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International Journal of Organ... 2018Tissue engineering and cell-based therapies are promising therapeutic approaches in structural and functional defects of the trachea. Researchers have focused on these... (Review)
Review
Tissue engineering and cell-based therapies are promising therapeutic approaches in structural and functional defects of the trachea. Researchers have focused on these approaches to overcome the complications related to such diseases. Patients exposed to mustard gas suffer from massive damage to the respiratory system. Current treatment plans are only palliative and include anti-inflammatory drugs, broncholytics, long-acting β-agonists, and inhaled corticosteroids. As mustard gas exposure leads to chronic airway inflammation, it seems that tracheobronchomalacia, because of chronic inflammation and weakness of the supporting cartilage, is an important factor in the development of chronic and refractory respiratory symptoms. The previous studies show that regenerative medicine approaches have promising potential to improve the life quality of patients suffering from tracheal defects. It seems that the engineered tracheal graft may improve the respiratory function and decrease symptoms in patients who suffer from asthma-like attacks due to mustard gas exposure. There are several successful case reports on the transplantation of stem cell-based bioartificial grafts in structural airway diseases. Therefore, we hope that the reconstruction of tracheobronchial structure can lead to a decrease in respiratory difficulties in mustard gas-exposed patients who suffer from tracheomalacia. In the present review, we summarize the main aspects of tracheal tissue engineering and cell-based therapies and the possibilities of the application of these approaches in mustard gas-exposed patients.
PubMed: 30863517
DOI: No ID Found -
Annals of the New York Academy of... Nov 2020Exposure to vesicants, including sulfur mustard and nitrogen mustard, causes damage to the epithelia of the respiratory tract and the lung. With time, this progresses to... (Review)
Review
Exposure to vesicants, including sulfur mustard and nitrogen mustard, causes damage to the epithelia of the respiratory tract and the lung. With time, this progresses to chronic disease, most notably, pulmonary fibrosis. The pathogenic process involves persistent inflammation and the release of cytotoxic oxidants, cytokines, chemokines, and profibrotic growth factors, which leads to the collapse of lung architecture, with fibrotic involution of the lung parenchyma. At present, there are no effective treatments available to combat this pathological process. Recently, much interest has focused on nutraceuticals, substances derived from plants, herbs, and fruits, that exert pleiotropic effects on inflammatory cells and parenchymal cells that may be useful in reducing fibrogenesis. Some promising results have been obtained with nutraceuticals in experimental animal models of inflammation-driven fibrosis. This review summarizes the current knowledge on the putative preventive/therapeutic efficacy of nutraceuticals in progressive pulmonary fibrosis, with a focus on their activity against inflammatory reactions and profibrotic cell differentiation.
Topics: Animals; Chemical Warfare Agents; Dietary Supplements; Disease Models, Animal; Humans; Irritants; Mechlorethamine; Mustard Gas; Pulmonary Fibrosis
PubMed: 32725637
DOI: 10.1111/nyas.14442 -
Journal of Ophthalmic & Vision Research 2017
PubMed: 28298999
DOI: 10.4103/2008-322X.200166 -
Mutation Research Aug 2009Sulfur mustard (SM), also known as mustard gas, is an alkylating compound used as a chemical weapon in World War I and by Iraqi forces against Iranians and indigenous...
UNLABELLED
Sulfur mustard (SM), also known as mustard gas, is an alkylating compound used as a chemical weapon in World War I and by Iraqi forces against Iranians and indigenous Iraqi Kurds during the Iran-Iraq War of the 1980s. Although SM is a proven carcinogen there are conflicting views regarding the carcinogenicity of a single exposure. The present study characterizes lung cancers formed in mustard gas victims from the Iran-Iraq War.
METHODS AND MATERIALS
Demographic information and tumor specimens were collected from 20 Iranian male lung cancer patients with single high-dose SM exposures during the Iran-Iraq War. Formalin-fixed, paraffin-embedded lung cancers were analyzed by immunohistochemistry for p53 protein. In addition, DNA was extracted from the tissues, PCR amplified and sequenced to identify mutations in the p53 and KRAS genes associated with SM exposure.
RESULTS
A relatively early age of lung cancer onset (ranging from 28 to 73 with a mean of 48) in mustard gas victims, particularly those in the non-smoking population (mean age of 40.7), may be an indication of a unique etiology for these cancers. Seven of the 20 patients developed lung cancer before the age of 40. Five of 16 cancers from which DNA sequence data was obtainable provided information on eight p53 mutations (within exons 5-8). These mutations were predominately G to A transitions; a mutation consistent with the DNA lesion caused by SM. Two of the lung cancers had multiple p53 point mutations, similar to results obtained from factory workers chronically exposed to mustard agent. No mutations were detected in the KRAS gene.
DISCUSSION
The distinguishing characteristics of lung carcinogenesis in these mustard gas victims suggest that a single exposure may increase the risk of lung cancer development in some individuals.
Topics: Adult; Aged; Chemical Warfare Agents; Genes, p53; Humans; Inhalation Exposure; Lung Neoplasms; Male; Middle Aged; Mustard Gas; Mutation
PubMed: 19559099
DOI: 10.1016/j.mrgentox.2009.05.022 -
Caspian Journal of Internal Medicine 2019Among the blistering (vesicant) chemical warfare agents (CWA), sulfur mustard is the most important since it is known as the "King of chemical warfare agents". The use... (Review)
Review
Among the blistering (vesicant) chemical warfare agents (CWA), sulfur mustard is the most important since it is known as the "King of chemical warfare agents". The use of sulfur mustard has caused serious damages in several organs, especially the eyes, skin, respiratory, central and peripheral nervous systems after short and long term exposure, incapacitating and even killing people and troops. In this review, chemical properties, mechanism of actions and their effects on each organ, clinical manifestations, diagnostic evaluation of the actions triage, and treatment of injuries have been described.
PubMed: 31558985
DOI: 10.22088/cjim.10.3.241 -
Toxicology and Applied Pharmacology Dec 2020Pulmonary fibrosis is characterized by destruction and remodeling of the lung due to an accumulation of collagen and other extracellular matrix components in the tissue.... (Review)
Review
Pulmonary fibrosis is characterized by destruction and remodeling of the lung due to an accumulation of collagen and other extracellular matrix components in the tissue. This results in progressive irreversible decreases in lung capacity, impaired gas exchange and eventually, hypoxemia. A number of inhaled and systemic toxicants including bleomycin, silica, asbestos, nanoparticles, mustard vesicants, nitrofurantoin, amiodarone, and ionizing radiation have been identified. In this article, we review the role of innate and adaptive immune cells and mediators they release in the pathogenesis of fibrotic pathologies induced by pulmonary toxicants. A better understanding of the pathogenic mechanisms underlying fibrogenesis may lead to the development of new therapeutic approaches for patients with these debilitating and largely irreversible chronic diseases.
Topics: Adaptive Immunity; Animals; Chronic Disease; Hazardous Substances; Humans; Immunity, Innate; Lung; Pulmonary Fibrosis
PubMed: 33031836
DOI: 10.1016/j.taap.2020.115272 -
Military Medical Research Sep 2018AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase (SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has... (Review)
Review
AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase (SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard (SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome (ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM, chlorine gas and radiation exposure studies.
Topics: Animals; Antioxidants; Chemical Warfare Agents; Humans; Lung Injury; Metalloporphyrins; Mice; Mustard Gas; Oxidative Stress; Radiation Injuries, Experimental; Radiation Pneumonitis
PubMed: 30185231
DOI: 10.1186/s40779-018-0176-3 -
Annals of the New York Academy of... Jun 2016Sulfur mustard (SM; bis-(2-chlororethyl) sulfide) is a highly reactive, potent warfare agent that has recently reemerged as a major threat to military and civilians.... (Review)
Review
Sulfur mustard (SM; bis-(2-chlororethyl) sulfide) is a highly reactive, potent warfare agent that has recently reemerged as a major threat to military and civilians. Exposure to SM is often fatal, primarily due to pulmonary injuries and complications caused by its inhalation. Profound inflammation, hypercoagulation, and oxidative stress are the hallmarks that define SM-induced pulmonary toxicities. Despite advances, effective therapies are still limited. This current review focuses on inflammatory and coagulation pathways that influence the airway pathophysiology of SM poisoning and highlights the complexity of developing an effective therapeutic target.
Topics: Animals; Blood Coagulation; Humans; Inflammation; Models, Biological; Molecular Targeted Therapy; Mustard Gas; Oxidative Stress
PubMed: 27285828
DOI: 10.1111/nyas.13095 -
Annals of the New York Academy of... May 2021Mustard gas (sulfur mustard, SM), a highly vesicating chemical warfare agent, was first deployed in warfare in 1917 and recently during the Iraq-Iran war (1980s) and... (Review)
Review
Mustard gas (sulfur mustard, SM), a highly vesicating chemical warfare agent, was first deployed in warfare in 1917 and recently during the Iraq-Iran war (1980s) and Syrian conflicts (2000s); however, the threat of exposure from stockpiles and old artillery shells still looms large. Whereas research has been long ongoing on SM-induced toxicity, delineating the precise molecular pathways is still an ongoing area of investigation; thus, it is important to attempt novel approaches to decipher these mechanisms and develop a detailed network of pathways associated with SM-induced toxicity. One such avenue is exploring the role of microRNAs (miRNAs) in SM-induced toxicity. Recent research on the regulatory role of miRNAs provides important results to fill in the gaps in SM toxicity-associated mechanisms. In addition, differentially expressed miRNAs can also be used as diagnostic markers to determine the extent of toxicity in exposed individuals. Thus, in our review, we have summarized the studies conducted so far in cellular and animal models, including human subjects, on the expression profiles and roles of miRNAs in SM- and/or SM analog-induced toxicity. Further detailed research in this area will guide us in devising preventive strategies, diagnostic tools, and therapeutic interventions against SM-induced toxicity.
Topics: Animals; Cell Line; Chemical Warfare Agents; Drug Resistance; Humans; MicroRNAs; Models, Animal; Mustard Gas; Respiratory System; Skin
PubMed: 33305460
DOI: 10.1111/nyas.14539 -
Archives of Iranian Medicine Sep 2022Sulfur mustard (SM) is a lethal chemical agent that affects many organs, particularly the eyes, respiratory system and skin. Even asymptomatic patients with documented... (Review)
Review
Sulfur mustard (SM) is a lethal chemical agent that affects many organs, particularly the eyes, respiratory system and skin. Even asymptomatic patients with documented SM vapor exposure may develop organ disorder many years later. Patients with even minor signs in the acute stage may experience late complications that necessitate surgery. Early decontamination and conservative measures could help the patients and decrease the complications. Despite decades of research, there is still no effective treatment for either acute or long-term SM-induced ocular complications. Even after multiple medications and surgical procedures, the majority of patients continue to have symptoms. For dry eye, punctual occlusion, autologous eye drops, and aggressive lubrication are used; for persistent epithelial defects (PED), tarsorrhaphy, amniotic membrane transplant, and stem cell transplantation are used; for total limbal stem cell deficiency (LSCD), living-related conjunctivolimbal allograft and keratolimbal allograft are used; for corneal vascularization, steroids, non-steroidal anti-inflammatory drugs, and anti-vascular endothelial growth factor prescribed; and for corneal opacities, corneal transplantation is done. Platelet rich plasma and topical drops containing stem cell transplantation for LSCD, photodynamic therapy paired with subconjunctival or topical anti-vascular endothelial growth factors for corneal vascularization, topical curcumin and topical ciclosporin-A for dry eye, and orbital fat-derived stem cells for PED are all alternative treatments that can be suggested. Despite the experimental and clinical research on the complications of SM exposure over the past decades, there is still no effective treatment for eye complications. However, supportive medical and surgical management has been applied with relatively good outcome.
Topics: Humans; Mustard Gas; Stem Cells; Skin; Treatment Outcome
PubMed: 37543890
DOI: 10.34172/aim.2022.100