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

• 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

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

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

Changes of QT Dispersion in Patients Suffering from Aluminium Phosphide Poisoning (Rice Pill)

BACKGROUND: Aluminium phosphide (ALP) or rice pill is a substance used in developing countries due to its low cost as pesticides. The availability of this substance has been lead to an increased rate of the use of this toxic inorganic compound for suicide. Complications are considered to be dose-related toxicity and hospitalisation time, varying from hemodynamic disorder, hypoglycemia, hyperglycemia, shock, cardiotoxicity, pulmonary and renal failures. The consumption of this substance is one of the major causes of mortality due to heart arrhythmia. QT dispersion represents a regional difference in ventricular repolarisation and electrical instability of the heart. AIM: The purpose of this study was to investigate the effect of ALP poisoning on QT dispersion. METHODS: In this study, 70 patients with ALP poisoning were enrolled, and 10 patients were excluded due to the exclusion criteria. QT dispersion rate was calculated in 60 patients using the standard electrocardiography at the time of referral. The above data were compared with the control group, which included 40 subjects with normal coronary angiography, and without cardiovascular risk factors. RESULTS: The findings presented herein indicated a significant correlation between QT dispersion and control group (P &lt; 0.0.5). There was a significant relationship between the severity of acidosis and the patient's tablets –taking a number (P &lt; 0.05). However, there was no relationship between QT dispersion with the severity of acidosis and mortality in patients. CONCLUSION: Because there is no CAD risk factor in the population, it can be concluded that increase in QT dispersion in these individuals can be due to ALP poisoning; nevertheless, this is not considered to be a factor in increasing the morbidity of these patients

Highly sensitive C-reactive protein levels in Iranian patients with pulmonary complication of sulfur mustard poisoning and its correlation with severity of airway diseases

Background: Sulfur mustard (SM) is a chemical warfare agent that can cause serious pulmonary complications. This study was designed to determine serum highly sensitive C-reactive protein (hs-CRP) and evaluate its correlation with lung function parameters in patients with chronic obstructive pulmonary disease (COPD) due to SM poisoning. Methods: Fifty consecutive SM patients with stable COPD and a mean age 46.3 + 9.18 years were enrolled in this cross sectional study. Thirty healthymen were selected as controls. Lung function parameters were evaluated. Serum hs-CRP by immunoturbidometry assay was measured in both the patients and controls. Results: In the case group, the mean forced expiratory volume in one second (FEV1) was 2.14 + 0.76 L (58.98%+17.51% predicted). The mean serum hs-CRP was 9.4+6.78 SD and 3.9+1.92 SDmg/L in the cases and controls, respectively, with significant statistical differences (p < .001). There was negative correlation between the serum hs-CRP and FEV1 levels (p ¼ .01). The serum hs-CRP levels were also correlated with Global Initiative for ChronicObstructive Lung disease (GOLD) stages (r ¼ .45, p < .001). Conclusions:Our findings suggest that the serum hs-CRP level is increased in SM patients with COPD and may have a direct correlation with disease severity. It may then be used as a marker for the severity of COPD in patients with SM poisoning

Effect of Sulfur Mustard Toxicity on FLT3-ITD Gene Mutation in Sulfur Mustard Veterans

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

Sulphur Mustard Poisoning and Its Complications in Iranian Veterans

Sulphur mustard is a chemical warfare agent, which was largelyused during the World War One and in Iraq-Iran conflict. It mayalso be used as a chemical terrorism agent. Therefore, medicalprofessions should have sufficient knowledge and be preparedfor medical intervention of any such chemical attack.Sulphur mustard exerts direct toxic effects on the eyes, skin,and respiratory tract, with subsequent systemic actions on thenervous, immunologic, hematologic, digestive, and reproductivesystems. It is an alkylating agent that affects DNA synthesis andthus, delayed complications have been considered since theWorld War One. Cases of malignancies in the target organs particularlyin hematopoietic, respiratory, and digestive systemswere reported. Common delayed respiratory complications includechronic bronchitis, bronchiectasis, frequent bronchopneumonia,and pulmonary fibrosis, all of which tend to deterioratewith time. Severe dry skin, delayed keratitis, and reduction ofnatural killer cells with subsequent increased risk of infectionsand malignancies are also among the most distressing long-termconsequences of sulphur mustard intoxication. However, despiteextensive research that has been conducted on Iranian veteransduring the past decades, major gaps continue to remain in thesulphur mustard literature. Immunological and neurological dysfunctionsand the relationship between exposure to sulphur mustardand mutagenicity, carcinogenicity, and teratogenicity areimportant fields that require further studies, particularly on Iranianveterans with chronic health problems caused by sulphurmustard poisoning. There is also a paucity of information on themedical management of acute and delayed toxic effects of sulphurmustard poisoning, a subject that greatly challenges themedical professions

Balali-Mood K: Neurotoxic disorders of organophosphorus compounds and their managements

Organophosphorus compounds have been used as pesticides and as chemical warfare nerve agents. The mechanism of toxicity of organophosphorus compounds is the inhibition of acetylcholinesterase, which results in accumulation of acetylcholine and the continued stimulation of acetylcholine receptors. Therefore, they are also called anticholinesterase agents. Organophosphrus pesticides have largely been used worldwide, and poisoning by these agents, particularly in developing countries, is a serious health problem. Organophosphorus nerve agents were used by Iraqi army against Iranian combatants and even civilian population in 1983 -1988. They were also used for chemical terrorism in Japan in 1994 -1995. Their use is still a constant threat to the population. Therefore, medical and health professionals should be aware and learn more about the toxicology and proper management of organophosphorus poisoning. Determination of acetylcholinesterase and butyrylcholinesterase activity in blood remains a mainstay for the fast initial screening of organophosphorus compounds but lacks sensitivity and specificity. Quantitative analysis of organophosphorus compounds and their degradation products in plasma and urine by mass spectrometric methods may prove exposure but is expensive and is limited to specialized laboratories. However, history of exposure to organophosphorous compounds and clinical manifestations of a cholinergic syndrome are sufficient for management of the affected patients. The standard management of poisoning with organophosphorous compounds consists of decontamination, and injection of atropine sulfate with an oxime. Recent advances on treatment of organophosphorus pesticides poisoning revealed that blood alkalinization with sodium bicarbonate and also magnesium sulfate as adjunctive therapies are promising. Patients who receive prompt proper treatment usually recover from acute toxicity but may suffer from neurologic complications

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

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

Sulfur Mustard Exposure and Non-Ischemic Central Retinal Vein Occlusion

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