A Randomized Clinical Trial on Therapeutic Effects of Myrtus communis L. Cream on Chronic Skin Lesions and Quality of Life of Sulfur Mustard-exposed Veterans

Abstract: Sulfur mustard is one of the chemical warfare agent. It rapidly reacts with the cutaneous tissues and other tissues, leading to various devastating long-term effects on human health. Mustard-exposed veterans suffer from its chronic skin problems, including itching, burning sensation, and eczema. We aimed to evaluate the protective effects of Myrtus communis L. (myrtle) on chronic skin lesions and quality of life of sulfur mustard-exposed veterans. In this randomized, double-blind clinical trial, 60 sulfur mustard-exposed patients were evaluated. Thirty patients received myrtle essence 5% cream (case group) and 30 patients received Eucerin cream (placebo group) twice in a day for one month. Then, We assessed the chronic skin problems and itching-related parameters (such as the itching time, severity, distribution, frequency, and calculated itching score), duration of sleep, number of waking up at night, and quality of life in the both groups. Our analysis of data revealed that application of myrtle cream effectively decreased skin problems including; itching and burning sensation. Additionally, myrtle markedly decreased skin lesion symptoms such as excoriation in the case group as compared with before treatment. Noticeably, myrtle cream significantly improved quality of life of the patients in the case group. The present study provides more in-depth information regarding the protective role of myrtle on the sulfur mustard-induces skin complication. Also, myrtle effectively improved quality of life of the sulfur mustard-exposed veterans.

Paraclinical findings in Iranian veterans exposed to sulfur mustard gas: A literature review / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>Sulfur mustard (SM) causes various systemic disturbances in human beings. This study aimed to assess paraclinical changes caused by exposure to SM gas in Iranian veterans during the war between Iraq and Iran.</p><p><b>METHODS</b>A literature review was carried out in international and national medical databases including ISI, Medline, Scopus, Iranmedex and Irandoc. Both Farsi and English literature were searched.</p><p><b>RESULTS</b>Search of the literature yielded 422 medical articles related to SM poisoning. Among them, 30 relevant articles were thoroughly reviewed. The most important reported complications were leukopenia, neutropenia, lymphopenia, eosinophilia, thrombocytopenia, increased bleeding time, positive C-reactive protein (CRP), rheumatoid factor (RF), antinuclear antibody (ANA), decreased T helper cells, natural killer cells, IL6, and IL8 levels, elevation of serum immunoglobulins, decreased levels of T3, T4 and cortisol, increased level of adrenocorticotropic hormone (ACTH), proteinuria, hematuria, and elevated liver enzymes. Also, there were some changes in chest assessments.</p><p><b>CONCLUSIONS</b>SM causes profound systemic complications in victims, even years after exposure. The paraclinical changes can be observed in hematology, immune system, biochemistry, hormonal profile and some imaging studies.</p>

Adipose-derived mesenchymal stem cells for treatment of airway injuries in a patient after long-term exposure to sulfur mustard

Objective: Sulfur mustard [SM] is a potent mutagenic agent that targets several organs, particularly lung tissue. Changes in morphological structure of the airway system are associated with chronic obstructive pulmonary deficiency following exposure to SM. Although numerous studies have demonstrated pathological effects of SM on respiratory organs, unfortunately there is no effective treatment to inhibit further respiratory injuries or induce repair in these patients. Due to the extensive progress and achievements in stem cell therapy, we have aimed to evaluate safety and potential efficacy of systemic mesenchymal stem cell [MSC] administration on a SM-exposed patient with chronic lung injuries

Materials and Methods: In this clinical trial study, our patient received 100x106 cells every 20 days for 4 injections over a 2-month period. After each injection we evaluated the safety, pulmonary function tests [PFT], chronic obstructive pulmonary disease [COPD] Assessment Test [CAT], St. George's Respiratory Questionnaire [SGRQ], Borg Scale Dyspnea Assessment [BSDA], and 6 Minute Walk Test [6MWT]. One-way ANOVA test was used in this study which was not significant [P>0.05]

Results: There were no infusion toxicities or serious adverse events caused by MSC administration. Although there was no significant difference in PFTs, we found a significant improvement for 6MWT, as well as BSDA, SGRQ, and CAT scores after each injection

Conclusion: Systemic MSC administration appears to be safe in SM-exposed patients with moderate to severe injuries and provides a basis for subsequent cell therapy investigations in other patients with this disorder

Morphological assessment of sulfur mustard-induced acute lung injury in rats through different routes / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To establish an animal model of sulfur mustard (SM)-induced acute lung injury in rats through different routes and compare the morphological changes in lung tissue and cells.</p><p><b>METHODS</b>One hundred and thirty-six male rats were selected and randomly divided into 5 groups, namely peritoneal cavity SM group (n=32), trachea SM group (n=32), peritoneal cavity propylene glycol group (n=32), trachea propylene glycol group (n=32), and normal control group (n=8). The rats in peritoneal cavity SM group were injected intraperitoneally with diluted SM (0.1 ml, 8 mg/kg), and the rats in trachea SM group were injected intratracheally with diluted SM (0.1 ml, 2 mg/kg). Once the rats were sacrificed at 6, 24, 48, and 72 h after SM treatment, morphological changes in lung tissue and cells were observed by light and electron microscopy.</p><p><b>RESULTS</b>In the peritoneal cavity SM group, the epithelial cells of bronchioles maintained intact with increased exudate and bleeding in alveolar cavity and large areas of pulmonary consolidation under the light microscope. In the tracheal SM group, focal ulcer formed in the epithelial cells of bronchioles with increased exudate and bleeding in alveolar cavity, partial pulmonary consolidation, and compensatory emphysema in peripheral alveolar space under the light microscope. The alveolar interval areas were widened obviously in both groups in a time-dependent manner. Under the electron microscope, we observed local loss of cellular membrane in type I alveolar epithelium, broken or lost microvilli in cells of typeⅡalveolar epithelium and fuzzy mitochondrial crista as well as the appearance of ribosome detached from rough endoplasmic reticulum in both two groups. Compared with those in the trachea SM group and the control group, the ratio of the alveolar septum average area to the visual field area in the peritoneal cavity SM group at 6, 24, 48, and 72 h was significantly higher (P<0.05).</p><p><b>CONCLUSION</b>The lung tissue injury through the intraperitoneal route is more severe than that through the tracheal route, while focal ulceration of bronchioles epithelial cells appears in the case of tracheal route. The degree of injury increases over time in both groups, and the cellular damage is approximately the same in both groups.</p>

Mechanism and treatment of sulfur mustard-induced cutaneous injury / 中华创伤杂志(英文版)

Skin is the first organ exposed to sulfur mustard (SM). The mechanism of SM-induced cutaneous injury has not been fully clarified so far, which is a major obstacle to the development of effective treatments for SM-induced injury. So far, there is no satisfactory therapy for acute symptoms and long-term complications. This review summarized recent researches on the mechanisms of SM-induced cutaneous injuries and the therapies for acute symptoms and long-term complications.

Coronary angiography findings in lung injured patients with sulfur mustard compared to a control group.

Aims and Objectives: We evaluated the incidence of coronary artery disease (CAD) in Sulfur mustard (SM) exposed veterans. We also evaluated the relationship between exposure to SM and angiography findings and compared angiography findings of SM exposed individuals with unexposed ones after two decades from the time of exposure to SM. Materials and Methods: A case-control study was conducted on 200 consecutive patients (100 SM exposed vs. 100 unexposed) undergoing angiographic assessments due to CAD. Results: The coronary angiography findings between two groups were significantly different ( P < 0.001). Ninety two (92%) patients in SM exposed group and 82 (82%) in unexposed group had abnormal findings in their coronary arteries ( P = 0.031). Conclusions: The incidence of CAD and angiographic changes were significantly increased with exposure to SM. Further studies on cardiovascular effects of SM are needed.

Long-term effects of mustard gas on respiratory system of Iranian veterans after Iraq-Iran war: a review / 中华创伤杂志(英文版)

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

Computed tomography imaging findings in chemical warfare victims with pulmonary complications

Data on imaging findings in pulmonary complications of chemical agents is scarce. The current study aimed to evaluate radiological findings of late onset pulmonary complications in chemical warfare victims [CWV] and to guide pulmonologists in diagnosis of these subjects. Ninety- three male CWV were enrolled in this prospective study, 20-25 years [mean=23] after exposure. Demographic and clinical data were recorded. High resolution computed Tomography [HRCT] of the lung was performed during inspiration and expiration and was double reported blindly by two radiologists. Final diagnosis was made according to HRCT findings. The HRCT findings, final diagnosis, and distribution of the abnormalities were compared between subjects whom had been exposed to more complex chemical agents used during the second half of the war and simpler agents during the first half. The most frequent HRCT findings were air trapping [56.7%] and mosaic attenuation [35.1%]. The distribution of abnormalities was mostly local [79.4%] and bilateral [73%] especially in lower regions [61.3%]. The diagnosed respiratory diseases included bronchiolitis obliterans [43%], chronic obstructive pulmonary disease [COPD] [27.9%], asthma [23.6%], bronchiectasis [13.9%] and interstitial lung disease [ILD] [9.6%]. Frequency of subjects involved in the second half of the period of war was more than the first period [P-value < 0.05] but the HRCT findings were similar. Bronchiolitis obliterans with picture of focal bilateral air trapping was the most common finding in CWV but asthma appeared to have become a new problem in these subjects

Effect of mindfulness based stress reduction on quality of life [SF-36] and spirometry parameters, in chemically pulmonary injured veterans

Studies have shown that Mindfulness Based Stress Reuction [MBSR] has positive effect on physical and psychological dimensions of chronic illnesses. In this study for the first time we examine the effect of this new technique on quality of life and pulmonary function in chemically pulmonary injured veterans who have chronic pulmonary problem, psychological problems and low quality of life. Forty male pulmonary injured veterans were randomly replaced in two groups with 20 participants [MBSR and control Wait List [WL]]. Then MBSR group received 8-weekly session intervention. We evaluate quality of life [used SF-36 questionnaire] and Spirometry parameters two times; before and after intervention in two group. We used "mixed factorial analyses of variance" test for analyzing data in each dependent variables. Then if we have significant interactional effect, we used "paired - sample t-test" for comparing before and after intervention data of each group, and "Independent-Sample t-test" for comparing after intervention data of two groups. The MBSR compare to WL group improved SF-36 total score, [F[1,38] =12.09, P=0.001], "Role limitations due to physical problems" [F[1,38]= 6.92, P=0.01], "Role limitations due to emotional problems" [F[1,38]= 7.75, P=0.008], "Social functioning" [F[1,38]= 9.89, P=0.003], "Mental health" [F[1,38]= 15.93, P=0], "Vitality" [F[1,38]= 40.03, P

Experiences Living with Fatigue in Iranian Veterans Chemically Injured by Sulfur Mustard Gas: A Phenomenological Study

PURPOSE: Fatigue affects the quality of life. Evidence shows that the phenomenon of fatigue is experienced differently depending on the type of disease and its consequences. The aim of the study was to explicate the meanings of the experience of living with fatigue in chemically injured veterans. METHODS: The hermeneutic phenomenology approach was used in this study, with an emphasis on Van Mennen's viewpoint and approach. According to Van Mennen, six overlapping dynamic activities are recommended to conduct a phenomenological study. During unstructured interviews, the participants were asked to describe their daily living experiences with fatigue. The participants were individuals who were chemically injured due to exposure to mustard gas. After examining every statement in the interview text, extractions of the meaning units, clustering, and themes were performed. RESULTS: The data explication was based on the third to sixth stages of Van Mennen's approach. The experience living with fatigue was classified into four essential themes: fatigue as a chronic condition, as an unstable and affected situation, as a physical condition of the entire individual, and as a mental condition of the entire individual. CONCLUSION: Due to unique social interactions and pathogenicity, victims of mustard gas experience fatigue differently than patients with other chronic diseases.

[Study of the prophylactic effects of amifostine on decrease of lung tissue injuries in the acute phase in rats exposed to sulfur mustard]

Inhalation of Sulfur mustard [HD] will cause lung epithelial inflammation and injury. There are different results from the prophylactic effects of amifostine [AM] on protection of lung epithelial tissue against HD. The aim of this study was to evaluate the prophylactic effects of AM on protection of rat lung tissue exposed to HD. In this study twenty Albino Wistar adult male rats weighting 200 +/- 20 grams were used. Rats were divided randomly into 4 groups [5 rats in each group] as below: Normal saline group [NS], AM group, HD group [0.25% HD] and HD+AM group. Normal saline and HD solution were injected by intra tracheal catheter. Animals in AM and HD+AM groups received AM by intra peritoneal injection for 14 days daily. All rats were killed after 14 days; parts of the base of right lungs were removed, fixed and processed for histological evaluation by Toluidine blue, H and E staining and apoptotic cell death study by the TUNEL Apoptosis Detection Kit. In addition, glutathione level was measured in all specimens. No significant differences were revealed between Saline and AM groups in any of the aforementioned tests. Significant reduction of mast cells in lung tissue of the HD+AM group was shown when compared to the HD group. Lung tissue inflammation in the HD group was significantly more severe as compared to HD+AM group. In addition, amifostine in HD+AM group could prevent excess reduction of GSH level. The number of apoptotic cells in the HD group was significantly higher than the HD+AM group. Administration of amifostine before exposure to HD in rats prevents collection of mast cells, and excess reduction of GSH level in lung tissue; in addition it can partially reduce pulmonary edema and alveolar cell death apoptosis

Correlation between the degree of air trapping in chest HRCT and cardiopulmonary exercise test parameters: could HRCT be a predictor of disease severity?

The purpose of this study was to examine whether the degree of air trapping in high resolution computed tomography [HRCT] of patients with histories of sulfur mustard gas exposure during suspended full expiration correlated with various parameters of the cardiopulmonary exercise test as the gold standard for assessment of pulmonary function. In this analytic study 75 male patients, each with a history of sulfur mustard gas exposure, were investigated. Each participant underwent an incremental cardiopulmonary exercise test, pulmonary function test and arterial oxygen saturation for hemoglobin measurement. For HRCT examination, both lungs were divided into three parts [upper, middle, and lower] and in each part images were separately observed from the involved area point of view [<25% = 6/24; >/= 25%= >/= 6/24]. A total of 49.3% of the patients of >/= 25% or < 25% were 41.1 +/- 6.8 and 39.7 +/- 4.0 years, respectively [P=0.281]. In our study there was no significant difference in pulmonary function test findings [FEV1, FVC and FEV1/FVC] between the two groups. There was no significant correlation with air trapping of >/= 25% and any of the exercise test parameters. Also, no correlation was found between significant air trapping and exercise test finding in maximum exercise and anaerobic situations. No correlation was found between HRCT and cardiopulmonary exercise test findings. HRCT is neither pathognomic of the disease nor a good predictor of disease severity but it might be suggestive of mustard lung injuries

[Study of the effects of hexamethylentetramine on decrease of defects of the lung tissue in the rat exposed to sulfur mustard]

The aim of this study was to evaluate the effects of HMT on protection of lung tissue exposed to HD in the rat. In this study twenty Albino Wistar adult male rats weighting 200 +/- 20 gram were used. Rats divided randomly into 4 groups [each group has 5 rats] as below: Normal saline group [NS], HMT group, HD group [0.25% HD] and HD+HMT group. Normal saline and HD solution were injected by intra tracheal catather. Animals in HMT and HD+HMT groups received HMT by intra peritoneal injection for 14 days daily. All rats were killed after 14 days, a part of lung tissue were removed, fixed and processed for histological evaluation by H and E staining and apoptotic cell death study by TUNEL kit. In addition, biochemical study [catalase enzyme] was measured in all groups. Histological examination and cell counting data revealed that there were no significant differences between Saline and HMT groups. Alveolar hemorrhage and inflammation, as well as, the number of apoptotic cells in the HD group was significantly increased when compared to HD+HMT group. HMT have prophylactic and therapeutics effects in the lung tissue against HD

Diffusing capacity for lung carbon monoxide [DLCO] in chemical lung injuries due to the use of mustard gas in the poisoned soldiers of Iran-Iraq war 2006

To assess the Mustard gas exposure effects on pulmonary system, particularly on diffusing capacity for lung carbon monoxide [DLCO] and simple spirometry. Sixty-five sulfur mustard- poisoned soldiers from Mostazafan and Janbazan organization were referred to our center in 2005. Complete history, physical examination, chest X ray, Echocardiography, Arterial blood gas, high - resolution computerized tomography, diffusion capacity for lung carbon monoxide and spirometry of these were performed and compared this result with normal value. The mean value of indices in studied injured subjects was: Spirometry: forced expiratory volume in one second [FEV1] = 70.4, Forced vital capacity [FVC] = 66.5, EFE 25-75=81.1, FEV1/FVC=101.9, Flow 25% = 28.7, Flow 50%= 72.9, Flow 75%= 100.1, Sample volume: Functional residual capacity of lungs [FRC] = 131.5, residual volume [RV] = 157.3, RV/TLC= 169.1, Total lung capacity [TLC] = 91.3, KCO= 131.6, TLCO= 116.3. No significant correlation was observed between TLCO values with HRCT, echocardiography, ABG and spirometry values [P>0.05]. We recommend TLCO and RV/TLV tests to assess severity of Injuries as there is no a suitable criterion to measure the real consequences of mustard gas on affected combatants and Biological markers are also needed to determine cause- effect relations

Acute effects of sulphur mustard gas on the number of lymphocytes in the rat's spleen / Efectos agudos del gas mostaza sobre el número de linfocitos en el bazo de rata

Sulphur mustard (SM), commonly known as mustard gas is an alkylating agent that causes serious blisters upon contact with human skin. SM is frequently used as a chemical warfare agent. There is some evidence for sulfur mustard-induced lymph system effects in humans. Between 2000-2001, 42 male albino Wistar rats were used. After accommodation with environment, we divided rats to control, sham and experimental groups (2.5 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg and 40 mg/kg). Then we injected sulphur mustard oil in rat's intraperitoneal space. Then their spleens were removed for histological verification. Our results showed that significant difference in lymphocytes number in experimental groups after 24 hours. The number of lymphocytes in 5, 10, 20 and 40 mg/kg groups was increased and this increase in 40 mg/kg group was more than the other groups. We concluded that the number of lymphocytes increased due to exposure of mustard gas and there is a relationship between the increase of lymphocytes and dose of exposure.

El sulfuro de mostaza (SM), comúnmente conocido como gas mostaza, es un agente alquilante que causa graves ampollas en contacto con la piel humana. SM se utiliza con frecuencia como un agente de guerra química. Hay algunas evidencias que indican que el SM induce efectos en el sistema linfático en seres humanos. Entre los años 2000-2001, fueron utilizadas 42 ratas albinas Wistar macho. Después de la acomodación con el medio ambiente, las ratas se dividieron en grupos control, impostor y experimental (2,5 mg / kg, 5 mg / kg, 10 mg / kg, 20 mg / kg y 40 mg / kg). Luego se inyectó aceite de SM en el espacio intraperitoneal de las ratas. A continuación, sus bazos fueron removidos para la verificación histológica. Los resultados mostraron una diferencia significativa en el número de linfocitos en el grupo experimental después de 24 horas. El número de linfocitos en los grupos de 5, 10, 20 y 40 mg / kg fue mayor siendo este incremento en el grupo de 40 mg / kg más alto que en los otros grupos. Concluimos que el número de linfocitos aumenta debido a la exposición de gas mostaza existiendo una relación entre el aumento de linfocitos y la dosis de exposición.

Markel cell carcinoma on mustard Gas scar: a case report

Merkel cell carcinoma [MCC] is a rare primary neuroendocrine carcinoma of the skin in elderly individuals, on sun exposed areas of the body, with the head and neck being the most common sites. Excessive ultraviolet exposure may play an etiologic role in the development of it. Exposure to mustard gas can cause skin reactions and increase risk of skin neoplasms and probably MCC. The Aim of this study was to report this interesting case and review the published literature on MCC. In this article a 60 year old man with a history of exposure to chemical warfare sulphur Mustard gas in Iraq-Iran conflict and development of a hemorrhagic nodular mass with a duration of 3 months on his scalp, that based on histology, immunohistochemical staining and was diagnosed as MCC is presented. This was the first reported case of Merkel cell carcinoma in Iran exposed to sulphur Mustard gas. Sulphur Mustard gas can be an etiologic factor for this tumour

Bcl-2 protein expression in pulmonary specimens of sulfur mustard victims

Considering the role of sulfur mustard gas in development of acute and chronic pulmonary complications and the role of some genes including Bcl-2 in pulmonary fibrosis, we decided to study Bcl-2 gene expression in lung biopsy specimens of victims in comparison with normal lung. Lung biopsy specimens were taken from 13 sulfur mustard [SM] victims with pulmonary complication and were stained by Hematoxylin and Eosin [H and E] and avidin-biotin methods. We used normal lung blocks from forensic medicine as the normal group. These blocks were treated and stained with the same procedure as the case group. Both groups' blocks were studied by a pathologist simultaneously. The percentage of macrophages in sulfur mustard victims' specimens was significantly lower than that of the control group. There was also a significant increase in lymphocytes of victims in comparison with the normal group. Neutrophil percentage and Bcl-2 protein in these cells showed no significant difference between the two groups. Bcl-2 protein in fibroblasts and epithelial cells of sulfur mustard victims was significantly higher than the control group. According to the results of this study in comparison with the results of patients with idiopathic pulmonary fibrosis [IPF], pulmonary fibrosis can be confirmed as one of the late complications of SM victims. According to these results, upregulation of Bcl-2 protein and subsequent alveolar epithelial cell hyperplasia and proliferation of fibroblasts may be a mechanism for pulmonary fibrosis induced by mustard gas. It could be important for developing new strategies for the treatment of fatal complications of this chemical warfare