

    PubMed

    Hymbaugh Bergman, Sarah J; Comstock, Lindsay R

    2015-08-01

    Nucleosomes, the fundamental building blocks of eukaryotic chromatin, undergo post-synthetic modifications and play a major role in the regulation of transcriptional processes. Combinations of these modifications, including methylation, regulate chromatin structure, determining its different functional states and playing a central role in differentiation. The biological significance of cellular methylation, particularly on chromatin, is widely recognized, yet we know little about the mechanisms that link biological methylation events. To characterize and fully understand protein methylation, we describe here novel N-mustard analogs of S-adenosyl-l-methionine (SAM) as biochemical tools to better understand protein arginine methylation events using protein arginine methyltransferase 1 (PRMT1). Specifically, azide- and alkyne-functionalized N-mustard analogs serve as cofactor mimics of SAM and are enzymatically transferred to a model peptide substrate in a PRMT1-dependent fashion. Once incorporated, the resulting alkynes and azides can be modified through chemoselective ligations, including click chemistry and the Staudinger ligation. These results readily demonstrate the feasibility of utilizing N-mustard analogs as biochemical tools to site-specifically label substrates of PRMT1 and serve as an alternative approach to study protein methylation events. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Dermostyx (IB1) - High efficacy and safe topical skin protectant against percutaneous toxic agents.

    PubMed

    Dachir, Shlomit; Barness, Izhak; Fishbine, Eliezer; Meshulam, Jacob; Sahar, Rita; Eisenkraft, Arik; Amir, Adina; Kadar, Tamar

    2017-04-01

    Prevention of the penetration of toxic agents through the skin is crucial for both military troops and civilian populations. We have developed a novel topical skin protectant (TSP), coded as IB1 and commercially available as Dermostyx protective solution (Rekah Pharm, Israel). The formulation afforded significant protection against chemical warfare agents such as sulfur mustard (SM) and VX (2LD50), pesticides such as parathion and irritants such as acrolein. The efficacy of the protectant was evaluated in the pig model using clinical, histological and biochemical monitoring. A single topical application prior to exposure to the toxic agents reduced significantly the size and severity of skin lesions and ameliorated or prevented systemic clinical symptoms. The barrier properties of IB1 are immediate upon application and remain effective for at least 12 h. It is absorbed into the stratum corneum of the skin and remains there until rinsing with water, yet the ingredients are not absorbed into the body. The formulation is a hydrophilic water-based solution, composed of magnesium sulfate and glycerin that are widely used in cosmetic and medicine, and was shown to be safe in preclinical and in Phase I clinical studies. The suggested mode of action is based on the unique interaction of glycerin with the stratum corneum, changing its properties to hydrophilic and on the "salting out" effect of magnesium sulfate. The expected use of the TSP is by application on exposed skin areas and sensitive skin sites (e.g. armpits, groin, waist), when necessary. A quantity of 10 ml is sufficient for one application covering approximately 20% of the body surface area. The formulation was approved for human use by the Israel Ministry of Health and a CE mark certificate in Europe has been recently issued (Class I). Dermostyx has been adopted by the IDF and first responders as a skin protectant for special needs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. 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.

  8. Effect of calcinations temperature of CuO nanoparticle on the kinetics of decontamination and decontamination products of sulphur mustard.

    PubMed

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

    2011-09-15

    Present study investigates the potential of CuO nanoparticles calcined at different temperature for the decontamination of persistent chemical warfare agent sulphur mustard (HD) at room temperature (30 ± 2 °C). Nanoparticles were synthesized by precipitation method and characterized by using SEM, EDAX, XRD, and Raman Spectroscopy. Synthesized nanoparticles were tested as destructive adsorbents for the degradation of HD. Reactions were monitored by GC-FID technique and the reaction products characterized by GC-MS. It was observed that the rate of degradation of HD decreases with the increase in calcination temperature and there is a change in the percentage of product of HD degradation. GC-MS data indicated that the elimination product increases with increase in calcination temperature whereas the hydrolysis product decreases. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Interleukin-6 and airflow limitation in chemical warfare patients with chronic obstructive pulmonary disease

    PubMed Central

    Attaran, Davood; Lari, Shahrzad M; Towhidi, Mohammad; Marallu, Hassan Ghobadi; Ayatollahi, Hossein; Khajehdaluee, Mohammad; Ghanei, Mostafa; Basiri, Reza

    2010-01-01

    Objectives Chronic obstructive pulmonary disease (COPD) is one of the main late complications of sulfur mustard poisoning. The aim of this study was to evaluate serum levels of interleukin (IL)-6 in war veterans with pulmonary complications of sulfur mustard poisoning and their correlation with severity of airways disease. Methods Fifty consecutive patients with sulfur mustard poisoning and stable COPD, and of mean age 46.3 ± 9.18 years were enrolled in this study. Thirty healthy men were selected as controls and matched to cases by age and body mass index. Spirometry, arterial blood gas, six- minute walk test, BODE (body mass index, obstruction, dyspnea, and exercise capacity), and St George’s Respiratory Questionnaire about quality of life were evaluated. Serum IL-6 was measured in both patient and control groups. Results Fifty-four percent of patients had moderate COPD. Mean serum IL-6 levels were 15.01 ± standard deviation (SD) 0.61 pg/dL and 4.59 ± 3.40 pg/dL in the case and control groups, respectively (P = 0.03). There was a significant correlation between IL-6 levels and Global Initiative for Chronic Obstructive Lung Disease stage (r = 0.25, P = 0.04) and between IL-6 and BODE index (r = 0.38, P = 0.01). There was also a significant negative correlation between serum IL-6 and forced expiratory volume in one second (FEV1, r = −0.36, P = 0.016). Conclusion Our findings suggest that serum IL-6 is increased in patients with sulfur mustard poisoning and COPD, and may have a direct association with airflow limitation. PMID:21037957

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

    PubMed

    Ferguson, L R; Denny, W A

    1995-06-01

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

  11. Method of preparing graphene-sulfur nanocomposites for rechargeable lithium-sulfur battery electrodes

    DOEpatents

    Liu, Jun; Lemmon, John P; Yang, Zhenguo; Cao, Yuliang; Li, Xiaolin

    2015-04-07

    A method of preparing a graphene-sulfur nanocomposite for a cathode in a rechargeable lithium-sulfur battery comprising thermally expanding graphite oxide to yield graphene layers, mixing the graphene layers with a first solution comprising sulfur and carbon disulfide, evaporating the carbon disulfide to yield a solid nanocomposite, and grinding the solid nanocomposite to yield the graphene-sulfur nanocomposite. Rechargeable-lithium-sulfur batteries having a cathode that includes a graphene-sulfur nanocomposite can exhibit improved characteristics. The graphene-sulfur nanocomposite can be characterized by graphene sheets with particles of sulfur adsorbed to the graphene sheets. The sulfur particles have an average diameter of less than 50 nm.

  12. Speciation of Reactive Sulfur Species and their Reactions with Alkylating Agents: Do we have any clue about what is present inside the cell?

    PubMed

    Bogdándi, Virág; Ida, Tomoaki; Sutton, Thomas R; Bianco, Christopher; Ditrói, Tamás; Koster, Grielof; Henthorn, Hillary A; Minnion, Magda; Toscano, John P; van der Vliet, Albert; Pluth, Michael D; Feelisch, Martin; Fukuto, Jon M; Akaike, Takaaki; Nagy, Péter

    2018-06-17

    Posttranslational modifications of cysteine (Cys) residues represent a major aspect of redox biology, and their reliable detection is key in providing mechanistic insights. The metastable character of these modifications and cell lysis-induced artifactual oxidation render current state-of-the-art protocols to rely on alkylation-based stabilization of labile Cys derivatives before cell/tissue rupture. An untested assumption in these procedures is that for all Cys derivatives alkylation rates are faster than their dynamic interchange. However, when the interconversion of Cys derivatives is not rate-limiting, then electrophilic labeling is under Curtin-Hammett control and hence the final alkylated mixture may not represent the speciation that prevailed before alkylation. We here present evidence that in the majority of cases, the speciation of alkylated polysulfide/thiol derivatives indeed depends on the experimental conditions. Our results reveal that alkylation perturbs sulfur speciation in both a concentration- and time-dependent manner, and that strong alkylating agents can cleave polysulfur chains. Moreover, we show that labeling of sulfenic acids with dimedone also affects Cys speciation, suggesting that part of the endogenous pool of products previously believed to represent sulfenic acid species may in fact represent polysulfides. These observations were obtained using buffered aqueous solutions of inorganic-, organic-, cysteine-, glutathione- and GAPDH-polysulfide species. Additional experiments in human plasma and serum revealed that monobromobimane can extract sulfide from the endogenous sulfur pool by shifting speciation equilibria, suggesting caution should be exercised when interpreting experimental results using this tool. We highlight methodological caveats potentially arising from these pitfalls and conclude that current derivatization strategies often fail to adequately capture physiologic speciation of sulfur species. This article is protected by

  13. Anionic carbonato and oxalato cobalt(III) nitrogen mustard complexes.

    PubMed

    Craig, Peter R; Brothers, Penelope J; Clark, George R; Wilson, William R; Denny, William A; Ware, David C

    2004-02-21

    Synthetic approaches to cobalt(III) complexes [Co(L)(L')2] containing the bidentate dialkylating nitrogen mustard N,N-bis(2-chloroethyl)-1,2-ethanediamine (L = dce) together with anionic ancilliary ligands (L') which are either carbonato (CO3(2-)), oxalato (ox2-), bis(2-hydroxyethyl)dithiocarbamato (bhedtc-), 2-pyridine carboxylato (pico-) or 2-pyrazine carboxylato (pyzc-) were investigated. Synthetic routes were developed using the related amines N,N-diethyl-1,2-ethanediamine (dee) and 1,2-ethanediamine (en). The complexes [Co(CO3)2(L)]- (L = dee 1, dce 2), [Co(ox)2(L)]- (L = dee 3, dce 4), [Co(bhedtc)2(dee)]+ 5, [Co(bhedtc)2(en)]+ 6, mer-[Co(pico)3], mer-[Co(pyzc)]3 7 and [Co(pico)2(dee)]+ 8 were prepared and were characterised by IR, UV-Vis, 1H and 13C[1H] NMR spectroscopy, mass spectrometry and cyclic voltammetry. [Co(bhedtc)2(en)]BPh4 6b and trans(O)-[Co(pico)2(dee)]ClO4 8 were characterised by X-ray crystallography. In vitro biological tests were carried out on complexes 1-4 in order to assess the degree to which coordination of the mustard to cobalt attenuated its cytotoxicity, and the differential toxicity in air vs. nitrogen.

  14. Synthesis and DNA cleavage activity of Bis-3-chloropiperidines as alkylating agents.

    PubMed

    Zuravka, Ivonne; Roesmann, Rolf; Sosic, Alice; Wende, Wolfgang; Pingoud, Alfred; Gatto, Barbara; Göttlich, Richard

    2014-09-01

    Nitrogen mustards are an important class of bifunctional alkylating agents routinely used in chemotherapy. They react with DNA as electrophiles through the formation of highly reactive aziridinium ion intermediates. The antibiotic 593A, with potential antitumor activity, can be considered a naturally occurring piperidine mustard containing a unique 3-chloropiperidine ring. However, the total synthesis of this antibiotic proved to be rather challenging. With the aim of designing simplified analogues of this natural product, we developed an efficient bidirectional synthetic route to bis-3-chloropiperidines joined by flexible, conformationally restricted, or rigid diamine linkers. The key step involves an iodide-catalyzed double cyclization of unsaturated bis-N-chloroamines to simultaneously generate both piperidine rings. Herein we describe the synthesis and subsequent evaluation of a series of novel nitrogen-bridged bis-3-chloropiperidines, enabling the study of the impact of the linker structure on DNA alkylation properties. Our studies reveal that the synthesized compounds possess DNA alkylating abilities and induce strand cleavage, with a strong preference for guanine residues. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Apoptotic cell death in rat lung following mustard gas inhalation.

    PubMed

    Andres, Devon K; Keyser, Brian M; Melber, Ashley A; Benton, Betty J; Hamilton, Tracey A; Kniffin, Denise M; Martens, Margaret E; Ray, Radharaman

    2017-06-01

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

  16. Proceedings of the Army Numerical Analysis Conference (11th) Held at Frankford Arsenal, Philadelphia, Pa., on 13-14 February 1974

    DTIC Science & Technology

    1974-12-01

    incineration of chemical agent mustard and pesticides are presented. 1. EDGEWOOD ARSENAL INCINERATION PROGRAM The name of the program which we...only 5 elements to a compound read. -This was fine for mustard, but had to be altered when we wished to simulate the incineration of a nerve agent VX...input data to this program. A process flow sheet of the scrubber system is shown in Figure 1. The incinerator burns Mustard Agent . The off gas from

  17. Rhodanese Functions as Sulfur Supplier for Key Enzymes in Sulfur Energy Metabolism

    PubMed Central

    Aussignargues, Clément; Giuliani, Marie-Cécile; Infossi, Pascale; Lojou, Elisabeth; Guiral, Marianne; Giudici-Orticoni, Marie-Thérèse; Ilbert, Marianne

    2012-01-01

    How microorganisms obtain energy is a challenging topic, and there have been numerous studies on the mechanisms involved. Here, we focus on the energy substrate traffic in the hyperthermophilic bacterium Aquifex aeolicus. This bacterium can use insoluble sulfur as an energy substrate and has an intricate sulfur energy metabolism involving several sulfur-reducing and -oxidizing supercomplexes and enzymes. We demonstrate that the cytoplasmic rhodanese SbdP participates in this sulfur energy metabolism. Rhodaneses are a widespread family of proteins known to transfer sulfur atoms. We show that SbdP has also some unusual characteristics compared with other rhodaneses; it can load a long sulfur chain, and it can interact with more than one partner. Its partners (sulfur reductase and sulfur oxygenase reductase) are key enzymes of the sulfur energy metabolism of A. aeolicus and share the capacity to use long sulfur chains as substrate. We demonstrate a positive effect of SbdP, once loaded with sulfur chains, on sulfur reductase activity, most likely by optimizing substrate uptake. Taken together, these results lead us to propose a physiological role for SbdP as a carrier and sulfur chain donor to these key enzymes, therefore enabling channeling of sulfur substrate in the cell as well as greater efficiency of the sulfur energy metabolism of A. aeolicus. PMID:22496367

  18. Determination of total sulfur content via sulfur-specific chemiluminescence detection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kubala, S.W.; Campbell, D.N.; DiSanzo, F.P.

    A specially designed system, based upon sulfur-specific chemiluminescence detection (SSCD), was developed to permit the determination of total sulfur content in a variety of samples. This type of detection system possesses several advantages such as excellent linearity and selectivity, low minimum detectable levels, and an equimolar response to various sulfur compounds. This paper will focus on the design and application of a sulfur-specific chemiluminescence detection system for use in determining total sulfur content in gasoline.

  19. Preliminary screening of alternative technologies to incineration for treatment of chemical-agent-contaminated soil, Rocky Mountain Arsenal

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shem, L.M.; Rosenblatt, D.H.; Smits, M.P.

    1995-12-01

    In support of the U.S. Army`s efforts to determine the best technologies for remediation of soils, water, and structures contaminated with pesticides and chemical agents, Argonne National Laboratory has reviewed technologies for treating soils contaminated with mustard, lewisite, sarin, o-ethyl s-(2- (diisopropylamino)ethyl)methyl-phosphonothioate (VX), and their breakdown products. This report focuses on assessing alternatives to incineration for dealing with these contaminants. For each technology, a brief description is provided, its suitability and constraints on its use are identified, and its overall applicability for treating the agents of concern is summarized. Technologies that merit further investigation are identified.

  20. Dual-Function Metal-Organic Framework as a Versatile Catalyst for Detoxifying Chemical Warfare Agent Simulants.

    PubMed

    Liu, Yangyang; Moon, Su-Young; Hupp, Joseph T; Farha, Omar K

    2015-12-22

    The nanocrystals of a porphyrin-based zirconium(IV) metal-organic framework (MOF) are used as a dual-function catalyst for the simultaneous detoxification of two chemical warfare agent simulants at room temperature. Simulants of nerve agent (such as GD, VX) and mustard gas, dimethyl 4-nitrophenyl phosphate and 2-chloroethyl ethyl sulfide, have been hydrolyzed and oxidized, respectively, to nontoxic products via a pair of pathways catalyzed by the same MOF. Phosphotriesterase-like activity of the Zr6-containing node combined with photoactivity of the porphyrin linker gives rise to a versatile MOF catalyst. In addition, bringing the MOF crystals down to the nanoregime leads to acceleration of the catalysis.

  1. Operando Spectromicroscopy of Sulfur Species in Lithium-Sulfur Batteries

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miller, Elizabeth C.; Kasse, Robert M.; Heath, Khloe N.

    Here, a novel cross-sectional battery cell was developed to characterize lithium-sulfur batteries using X-ray spectromicroscopy. Chemically sensitive X-ray maps were collected operando at energies relevant to the expected sulfur species and were used to correlate changes in sulfur species with electrochemistry. Significant changes in the sulfur/carbon composite electrode were observed from cycle to cycle including rearrangement of the elemental sulfur matrix and PEO10LiTFSI binder. Polysulfide concentration and area of spatial diffusion increased with cycling, indicating that some polysulfide dissolution is irreversible, leading to polysulfide shuttle. Fitting of the maps using standard sulfur and polysulfide XANES spectra indicated that upon subsequentmore » discharge/charge cycles, the initial sulfur concentration was not fully recovered; polysulfides and lithium sulfide remained at the cathodes with higher order polysulfides as the primary species in the region of interest. Quantification of the polysulfide concentration across the electrolyte and electrode interfaces shows that the polysulfide concentration before the first discharge and after the third charge is constant within the electrolyte, but while cycling, a significant increase in polysulfides and a gradient toward the lithium metal anode forms. Finally, this chemically and spatially sensitive characterization and analysis provides a foundation for further operando spectromicroscopy of lithium-sulfur batteries.« less

  2. Operando Spectromicroscopy of Sulfur Species in Lithium-Sulfur Batteries

    DOE PAGES

    Miller, Elizabeth C.; Kasse, Robert M.; Heath, Khloe N.; ...

    2017-11-03

    Here, a novel cross-sectional battery cell was developed to characterize lithium-sulfur batteries using X-ray spectromicroscopy. Chemically sensitive X-ray maps were collected operando at energies relevant to the expected sulfur species and were used to correlate changes in sulfur species with electrochemistry. Significant changes in the sulfur/carbon composite electrode were observed from cycle to cycle including rearrangement of the elemental sulfur matrix and PEO10LiTFSI binder. Polysulfide concentration and area of spatial diffusion increased with cycling, indicating that some polysulfide dissolution is irreversible, leading to polysulfide shuttle. Fitting of the maps using standard sulfur and polysulfide XANES spectra indicated that upon subsequentmore » discharge/charge cycles, the initial sulfur concentration was not fully recovered; polysulfides and lithium sulfide remained at the cathodes with higher order polysulfides as the primary species in the region of interest. Quantification of the polysulfide concentration across the electrolyte and electrode interfaces shows that the polysulfide concentration before the first discharge and after the third charge is constant within the electrolyte, but while cycling, a significant increase in polysulfides and a gradient toward the lithium metal anode forms. Finally, this chemically and spatially sensitive characterization and analysis provides a foundation for further operando spectromicroscopy of lithium-sulfur batteries.« less

  3. 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.

  4. 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.

  5. 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.

  6. Cytochromes and iron sulfur proteins in sulfur metabolism of phototrophic bacteria

    NASA Technical Reports Server (NTRS)

    Fischer, U.

    1985-01-01

    Dissimilatory sulfur metabolism in phototrophic sulfur bacteria provides the bacteria with electrons for photosynthetic electron transport chain and, with energy. Assimilatory sulfate reduction is necessary for the biosynthesis of sulfur-containing cell components. Sulfide, thiosulfate, and elemental sulfur are the sulfur compounds most commonly used by phototrophic bacteria as electron donors for anoxygenic photosynthesis. Cytochromes or other electron transfer proteins, like high-potential-iron-sulfur protein (HIPIP) function as electron acceptors or donors for most enzymatic steps during the oxidation pathways of sulfide or thiosulfate. Yet, heme- or siroheme-containing proteins themselves undergo enzymatic activities in sulfur metabolism. Sirohemes comprise a porphyrin-like prosthetic group of sulfate reductase. eenzymatic reactions involve electron transfer. Electron donors or acceptors are necessary for each reaction. Cytochromes and iron sulfur problems, are able to transfer electrons.

  7. Distribution of chemical warfare agent, energetics, and metals in sediments at a deep-water discarded military munitions site

    NASA Astrophysics Data System (ADS)

    Briggs, Christian; Shjegstad, Sonia M.; Silva, Jeff A. K.; Edwards, Margo H.

    2016-06-01

    There is a strong need to understand the behavior of chemical warfare agent (CWA) at underwater discarded military munitions (DMM) sites to determine the potential threat to human health or the environment, yet few studies have been conducted at sites in excess of 250 m, the depth at which most U.S. chemical munitions were disposed. As part of the Hawai'i Undersea Military Munitions Assessment (HUMMA), sediments adjacent to chemical and conventional DMM at depths of 400-650 m were sampled using human occupied vehicles (HOVs) in order to quantify the distribution of CWA, energetics, and select metals. Sites in the same general area, with no munitions within 50 m in any direction were sampled as a control. Sulfur mustard (HD) and its degradation product 1,4-dithiane were detected at each CWA DMM site, as well as a single sample with the HD degradation product 1,4-thioxane. An energetic compound was detected in sediment to a limited extent at one CWA DMM site. Metals common in munitions casings (i.e., Fe, Cu, and Pb) showed similar trends at the regional and site-wide scales, likely reflecting changes in marine sediment deposition and composition. This study shows HD and its degradation products can persist in the deep-marine environment for decades following munitions disposal.

  8. Formation of Multilayer Graphene Domains with Strong Sulfur-Carbon Interaction and Enhanced Sulfur Reduction Zones for Lithium-Sulfur Battery Cathodes.

    PubMed

    Perez Beltran, Saul; Balbuena, Perla B

    2018-02-12

    A newly designed sulfur/graphene computational model emulates the electrochemical behavior of a Li-S battery cathode, promoting the S-C interaction through the edges of graphene sheets. A random mixture of eight-membered sulfur rings mixed with small graphene sheets is simulated at 64 wt %sulfur loading. Structural stabilization and sulfur reduction calculations are performed with classical reactive molecular dynamics. This methodology allowed the collective behavior of the sulfur and graphene structures to be accounted for. The sulfur encapsulation induces ring opening and the sulfur phase evolves into a distribution of small chain-like structures interacting with C through the graphene edges. This new arrangement of the sulfur phase not only leads to a less pronounced volume expansion during sulfur reduction but also to a different discharge voltage profile, in qualitative agreement with earlier reports on sulfur encapsulation in microporous carbon structures. The Li 2 S phase grows around ensembles of parallel graphene nanosheets during sulfur reduction. No diffusion of sulfur or lithium between graphene nanosheets is observed, and extended Li 2 S domains bridging the space between carbon ensembles are suppressed. The results emphasize the importance of morphology on the electrochemical performance of the composite material. The sulfur/graphene model outlined here provides new understanding of the graphene effects on the sulfur reduction behavior and the role that van der Waals interactions may play in promoting formation of multilayer graphene ensembles and small Li 2 S domains during sulfur reduction. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Understanding Sulfur Systematics in Large Igneous Provinces Using Sulfur Isotopes

    NASA Astrophysics Data System (ADS)

    Novikova, S.; Edmonds, M.; Turchyn, A. V.; Maclennan, J.; Svensen, H.; Frost, D. J.; Yallup, C.

    2013-12-01

    The eruption of the Siberian Traps coincided with perhaps the greatest environmental catastrophe in Earth's history, at the Permo-Triassic boundary. The source and magnitude of the volatile emissions, including sulfur, associated with the eruption remain poorly understood yet were critical in forcing environmental change. Two of the primary questions are how much sulfur gases were emitted during the eruptions and from where they were sourced. Primary melts carry dissolved sulfur from the mantle. Magmas ponding in sills and ascending through dykes may also assimilate sulfur from country rocks, as well as heat the country rocks and generate fluids through contact metamorphism. If the magmas interacted thermally, for prolonged periods, with sulfur-rich country rocks then it is probable that the sulfur budget of these eruptions might have been augmented considerably. This is exactly what we have shown recently for a basaltic sill emplaced in oil shale that fed eruptions of the British Tertiary Province, where surrounding sediments showed extensive desulfurization (Yallup et al. Geoch. Cosmochim. Acta, online, 2013). In the current study sulfur isotopes and trace element abundances are used to discriminate sulfur sources and to model magmatic processes for a suite of Siberian Traps sill and lava samples. Our bulk rock and pyrite geochemical analyses illustrate clearly their high abundance of 34S over 32S. The high 34S/32S has been noted previously and linked to assimilation of sulfur from sediments but may alternatively be inherited from the mantle plume source. With the aim of investigating the sulfur isotopic signature in the melt prior to devolatilization, we use secondary ion mass spectrometry (SIMS), for which a specific set of glass standards was synthesised. In order to understand how sulfur isotopes fractionate during degassing we have also conducted a parallel study of well-characterized tephras from Kilauea Volcano, where sulfur degassing behavior is well

  10. Augmenting Sulfur Metabolism and Herbivore Defense in Arabidopsis by Bacterial Volatile Signaling.

    PubMed

    Aziz, Mina; Nadipalli, Ranjith K; Xie, Xitao; Sun, Yan; Surowiec, Kazimierz; Zhang, Jin-Lin; Paré, Paul W

    2016-01-01

    Sulfur is an element necessary for the life cycle of higher plants. Its assimilation and reduction into essential biomolecules are pivotal factors determining a plant's growth and vigor as well as resistance to environmental stress. While certain soil microbes can enhance ion solubility via chelating agents or oxidation, microbial regulation of plant-sulfur assimilation has not been reported. With an increasing understanding that soil microbes can activate growth and stress tolerance in plants via chemical signaling, the question arises as to whether such beneficial bacteria also regulate sulfur assimilation. Here we report a previously unidentified mechanism by which the growth-promoting rhizobacterium Bacillus amyloliquefaciens (GB03) transcriptionally activates genes responsible for sulfur assimilation, increasing sulfur uptake and accumulation in Arabidopsis. Transcripts encoding for sulfur-rich aliphatic and indolic glucosinolates are also GB03 induced. As a result, GB03-exposed plants with elevated glucosinolates exhibit greater protection against the generalist herbivore, Spodoptera exigua (beet armyworm, BAW). In contrast, a previously characterized glucosinolate mutant compromised in the production of both aliphatic and indolic glucosinolates is also compromised in terms of GB03-induced protection against insect herbivory. As with in vitro studies, soil-grown plants show enhanced glucosinolate accumulation and protection against BAW feeding with GB03 exposure. These results demonstrate the potential of microbes to enhance plant sulfur assimilation and emphasize the sophisticated integration of microbial signaling in plant defense.

  11. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity Study of Lewisite in Rats

    DTIC Science & Technology

    1989-07-31

    buffered formalin (NBF). To standardize the degree of distension of pulmonary alveoli with fixative, the lungs were fixed by inserting a blunted needle into...the thickness of the mucosa, submucosa and muscular layers of the stomach and involved the serosa. Epithelial hyperplasia and hyperkeratosis of the

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

    DTIC Science & Technology

    1987-12-31

    virus of mice (PCM), rat corona virus /sialodacryoadenitis virus (RCV/SDA), H-1 virus and Kilham rat virus (KRV) by Microbiological Associates...Pneumonia virus of mice RCV/SDA = Rat corona virus /sialodacryoadenitis virus RH = Relative humidity SC = Subcutaneous SD = Standard deviation SE = Standard... cat , rabbit and human but apparently did not cross the placental membranes readily. The accumulation of a sufficient quantity of arsenate to induce a

  13. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brimfield, A.A.; Mancebo, A.M.; Mason, R.P.

    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 electronmore » 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.« less

  14. Pretreatment of Sugar Beet Pulp with Dilute Sulfurous Acid is Effective for Multipurpose Usage of Carbohydrates.

    PubMed

    Kharina, M; Emelyanov, V; Mokshina, N; Ibragimova, N; Gorshkova, T

    2016-05-01

    Sulfurous acid was used for pretreatment of sugar beet pulp (SBP) in order to achieve high efficiency of both extraction of carbohydrates and subsequent enzymatic hydrolysis of the remaining solids. The main advantage of sulfurous acid usage as pretreatment agent is the possibility of its regeneration. Application of sulfurous acid as hydrolyzing agent in relatively low concentrations (0.6-1.0 %) during a short period of time (10-20 min) and low solid to liquid ratio (1:3, 1:6) allowed effective extraction of carbohydrates from SBP and provided positive effect on subsequent enzymatic hydrolysis. The highest obtained concentration of reducing substances (RS) in hydrolysates was 8.5 %; up to 33.6 % of all carbohydrates present in SBP could be extracted. The major obtained monosaccharides were arabinose and glucose (9.4 and 7.3 g/l, respectively). Pretreatment of SBP with sulfurous acid increased 4.6 times the yield of glucose during subsequent enzymatic hydrolysis of remaining solids with cellulase cocktail, as compared to the untreated SBP. Total yield of glucose during SBP pretreatment and subsequent enzymatic hydrolysis amounted to 89.4 % of the theoretical yield. The approach can be applied directly to the wet SBP. Hydrolysis of sugar beet pulp with sulfurous acid is recommended for obtaining of individual monosaccharides, as well as nutritional media.

  15. Method for removing sulfur oxide from waste gases and recovering elemental sulfur

    DOEpatents

    Moore, Raymond H.

    1977-01-01

    A continuous catalytic fused salt extraction process is described for removing sulfur oxides from gaseous streams. The gaseous stream is contacted with a molten potassium sulfate salt mixture having a dissolved catalyst to oxidize sulfur dioxide to sulfur trioxide and molten potassium normal sulfate to solvate the sulfur trioxide to remove the sulfur trioxide from the gaseous stream. A portion of the sulfur trioxide loaded salt mixture is then dissociated to produce sulfur trioxide gas and thereby regenerate potassium normal sulfate. The evolved sulfur trioxide is reacted with hydrogen sulfide as in a Claus reactor to produce elemental sulfur. The process may be advantageously used to clean waste stack gas from industrial plants, such as copper smelters, where a supply of hydrogen sulfide is readily available.

  16. Antioxidant efficacy of extracts produced from pickled and dried mustard in rapeseed and peanut oils.

    PubMed

    Li, Chang; Tang, Zhongfeng; Huang, Meng; Tao, Nengguo; Feng, Bo; Huang, Shirong

    2012-04-01

    Antioxidant efficacy of 70% ethanol extract (EE), 70% methanol extract (ME), and water extract (WE) produced from pickled and dried mustard (Brassica juncea Coss. var. foliosa Bailey) was evaluated in rapeseed and peanut oils by using the Schaal oven method. The protective effects of aforesaid 3 extracts in stabilizing vegetable oils were tested by measuring their peroxide values, conjugated diene values, and p-anisidine values during storage of 15 d at 60 °C. Results showed that the different solvent extracts produced from pickled and dried mustard, at concentrations of 0.5% and 1.0% (w/w) in vegetable oils, could significantly (P < 0.05) lower the peroxide value, conjugated diene value, and p-anisidine value of oils during storage at 60 °C. However, the extracts at various concentrations showed a less antioxidant effect than butylated hydroxytoluene (BHT) at 200 ppm. The ultraviolet spectra of different extracts exhibited a single maximum absorbance at 268 nm. The qualitative analysis of antioxidants present in the extracts was carried out by reverse phase high performance liquid chromatography (HPLC) using a C18 column. Two phenolic compounds, gallic and protocatechuric acids, were identified. The antioxidant activity of the extracts might be attributed to the presence of these phenolics. These results indicated that the pickled and dried mustard could be used as a potential source of natural antioxidants. The antioxidant activity of extracts produced from pickled and dried mustard toward rapeseed and peanut oils oxidation and the characterization of active phenolic compounds may be useful in developing natural antioxidants for vegetable oils. Moreover, the extracts could safely be used as potential antioxidant to suppress lipid oxidation in lipid-containing food products. © 2012 Institute of Food Technologists®

  17. Beneficial role of carbon nanotubes on mustard plant growth: an agricultural prospect

    NASA Astrophysics Data System (ADS)

    Mondal, Anindita; Basu, Ruma; Das, Sukhen; Nandy, Papiya

    2011-10-01

    Nowadays an increasing application of nanotechnology in different fields has arisen an extensive debate about the effect of the engineered nanoparticles on environment . Phytotoxicity of nanoparticles has come into limelight in the last few years. However, very few studies have been done so far on the beneficial aspects of nanoparticles on plants. In this article, we report the beneficial effect of multi-walled carbon nanotubes (MWCNTs) having diameter of 30 nm on Brassica juncea (mustard) seeds. Measurements of germination rate, T 50 (time taken for 50% germination), shoot and root growth have shown encouraging results using low concentration of oxidized MWCNT (OMWCNT) treated seeds as compared to non-oxidized as well as high concentration OMWCNT treated seeds. For toxicity study we measured the germination index and relative root elongation, while conductivity test and infra-red spectra were also performed to study the overall effect of oxidized and non-oxidized nanotubes on mustard seeds and seedlings.

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

    DTIC Science & Technology

    2014-03-01

    studies , we show that subtoxic levels of 2-chloroethyl ethylsulfide (2-CEES), a mustard gas analog, also induce centrosome amplification and chromosome...instability in cells, which may hasten the mutation rate necessary for tumorigenesis. These studies offer an explanation why those exposed to mustard...unequally, resulting in chromosome  instability,  a common  phenotype of cancer cells.  In our  studies , we show that subtoxic levels of 2

  19. Properties of Sulfur Concrete.

    DTIC Science & Technology

    1979-07-06

    36 Thermal Contraction . . . . . . . . . . . 37 Summary of Sulfur Concrete (unmodified) . . . 39 Modified Sulfur Concrete............ 40...Compressive strength of PCPD- modified sulfur concrete 47 20 Functional connection between reaction time and temperature in making DCPD- modified sulfur concrete...39 MODIFIED SULFUR CONCRETE In the previous section it was shown that sulfur concrete exhibits several undesirable properties, such as 1 poor

  20. Sulfur-Containing Agrochemicals.

    PubMed

    Devendar, Ponnam; Yang, Guang-Fu

    2017-10-09

    Modern agricultural chemistry has to support farmers by providing innovative agrochemicals. In this context, the introduction of sulfur atoms into an active ingredient is still an important tool in modulating the properties of new crop-protection compounds. More than 30% of today's agrochemicals contain at least one sulfur atom, mainly in fungicides, herbicides and insecticides. A number of recently developed sulfur-containing agrochemical candidates represent a novel class of chemical compounds with new modes of action, so we intend to highlight the emerging interest in commercially active sulfur-containing compounds. This chapter gives a comprehensive overview of selected leading sulfur-containing pesticidal chemical families namely: sulfonylureas, sulfonamides, sulfur-containing heterocyclics, thioureas, sulfides, sulfones, sulfoxides and sulfoximines. Also, the most suitable large-scale synthetic methods of the recently launched or provisionally approved sulfur-containing agrochemicals from respective chemical families have been highlighted.

  1. Proposals for chemical weapons during the American Civil War.

    PubMed

    Hasegawa, Guy R

    2008-05-01

    Proposals for chemical weapons that arose during the American Civil War are described. Most incendiary and all biological agents are excluded. The described proposals appeared primarily in periodicals or letters to government officials on both sides. The weapons were usually meant to temporarily disable enemy combatants, but some might have been lethal, and Civil War caregivers were ill-prepared to deal with the weapons' effects. Evidently, none of the proposed weapons were used. In only one instance was use against civilians mentioned. Among the agents most commonly proposed were cayenne pepper or other plant-based irritants such as black pepper, snuff, mustard, and veratria. Other suggested agents included chloroform, chlorine, hydrogen cyanide, arsenic compounds, sulfur, and acids. Proponents usually suggested that the chemicals be included in explosive artillery projectiles. Less commonly proposed vehicles of delivery included fire engines, kites, and manned balloons. Some of the proposed weapons have modern counterparts.

  2. Effects of adding bulking agents on the biodrying of kitchen waste and the odor emissions produced.

    PubMed

    Yuan, Jing; Li, Yun; Zhang, Hongyu; Zhang, Difang; Chadwick, David; Li, Guoxue; Wang, Guoying; Chi, Menghao; Yang, Fan

    2018-05-01

    The effects of adding a bulking agent on the performance and odor emissions (ammonia and eight sulfur-containing odorous compounds) when biodrying kitchen waste were investigated. Three treatments were considered: the addition of either cornstalks (CS) or wood peat (WP) to kitchen waste as a bulking agent before biodrying, and a control treatment (CK). The water-removal rates for CK, CS, and WP treatments were 0.35, 0.56, and 0.43kg/kg, respectively. Addition of bulking agents to kitchen waste produced less leachate, higher moisture-removal rates, and lower consumption of volatile solids. The CS treatment had the highest biodrying index (4.07), and those for the WP and CK treatments were 3.67 and 1.97, respectively. Adding cornstalks or wood peat decreased NH 3 emissions by 55.8% and 71.7%, respectively. Total sulfur losses were 3.6%-21.6% after 21days biodrying, and H 2 S and Me 2 SS were the main (>95%) sulfur compounds released. The smallest amounts of sulfur-containing odorous compounds were emitted when cornstalks were added, and adding cornstalks and wood peat decreased total sulfur losses by 50.6%-64.8%. Copyright © 2017. Published by Elsevier B.V.

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

    USDA-ARS?s Scientific Manuscript database

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

  4. Impact of mustard seed meal applications on direct-seeded cucurbits and weed control

    USDA-ARS?s Scientific Manuscript database

    Weed control in organic production systems can be a labor intensive and expensive process. Mustard seed meal (MSM) is phytotoxic and a potential pre-emergent and preplant-incorporated organic herbicide for controlling germinating and emerging weed seedlings: unfortunately, MSM may also adversely imp...

  5. Cathode Loading Effect on Sulfur Utilization in Lithium–Sulfur Battery

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sun, Ke; Liu, Helen; Gan, Hong

    The Lithium-Sulfur (Li-S) battery is under intensive research in recent years due to its potential to provide higher energy density and lower cost than the current state-of-the-art lithium-ion battery technology. To meet cost target for transportation application, high sulfur loading up to 8 mAh cm -2 is predicted by modeling. In this work, we have investigated the sulfur loading effect on the galvanostatic charge/discharge cycling performance of Li-S cells with theoretical sulfur loading ranging from 0.5 mAh cm -2 to 7.5 mAh cm -2. We found that the low sulfur utilization of electrodes with sulfur loading of > 3.0 mAhmore » cm-2 is due to their inability to deliver capacities at the 2.1V voltage plateau, which corresponds to the conversion of soluble Li 2S 4 to insoluble Li 2S 2/Li 2S. This electrochemical conversion process recovers to deliver the expected sulfur utilization after several activation cycles for electrodes with sulfur loading up to 4.5 mAh cm -2. For electrodes with 7.0 mAh cm -2 loading, no sulfur utilization recovery was observed for 100 cycles. The root cause of this phenomenon is elucidated by SEM/EDS and EIS investigation. Carbon interlayer cell design and low rate discharge activation are demonstrated to be effective mitigation methods.« less

  6. Cathode Loading Effect on Sulfur Utilization in Lithium–Sulfur Battery

    DOE PAGES

    Sun, Ke; Liu, Helen; Gan, Hong

    2016-05-01

    The Lithium-Sulfur (Li-S) battery is under intensive research in recent years due to its potential to provide higher energy density and lower cost than the current state-of-the-art lithium-ion battery technology. To meet cost target for transportation application, high sulfur loading up to 8 mAh cm -2 is predicted by modeling. In this work, we have investigated the sulfur loading effect on the galvanostatic charge/discharge cycling performance of Li-S cells with theoretical sulfur loading ranging from 0.5 mAh cm -2 to 7.5 mAh cm -2. We found that the low sulfur utilization of electrodes with sulfur loading of > 3.0 mAhmore » cm-2 is due to their inability to deliver capacities at the 2.1V voltage plateau, which corresponds to the conversion of soluble Li 2S 4 to insoluble Li 2S 2/Li 2S. This electrochemical conversion process recovers to deliver the expected sulfur utilization after several activation cycles for electrodes with sulfur loading up to 4.5 mAh cm -2. For electrodes with 7.0 mAh cm -2 loading, no sulfur utilization recovery was observed for 100 cycles. The root cause of this phenomenon is elucidated by SEM/EDS and EIS investigation. Carbon interlayer cell design and low rate discharge activation are demonstrated to be effective mitigation methods.« less

  7. Replacement of hazardous chromium impregnating agent from silver/copper/chromium-impregnated active carbon using triethylenediamine to remove hydrogen sulfide, trichloromethane, ammonia, and sulfur dioxide.

    PubMed

    Wu, Li-Chun; Chung, Ying-Chien

    2009-03-01

    Activated carbon (AC) is widely used as an effective adsorbent in many applications, including industrial-scale air purification systems and air filter systems in gas masks. In general, ACs without chemical impregnation are good adsorbents of organic vapors but poor adsorbents of low-molecular-weight or polar gases such as chlorine, sulfur dioxide (SO2), formaldehyde, and ammonia (NH3). Impregnated ACs modified with metallic impregnating agents (ASC-carbons; e.g., copper, chromium, and silver) enhance the adsorbing properties of the ACs for simultaneously removing specific poisonous gases, but disposal of the chromium metal salt used to impregnate the ACs has the potential to result in situations that are toxic to both humans and the environment, thereby necessitating the search for replaceable organic impregnating agents that represent a much lower risk. The aim of this study was to assess the gas removal efficiency of an AC in which the organic impregnating agent triethylenediamine (TEDA) largely replaced the metallic impregnating agent chromium. We assessed batch and continuous adsorption capacities in situ for removing simulated hydrogen sulfide (H2S), trichloromethane (CHCl3), NH3, and SO2 gases. Brunauer-Emmet-Teller measurements and scanning electron microscopy analyses identified the removal mechanism by which TEDA-impregnated AS-carbon (dechromium ASC-carbon) adsorbs gases and determined the removal capacity for H2S, CHCl3, NH3, and SO2 to be 311, 258, 272, and 223 mg/g-C, respectively. These results demonstrate that TEDA-impregnated AS-carbon is significantly more efficient than ASC-carbon in adsorbing these four gases. Organic TEDA-impregnating agents have also been proven to be a reliable and environmental friendly agent and therefore a safe replacement of the hazardous chromium found in conventional ASC-carbon used in removing toxic gases from the airstream.

  8. 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.

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

    PubMed

    Weisenseel, P; Woitalla, S

    2005-12-15

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

  10. Measurements of Raman scattering in the middle ultraviolet band from persistent chemical warfare agents

    NASA Astrophysics Data System (ADS)

    Kullander, Fredrik; Landström, Lars; Lundén, Hampus; Mohammed, Abdesalam; Olofsson, Göran; Wästerby, Pär.

    2014-05-01

    The very low Raman scattering cross section and the fluorescence background limit the measuring range of Raman based instruments operating in the visible or infrared band. We are exploring if laser excitation in the middle ultraviolet (UV) band between 200 and 300 nm is useful and advantageous for detection of persistent chemical warfare agents (CWA) on various kinds of surfaces. The UV Raman scattering from tabun, mustard gas, VX and relevant simulants in the form of liquid surface contaminations has been measured using a laboratory experimental setup with a short standoff distance around 1 meter. Droplets having a volume of 1 μl were irradiated with a tunable pulsed laser swept within the middle UV band. A general trend is that the signal strength moves through an optimum when the laser excitation wavelength is swept between 240 and 300 nm. The signal from tabun reaches a maximum around 265 nm, the signal from mustard gas around 275 nm. The Raman signal from VX is comparably weak. Raman imaging by the use of a narrow bandpass UV filter is also demonstrated.

  11. Freeze-Dried Sulfur-Graphene Oxide-Carbon Nanotube Nanocomposite for High Sulfur-Loading Lithium/Sulfur Cells.

    PubMed

    Hwa, Yoon; Seo, Hyeon Kook; Yuk, Jong-Min; Cairns, Elton J

    2017-11-08

    The ambient-temperature rechargeable lithium/sulfur (Li/S) cell is a strong candidate for the beyond lithium ion cell since significant progress on developing advanced sulfur electrodes with high sulfur loading has been made. Here we report on a new sulfur electrode active material consisting of a cetyltrimethylammonium bromide-modified sulfur-graphene oxide-carbon nanotube (S-GO-CTA-CNT) nanocomposite prepared by freeze-drying. We show the real-time formation of nanocrystalline lithium sulfide (Li 2 S) at the interface between the S-GO-CTA-CNT nanocomposite and the liquid electrolyte by in situ TEM observation of the reaction. The combination of GO and CNT helps to maintain the structural integrity of the S-GO-CTA-CNT nanocomposite during lithiation/delithiation. A high S loading (11.1 mgS/cm 2 , 75% S) S-GO-CTA-CNT electrode was successfully prepared using a three-dimensional structured Al foam as a substrate and showed good S utilization (1128 mAh/g S corresponding to 12.5 mAh/cm 2 ), even with a very low electrolyte to sulfur weight ratio of 4. Moreover, it was demonstrated that the ionic liquid in the electrolyte improves the Coulombic efficiency and stabilizes the morphology of the Li metal anode.

  12. Concise Access to 2-Aroylbenzothiazoles by Redox Condensation Reaction between o-Halonitrobenzenes, Acetophenones, and Elemental Sulfur.

    PubMed

    Nguyen, Thanh Binh; Pasturaud, Karine; Ermolenko, Ludmila; Al-Mourabit, Ali

    2015-05-15

    A wide range of 2-aroylbenzothiazoles 3 including some pharmacologically relevant derivatives can be obtained in high yields by simply heating o-halonitrobenzenes 1, acetophenones 2, elemental sulfur, and N-methylmorpholine. This three-component nitro methyl coupling was found to occur in an excellent atom-, step-, and redox-efficient manner in which elemental sulfur played the role of nucleophile building block and redox moderating agent to fulfill electronic requirements of the global reaction.

  13. Catalyst for the reduction of sulfur dioxide to elemental sulfur

    DOEpatents

    Jin, Y.; Yu, Q.; Chang, S.G.

    1996-02-27

    The inventive catalysts allow for the reduction of sulfur dioxide to elemental sulfur in smokestack scrubber environments. The catalysts have a very high sulfur yield of over 90% and space velocity of 10,000 h{sup {minus}1}. They also have the capacity to convert waste gases generated during the initial conversion into elemental sulfur. The catalysts have inexpensive components, and are inexpensive to produce. The net impact of the invention is to make this technology practically available to industrial applications. 21 figs.

  14. Catalyst for the reduction of sulfur dioxide to elemental sulfur

    DOEpatents

    Jin, Yun; Yu, Qiquan; Chang, Shih-Ger

    1996-01-01

    The inventive catalysts allow for the reduction of sulfur dioxide to elemental sulfur in smokestack scrubber environments. The catalysts have a very high sulfur yield of over 90% and space velocity of 10,000 h.sup.-1. They also have the capacity to convert waste gases generated during the initial conversion into elemental sulfur. The catalysts have inexpensive components, and are inexpensive to produce. The net impact of the invention is to make this technology practically available to industrial applications.

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

    PubMed

    Olaimat, Amin N; Holley, Richard A

    2016-08-01

    Ready-to-eat meats are considered foods at high risk to cause life-threatening Listeria monocytogenes infections. This study screened 5 L. monocytogenes strains for their ability to hydrolyze sinigrin (a glucosinolate in Oriental mustard), which formed allyl isothiocyanate (AITC) and reduced L. monocytogenes viability on inoculated vacuum-packed, cooked, cured roast chicken slices at 4 °C. Tests involved incorporation of 25-50 μl/g AITC directly or 100-250 mg/g Oriental mustard extract in 0.5% (w/v) κ-carrageenan/2% (w/v) chitosan-based coatings prepared using 1.5% malic or acetic acid. L. monocytogenes strains hydrolyzed 33.6%-48.4% pure sinigrin in MH broth by 21 d at 25 °C. Acidified κ-carrageenan/chitosan coatings containing 25-50 μl/g AITC or 100-250 mg/g mustard reduced the viability of L. monocytogenes and aerobic bacteria on cooked, cured roast chicken slices by 4.1 to >7.0 log10 CFU/g compared to uncoated chicken stored at 4 °C for 70 d. Coatings containing malic acid were significantly more antimicrobial than those with acetic acid. During storage for 70 d, acidified κ-carrageenan/chitosan coatings containing 25-50 μl/g AITC or 250 mg/g mustard extract reduced lactic acid bacteria (LAB) numbers 3.8 to 5.4 log10 CFU/g on chicken slices compared to uncoated samples. Acidified κ-carrageenan/chitosan-based coatings containing either AITC or Oriental mustard extract at the concentrations tested had the ability to control L. monocytogenes viability and delay growth of potential spoilage bacteria on refrigerated, vacuum-packed cured roast chicken. Copyright © 2016. Published by Elsevier Ltd.

  16. Sulfur Mustard Penetration of Thermoplastic Elastomers

    DTIC Science & Technology

    2008-10-01

    blend of polypropylene and finely dispersed, highly vulcanised EPDM rubber [4]. However its exact composition is a trade secret. The Santoprene grade... rubber or silicone rubber . Compared to thermoplastic elastomers, these thermosetting elastomers are expensive and difficult to process. Therefore a...the last few decades, CBR respirators have generally been manufactured from either butyl rubber (as in the British and Australian S10), or silicone

  17. Molecular Strategies Against Sulfur Mustard Toxicity

    DTIC Science & Technology

    2010-04-01

    Stephenson JM, Abrahamian H, Keipes M, Castellarin A, Rogulja- Pepeonik Z, Fuller JH. Effect of lisinopril on progression of retinopathy in normotensive...people with type 1 diabetes . The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin- Dependent Diabetes Mellitus. Lancet 1998;351:28...metabolic syndrome: new perspective against the epidemic. Diabetes 2005;54:1899. [46] McLachlan JA, Burow M, Chiang TC, Li SF. Gene imprinting in

  18. Limits to sulfur accumulation in transgenic lupin seeds expressing a foreign sulfur-rich protein.

    PubMed

    Tabe, Linda M; Droux, Michel

    2002-03-01

    The low sulfur amino acid content of legume seeds restricts their nutritive value for animals. We have investigated the limitations to the accumulation of sulfur amino acids in the storage proteins of narrow leaf lupin (Lupinus angustifolius) seeds. Variation in sulfur supply to lupin plants affected the sulfur amino acid accumulation in the mature seed. However, when sulfur was in abundant supply, it accumulated to a large extent in oxidized form, rather than reduced form, in the seeds. At all but severely limiting sulfur supply, addition of a transgenic (Tg) sink for organic sulfur resulted in an increase in seed sulfur amino acid content. We hypothesize that demand, or sink strength for organic sulfur, which is itself responsive to environmental sulfur supply, was the first limit to the methionine (Met) and cysteine (Cys) content of wild-type lupin seed protein under most growing conditions. In Tg, soil-grown seeds expressing a foreign Met- and Cys-rich protein, decreased pools of free Met, free Cys, and glutathione indicated that the rate of synthesis of sulfur amino acids in the cotyledon had become limiting. Homeostatic mechanisms similar to those mediating the responses of plants to environmental sulfur stress resulted in an adjustment of endogenous protein composition in Tg seeds, even when grown at adequate sulfur supply. Uptake of sulfur by lupin cotyledons, as indicated by total seed sulfur at maturity, responded positively to increased sulfur supply, but not to increased demand in the Tg seeds.

  19. Limits to Sulfur Accumulation in Transgenic Lupin Seeds Expressing a Foreign Sulfur-Rich Protein

    PubMed Central

    Tabe, Linda M.; Droux, Michel

    2002-01-01

    The low sulfur amino acid content of legume seeds restricts their nutritive value for animals. We have investigated the limitations to the accumulation of sulfur amino acids in the storage proteins of narrow leaf lupin (Lupinus angustifolius) seeds. Variation in sulfur supply to lupin plants affected the sulfur amino acid accumulation in the mature seed. However, when sulfur was in abundant supply, it accumulated to a large extent in oxidized form, rather than reduced form, in the seeds. At all but severely limiting sulfur supply, addition of a transgenic (Tg) sink for organic sulfur resulted in an increase in seed sulfur amino acid content. We hypothesize that demand, or sink strength for organic sulfur, which is itself responsive to environmental sulfur supply, was the first limit to the methionine (Met) and cysteine (Cys) content of wild-type lupin seed protein under most growing conditions. In Tg, soil-grown seeds expressing a foreign Met- and Cys-rich protein, decreased pools of free Met, free Cys, and glutathione indicated that the rate of synthesis of sulfur amino acids in the cotyledon had become limiting. Homeostatic mechanisms similar to those mediating the responses of plants to environmental sulfur stress resulted in an adjustment of endogenous protein composition in Tg seeds, even when grown at adequate sulfur supply. Uptake of sulfur by lupin cotyledons, as indicated by total seed sulfur at maturity, responded positively to increased sulfur supply, but not to increased demand in the Tg seeds. PMID:11891268

  20. The Scarlet Letter of Alkylation: A Mini Review of Selective Alkylating Agents

    PubMed Central

    Oronsky, Bryan T; Reid, Tony; Knox, Susan J; Scicinski, Jan J

    2012-01-01

    If there were a stigma scale for chemotherapy, alkylating agents would be ranked at the top of the list. The chemical term alkylation is associated with nonselective toxicity, an association that dates back to the use of nitrogen mustards during World War I as chemical warfare agents. That this stigma persists and extends to compounds that, through selectivity, attempt to “tame” the indiscriminate destructive potential of alkylation is the subject of this review. Selective alkylation, as it is referred to herein, constitutes an extremely nascent and dynamic field in oncology. The pharmacodynamic response to this selective strategy depends on a delicate kinetic balance between specificity and the rate and extent of binding. Three representative compounds are presented: RRx-001, 3-bromopyruvate, and TH-302. The main impetus for the development of these compounds has been the avoidance of the serious complications of traditional alkylating agents; therefore, it is the thesis of this review that they should not experience stigma by association. PMID:22937173

  1. Effect of pretreatments and endo-1,4-β-xylanase hydrolysis of canola meal and mustard bran for production of oligosaccharides.

    PubMed

    Yuan, Lin; Scanlon, Martin G; Eskin, N A Michael; Thiyam-Hollander, Usha; Aachary, Ayyappan A

    2015-01-01

    Alkali/acid-pretreated canola meal and mustard bran were subjected to endo-1,4-β-xylanase (T. longibrachiatum) hydrolysis for oligosaccharide production. Pretreatments significantly (α = 0.05) increased the relative content of pentose sugars, especially in alkali-pretreated canola meal (∼44 %) and mustard bran (∼72 %). The amounts of pentosan (g/100 g) in acid- and alkali-pretreated canola meal were 7.50 and 8.21 and in corresponding mustard bran were 8.67 and 10.39, respectively. These pretreated substrates produced a pentose content (g/100 g) of 2.10 ± 0.14 (18 h) and 2.95 ± 0.10 (24 h), respectively, during hydrolysis. As per UPLC-MS data, the main oligosaccharides in the hydrolyzates of alkali-pretreated substrates are xylo-glucuronic acid and xylobiose. The release of total phenolics of the hydrolyzates increased until 18 h irrespective of the type of substrate or pretreatment. Hydrolyzates of acid-pretreated substrates indicated more total antioxidant activity than alkali-pretreated substrates, attributed to its high phenolic content. The study suggests the potential of canola meal and mustard bran for the production of oligosaccharides, wherein the use of various combinations of cell-wall-degrading enzymes and its optimization may result in a better yield, with simultaneous production of endogenous phenolics.

  2. Characterization of Sulfur and Nanostructured Sulfur Battery Cathodes in Electron Microscopy Without Sublimation Artifacts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Levin, Barnaby D. A.; Zachman, Michael J.; Werner, Jörg G.

    Abstract Lithium sulfur (Li–S) batteries have the potential to provide higher energy storage density at lower cost than conventional lithium ion batteries. A key challenge for Li–S batteries is the loss of sulfur to the electrolyte during cycling. This loss can be mitigated by sequestering the sulfur in nanostructured carbon–sulfur composites. The nanoscale characterization of the sulfur distribution within these complex nanostructured electrodes is normally performed by electron microscopy, but sulfur sublimates and redistributes in the high-vacuum conditions of conventional electron microscopes. The resulting sublimation artifacts render characterization of sulfur in conventional electron microscopes problematic and unreliable. Here, we demonstratemore » two techniques, cryogenic transmission electron microscopy (cryo-TEM) and scanning electron microscopy in air (airSEM), that enable the reliable characterization of sulfur across multiple length scales by suppressing sulfur sublimation. We use cryo-TEM and airSEM to examine carbon–sulfur composites synthesized for use as Li–S battery cathodes, noting several cases where the commonly employed sulfur melt infusion method is highly inefficient at infiltrating sulfur into porous carbon hosts.« less

  3. Sulfur-binding in recent environments: II. Speciation of sulfur and iron and implications for the occurrence of organo-sulfur compounds

    NASA Astrophysics Data System (ADS)

    Hartgers, Walter A.; Lòpez, Jordi F.; Sinninghe Damsté, Jaap S.; Reiss, Christine; Maxwell, James R.; Grimalt, Joan O.

    1997-11-01

    Speciation of iron and sulfur species was determined for two recent sediments (La Trinitat and Lake Cisó) which were deposited in environments with a high biological productivity and sulfate-reducing activity. In sediments from calcite ponds of La Trinitat an excess of reactive iron species (iron monosulfides, iron hydroxides) results in a depletion of reactive sulfur which is accompanied by a virtual absence of organo-sulfur compounds, both in low (LMW) and high molecular-weight (HMW) fractions. Small amounts of phytanyl and highly branched isoprenoid (HBI) thiophenes in the extract demonstrate that these molecules exhibit a higher reactivity towards reduced sulfur species as compared to detrital iron. Euxinic sediments from Lake Cisó are characterised by an excess of reduced sulfur species which can rapidly trap reactive iron. High concentrations of H 2S results in the formation of organo-sulfur compounds which were encountered in both LMW and HMW fractions. The major part of the organic sulfur is bound to the carbohydrate portion of woody tissues, whose presence was revealed by a specific alkylthiophene distribution in the flash pyrolysate and by Li/EtNH 2 desulfurisation of the kerogen which resulted in the solubilisation of the sulfur-enriched hemicellulose fraction. Relatively high amounts of sulfurised C 25 HBI compounds in the sediment extract of Lake Cisó reflect the incorporation of sulfur into algal derived organic matter upon early diagenesis. The combined approach of the speciation of iron and sulfur species and the molecular analysis of sedimentary fractions demonstrates that abiotic sulfur binding to organic matter occurs at the earliest stages of diagenesis under specific depositional conditions (anoxic, stratified water column) in which an excess of reduced sulfur species relative to the amount of reactive iron is a controlling factor.

  4. Lithium sulfur batteries and electrolytes and sulfur cathodes thereof

    DOEpatents

    Visco, Steven J.; Goncharenko, Nikolay; Nimon, Vitaliy; Petrov, Alexei; Nimon, Yevgeniy S.; De Jonghe, Lutgard C.; Katz, Bruce D.; Loginova, Valentina

    2017-05-23

    Lithium sulfur battery cells that use water as an electrolyte solvent provide significant cost reductions. Electrolytes for the battery cells may include water solvent for maintaining electroactive sulfur species in solution during cell discharge and a sufficient amount of a cycle life-enhancing compound that facilitates charging at the cathode. The combination of these two components enhances one or more of the following cell attributes: energy density, power density and cycle life. For instance, in applications where cost per Watt-Hour (Wh) is paramount, such as grid storage and traction applications, the use of an aqueous electrolyte in combination with inexpensive sulfur as the cathode active material can be a key enabler for the utility and automotive industries, for example, providing a cost effective and compact solution for load leveling, electric vehicles and renewable energy storage. Sulfur cathodes, and methods of fabricating lithium sulfur cells, in particular for loading lithium sulfide into the cathode structures, provide further advantages.

  5. Seeded growth of gold nanorods: the effect of sulfur-containing quenching agents

    NASA Astrophysics Data System (ADS)

    Gobbo, Alberto; Marin, Riccardo; Canton, Patrizia

    2018-03-01

    Herein we present a study on the efficacy of selected sulfur-containing species as growth quenchers and metal ion scavengers in the framework of gold nanorod (GNR) synthesis. The here utilized seeded growth method is the reference GNR synthesis approach. However, GNRs synthesized according to it are prone to morphological changes upon aging, promoted by the presence of unreacted metal ions in the stock suspension. This, in turn, leads to optical property changes. Sodium sulfide is an efficient GNR growth quencher and metal ion scavenger, because sulfide ion has a strong affinity towards noble metals used for the GNRs' synthesis. Moving from these considerations, different sulfur-containing molecules were selected and their interaction with GNR surface was investigated: sulfate, sulfite, thiourea, and dodecyl sulfate were chosen for their difference in terms of net charge, size, and hydrophobicity. We initially assessed the best synthesis conditions in terms of reaction time, seed amount, silver concentration, and quencher amount. Consequently, the quencher/scavenger was varied. Thiourea, sulfite, and sulfate ions all showed a feeble, yet non-negligible, interaction with metals. Although sodium sulfide turned out to be the most efficient quencher/scavenger, also dodecyl sulfate showed evidences of adsorption on the GNR surface, probably prompted by hydrophobic interactions. These findings are expected to contribute as a background for further advancements in the perfection of GNR synthetic approaches specifically in terms of post-synthesis treatments.

  6. Sulfur vesicles from Thermococcales: A possible role in sulfur detoxifying mechanisms

    PubMed Central

    Gorlas, A.; Marguet, E.; Gill, S.; Geslin, C.; Guigner, J.-M.; Guyot, F.; Forterre, P.

    2015-01-01

    The euryarchaeon Thermococcus prieurii inhabits deep-sea hydrothermal vents, one of the most extreme environments on Earth, which is reduced and enriched with heavy metals. Transmission electron microscopy and cryo-electron microscopy imaging of T. prieurii revealed the production of a plethora of diverse membrane vesicles (MVs) (from 50 nm to 400 nm), as is the case for other Thermococcales. T. prieurii also produces particularly long nanopods/nanotubes, some of them containing more than 35 vesicles encased in a S-layer coat. Notably, cryo-electron microscopy of T. prieurii cells revealed the presence of numerous intracellular dark vesicles that bud from the host cells via interaction with the cytoplasmic membrane. These dark vesicles are exclusively found in conjunction with T. prieurii cells and never observed in the purified membrane vesicles preparations. Energy-Dispersive-X-Ray analyses revealed that these dark vesicles are filled with sulfur. Furthermore, the presence of these sulfur vesicles (SVs) is exclusively observed when elemental sulfur was added into the growth medium. In this report, we suggest that these atypical vesicles sequester the excess sulfur not used for growth, thus preventing the accumulation of toxic levels of sulfur in the host's cytoplasm. These SVs transport elemental sulfur out of the cell where they are rapidly degraded. Intriguingly, closely related archaeal species, Thermococcus nautili and Thermococcus kodakaraensis, show some differences about the production of sulfur vesicles. Whereas T. kodakaraensis produces less sulfur vesicles than T. prieurii, T. nautili does not produce such sulfur vesicles, suggesting that Thermococcales species exhibit significant differences in their sulfur metabolic pathways. PMID:26234734

  7. Imaging of irradiated liver with Tc-99m-sulfur colloid and Tc-99m-IDA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gelfand, M.J.; Saha, S.; Aron, B.S.

    1981-09-01

    In three cases, irradiated regions of liver failed to concentrate Tc-99m-sulfur colloid. In two of these three, imaging with Tc-99m-acetanilide iminodiacetic acid (IDA) agents within five days showed near normal hepatic uptake of this hepatobiliary imaging agent. The hepatic parenchymal cells may be imaged with Tc-99m-IDA in some irradiated regions of liver, despite loss of reticuloendothelial cell function.

  8. Effects of Chemical Agents on the Cholinergic Neurotransmitter System: Mechanisms of Adaptation.

    DTIC Science & Technology

    1984-06-20

    DFP; 19h cholinergic agonist, oxotremorine ; oxotremorine analogs, A ~ mustards BM 123 and BM 130; pharmacological, (see reverse i - = V u M pan...anticholinesterase, DFP; a cholinergic agonist, oxotremorine ; and two oxotremorine mustards, BM 123 and BM 130. The studies were of four major kinds...findings. The general pharmacological investigations were directed primarily toward the mustard analogs of oxotremorine and used in vitro and in vivo

  9. Sulfur Species as Redox Partners and Electron Shuttles for Ferrihydrite Reduction by Sulfurospirillum deleyianum

    PubMed Central

    Lohmayer, Regina; Kappler, Andreas; Lösekann-Behrens, Tina

    2014-01-01

    Iron(III) (oxyhydr)oxides can represent the dominant microbial electron acceptors under anoxic conditions in many aquatic environments, which makes understanding the mechanisms and processes regulating their dissolution and transformation particularly important. In a previous laboratory-based study, it has been shown that 0.05 mM thiosulfate can reduce 6 mM ferrihydrite indirectly via enzymatic reduction of thiosulfate to sulfide by the sulfur-reducing bacterium Sulfurospirillum deleyianum, followed by abiotic reduction of ferrihydrite coupled to reoxidation of sulfide. Thiosulfate, elemental sulfur, and polysulfides were proposed as reoxidized sulfur species functioning as electron shuttles. However, the exact electron transfer pathway remained unknown. Here, we present a detailed analysis of the sulfur species involved. Apart from thiosulfate, substoichiometric amounts of sulfite, tetrathionate, sulfide, or polysulfides also initiated ferrihydrite reduction. The portion of thiosulfate produced during abiotic ferrihydrite-dependent reoxidation of sulfide was about 10% of the total sulfur at maximum. The main abiotic oxidation product was elemental sulfur attached to the iron mineral surface, which indicates that direct contact between microorganisms and ferrihydrite is necessary to maintain the iron reduction process. Polysulfides were not detected in the liquid phase. Minor amounts were found associated either with microorganisms or the mineral phase. The abiotic oxidation of sulfide in the reaction with ferrihydrite was identified as rate determining. Cysteine, added as a sulfur source and a reducing agent, also led to abiotic ferrihydrite reduction and therefore should be eliminated when sulfur redox reactions are investigated. Overall, we could demonstrate the large impact of intermediate sulfur species on biogeochemical iron transformations. PMID:24632263

  10. Process for removing sulfur from sulfur-containing gases

    DOEpatents

    Rochelle, Gary T.; Jozewicz, Wojciech

    1989-01-01

    The present disclosure relates to improved processes for treating hot sulfur-containing flue gas to remove sulfur therefrom. Processes in accorda The government may own certain rights in the present invention pursuant to EPA Cooperative Agreement CR 81-1531.

  11. Graphene oxide as a sulfur immobilizer in high performance lithium/sulfur cells

    DOEpatents

    Zhang, Yuegang; Cairns, Elton J.; Ji, Liwen; Rao, Mumin

    2017-06-06

    The loss of sulfur cathode material as a result of polysulfide dissolution causes significant capacity fading in rechargeable lithium/sulfur cells. Embodiments of the invention use a chemical approach to immobilize sulfur and lithium polysulfides via the reactive functional groups on graphene oxide. This approach obtains a uniform and thin (.about.tens of nanometers) sulfur coating on graphene oxide sheets by a chemical reaction-deposition strategy and a subsequent low temperature thermal treatment process. Strong interaction between graphene oxide and sulfur or polysulfides demonstrate lithium/sulfur cells with a high reversible capacity of 950-1400 mAh g.sup.-1, and stable cycling for more than 50 deep cycles at 0.1 C.

  12. Graphene oxide as a sulfur immobilizer in high performance lithium/sulfur cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Yuegang; Cairns, Elton J.; Ji, Liwen

    The loss of sulfur cathode material as a result of polysulfide dissolution causes significant capacity fading in rechargeable lithium/sulfur cells. Embodiments of the invention use a chemical approach to immobilize sulfur and lithium polysulfides via the reactive functional groups on graphene oxide. This approach obtains a uniform and thin (.about.tens of nanometers) sulfur coating on graphene oxide sheets by a chemical reaction-deposition strategy and a subsequent low temperature thermal treatment process. Strong interaction between graphene oxide and sulfur or polysulfides demonstrate lithium/sulfur cells with a high reversible capacity of 950-1400 mAh g.sup.-1, and stable cycling for more than 50 deepmore » cycles at 0.1 C.« less

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

    PubMed

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

    2013-01-01

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

  14. Method of removing and recovering elemental sulfur from highly reducing gas streams containing sulfur gases

    DOEpatents

    Gangwal, Santosh K.; Nikolopoulos, Apostolos A.; Dorchak, Thomas P.; Dorchak, Mary Anne

    2005-11-08

    A method is provided for removal of sulfur gases and recovery of elemental sulfur from sulfur gas containing supply streams, such as syngas or coal gas, by contacting the supply stream with a catalyst, that is either an activated carbon or an oxide based catalyst, and an oxidant, such as sulfur dioxide, in a reaction medium such as molten sulfur, to convert the sulfur gases in the supply stream to elemental sulfur, and recovering the elemental sulfur by separation from the reaction medium.

  15. 40 CFR 50.4 - National primary ambient air quality standards for sulfur oxides (sulfur dioxide).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... standards for sulfur oxides (sulfur dioxide). 50.4 Section 50.4 Protection of Environment ENVIRONMENTAL....4 National primary ambient air quality standards for sulfur oxides (sulfur dioxide). (a) The level...). (c) Sulfur oxides shall be measured in the ambient air as sulfur dioxide by the reference method...

  16. 40 CFR 50.4 - National primary ambient air quality standards for sulfur oxides (sulfur dioxide).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... standards for sulfur oxides (sulfur dioxide). 50.4 Section 50.4 Protection of Environment ENVIRONMENTAL....4 National primary ambient air quality standards for sulfur oxides (sulfur dioxide). (a) The level...). (c) Sulfur oxides shall be measured in the ambient air as sulfur dioxide by the reference method...

  17. 40 CFR 50.4 - National primary ambient air quality standards for sulfur oxides (sulfur dioxide).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... standards for sulfur oxides (sulfur dioxide). 50.4 Section 50.4 Protection of Environment ENVIRONMENTAL....4 National primary ambient air quality standards for sulfur oxides (sulfur dioxide). (a) The level...). (c) Sulfur oxides shall be measured in the ambient air as sulfur dioxide by the reference method...

  18. 40 CFR 50.4 - National primary ambient air quality standards for sulfur oxides (sulfur dioxide).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... standards for sulfur oxides (sulfur dioxide). 50.4 Section 50.4 Protection of Environment ENVIRONMENTAL....4 National primary ambient air quality standards for sulfur oxides (sulfur dioxide). (a) The level...). (c) Sulfur oxides shall be measured in the ambient air as sulfur dioxide by the reference method...

  19. THE ANTIBACTERIAL PROPERTIES OF SULFUR

    PubMed Central

    Weld, Julia T.; Gunther, Anne

    1947-01-01

    1. Saturated solutions of sulfur in alcohol (alcohol-sulfur) when diluted with broth are inhibitory to the growth of various Gram-positive bacteria and to C. hominis. By an arbitrary method of unitage with S. aureus as the test organism, our alcohol-sulfur contains 1,600 to 2,000 units per cc. and one unit contains between 0.24 and 0.34 gamma sulfur. The activity of a preparation is in general directly proportional to its sulfur content. 2. Solutions of sulfur in carbowax (carbowax-sulfur) when diluted with broth are likewise inhibitory to the growth of various Gram-positive bacteria and to C. hominis. When S. aureus is used as test organism, 1 unit contains between 0.1 and 0.2 gamma sulfur. The activity of these preparations is also in general directly proportional to their sulfur content. 3. Carbowax-sulfur when incorporated in agar in 1–500 to 1–2,000 dilution inhibits the growth of various Gram-positive aerobic and anaerobic bacteria, C. hominis, and certain dermatophytes. 4. Our experiments appear to show that both alcohol-sulfur and carbowax-sulfur owe their inhibitory properties to the sulfur particles that are dispersed throughout the medium when these sulfur preparations are diluted with broth. The inhibitory effect of these particles may or may not be due to a combination of the sulfur particles with substances in the medium in which they are suspended. 5. Evidence suggests that the activity of both alcohol-sulfur and carbowax-sulfur is due to sulfur in the same form. The inhibitory effect is characterized by prolonged bacteriostasis with similar activity over a wide range of dilutions. There is no evidence of true bactericidal action even with the highest concentrations used. PMID:19871634

  20. The life sulfuric: microbial ecology of sulfur cycling in marine sediments.

    PubMed

    Wasmund, Kenneth; Mußmann, Marc; Loy, Alexander

    2017-08-01

    Almost the entire seafloor is covered with sediments that can be more than 10 000 m thick and represent a vast microbial ecosystem that is a major component of Earth's element and energy cycles. Notably, a significant proportion of microbial life in marine sediments can exploit energy conserved during transformations of sulfur compounds among different redox states. Sulfur cycling, which is primarily driven by sulfate reduction, is tightly interwoven with other important element cycles (carbon, nitrogen, iron, manganese) and therefore has profound implications for both cellular- and ecosystem-level processes. Sulfur-transforming microorganisms have evolved diverse genetic, metabolic, and in some cases, peculiar phenotypic features to fill an array of ecological niches in marine sediments. Here, we review recent and selected findings on the microbial guilds that are involved in the transformation of different sulfur compounds in marine sediments and emphasise how these are interlinked and have a major influence on ecology and biogeochemistry in the seafloor. Extraordinary discoveries have increased our knowledge on microbial sulfur cycling, mainly in sulfate-rich surface sediments, yet many questions remain regarding how sulfur redox processes may sustain the deep-subsurface biosphere and the impact of organic sulfur compounds on the marine sulfur cycle. © 2017 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.