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The destruction of chemical warfare agents (CWAs) is a crucial area of research due to the ongoing evolution of toxic chemicals. Metal–organic frameworks (MOFs), a class of porous crystalline solids, have emerged as promising materials for this purpose. Their remarkable porosity and large surface areas enable superior adsorption, reactivity, and catalytic abilities, making them ideal for capturing and decomposing target species. Moreover, the tunable networks of MOFs allow customization of their chemical functionalities, making them practicable in personal protective equipment and adjustable to dynamic environments. This review paper focuses on experimental and computational studies investigating the removal of CWAs by MOFs, specifically emphasizing the removal of nerve agents (GB, GD, and VX) via hydrolysis and sulfur mustard (HD) via selective photooxidation. Among the different MOFs, zirconium-based MOFs exhibit extraordinary structural stability and reusability, rendering them the most promising materials for the hydrolytic and photooxidative degradation of CWAs. Accordingly, this work primarily concentrates on exploring the intrinsic catalytic reaction mechanisms in Zr-MOFs through first-principles approximations, as well as the design of efficient degradation strategies in the aqueous and solid phases through the establishment of Zr-MOF structure–property relationships. Recent progress in the tuning and functionalization of MOFs is also examined, aiming to enhance practical CWA removal under realistic battlefield conditions. By providing a comprehensive overview of experimental findings and computational insights, this review paper contributes to the advancement of MOF-based strategies for the destruction of CWAs and highlights the potential of these materials to address the challenges associated with chemical warfare. [ABSTRACT FROM AUTHOR]

Understanding the molecular and cellular mechanisms involved in the pathogenesis of ocular injured induced by mustard gas can help better identify complications and discover appropriate therapies. This study aimed to analyze the proteomics of tears of chemical warfare victims with mustard gas ocular injuries and compare it with healthy individuals. In this case-control research, 10 mustard gas victims with long-term ocular difficulties (Chronic) were included in the patient group, while 10 healthy persons who were age and sex matched to the patients were included in the control group. Schirmer strips were used to collect the tears of the participants. Proteomics experiments were performed using the high-efficiency TMT10X method to evaluate the tear protein profile, and statistical bioinformatics methods were used to identify the differently expressed proteins. 24 proteins had different expressions between the two groups. Among these 24 proteins, 8 proteins had increased expression in veterans' tears, while the remaining 16 proteins had decreased expression. Reactome pathways were used to look at proteins with various expressions, and 13 proteins were found to be engaged in the immune system, 9 of which were effective in the innate immune system, and 5 proteins were effective in the complement cascade. Ocular mustard gas exposure may cause a compromised immune system on the eye's surface, exposing the cornea to external and endogenous infections, and eventually causing corneal opacity and reduced vision. [ABSTRACT FROM AUTHOR]

Understanding the molecular and cellular mechanisms involved in the pathogenesis of ocular injured induced by mustard gas can help better identify complications and discover appropriate therapies. This study aimed to analyze the proteomics of tears of chemical warfare victims with mustard gas ocular injuries and compare it with healthy individuals. In this case-control research, 10 mustard gas victims with long-term ocular difficulties (Chronic) were included in the patient group, while 10 healthy persons who were age and sex matched to the patients were included in the control group. Schirmer strips were used to collect the tears of the participants. Proteomics experiments were performed using the high-efficiency TMT10X method to evaluate the tear protein profile, and statistical bioinformatics methods were used to identify the differently expressed proteins. 24 proteins had different expressions between the two groups. Among these 24 proteins, 8 proteins had increased expression in veterans' tears, while the remaining 16 proteins had decreased expression. Reactome pathways were used to look at proteins with various expressions, and 13 proteins were found to be engaged in the immune system, 9 of which were effective in the innate immune system, and 5 proteins were effective in the complement cascade. Ocular mustard gas exposure may cause a compromised immune system on the eye's surface, exposing the cornea to external and endogenous infections, and eventually causing corneal opacity and reduced vision. [ABSTRACT FROM AUTHOR]

In the long and intensive search for effective treatments to counteract the toxicity of the chemical warfare (CW) agent sulphur mustard (H; bis(2-chloroethyl) sulphide), the most auspicious and consistent results have been obtained with the drug N -acetylcysteine (NAC), particularly with respect to its therapeutic use against the effects of inhaled H. It is a synthetic cysteine derivative that has been used in a wide variety of clinical applications for decades and a wealth of information exists on its safety and protective properties against a broad range of toxicants and disease states. Its primary mechanism of action is as a pro-drug for the synthesis of the antioxidant glutathione (GSH), particularly in those circumstances where oxidative stress has exhausted intracellular GSH stores. It impacts a number of pathways either directly or through its GSH-related antioxidant and anti-inflammatory properties, which make it a prime candidate as a potential treatment for the wide range of deleterious cellular effects that H is acknowledged to cause in exposed individuals. This report reviews the available literature on the protection afforded by NAC against the toxicity of H in a variety of model systems, including its efficacy in treating the long-term chronic lung effects of H that have been demonstrated in Iranian veterans exposed during the Iran-Iraq War (1980–1988). Although there is overwhelming evidence supporting this drug as a potential medical countermeasure against this CW agent, there is a requirement for carefully controlled clinical trials to determine the safety, efficacy and optimal NAC dosage regimens for the treatment of inhaled H. Image 1 • N -Acetylcysteine (NAC) reduces the toxicity of sulphur mustard (H) in multiple cell types. • NAC reduces the toxic effects of H lung exposure in animal models. • Delayed (~18 yrs) NAC treatment improves lung function in individuals exposed to H. • NAC is considered to be a safe and well tolerated medication in humans. [ABSTRACT FROM AUTHOR]

Background: War causes more death and disability than many major diseases. There are few studies in the context of the deleterious impact of war on fertility potential; therefore, in this study, we tried to review articles about the adverse effects of war on male/ female fertility potential Methods: In this study, a total of 183 articles related to the effects of war on fertility potential were examined by a systematic search using known international medical databases. Results: Among these studies, there were limited studies on the effects of war on female infertility and most studies examined the effects of war on sperm parameters and male infertility. The physical and psychological trauma of war can increase the risk of infertility in men and women. Presence of reproductive system toxins in weapons, stressful periods of war and direct damage to the reproductive system can impair the fertility of men and women. The way war affects male fertility is not clear, but the higher degree of stress during wartime seems to play an important role. Using reproductive toxicants during the war also increases the risk of impairment in reproductive function in men. Some studies have shown the harmful effects of Sulfur mustard as a war chemical toxin especially on sperm quality and male infertility. Oxidative stress induced by free radicals is a major mechanism for the direct effects of Sulfur mustard on male infertility. Conclusion: The study of past research suggests that exposure to war may be an independent risk factor for reproductive disorders and infertility in men. For female infertility, war leads to menstrual dysfunction. [ABSTRACT FROM AUTHOR]

Background: In 1988, Halabja came under heavy chemical warfare attack using chemicals such as sulfur mustard (SM). Thousands of survivors of SM exposure in the city today live with multiple health complaints, such as severe, long-lasting respiratory symptoms; but their perceptions of health have never been adequately researched. We aimed to explore current major health concern topics in civilian survivors with long-term respiratory symptoms. Method: Sixteen subjects (f:m10:6, mean age 45.5 years (range 34–67)) were interviewed. Study participants were recruited in 2016 via a purposive sampling strategy among civilian survivors of chemical warfare in the city of Halabja in Kurdistan-Iraq. A qualitative research design was applied including semi-structured, face-to-face interviews. Data was analyzed using systematic text condensation. Results: The analysis yielded fourteen themes related to: (1) General health: all participants described a deterioration in physical and psychological health, following the SM exposure, foremost involving respiratory symptoms, fatigue, sleeping disorders, ocular problems, depressive symptoms, and anxiety; (2) Quality of life: most notably, they reported a limited family life, limited social relations, lack of work ability, and concern about their financial situation. Moreover, many lived in constant fear of a renewed attack; (3) access to health care services: all participants reported that they had no, or only poor, access to health care services and limited access to specialist care, and all reported lack of financial resources to obtain treatment. Conclusions: The post-exposure somatic and psychosocial effects such as respiratory symptoms of CWA are plausible contributor to poor general health and quality of life among survivors. We conclude that multidisciplinary interventions are needed to tackle the biopsychosocial complications in survivors of SM exposure to minimize further health damage in the future, as well as to promote their health-related quality of life. [ABSTRACT FROM AUTHOR]

Abstract Sulfur mustard (SM) is a chemical warfare agent that was applied in a series of military conflicts and still poses a severe threat to civilians and military personnel. Although the cellular and molecular mechanisms of SM toxicity are still not fully understood, oxidative stress has been considered as the initial vital process for damage. Polydatin, the product of resveratrol and glucose, is a promising candidate for the treatment of oxidative stress-related diseases. However, its effects on SM-induced hepatic injury remain unknown. Thus, we investigated the protective effects of polydatin against SM-induced hepatic injury and its possible mechanism. We found that treatment with polydatin remarkably improved the survival rate of mice bear subcutaneously injected with SM. Polydatin decreased the SM-induced increase of serum aminotransferase levels and ameliorated hepatic pathological damage. We also found that indexes of oxidative stress were improved in mouse liver samples and L02 cells. Meanwhile, changes in the Sirtuin family after treatment with SM were explored in mice and cells since polydatin is a potent activator of Sirt1 and Sirt3. Polydatin significantly increased the expression of Sirt1, HO-1, and NQO1; and the nuclear translocation of Nrf2 in mouse liver and L02 cells. Furthermore, we also observed that either Sirt1 or Nrf2 knockdown abolished the protective effect of polydatin. Our data indicated that polydatin could provide protection against SM-induced hepatic injury through the Sirt1/Nrf2 pathway, suggesting that polydatin is a novel potential antidote for sulfur mustard. Highlights • Polydatin could improve the survival rate of SM-treated mice. • Sirt1 was significantly reduced after SM-treatment. • Polydatin protects against SM-induced liver injury via Sirt1/Nrf2. • First correlation between polydatin and a chemical warfare agent [ABSTRACT FROM AUTHOR]

A decontaminating composite, Mg3Al‐LDH‐Nb6, has been successfully prepared by immobilizing Lindqvist [H3Nb6O19]5− (Nb6) into a Mg3Al‐based layered double hydroxide (Mg3Al‐LDH). To our knowledge, this represents the first successful approach to the immobilization of polyoxoniobate. As a versatile catalyst, Mg3Al‐LDH‐Nb6 can effectively catalyze the degradation of both vesicant and nerve agent simulants by multiple pathways under mild conditions. Specifically, the sulfur mustard simulant, 2‐chloroethyl ethyl sulfide (CEES), is converted into the corresponding nontoxic 2‐chloroethyl ethyl sulfoxide (CEESO) by selective oxidation, whereas the Tabun (G‐type nerve agent) simulant, diethyl cyanophosphonate (DECP), and the VX (V‐type nerve agent) simulant, O,S‐diethyl methylphosphonothioate (OSDEMP), are detoxified through hydrolysis and perhydrolysis, respectively. A possible mechanism is proposed on the basis of control experiments and spectroscopic studies. The Mg3Al‐LDH‐Nb6 composite exhibits remarkable robustness and can be readily reused for up to ten cycles with negligible loss of its catalytic activity. More importantly, a protective "self‐detoxifying" material has easily been constructed by integrating Mg3Al‐LDH‐Nb6 into textiles. In this way, the flexible and permeable properties of textiles have been combined with the catalytic activity of polyoxoniobate to remove 94 % of CEES in 1 h by using nearly stoichiometric dilute H2O2 (3 %) as oxidant with 96 % selectivity. Detox done well! A novel decontaminating material, Mg3Al‐LDH‐Nb6, has been prepared by immobilizing hexaniobate into a layered double hydroxide (LDH). As a versatile catalyst, Mg3Al‐LDH‐Nb6 effectively degrades a sulfur mustard simulant by selective oxidation and a G‐ and V‐type nerve agent simulant by hydrolysis and perhydrolysis, respectively (see figure). Furthermore, this catalyst can be integrated into textiles to construct portable and permeable self‐detoxifying clothing. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

The skin is highly sensitive to the chemical warfare agent in mustard gas, sulfur mustard (SM) that initiates a delayed injury response characterized by erythema, inflammation and severe vesication (blistering). Although SM poses a continuing threat, used as recently as in the Syrian conflict, no mechanism-based antidotes against SM are available. Recent studies demonstrated that Transient Receptor Potential Ankyrin 1 (TRPA1), a chemosensory cation channel in sensory nerves innervating the skin, is activated by SM and 2‐chloroethyl ethyl sulfide (CEES), an SM analog, in vitro , suggesting it may promote vesicant injury. Here, we investigated the effects of TRPA1 inhibitors, and an inhibitor of Calcitonin Gene Related Peptide (CGRP), a neurogenic inflammatory peptide released upon TRPA1 activation, in a CEES-induced mouse ear vesicant model (CEES-MEVM). TRPA1 inhibitors (HC-030031 and A-967079) and a CGRP inhibitor (MK-8825) reduced skin edema, pro-inflammatory cytokines (IL-1β, CXCL1/KC), MMP-9, a protease implicated in skin damage, and improved histopathological outcomes. These findings suggest that TRPA1 and neurogenic inflammation contribute to the deleterious effects of vesicants in vivo , activated either directly by alkylation, or indirectly, by reactive intermediates or pro-inflammatory mediators. TRPA1 and CGRP inhibitors represent new leads that could be considered for validation and further development in other vesicant injury models. [ABSTRACT FROM AUTHOR]

Background: Sulfur mustard (SM) is a chemical blistering warfare that affects different organs especially hematopoietic system. Prevalence of acute myeloblastic and lymphoblastic leukemia is increased by sulfur mustard exposure. FLT3-ITD mutation can be effective on leukemogenesis. Therefore, the aim of this study was to verify the frequency of FLT3-ITD mutation in the patients who exposed to SM. Methods: This study was implemented on 42 people poisoned by SM during Iraq-Iran war about three decades ago and is now resident in Mashhad, Iran. The control group included 30 healthy males that are relatives of the patients with first-degree. After DNA extraction, PCR was performed for FLT3-ITD analysis. Results: By analysis of PCR products, no FLT3-ITD mutation was detected in the patient or control groups. There was no significant difference in hematological factors between the two groups. Conclusion: Other mechanisms can lead to leukemia in SM exposed persons. Elapsed time after exposure to sulfur mustard can be effective on leukemogenesis, then future more study may be beneficial for early diagnosis of leukemia in SM exposed veterans. [ABSTRACT FROM AUTHOR]

In recent years, people pay more attention to the protection against chemical warfare agents, due to the increase in the probability of usage of these chemical warfare agents in wars or terrorist attacks. In this work, MgO nanoparticles were in-situ growth on the surface of poly(m-phenylene Isophthalamide) (PMIA) forming a flexible and breathable fabric for the detoxification of mustard gas surrogate. The as-prepared nanofibrous membrane possesses a “flower-like” structure of which endows not only increase the specific surface area of the composite but also prevent the agglomeration of the MgO nanoparticles. The detoxification ability of the PMIA@MgO nanofibrous fabric was demonstrated by gas chromatography-mass spectrometer (GC–MS). It is found that after 20 h of reaction time, 70.56% of the mustard gas surrogate have been decomposed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

Nanosized inorganic metal oxides, such as TiO 2 , ZnO, γ -Al 2 O 3 , are proposed as heterogeneous catalysts for the oxidative degradation of chemical warfare agents (CWA), particularly of organosulfur toxic agents, into oxidised products with reduced toxicity. The morphology, structural and textural properties of the catalysts were investigated. Furthermore, their catalytic properties were evaluated in the oxidative abatement of (2-chloroethyl)ethylsulfide, CEES, a simulant of sulfur mustard (blistering CWA). Their performance was also compared to a conventional decontamination powder and a commercial Nb 2 O 5 sample. The metal oxides powders were then employed in the active oxidative decontamination of CEES from a cotton textile substrate, mimicking a real contamination occurrence. Remarkable results in terms of abatement and degradation into desired products were recorded, achieving good conversions and decontamination efficiency with Nb 2 O 5 , TiO 2 and γ -Al 2 O 3 , under very mild conditions, with hydrogen peroxide (as aqueous solution or as urea-hydrogen peroxide adduct), at room temperature and ambient pressure. In the aim of a real on-field use, the potential environmental impact of these solids was also evaluated by bioluminescence toxicity tests on reference bacteria ( Photobacterium leiognathi Sh1), showing a negligible negative impact for TiO 2 , γ -Al 2 O 3 , and Nb 2 O 5 . A major biotoxic effect was only found for ZnO. [ABSTRACT FROM AUTHOR]

Context: Sulfur mustard (SM) and lewisite are vesicant chemical warfare agents that can cause skin blistering and chronic lung complications. During 1929–1945, a Japanese factory produced poisonous gases, which included SM, lewisite and other chemical weapons. The aim of this study was to investigate the chest computed tomography (CT) findings among long-term survivors who worked at this factory. Methods: During 2009–2012, we evaluated chest CT findings from 346 long-term survivors who worked at the poison gas factory. Skin lesions were used as an indicator of significant exposure to vesicant agents. Results: Among the 346 individuals, 53 (15%) individuals experienced skin lesions while working at the factory, and chest CT revealed abnormal findings in 179 individuals (52%). Emphysema was the most common CT finding and was observed in 75 individuals (22%), while honeycombing was observed in 8 individuals (2%). Emphysema and honeycombing were more prevalent among individuals with skin lesions, compared to individuals without skin lesions. Multivariate analyses revealed significant associations between the presence of emphysema and skin lesions (p = 0.008). Among individuals who never smoked, individuals with skin lesions (n = 26) exhibited a significantly higher rate of emphysema, compared to individuals without skin lesions (n = 200) (35% versus 7%, respectively;p < 0.001). Conclusion: Among the long-term survivors who worked at the poison gas factory, a history of skin lesions was associated with the presence of emphysema, even among never smokers, which suggests that emphysema might be a long-term complication of exposure to chemical warfare agents. [ABSTRACT FROM PUBLISHER]

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

Selective detection of sulfur mustard simulant, 2-chloroethyl ethyl sulfide ( CEES ) is performed using specifically designed pyridine appended Mg–porphyrazine complex ( 1 ). Interaction of CEES with pyridine units of 1 leads to perturbation/reduction in absorbance of the Q-band of 1 and the process is, thus, monitored using UV–vis spectroscopic method. Interestingly, treating the CEES- 1 solution with KMnO 4 solution results in reappearance of Q-band of 1 and allows reuse of 1 by simple filtration. The alkylating ability of CEES and KMnO 4 oxidation of CEES- 1 appears to be playing an important role in the detection/degradation process, thereby serving the dual purpose. The chemical sensing is then used as a platform for generating different input-based combinatorial and sequential molecular logic gate(s) allowing facile information processing and as an information security system in the form of a keypad lock. [ABSTRACT FROM AUTHOR]

A novel sensitive screening method based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) has shown the feasibility of separation and detection of thiodiglycolic acid in aqueous samples. The analysis of this compound is of interest since it is specific microbiological metabolite of thiodiglycol, which is precursor and degradation product of chemical warfare agent sulfur mustard. The LC–electrospray ionisation (ESI)–MS method provides a sensitive and direct approach for thiodiglycolic acid identification and quantification using non-extracted non-derivitised samples from aqueous solutions. Chromatographic separation of the thiodiglycolic acid was produced using a reverse phase LC column with gradient mobile phases consisting of 0.1% formic acid in water and acetonitrile. Identification and quantification of species were achieved using ESI–tandem MS monitoring two precursor-to-product ion transitions for thiodiglycolic acid. The method demonstrates linearity over at least two orders of magnitude and detection limit of 10 ng...mL–1in environmental water samples. [ABSTRACT FROM AUTHOR]

The subject of the work is the use of differential mobility spectrometry (DMS) for the detection of chemical warfare agents (CWA). Studies were performed for mustard gas, i.e., bis(2-chloroethyl)sulfide (HD), sarin, i.e., O-isopropyl methylphosphonofluoridate (GB) and methyl salicylate (MS) used as test compounds. Measurements were conducted with two ceramic DMS analyzers of different constructions allowing the generation of an electric field with an intensity of more than 120 Td. Detector signals were measured for positive and negative modes of operation in a temperature range from 0 to 80 °C. Fragmentations of ions containing analyte molecules were observed for all tested compounds. The effective temperatures of fragmentation estimated on the basis of dispersion plots were equal from about 148 °C for GB to 178 °C for MS. It was found that values of separation voltage (SV) and compensation voltage (CV) at which the fragmentation of sample ions is observed may be the parameters improving the certainty of detection for different analytes. The DMS analyzers enabling the observation of ion fragmentation can be successfully used for effective CWA detection. [ABSTRACT FROM AUTHOR]

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 0.2 pL and 100 pL for sarin, soman, tabun, cyclohexylsarin, and sulfur mustard; and between 2 pL and 100 pL 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 (100 mL) prepared in a 500 mL gas sampling cylinder. In the concentration range of 0.2–2.5 mg/m 3 , >50% of sarin, soman, tabun, cyclohexylsarin, and HD were recovered, whereas <1% of VX and Russian VX were recovered in the same concentration range. The results indicate that CWA vapors, with the exception of VX and Russian VX, can be measured by an on-site collection procedure using the Tenax ® TA resin tubes, followed by a subsequent TD–GC/MS analysis. [ABSTRACT FROM AUTHOR]

Pulmonary complications due to mustard gas exposure range from no effect to severe bronchial stenosis. Pulmonary function tests (PFTs) and respiratory symptoms in chemical war victims were studied 23–25 years after exposure to sulfur mustard (SM). Respiratory symptoms were evaluated in a sample of 142 chemical war victims and 120 control subjects with similar age from the general population using a questionnaire including questions on respiratory symptoms in the past year. PFT values were also measured in chemical war victims before and 15 min after the inhalation of 200 µg salbutamol and baseline PFT in controls. All chemical war victims (100%) reported respiratory symptoms. Wheezing (66.19%), cough (64.78%), and chest tightness (54.4%) were the most common symptoms and only 15.5% of chemical war victims reported sputum (p < 0.01 for sputum and p < 0.001 for other symptoms compared with control group). In addition, 49.3% of chemical war victims had wheeze in chest examination, which were significantly higher than control group (p < 0.001). The severity of respiratory symptoms was also significantly higher than control subjects (p < 0.05 for sputum and p < 0.001 for other symptoms). All the PFT values were also significantly lower in chemical war victims than that in control subjects (p < 0.001 for all cases). In addition, all the PFT values improved significantly after the inhalation of 200 µg salbutamol (p < 0.05–p < 0.001). These results showed that chemical war victims, 23–25 years after exposure to chemical warfare have higher frequencies and severity of respiratory symptoms. PFT values were also significantly reduced among chemical war victims, which showed reversibility due to the inhalation of 200 µg salbutamol. [ABSTRACT FROM PUBLISHER]

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

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. [ABSTRACT FROM AUTHOR]

Some studies have already addressed the effects of occupational organic solvent exposure on the visually evoked potentials (VEPs). Visual system is an important target for Sulphur Mustard (SM) toxicity. A number of Iranian victims of Sulphur Mustard (SM) agent were apprehensive about the delay effect of SM on their vision and a possible delay effect of SM on their visual cortex. This investigation was performed on 34 individuals with a history of chemical exposure and a control group of 15 normal people. The Toennies electro-diagnosis device was used and its signals were saved as the latencies. The mean of N75, N140 and P100 of victims of chemical warfare (VCWs) and control group indicated no significant results (P>0.05). The VCWs did not show any visual symptoms and there was no clear deficit in their VEPs. [ABSTRACT FROM AUTHOR]

Abstract: 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 (50?M) 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 &y& Elsevier]

Background Chronic obstructive pulmonary disease ( COPD) is one of the serious late pulmonary complications caused by sulphur mustard exposure. Health status evaluations of chemical warfare patients with COPD are important to the management of these patients. The aim of this study was to determine the efficacy of the COPD assessment test ( CAT) in evaluating the health-related quality of life ( HRQOL) of chemical warfare patients with COPD. Methods Eighty-two consecutive patients with stable COPD were enrolled in this study. All subjects were visited by one physician, and the HRQOL was evaluated by the CAT and St. George Respiratory Questionnaires ( SGRQs). In addition, a standard spirometry test, 6-min walk distance test and pulse oxymetry were conducted. The severity of the COPD was determined using Global Initiative for Chronic Obstructive Lung Disease ( GOLD) staging and the body mass index, obstruction, dyspnoea and exercise ( BODE) index. Results The mean age of the patients was 47.30 ± 7.08 years. The mean CAT score was 26.03 ± 8.28. Thirty-five (43%) patients were in CAT stage 3. There were statistically significant correlations between the CAT and the SGRQ ( r = 0.70, P = 0.001) and the BODE index ( r = 0.70, P = 0.001). A statistically significant inverse correlation was found between the CAT score and the forced expiratory volume in 1 s ( r = −0.30, P = 0.03). Conclusions Our results demonstrated that the CAT is a simple and valid tool for assessment of HRQOL in chemical warfare patients with COPD and can be used in clinical practice. [ABSTRACT FROM AUTHOR]

Highlights: [•] Medical measures against chemical warfare agents have to be prepared in advance. [•] Medical countermeasures consist a huge burden for health care systems. [•] For nerve agent poisoning therapy of acute effects has to be improved. [•] Ongoing treatment of nerve agent poisoning is necessary to keep patients alive. [•] Pathophysiological changes are important for therapy of sulfur mustard poisoning. [ABSTRACT FROM AUTHOR]

Respirable toxicants are a spectrum of irritant and nonirritant gases, vapors, fumes, and airborne particles that can be entrained into the body through the respiratory tract, resulting in exposures that cause pulmonary injury and/or systemic disease. Sources of respirable toxicants include structural fires, industrial accidents, domestic mishaps, and intentional releases of injurious agents on the battleground (warfare) or in civilian settings (acts of terrorism). Acute toxic inhalational exposures may result in respiratory failure, multisystem organ dysfunction, and death. Management of victims includes assessment and protection of the airway, monitoring and treatment of systemic toxicity, and delivery of exposure-specific and nonspecific therapies that improve outcomes. Treatments may include antidotes, hyperbaric oxygen, and other nonspecific life-supporting interventions. [ABSTRACT FROM PUBLISHER]

A thermal desorption associative ionization time-of-flight mass spectrometer was developed for ultrasensitive detection of semi-volatile chemical warfare agents (CWAs). The excited-state CH 2 Cl 2 -induced associative ionization method presented a soft ionization characterization and an excellent sensitivity towards CWAs. The detection sensitivities of the investigated nine CWA-related substances were 2.56 × 105–5.01 × 106 counts ng−1 in a detection cycle (30 s or 100 s). The corresponding 3σ limits of detection (LODs) were 0.08–3.90 pg. Compared with the best-documented LODs via the dielectric barrier discharge ionization (DBDI) and secondary electrospray ionization (SESI), the obtained LODs of the investigated compounds were improved by 2–76 times. Additionally, the measured sensitivity of 2-Chloroethyl ethyl, a proxy for mustard gas, is 550 counts pptv−1, which exceeds the DBDI and SESI's corresponding values (4.4 counts pptv−1 and 6.5 counts pptv−1) nearly by two orders of magnitude. A field application simulation was conducted by putting a strip of PTFE film contaminated with the CWA-related agent into the thermal desorption unit. The simulation showed that the sensitivities of the instrument via swipe surveying could achieve 2.19 × 105 to 5.23 × 106 counts ng−1. The experimental results demonstrate that the excited-state CH 2 Cl 2 -induced associative ionization is an ultrasensitive ionization method for CWAs and reveal a prospect for improving the detection of CWA species future. [Display omitted] • A new associative ionization ion source is used to detect chemical warfare agents. • Associative ionization is efficient 200 times higher than VUV photoionzation. • The detection sensitivity of associative ionization to chemical warfare agents is over 105 counts ng−1. • The detection of chemical warfare agents at the pg level is achieved. [ABSTRACT FROM AUTHOR]

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

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

BACKGROUND: More than 100,000 Iranian veterans and civilians still suffer from various long-term complications due to their exposure to sulfur mustard (SM) during the Iran-Iraq war in 1983-88. The aim of the study was to investigate DNA damage of SM in veterans who were exposed to SM, 23-27 years prior to this study. MATERIALS AND METHODS: Blood samples were obtained from the veterans and healthy volunteers as negative controls. Lymphocytes were isolated from blood samples and DNA breaks were measured using single-cell microgel electrophoresis technique under alkaline conditions (comet assay). Single cells were analyzed with "Tri Tek Comet Score version 1.5" software and DNA break was measured based on the percentage of tail DNA alone, or in the presence of H2O2 (25 μM) as a positive control. RESULTS: A total of 25 SM exposed male veterans and 25 male healthy volunteers with similar ages (44.66 ± 6.2 and 42.12 ± 5.75 years, respectively) were studied. Percentage of the lymphocyte DNA damage was significantly (P < 0.01) higher in the SM-exposed individuals than in the controls (6.47 ± 0.52 and 1.31 ± 0.35, respectively). Percentages of DNA damage in the different age groups of 35-39, 40-44, 45-49, and 50-54 years in SM-exposed veterans (5.48 ± 0.17, 6.7 3 ± 1.58, 6.42 ± 0.22, and 7.27 ± 0.38, respectively) were all significantly (P < 0.05) higher than the controls (1.18 ± 0.25, 1.53 ± 0.22, 1.27 ± 0.20, and 1.42 ± 0.10, respectively). The lymphocytes incubated with H2O2 had much higher DNA damage as expected. The average of tail DNA is 42.12 ± 2.75% for control cells + H2O2 and 18.48 ± 2.14% for patients cells + H2O2; P < 0.001. CONCLUSION: SM exposure of the veterans revealed DNA damage as judged by the comet assay. [ABSTRACT FROM AUTHOR]

Background: Long-term effects of sulfur mustard poisoning have been investigated in several studies. This study was performed to systematically summarize the results of papers about physical effects of sulfur mustard poisoning in Iranian chemical warfare victims. Methods: Scientific Information Databases (SID), IranMedex, and Magiran were searched for articles published from 1988 to November 2012. 128 papers were found by using sulfur mustard, complication, and chemical agent as keywords. Overall, 64 papers were excluded due to irrelevant abstracts or titles. After revisions, only 25 studies were selected for final assessments. Findings: The reviewed studies had reported prevalence of long-term dermatological, ophthalmological, and respiratory complications as 89.8%, 88.2%, and 83.6%, respectively. Chronic dermatological complications were mainly chronic severe itching, scars, dry skin, and skin discoloration. Ophthalmological complications included pinguecula, pterygium, chronic conjunctivitis, vascular tortuosity, limbal ischemia, thin corneas, diffuse corneal opacity, dry eye, and keratitis and their clinical symptoms. Respiratory complications were mainly obstructive chronic bronchitis, bronchiolitis, bronchiectasis, asthma, and fibrosis. Respiratory and ophthalmological symptoms were strongly associated with each other. Conclusion: Long-term dermatological complications were the most prevalent problems caused by sulfur mustard exposure. Ophthalmological and respiratory complications were the second and third most frequent problems. However, respiratory complications had more burden and severity and their incidence and severity increased by increasing age. Oligospermia was not confirmed. There was an increased incidence of leukemia but strong evidence for a direct effect of mustard gas on cancer (less than 30 years after exposure) was not found. [ABSTRACT FROM AUTHOR]

Abstract: Mustard gas, used in chemical warfare since 1917, is a mutagenic and carcinogenic agent that produces severe dermal lesions for which there are no effective therapeutics; it is currently seen as a potential terrorist threat to civilian populations. Sulforaphane, found in cruciferous vegetables, is known to induce enzymes that detoxify compounds such as the sulfur mustards that react through electrophilic intermediates. Here, we observe that a single topical treatment with sulforaphane induces mouse epidermal levels of the regulatory subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, and also increases epidermal levels of reduced glutathione. Furthermore, a glutathione S-transferase, GSTA4, is also induced in mouse skin by sulforaphane. In an in vivo model in which mice are given a single mutagenic application of the sulfur mustard analog 2-(chloroethyl) ethyl sulfide (CEES), we now show that therapeutic treatment with sulforaphane abolishes the CEES-induced increase in mutation frequency in the skin, measured four days after exposure. Sulforaphane, a natural product currently in clinical trials, shows promise as an effective therapeutic against mustard gas. [Copyright &y& Elsevier]

Abstract: Sulfur mustard [bis(2-chloroethyl)sulfide, SM] is a well-known DNA-damaging agent that has been used in chemical warfare since World War I, and is a weapon that could potentially be used in a terrorist attack on a civilian population. Dermal exposure to high concentrations of SM produces severe, long-lasting burns. Topical exposure to high concentrations of 2-(chloroethyl) ethyl sulfide (CEES), a monofunctional analog of SM, also produces severe skin lesions in mice. Utilizing a genetically engineered mouse strain, Big Blue, that allows measurement of mutation frequencies in mouse tissues, we now show that topical treatment with much lower concentrations of CEES induces significant dose- and time-dependent increases in mutation frequency in mouse skin; the mutagenic exposures produce minimal toxicity as determined by standard histopathology and immunohistochemical analysis for cytokeratin 6 and the DNA-damage induced phosphorylation of histone H2AX (γ-H2AX). We attempted to develop a therapeutic that would inhibit the CEES-induced increase in mutation frequency in the skin. We observe that multi-dose, topical treatment with 2,6-dithiopurine (DTP), a known chemical scavenger of CEES, beginning 1h post-exposure to CEES, completely abolishes the CEES-induced increase in mutation frequency. These findings suggest the possibility that DTP, previously shown to be non-toxic in mice, may be useful as a therapeutic agent in accidental or malicious human exposures to SM. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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

Extensive exposure to chemical weapons such as mustard gas, nerve gas and cyanide causes high mortality, morbidity, injuries, and chronic side effects in vital organs, especially the respiratory tract. Globally, chemical weapons have been documented as having been used since 429 BC, when they were used by the Spartans in the Peloponnesian War. In the First World War (WW1) the use of chemical agents caused an estimated 1,300,000 casualties, including 90,000 deaths. Chemical weapons were heavily used by Iraq against Iranian soldiers between1984-1986, then, against the Iraqi Kurds in Sheikh Wasan and Balisan valley, during April 1987 and in Halabja on 18th March 1988. Reports suggested that as many as 2.9% of the Kurdish population have been exposed to chemical weapons at some level. This case report describes a Kurdish lady who was exposed to mustard gas during a chemical attack in Sheikh Wasan in Iraq. A forty eight years old woman wearing black clothes presented to our center at 1999 complaining from shortness of breath (SOB). Her condition started 12 years ago when the Iraqi Government attacked her village Sheikh Wasan by Chemical weapons which included Mustard gas and nerve gases such as Sarin, Tabun and VX in April 1987. She described how the gas smelled like rotten apples as it spread over the village. During the attack she suffered from sever SOB, cough, skin burn and eye irritation and lacrimation. After several days of being without medical care, she received some medical attention by local medical staff in the area because the Iraqi authorities at that time refused and prohibited them from management at the major hospitals. When she returned to her home she found that several members of her family had died during the exposure to chemical gases. Among the dead people were her parents, two brothers, husband and son, in addition to other second and third degree relatives. Since that time she has suffered from repeated attacks of cough and SOB and wheezing that were increased by exertion and cold exposure. The attacks were more severe with time and the SOB has interfered with her daily activity and eventually she was suffering from SOB at rest and during sleep that made her unable to sleep lying down. Moreover she was suffering from severe depression since that time for which she consulted several doctors but without improvement. In the end of 2001, she suffered from severe cough and Hemoptysis associated with anorexia and loss of weight. She consulted our center for this purpose and we asked for a medical care for her. Available haematological and radiological investigations were done for her showing a preliminary diagnosis of non-small cell lung cancer. She was sent for further investigations and treatment, but since then she has been disappeared and no more information was recorded about her situation. This is one example of many of those who suffered from the effect of chemical weapons in Kurdistan of Iraq. [ABSTRACT FROM AUTHOR]

Objective: Exposure of DNA to sulfur mustard gas may increase the inheritance of asthma in chemical warfare victims' (CWV) offspring. The objective of this study was to determine the prevalence of asthma in children of CWV and compare it to asthmatic children in the general population. Methods: Four hundred and nine children from 130 CWV fathers and 440 children from 145 asthmatic parents from two cities in Iran participated in this study. The prevalence of asthma was determined by standard questionnaire released for epidemiological survey of asthma in children and compared between two groups. Findings: The prevalence of asthma in the CWV group was 15%; this was not significantly different from the control group (12.5%). The children of the CWV group reported a significantly greater incidence of wheezing (1.2±3.1 attacks) per year, but the control group reported more severe attacks leading to speech difficulties (3%) and coughing (7%). Regression analysis showed that with increasing family size in the control group, the number of subjects suffering from asthmatic symptoms decreases significantly (r=0.86, P=0.001). Conclusion: Chemical agents may increase the prevalence of asthma in the offspring of CWV. [ABSTRACT FROM AUTHOR]

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

Objective(s) Considering fair response to inhaled corticosteroids and reports of severe air way hyper responsiveness in chemical warfare victims (CWV), a role for eosinophilic inflammation (i.e. asthma) was postulated. The objective of this study was to determine the presence of eosinophilic inflammation in CWV by evaluation of Sputum cellularity and eosinophil cationic protein (ECP). Materials and Methods Forty CWV and 15 control subjects entered this cross sectional study. Demographic data, dyspnea severity scale, spirometry results and 6 min walk test were determined. Sputum was collected with inducing by nebulizing hypertonic saline and analyzed for total inflammatory cell count, the cellular differential count and ECP level. Control group was normal volunteers with PC20 more than 8 mg/ml. Results Mean±SD of eosinophil percentage (11.7±11.1%) and ECP level in sputum of CWV (46.1±19.5 ng/ml) were significantly more than control group. Regression analysis showed significant correlation between ECP level and percentage of eosinophils in sputum (r= +0.43, P< 0.01). ECP level of CWV subjects with obstructive pattern did not show any significant difference from CWV with normal spirometry. ECP level in CWV subjects who revealed more than 12% improvement in forced expiratory volume in one second (FEV1) was significantly higher than CWV who had improvement less than 12% (P= 0.01). BO and asthma as final clinical diagnosis of CWV did not show any significant difference of sputum ECP. Conclusion Bronchial inflammation in different types of pulmonary complication of CWV is eosinophil dependent. ECP level of sputum in CWV could guide physician to select CWV who would respond to corticosteroids. [ABSTRACT FROM AUTHOR]

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

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

Abstract: The effect of ionic environment on sulphur mustard (bis 2-chloroethyl sulphide; HD) toxicity was examined in CHO-K1 cells. Cultures were treated with HD in different ionic environments at constant osmolar conditions (320mOsM, pH 7.4). The cultures were refed with fresh culture medium 1h after HD exposure, and viability was assessed. Little toxicity was apparent when HD exposures were carried out in ion-free sucrose buffer compared to LC50 values of ~100–150μM when the cultures were treated with HD in culture medium. Addition of NaCl to the buffer increased HD toxicity in a salt concentration-dependent manner to values similar to those obtained in culture medium. HD toxicity was dependent on both cationic and anionic species with anionic environment playing a much larger role in determining toxicity. Substitution of NaI for NaCl in the treatment buffers increased HD toxicity by over 1000%. The activity of the sodium hydrogen exchanger (NHE) in recovering from cytosolic acidification in salt-free and in different chloride salts did not correlate with the HD-induced toxicity in these buffers. However, the inhibition by HD of intracellular pH regulation correlated with its toxicity in NaCl, NaI and sucrose buffers. Analytical chemical studies and the toxicity of the iodine mustard derivative ruled out the role of chemical reactions yielding differentially toxic species as being responsible for the differences in HD toxicity observed. This work demonstrates that the early events that HD sets into motion to cause toxicity are dependent on ionic environment, possibly due to intracellular pH deregulation. [Copyright &y& Elsevier]

There is a substantial number of Iranian war veterans, exposed to sulfur mustard, who suffer from serious long term progressive health problems involving their respiratory organs, eyes, and skin. Little is known, however, about these casualties’ experiences of living with the consequences of sulfur mustard poisoning. This qualitative study aims to provide greater insight into how war veterans live with the consequences of the poisoning and involved 17 Iranian war veterans who had been poisoned by sulfur mustard during the Iran–Iraq conflict. Each participant was interviewed using a semi-structured interview schedule and the data generated through this process was analyzed using constant comparative data analysis technique. Data analysis resulted in “religious beliefs and practices” as a main category, which included two sub-categories: religious value centered life and religious support. Findings suggest that religious belief assists veterans to accept the impact of poisoning on their lives and adapt their lifestyles accordingly, to participate in religious social activities and feel socially supported, and to be hopeful about the future and live their lives as fully as possible. [ABSTRACT FROM AUTHOR]

Background: Sulfur mustard (SM) is an alkylating chemical warfare agent that was widely used during Iran-Iraq war between 1983 and 1988. SM exposure leads to various late complications. The aim of this study was to determine the late cardiovascular effects of SM in war-disabled Iranian victims. Materials and Methods: This was a retrospective cohort case control study on 50 patients with symptoms of SM exposure and 50 cases who had been in Iran-Iraq war, without chemical injury. We performed exercise stress test and echocardiography for all of patients. Results: The study group comprised 100 males of mean age 45.6 ± 6.2 years. In chemical war injury group, two patients (4%) had positive exercise stress test. On coronary angiography, they were found to have coronary artery disease. One patient had severe mitral regurgitation and normal coronary angiography; he was referred for mitral valve replacement. Left ventricular (LV) diastolic abnormality was detected in 23% of these subjects. In another group, 5% had LV diastolic abnormality (P = 0.02) and all of them had normal stress test. Conclusions: Cardiovascular abnormalities are another late complication in chemical war disabled Iranian victims. Diastolic dysfunction was the most common abnormality in both groups of patients. [ABSTRACT FROM AUTHOR]

The challenges experienced by Iranian war veterans living with chemical warfare poisoning: a descriptive, exploratory study This exploratory, descriptive study investigates the experiences of Iranian war veterans living with chronic disease acquired as a result of chemical warfare. Sulphur mustard (SM) is considered one of the most important agents of chemical warfare and was widely used during the Iran–Iraq conflict in 1980–1988. There are approximately 100 000 Iranian SM casualties who suffer from serious long-term progressive health problems involving their respiratory organs, eyes and skin. Seventeen male Iranian war veterans aged between 30 and 59 years and four victims’ family members participated in the study. Data was generated during individual in-depth interviews that used open-ended questions. Grounded theory techniques, including the constant comparative method of concurrent data generation and analysis, were employed in the analysis of data. Preliminary results indicate two main thematic categories: social isolation and physical disability. It is argued that a lack of knowledge about the outcomes of SM poisoning, physical restrictions and difficulty in adjusting socially decreases war veterans’ functional capacity and levels of independence. [ABSTRACT FROM AUTHOR]