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BMC Health Services Research Dec 2023Sulfur Mustard (SM) is a chemical warfare agent that has serious short-term and long-term effects on health. Thousands of Iranians were exposed to SM during the...
BACKGROUND
Sulfur Mustard (SM) is a chemical warfare agent that has serious short-term and long-term effects on health. Thousands of Iranians were exposed to SM during the eight-year Iran-Iraq conflict and permanently injured while the socioeconomic imbalance in their healthcare utilization (HCU) and health expenditures remains. This study aims to describe the HCU of SM-exposed survivors in Iran from 2018 to 2021; identify high-risk areas; and apply an inequality analysis of utilization regarding the socioeconomic groups to reduce the gap by controlling crucial determinants.
METHODS
From Oct 2018 to June 2021, the Veterans and Martyrs Affairs Foundation (VMAF) recorded 58,888 living war survivors with eye, lung, and skin ailments. After cleaning the dataset and removing junk codes, we defined 11 HCU-related variables and predicted the HCU for the upcoming years using Bayesian spatio-temporal models. We explored the association of individual-level HCU and determinants using a Zero-inflated Poisson (ZIP) model and also investigated the provincial hotspots using Local Moran's I.
RESULTS
With ≥ 90% confidence, we discovered eleven HCU clusters in Iran. We discovered that the expected number of HCU 1) rises with increasing age, severity of complications in survivors' eyes and lungs, wealth index (WI), life expectancy (LE), and hospital beds ratio; and 2) decreases with growing skin complications, years of schooling (YOS), urbanization, number of hospital beds, length of stay (LOS) in bed, and bed occupancy rate (BOR). The concentration index (CInd) of HCU and associated costs in age and wealth groups were all positive, however, the signs of CInd values for HCU and total cost in YOS, urbanization, LOS, and Hospital beds ratio groups were not identical.
CONCLUSIONS
We observed a tendency of pro-rich inequity and also higher HCU and expenditures for the elderly population. Finally, health policies should tackle potential socioeconomic inequities to reduce HCU gaps in the SM-exposed population. Also, policymakers should allocate the resources according to the hotspots of HCU.
Topics: Humans; Bayes Theorem; Health Expenditures; Health Services Accessibility; Iran; Mustard Gas; Spatio-Temporal Analysis; Healthcare Disparities; Socioeconomic Factors
PubMed: 38093322
DOI: 10.1186/s12913-023-10352-7 -
Interdisciplinary Toxicology Jun 2008Sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. The toxicity of SM as an incapacitating agent is of much greater...
Sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. The toxicity of SM as an incapacitating agent is of much greater importance than its ability to cause lethality. Acute toxicity of SM is related to reactive oxygen and nitrogen species, DNA damage, poly(ADP-ribose) polymerase activation and energy depletion within the affected cell. Therefore melatonin shows beneficial effects against acute SM toxicity in a variety of manner. It scavenges most of the oxygen- and nitrogen-based reactants, inhibits inducible nitric oxide synthase, repairs DNA damage and restores cellular energy depletion. The delayed toxicity of SM however, currently has no mechanistic explanation. We propose that epigenetic aberrations may be responsible for delayed detrimental effects of mustard poisoning. 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 genetic mutations, epimutations can also involve in the pathogenesis of a variety of human diseases. Several actions of melatonin are now delineated by epigenetic actions including modulation of histone acetylation and DNA methylation. Future studies are warranted to clarify whether epigenetic mechanisms are involved in pathogenesis of delayed sulfur mustard toxicity and melatonin alleviates delayed toxicity of this warfare agent.
PubMed: 21218101
DOI: 10.2478/v10102-010-0027-x -
Basic & Clinical Pharmacology &... Oct 2006Sulfur mustard is an alkylating agent that reacts with ocular, respiratory, cutaneous, and bone marrow tissues, resulting in early and late toxic effects. We compare... (Review)
Review
Sulfur mustard is an alkylating agent that reacts with ocular, respiratory, cutaneous, and bone marrow tissues, resulting in early and late toxic effects. We compare these effects based on the experience in Iranian veterans exposed to the agent during the Iran-Iraq conflict (1983-88). The first clinical manifestations of sulfur mustard poisoning occurred in the eyes with a sensation of grittiness, lacrimation, photophobia, blepharospasm, and corneal ulceration. Respiratory effects appeared as rhinorhea, laryngitis, tracheobronchitis, and dyspnoea. Skin lesions varied from erythema to bullous necrotization. Initial leukocytosis and lymphopenia returned to normal within four weeks in recovered patients, but marked cytopenia with bone marrow failure occurred in fatal cases. Late toxic effects of sulfur mustard were most commonly found in lungs, skin and eyes. Main respiratory complications were chronic obstructive pulmonary disease, bronchiectasis, asthma, large airway narrowing, and pulmonary fibrosis. Late skin lesions were hyperpigmentation, dry skin, atrophy, and hypopigmentation. Fifteen of the severely intoxicated patients were diagnosed with delayed keratitis, having corneal vascularization, thinning, and epithelial defect. Respiratory complications exacerbated over time, while cutaneous and ocular lesions decreased or remained constant. Both the severity and frequency of bronchiectatic lesions increased during long-term follow-up. The only deteriorating cutaneous complication was dry skin. The maximum incidence of delayed kaeratitis was observed 15 to 20 years after initial exposure. Being suggested as the main cause ofassociated with malignancies and recurrent infections, natural killer cells were significantly lower 16 to 20 years after intoxication.
Topics: Chemical Warfare Agents; Humans; Inhalation Exposure; Iran; Mustard Gas; Respiratory Tract Diseases; Skin Diseases; Veterans
PubMed: 17040211
DOI: 10.1111/j.1742-7843.2006.pto_429.x -
Clinical Toxicology (Philadelphia, Pa.) 2007To evaluate bronchial challenges using three different stimuli as screening tools for bronchial hyper-responsiveness in sulfur mustard gas-induced asthma. (Comparative Study)
Comparative Study Randomized Controlled Trial
Comparison of bronchial responsiveness to ultrasonically nebulized distilled water (UNDW), methacholine, and ultrasonically nebulized distilled cold water (UDCW) in patients with sulfur mustard gas-induced asthma.
OBJECTIVE
To evaluate bronchial challenges using three different stimuli as screening tools for bronchial hyper-responsiveness in sulfur mustard gas-induced asthma.
DESIGN
Randomized, cross-over clinical study.
SETTING
University hospital.
PATIENTS
Eighteen veterans with mustard gas-induced asthma and 18 normal veterans as the control group.
INTERVENTION
Pulmonary function tests and inhalation challenges with ultrasonically nebulized distilled water (UNDW), methacholine, and ultrasonically nebulized cold water (UNDCW) were performed on all patients and subjects.
RESULTS
Six mustard gas-induced asthmatic veterans did not respond to a 20% in FEV(1) after distilled water (13.3%), and two of them (11.11%) did not respond with distilled cold water; all responded with methacholine. Only one healthy subject developed a PC20 FEV(1) after methacholine but did not with both distilled water and distilled cold water challenges. The asthmatic patients were sensitive to distilled water with a median PD20 of 7.24 +/- 3.83 ml (range 2.54 ml to 15.83 ml), and sensitive to cold water with a median PD20 of 6.42 +/- 6.24 ml (range 1.92 ml to 25.15 ml). The median PC20 methacholine was 1.90 +/- 1.88 mg/ml (range 0.14 mg/ml to 6.20 mg/ml). In patients with a positive response to the distilled water challenge test, no significant correlation was found between PC20 of methacholine and PD20 of distilled water (Rho = -0.34, p = 0.25), whereas in patients whose responses to distilled cold water (DCW) were positive, PD20 of distilled cold water (DCW) correlated well with PC20 of methacholine (Rho = -0.69, p = 0.006).
CONCLUSION
Overall, the methacholine challenge test is the best method to distinguish these asthmatic patients from normal subjects in this study. When compared to the methacholine challenge, although the airway response to ultrasonically nebulized distilled cold water test was somewhat less sensitive, it may be used as a simple, fast, inexpensive, and relatively reliable method to predict the absence of asthma in sulfur mustard gas-induced asthma.
Topics: Adult; Aerosols; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Cold Temperature; Cross-Over Studies; Humans; Male; Methacholine Chloride; Mustard Gas; Nebulizers and Vaporizers; Ultrasonics; Veterans; Water
PubMed: 17558630
DOI: 10.1080/15563650701382730 -
Frontiers in Plant Science 2021Melatonin has been recently known to stimulate plant growth and induce protective responses against different abiotic stresses. However, the mechanisms behind exogenous...
Melatonin has been recently known to stimulate plant growth and induce protective responses against different abiotic stresses. However, the mechanisms behind exogenous melatonin pretreatment and restoration of plant vigor from salinity stress remain poorly understood. The present study aimed to understand the effects of exogenous melatonin pretreatment on salinity-damaged green mustard ( L. Czern.) seedlings in terms of oxidative stress regulation and endogenous phytohormone production. Screening of several melatonin concentrations (0, 0.1, 1, 5, and 10 μM) on mustard growth showed that the 1 μM concentration revealed an ameliorative increase of plant height, leaf length, and leaf width. The second study aimed at determining how melatonin application can recover salinity-damaged plants and studying its effects on physiological and biochemical parameters. Under controlled environmental conditions, mustard seedlings were irrigated with distilled water or 150 mM of NaCl for 7 days. This was followed by 1 μM of melatonin application to determine its recovery impact on the damaged plants. Furthermore, several physiological and biochemical parameters were examined in stressed and unstressed seedlings with or without melatonin application. Our results showed that plant height, leaf length/width, and stem diameter were enhanced in 38-day-old salinity-stressed plants under melatonin treatment. Melatonin application obviously attenuated salinity-induced reduction in gas exchange parameters, relative water content, and amino acid and protein levels, as well as antioxidant enzymes, such as superoxide dismutase and catalase. HO accumulation in salinity-damaged plants was reduced by melatonin treatment. A decline in abscisic acid content and an increase in salicylic acid content were observed in salinity-damaged seedlings supplemented with melatonin. Additionally, chlorophyll content decreased during the recovery period in salinity-damaged plants by melatonin treatment. This study highlighted, for the first time, the recovery impact of melatonin on salinity-damaged green mustard seedlings. It demonstrated that exogenous melatonin supplementation significantly improved the physiologic and biochemical parameters in salinity-damaged green mustard seedlings.
PubMed: 33868325
DOI: 10.3389/fpls.2021.593717 -
Environmental Health Perspectives May 1996Mustard gas is known to have mutagenic and carcinogenic effects on animal and human cells. In this report, 1,632 male Japanese who worked in poison gas factories at some...
Mustard gas is known to have mutagenic and carcinogenic effects on animal and human cells. In this report, 1,632 male Japanese who worked in poison gas factories at some time between the years 1927 and 1945 were studied to determine comparative risk for development of cancer, the reference population being data on Japanese males overall. The standardized mortality ratio (SMR) for lung cancer in workers directly and indirectly involved in the production of mustard gas was significantly elevated. In addition, SMR for lung cancer in worker who had worked for more than 5 years was also significantly elevated. Thus, poison gas workers who had engaged in the production of mustard gas or related work for more than 5 years are a high-risk group for lung cancer. Under the cancer preventive program, Nocardia rubra cell-wall skeleton (N-CWS) was administered to 146 former poison gas workers. During a 4.5 year observation period, development of cancers was found in 7 treated workers and 17 untreated controls. After elimination of the influence of smoking level, a significant suppression of development of cancers was noted in the N-CWS-treated workers as compared to the untreated controls. Although the molecular mechanisms of carcinogenesis in former poison gas workers remains unclear, our study proposes the possible effect of biological response modifiers in the prevention of cancer development in high-risk human subjects.
Topics: Arsenicals; Cell Wall Skeleton; Chemical Warfare Agents; Humans; Hydrogen Cyanide; Immunologic Factors; Japan; Male; Mustard Gas; Neoplasms; Nocardia; Occupational Diseases; Phosgene; omega-Chloroacetophenone
PubMed: 8781369
DOI: 10.1289/ehp.96104s3485 -
Analytical Chemistry Mar 2021Route determination of sulfur mustard was accomplished through comprehensive nontargeted screening of chemical attribution signatures. Sulfur mustard samples prepared...
Route determination of sulfur mustard was accomplished through comprehensive nontargeted screening of chemical attribution signatures. Sulfur mustard samples prepared via 11 different synthetic routes were analyzed using gas chromatography/high-resolution mass spectrometry. A large number of compounds were detected, and multivariate data analysis of the mass spectrometric results enabled the discovery of route-specific signature profiles. The performance of two supervised machine learning algorithms for retrospective synthetic route attribution, orthogonal partial least squares discriminant analysis (OPLS-DA) and random forest (RF), were compared using external test sets. Complete classification accuracy was achieved for test set samples (2/2 and 9/9) by using classification models to resolve the one-step routes starting from ethylene and the thiodiglycol chlorination methods used in the two-step routes. Retrospective determination of initial thiodiglycol synthesis methods in sulfur mustard samples, following chlorination, was more difficult. Nevertheless, the large number of markers detected using the nontargeted methodology enabled correct assignment of 5/9 test set samples using OPLS-DA and 8/9 using RF. RF was also used to construct an 11-class model with a total classification accuracy of 10/11. The developed methods were further evaluated by classifying sulfur mustard spiked into soil and textile matrix samples. Due to matrix effects and the low spiking level (0.05% w/w), route determination was more challenging in these cases. Nevertheless, acceptable classification performance was achieved during external test set validation: chlorination methods were correctly classified for 12/18 and 11/15 in spiked soil and textile samples, respectively.
Topics: Gas Chromatography-Mass Spectrometry; Mass Spectrometry; Mustard Gas; Retrospective Studies; Soil
PubMed: 33709707
DOI: 10.1021/acs.analchem.0c04555 -
3 Biotech Sep 2018Here, accumulation of glucosinolates and expression of glucosinolates biosynthesis genes in green and red mustard hairy roots were identified and quantified by HPLC and...
Here, accumulation of glucosinolates and expression of glucosinolates biosynthesis genes in green and red mustard hairy roots were identified and quantified by HPLC and RT-PCR analyses. The total glucosinolates content of green mustard hairy root (10.09 µg/g dry weight) was 3.88 times higher than that of red mustard hairy root. Indolic glucosinolates (glucobrassicin, 4-methoxyglucobrassicin, and neoglucobrassicin) in green mustard were found at 30.92, 6.95, and 5.29 times higher than in red mustard hairy root, respectively. Conversely, levels of glucotropaeolin (aromatic glucosinolate) was significantly higher in red mustard than in green mustard. Accumulation of glucoraphasatin, an aliphatic glucosinolate, was only observed only in red mustard hairy roots. Quantitative real-time PCR analysis showed that the expression level of genes related to aliphatic and aromatic glucosinolate biosynthesis were higher in red mustard, exception . The expression of , which encodes a key enzyme involved in the indolic glucosinolate biosynthetic pathway, was higher in green mustard than in red mustard. Additionally, to further distinguish between green mustard and red mustard hairy roots, hydrophilic and lipophilic compounds were identified by gas chromatography-mass spectrometry and subjected to principal component analysis. The results indicated that core primary metabolites and glucosinolate levels were higher in the hairy roots of green mustard than in those of red mustard.
PubMed: 30148032
DOI: 10.1007/s13205-018-1393-x -
Experimental Eye Research Mar 2023Sulfur mustard (SM) remains a highly dangerous chemical weapon capable of producing mass casualties through liquid or vapor exposure. The cornea is highly sensitive to...
Sulfur mustard (SM) remains a highly dangerous chemical weapon capable of producing mass casualties through liquid or vapor exposure. The cornea is highly sensitive to SM toxicity and exposure to low vapor doses can cause incapacitating acute injuries. At higher doses, corneas fail to fully heal and subsequently develop a constellation of symptoms known as mustard gas keratopathy (MGK) that causes reduced quality of life and impaired or lost vision. Despite a century of research, there are no specific treatments for acute or persistent ocular SM injuries. Here I summarize toxicological, clinical and pathophysiological mechanisms of SM vapor injury in the cornea, describe a preclinical model of ocular SM vapor exposure for reproducible therapeutic studies, and propose new approaches to improve evaluation of therapeutic effects. I also describe recent findings illustrating the delayed development of a transient but severe recurrent corneal lesion that, in turn, triggers the emergence of secondary keratopathies characteristic of the chronic form of MGK. Development of this recurrent lesion is SM dose-dependent, although the severity of the recurrent lesion appears SM dose-independent. Similar recurrent lesions have been reported in multiple species, including humans. Given the mechanistic relationship between the recurrent lesion and chronic, secondary keratopathies, I hypothesize that preventing the development of the recurrent lesion represents a novel and potentially valuable therapeutic approach for treatment of severe corneal SM injuries. Although ocular exposure to SM vapor continues to be a challenging therapeutic target, establishing consistent and reproducible models of corneal injury that enhance mechanistic and pathophysiological understanding will help satisfy regulatory requirements and accelerate the development of effective therapies.
Topics: Humans; Mustard Gas; Chemical Warfare Agents; Quality of Life; Corneal Diseases; Corneal Injuries
PubMed: 36731603
DOI: 10.1016/j.exer.2023.109395 -
Basic & Clinical Pharmacology &... Nov 2005Chronic bronchitis is the most frequent late respiratory disease among Iranians exposed to mustard gas during the Iraq-Iran war. The aim of this study was to investigate... (Randomized Controlled Trial)
Randomized Controlled Trial
Chronic bronchitis is the most frequent late respiratory disease among Iranians exposed to mustard gas during the Iraq-Iran war. The aim of this study was to investigate efficacy of oral and intravenous corticosteroid therapy in improving lung function in mustard gas induced chronic bronchitis patients. 65 mustard gas-exposed chronic bronchitis patients, who were not responsive to standard treatments in exacerbation occasions, were randomly divided into two groups: an intravenous group (39 patients) receiving 500 mg intravenous methylprednisolone daily, and an oral group (26 patients) receiving 1 mg/kg oral prednisolone daily. Corticosteroid was tapered over the study period in both groups. Spirometery was performed on admission and on day 8 of therapy for assessment of effectiveness of therapy. There was significant improvement in spirometery indexes of both groups in approximately half of the patients over the study period. Furthermore, there was no difference between the pulse corticosteroid versus oral corticosteroid therapy in these patients. Since short-term corticosteroid therapy has a significant effect on lung function of almost fifty percent of patients with mustard gas-induced chronic bronchitis in exacerbation occasions, we suggest a short-term bolus steroid treatment to triage the patients into responders and non-responders for subsequent treatment.
Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Bronchitis, Chronic; Chemical Warfare Agents; Female; Forced Expiratory Flow Rates; Humans; Injections, Intravenous; Male; Methylprednisolone; Mustard Gas; Spirometry; Vital Capacity
PubMed: 16236142
DOI: 10.1111/j.1742-7843.2005.pto_187.x