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.

Therapeutic effects of proanthocyanidin and coenzyme Q10 on nitrogen mustard-induced ocular injury / Efeitos terapêuticos da proantocianidina e da coenzima q10 em lesão ocular induzida por mostarda de nitrogênio

ABSTRACT Purpose: Nitrogen mustard (NM) is a devastating casualty agent in chemical warfare. There is no effective antidote to treat NM-induced ocular injury. We aimed to assess the effects of proanthocyanidin (PAC) and coenzyme Q10 (CoQ10) on NM-induced ocular injury. Methods: Eighteen male rats were divided into the following 4 groups: NM, NM + PAC, NM + CoQ10, and control. The 3 NM groups received a single dose of NM (0.02 mg/μL) on the right eye to induce ocular injury. The control group received saline only. Thirty minutes after the application of NM, the NM + PAC group received PAC (100 mg/kg) via gastric gavage, while the NM + CoQ10 group received CoQ10 (10 mg/kg) via intraperitoneal injection. PAC and CoQ10 were administered once a day for 5 consecutive days. The rats were then sacrificed. Macroscopic images of the eyes were examined and eye tissues were collected for histology. Results: The treatment groups were compared to the control group with regard to both corneal opacity and lid injury scores. The findings were not significantly different for both the NM + PAC and NM + CoQ10 groups. In both the NM + PAC and NM + CoQ10 groups, the histological changes seen in the NM group demonstrated improvement. Conclusions: Our results indicate that PAC and CoQ10 treatments have therapeutic effects on NM-induced ocular injury in a rat model. PAC and CoQ10 may be novel options in patients with NM-induced ocular injury.

RESUMO Objetivo: A mostarda de nitrogênio (MN) é um agente de guerra química devastador. Não existe um antídoto eficaz para tratar lesões oculares induzidas por MN. Nosso objetivo foi avaliar os efeitos da proantocianidina (PAC) e da coenzima Q10 (CoQ10) na lesão ocular induzida por MN. Métodos: Dezoito ratos machos foram divididos em 4 grupos: MN, MN + PAC, MN + CoQ10 e Controle. Três grupos receberam uma dose única de MN (0,02 mg/μL) destilada no olho direito para gerar lesão ocular. Os animais do grupo controle receberam apenas solução salina. Trinta minutos após a aplicação de MN nos animais, o grupo MN + PAC recebeu PAC (100 mg/kg) por gavagem gástrica, enquanto a CoQ10 (10 mg/kg) foi administrada ao grupo MN + CoQ10 por meio de injeção intraperitoneal. A administração de PAC e de CoQ10 foi realizada uma vez por dia, durante 5 dias consecutivos. Os ratos foram, então, sacrificados. Imagens macroscópicas dos olhos foram examinadas e tecidos oculares foram coletados para histologia. Resultados: Os grupos de tratamento foram comparados ao grupo de controle quanto à opacidade da córnea e quanto aos escores de lesão da cobertura da córnea. Os resultados foram insignificantes para ambos os grupos. Ambos, o grupo MN+PAC e o grupo MN+CoQ10, apresentaram melhoras das alterações histológicas observadas no grupo MN. Conclusões: Nossos resultados indicam que os tratamentos com PAC e com CoQ10 têm efeitos terapêuticos sobre lesões oculares induzidas por MN em um modelo em ratos. A proantocianidina e a CoQ10 podem ser uma nova opção nesses casos.

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>

Factibilidad y pertinencia de una estrategia pedagógica para la preparación médica especial / Feasibility and pertinence of a pedagogical strategy for the special medical training

Fundamento: la preparación del profesional de la salud para enfrentar las consecuencias de las armas químicas y biológicas en humanos, es una misión de la universidad médica cubana. Objetivo: evaluar la factibilidad y pertinencia de una estrategia pedagógica de superación profesional médica para la enseñanza del diagnóstico y tratamiento de las consecuencias del empleo de las armas químicas y biológicas en humanos. Métodos: se realizó una investigación que culminó con la aplicación de un pre-experimento pedagógico en la sede universitaria Hospital Militar de Holguín, durante el curso 2010-2011. La muestra estuvo constituida por 20 especialistas en Medicina General Integral. Se utilizaron métodos teóricos: histórico-lógico, analítico-sintético y sistémico estructural y funcional; empíricos: la encuesta, criterio de especialistas por el método Delphi; del matemático: la estadística descriptiva con distribución de frecuencias absoluta y en porcientos y la prueba de signos. Resultados: se identificaron insuficiencias en los médicos para el diagnóstico y tratamiento de las consecuencias de las armas químicas y biológicas en humanos, por lo cual se diseñó y aplicó una estrategia pedagógica para la apropiación de los conocimientos y habilidades necesarios en estos casos. Conclusiones: la estrategia elaborada permitió resolver las dificultades para el desarrollo del proceso enseñanza aprendizaje de las enfermedades que resultan del empleo de las armas químicas y biológicas, y una mejor preparación en los médicos en cuanto al diagnóstico y tratamiento de ellas. Los especialistas consideran la estrategia de muy adecuada y bastante adecuada, lo que demuestra el grado de pertinencia y relevancia para su aplicación.

Background: the professional training in order to face the consequences in human beings of the chemical and biological weapons is a mission of the Cuban medical university. Objective: to devise a strategy for the teaching of the diagnosis and treatment of the effects in human beings of the chemical and biological weapons. Methods: a research project was done that culminated in the application of a pedagogical pre-experiment at the University Venue Military Hospital of Holguín during the 2010-2011 academic year. The sample was chosen through a non-probabilistic sampling, composed of 20 specialists in Integral General Medicine. Theoretical methods were used: historical-logical, analytical-synthetic, inductive-deductive, modeling and systemic, structural and functional; empirical: Delphi method and survey; mathematical: descriptive statistics with distribution of absolute frequency and in percentage. Results: insufficiencies were identified among the doctors for the diagnosis and treatment of the effects in human beings of chemical and biological weapons, being this reason why a pedagogical strategy was designed and applied for the acquisition of the knowledge and skills that are necessary in these cases. Conclusions: the designed strategy allows to solve the difficulties for the development of the learning-teaching process of the illnesses resulting from the use of chemical and biological weapons, as well as a better training in doctors regarding their diagnosis and treatment. The specialists assessed the strategy in general as very adequate, what shows the degree of relevance and pertinence for its application.

Effect of melatonin on p38MAPKsignaling pathway in rats with phosgene-induced lung injury / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of melatonin (MT) on p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with phosgene-induced lung injury.</p><p><b>METHODS</b>Fifty specific pathogen-free male Sprague-Dawley rats were randomly divided into phosgene inhalation group, air control group, saline control group, MT treatment group, and SB203580 (specific inhibitor of p38 MAPK) group, with 10 mice in each group. All groups except the air control group were exposed to phosgene, and the animals were sacrificed 6 h later. Lung wet/dry weight (W/D) ratio and the content of malondialdehyde (MDA) and nitric oxide (NO) and activity of myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF) were measured. The qualitative and quantitative expression of p38 MAPK and phospho-p38 MAPK (p-p38) was measured by immunohistochemistry (IHC) and Western blot, respectively. Inducible nitric oxide synthase (iNOS) level in lung tissue was determined by Western blot.</p><p><b>RESULTS</b>Compared with the air control group, the phosgene inhalation group had significantly increased lung W/D ratio and neutrophil count in BALF (P < 0.01); the MT treatment group had significantly lower neutrophil count and lung W/D ratio than the phosgene inhalation group (P < 0.05). IHC demonstrated that the air control group had relatively weak expression of p-p38 in lung tissue; the expression of p-p38 was significantly up-regulated after phosgene inhalation, and it was mainly distributed in infiltrating inflammatory cells and vascular endothelial cells, positive in the cytoplasm and nucleus of many cells. The distribution of p-p38-positive cells in the MT treatment and SB203580 groups was similar to that in the phosgene inhalation group, but the MT treatment and SB203580 groups had a significantly reduced number of cells with p-p38-positive nuclei and a significantly reduced intensity of p-p38 expression signals. The phosgene inhalation group had significantly increased content of MDA and NO and activity of MPO compared with the air control group (P < 0.01); the MT treatment and SB203580 groups had significantly reduced content of MDA and NO and activity of MPO compared with the phosgene inhalation group (P < 0.05), but had higher content of MDA and NO and activity of MPO than the air control group. The Western blot showed that the phosgene inhalation group had significantly increased expression of iNOS and p-p38 compared with the air control group (P < 0.01); the MT treatment and SB203580 groups had lower expression of iNOS and p-p38 than the phosgene inhalation group (P < 0.05).</p><p><b>CONCLUSION</b>MT and SB203580 have a significant protective effect in rats with phosgene-induced lung injury, and the mechanism may be associated with scavenging free radicals and inhibiting activation of p38 MAPK and expression of iNOS.</p>

Effects of adenovirus-delivered angiopoietin-1 siRNA on expression of matrix metalloproteinases in rats with acute lung injury induced by phosgene / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of adenovirus-delivered angiopoietin-1 siRNA (Ad. Ang-1siRNA) on the expression of matrix metalloproteinase-2, 9 (MMP-2, 9) and tissue inhibitor of metallopro-teinase-1 (TIMP-1) in rats with acute lung injury (ALI) induced by phosgene (Psg).</p><p><b>METHODS</b>We first established a rat model of Psg-induced acute lung injury (ALI). The rats were randomly divided into 6 groups: air control group with exposure to air, air+adenovirus (air+Ad) group with caudal vein injection of 1×10(8) pfu/ml adenovirus 1 h after air exposure, air+Ad/Ang1 group with caudal vein injection of 1×10(8) pfu/ml Ad.Ang-1siRNA 1 h after air exposure, Psg group with exposure to 8.33 mg/L Psg (purity 100%, of the same volume as the inhaled air in the air control group) for 5 min, Psg+Ad group with caudal vein injection of 1×10(8) pfu/ml adenovirus 1 h after exposure to the same dose of Psg, and Psg+Ad/Ang1 group with caudal vein injection of 1×10(8) pfu/ml Ad.Ang-1siRNA 1 h after exposure to the same dose of Psg. Serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected 36 h after exposure. The protein expression of Ang-1, MMP-2, 9, and TIMP-1 in serum and BALF was determined by double-antibody sandwich ELISA. RT-PCR was used to determine the mRNA levels of Ang-1, MMP-2, 9, and TIMP-1 in lung tissue. The protein expression of MMP-2, 9 and TIMP-1 in lung tissue was determined by Western blot.</p><p><b>RESULTS</b>A rat model of Psg-induced ALI was successfully established. The levels of MMP-2, 9 in serum, BALF, and lung tissue were significantly increased in the Psg group and Psg+Ad/Ang1 group as compared with the control group (P<0.01); no significant change was observed in serum TIMP-1 protein expression (P>0.05); interestingly, TIMP-1 protein expression in BALF and lung tissue was significantly increased (P<0.01). Compared with the Psg group, the Psg+Ad/Ang1 group showed a significant decrease in MMP-2, 9 expression in BALF, serum, and lung tissue (P<0.05), but no significant change in protein expression of TIMP-1 was discovered (P>0.05).</p><p><b>CONCLUSION</b>Ad.Ang-1siRNA has a potential beneficial effect in rats with Psg-induced ALI through inhibition of MMP-2, 9 expression, but has no significant effect on the expression of TIMP-1.</p>

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.

Usos y abusos de los gases lacrimógenos y la salud: prevención y manejo / Uses and abuses of teargas and health: prevention and management

Los gases lacrimógenos (GL) son métodos de control de manifestaciones públicas por los órganos represivos, muy utilizados y efectivos globalmente. El objetivo de esta revisión es actualizar información técnica sobre los gases lacrimógenos, añadiendo aspectos más recientes legales, éticos, médicos y preventivos del uso y abuso de estos agentes químicos durante las acciones de las fuerzas policiales y represivas. Las fuentes de información secundarias seleccionadas son portales generales con el buscador Google, académicos (Google académico), PubMed y de las organizaciones gubernamentales y no gubernamentales, también se incluyen hemerotecas de artículos periodísticos sobre su uso desde 2000 hasta 2014. La exposición aguda a (GL) se expresa con manifestaciones clínicas de afección respiratoria, irritación de los ojos y de la piel, requiriendo en la mayoría de los casos medidas generales de atención fuera del hospital. Sin embargo, en casos de personas con co-morbilidades respiratorias, alérgicas, glaucoma y del corazón, acarrean mayores consecuencias que requieren atención médica y hospitalaria. Se han reportado fatalidades relacionadas al uso y abuso de los agentes químicos. Desde el punto de vista de salud pública existe controversia sobre su uso, y definitivamente causan consternación en los afectados y los abusos de su utilización en manifestaciones pacíficas. Se hace un listado de recomendaciones ante exposiciones durante manifestaciones, como prevenir intoxicaciones severas y dar los primeros auxilios...

Tear gases (TG) are methods for public control used by police forces. The objective of this review is to update technical information about tear gas, adding more recent legal, ethical, medical and preventive aspects of the use and abuse of these chemicals during the actions of the police and repressive forces. Selected secondary sources of information are Google, Academic Google, PubMed and of governmental and non-governmental organizations, also included are newspaper archives about its use from 2000 to 2014. Acute exposure to (GL) is expressed with clinical manifestations of respiratory conditions, irritation of the eyes and skin, requiring in most cases general ambulatory measures of care. However, in persons with respiratory, allergic, glaucoma and heart comorbidities, they carry greater consequences requiring hospital care. Fatalities have been reported related to the use and abuse of chemical agents. From the viewpoint of public health there is a controversy about its use, and definitely cause consternation in the affected in peaceful demonstrations. A list of recommendations is made about how to prevent severe intoxications and give first aid...

[Relationship between sleep quality and quality of life in chemical warfare victims with bronchiolitis obliterans referred to Baqiyatallah hospital of Tehran, Iran]

Decrease of quality of life and undesirable sleep in individual with bronchiolitis due to chemical exposure reported in previous studies. This study was applied to assess relationship between sleep quality and quality of life in chemical warfare victims with bronchiolitis obliterans. In this descriptive correlative study, 93 chemical warfare victims with bronchiolitis obliterans referred to respiratory clinic of Baqyatallah hospital were selected by convenience sampling method. Quality of life and sleep quality was measuring the St George's Respiratory Questionnaire and Pittsburgh sleep Quality Index [PSQI]. Pearson correlation coefficient was showed a positive and significant correlation between sleep quality and quality of life. Also it was revealed significant relationship between psychological disorders and undesirable sleep quality [P<0.05]. The findings suggest there is need to improve sleep quality in this population in order to enhance their heathed-related quality of life

[Extra cellular superoxide dismutase activity in lung injuries due to sulfur mustard]

Pulmonary complications are known to occur in over half of the patients exposed to sulfur mustard [SM]. There is controversial regarding the role of extracellular superoxide dismutase [EC-SOD] in different airway diseases. The aim of this study was to evaluate the correlation between lung function and EC-SOD activity in patient with lung injuries due to SM. This was a case-control study carried out on 220 patients with lung complication due to SM in the city of Sardasht [Iran] in 2007. Spirometry was used to assess pulmonary function followed by measurement of EC-SOD activity. T test was employed to examine the differences between study groups. Pearson correlation coefficient was also used to find the possible correlation between EC-SOD activity and the lung function. The mean EC-SOD activity in control group [70.5 +/- 10.8U/L] was higher than that of moderate to severe group 67.0 +/- 6.1 U/L [p < 0.001]. There was no significant difference for mean EC-SOD activity between mild and control groups. Significant and direct association between EC-SOD activities and lung function was established [p < 0.001]. According to our findings, inactivation of EC-SOD may lead to progressive inflammation and lung injury due to sulfur mustard

Preparedness for terrorism: managing nuclear, biological and chemical threats

The management of nuclear, biological and chemical (NBC) terrorism events is critical to reducing morbidity and mortality in the next decade; however, initial patient care considerations and protective actions for staff are unfamiliar to most front-line clinicians. High explosive events (bomb and blast) remain the most common type of terrorism and are easy to detect. Conversely, some types of terrorist attacks are more likely to be unsuspected or covert. This paper explains the current threat of terrorism and describes clues for detection that an event has occurred. Specific criteria that should lead to a high suspicion for terrorism are illustrated. The manuscript outlines initial actions and clinical priorities for management and treatment of patients exposed to nuclear/radiological, biological, chemical and combined agents (for example an explosion involving a chemical agent). Examples of terrorist events include: a nuclear explosion, an aerosolised release of anthrax (biological), dissemination of sarin in a subway (chemical), and the detonation of a radiologic dispersion device or "dirty bomb" (combined explosive and radiological). Basic principles of decontamination include potential risks to healthcare providers from secondary exposure and contamination. Unique issues may hinder clinical actions. These include coordination with law enforcement for a crime scene, public health entities for surveillance and monitoring, hazardous materials teams for decontamination, and the media for risk communications. Finally, the importance of personal preparedness is discussed.

[Effects of betamethasone and diclofenac-Na on sulfur mustard induced conjunctival epithelial and goblet cells injuries of rabbits in acute phase]

Sulfur mustard, Bis [2-chlorethy1] sulfide [HD], is one of the first chemical warfare agents to be used on a large scale. Anti inflammatory treatments might have the potential to prevent some aspects of the primary development of HD-induced lesions. The aim of the present study was to evaluate treatment effects of topically applied betamethasone [B] and diclofenac-Na [D] on the conjunctival epithelial lesions following HD exposure. A total of 36 rabbits were used. Animals were randomly divided to three control groups: [1] normal; [2] solution; [3] HD and three experimental groups: [4] betamethasone; [5] diclofenac-Na and [6] betamethasone-diclofenac-Na [BD]. In each group six animals were examined. Right eye of all animals was selected for experiment. In the experimental groups betamethasone and diclofenac-Na were applied after using HD solution. Application of drugs was performed 3 times a day for 2 weeks. Slit-lamp examinations were performed before exposure and subsequently at days 1, 2, 5, 7, and 14 by professional ophthalmologists. Animals were sacrificed after two weeks with chloroform. The eyes were enucleated. Specimens of palpebra were obtained for histological examination. There was not any significant difference between normal and solution groups. HD caused a significant decrease in goblet cells and cell infiltration in conjunctiva, injection and chemosis. All experimental groups were better than the HD group. Betamethasone in combination with diclofenac-Na was more effective than betamethasone and diclofenac-Na alone in decreasing eye injuries. Combination of betamethasone and diclofenac-Na are potential candidates for the treatment of ocular lesions following HD exposure