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Sulphur mustard, also known as mustard gas, is a chemical warfare agent that was used extensively in World War I. It is a vesicant, painfully blistering the skin and damaging the respiratory tract, as well as causing eye lesions. The effects are magnified because the symptoms are not immediately apparent, occurring 6-24 hours after contact, so immediate treatment is not always possible. The agent also attacks proteins and DNA, changing their properties by alkylation and leading to a higher risk of cancer. The name mustard gas derives from the odour of mustard, garlic or onions associated with the impure agent. The pure compound is odourless. During WWI, there were no recognised methods of detoxification, although several methods have been developed recently, including the application of sulphur amines and peroxy acids. Sulphur mustard was also used against Iran during the Iran-Iraq war (1984-1987) and tens of thousands of victims are still suffering with conditions such as chronic obstructive lung disease, lung fibrosis and chronic conjunctivitis. The lung problems do not respond to the standard treatment with corticosteroids and there is no consensus of opinion on the pathophysiological basis of the chronic pulmonary disease. In order to try and expand the knowledge of sulphur mustard-induced lung disease, Iranian scientists at the Baqiyatallah University of Medical Sciences in Tehran have undertaken a proteomics study of bronchoalveolar lavage fluid (BAL). The results are described by senior reporter Hossein Mehrani in Proteomics - Clinical Applications. The team collected BAL from victims from the city of Sardasht in western Iran who had been subjected to sustained exposure to sulphur mustard during 1987. A total of 40 people were tested, ten each with mild, moderate and severe lung conditions and ten controls. Proteins were precipitated from BAL with trichloroacetic acid and separated by 2D gel electrophoresis on pH 4-7 IPG strips followed by 12% PAGE gels. This was followed by runs on pH 3-10 IPG strips and 15% PAGE gels to resolve low-molecular-weight proteins. Image analysis identified proteins with different abundances between subjects and controls and these were extracted from the gel and digested with trypsin for MALDI mass spectrometric analysis on a tandem time-of-flight instrument. Database searching for protein identification was carried out with the NRDB1 Homo sapiens database. Several differentially expressed proteins were observed and identified. Two isoforms of vitamin D binding protein were over-expressed in all patients compared with controls, being most prominent in the moderate and severe groups. S100 calcium-binding protein A8 (S100 A8) was increased in the moderate and severe groups but was absent from the mild group and healthy controls, indicating that it might have a protective effect against lung tissue damage. Conversely, the calcium-binding protein calyphosine, which is involved in cell growth and differentiation, was reduced, suggesting that these processes had been inhibited. The reduction in levels of surfactant protein A correlated with the severity of pulmonary dysfunction, indicating that sulphur mustard damages not only lung tissue, but also lung protection factors. Apolipoprotein A1 was found in all patients but not in healthy controls and its potential antioxidant effects could be implicated. In this first proteomics study of the BAL of sulphur mustard-exposed people, the panel of differentiated proteins provides the basis for identifying biomarkers of lung damage induced by the chemical warfare agent. In particular, the researchers picked out S100 A8 and calyphosine as good candidates. The results could also help to classify the degree of lung damage and predict which patients will develop severe lung damage, since some proteins are changed in moderate and severe patients but not in those with mild symptoms. This, in turn, could lead to new treatment protocols. Related links:
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Mustard gas bombs.