Tokyo , terrorist attacks

There are numerous methods for the analysis of alkyl methylphosphonic acids in urine and blood, mostly using GC-MS and GC-MS-MS. These have been recently reviewed (Black and Muir, 2003 Black and Noort, 2005) and only a representative selection is summarized here. Isolation from urine is usually achieved by hydrophobic SPE (Cis, Cs or polymeric) at low pH, or by anion-exchange SPE. Phosphonic acids require derivatization for GC-MS analysis, and at least four different derivatives have been applied to biomedical samples. Silylation (trimethylsilyl or rm-butyldimethylsilyl) are commonly used for environmental analysis and were used in the analyses of samples from casualties of the Mat-sumoto and Tokyo terrorist attacks (e.g. Minami et al, 1997 Nakajima et al, 1998). In these cases, the first samples were collected within hours of the exposure and the detection limits... 

Discovered in the late 1930s in Germany as improved poisonous insecticides, organophosphorus ChEIs were developed as chemical warfare agents (e.g. sarin, soman, and tabun) and were more recently employed in the 1995 terrorist attack in the Tokyo subway system [5]. 

Recently, Noort et al developed a procedure that is based on straightforward isolation of adducted BuChE from plasma by means of affinity chromatography with a procainamide column, followed by pepsin digestion and LC/electrospray tandem MS analysis of a specific nonapeptide containing the phosphonylated active site serine-198 residue (5). This method surpasses the limitations of the fluoride-reactivation method, since it can also deal with dealkylated ( aged ) phosphonylated BuChE. The method allowed the positive analysis of several serum samples of Japanese victims of the terrorist attack in the Tokyo subway in 1995. Furthermore, the method could be applied for detection of ChE modifications induced by, e.g., diethyl paraoxon and pyridostigmine bromide, illustrating the broad scope of this approach. This new approach... 

Unfortunately the time we are living now brought the terrifying shadow of terrorist attacks, and Nairobi, Tokyo and New York already experienced them. 

Today, everyone is aware of terrorist activity. A well-known terrorist attack involving chemicals occurred in 1995 with the release of the nerve gas sarin in the subway systems of Tokyo, resulting in the death of 12 people and injury of many more. Should chemicals again be used for terrorist activity, forensic pharmacologists and toxicologists may be called upon to analyze bodily samples in order to identify the chemical, determine its mechanism of action, and propose antidotes and preventive measures. 

Organophosphate and carbamate cholinesterase inhibitors (see Chapter 7) are widely used to kill insects and other pests. Most cases of serious organophosphate or carbamate poisoning result from intentional ingestion by a suicidal person, but poisoning has also occurred at work (pesticide application or packaging) or, rarely, as a result of food contamination or terrorist attack (eg, release of the chemical warfare nerve agent sarin in the Tokyo subway system in 1995). 

The only reported incidents of nerve agent poisoning, where biomedical samples have been obtained, are those resulting from terrorist dissemination of sarin in Matsumoto (1994) and the Tokyo subway (1995), plus an assassination using VX, also in Japan (60). In contrast to the CW incidents involving sulfur mustard, many of the biomedical samples associated with these terrorist attacks were collected within hours of the event. 

Y. Matsuda, M. Nagao, T. Takatori, H. Niijima, M. Nakajima, H. Iwase, M. Kobayashi and K. Iwadate, Detection of sarin hydrolysis product in formalin-fixed brain tissues of victims of the Tokyo subway terrorist attack, Toxicol. Appl Pharmacol, 150, 310-320 (1998). 

Nevertheless, the Tokyo incident certainly changed the way the world viewed terrorism—the prospect of true mass casualty events was brought home to many for the first time. Japan found itself ill-equipped to deal with a large-scale terrorist attack using chemical agents. Furthermore, some analysts concluded the Tokyo attack removed the taboo against the use of WMD by terrorists. 

Distribution, metabolism, and elimination of sarin in humans appear to resemble findings in animals. Minami and colleagues (1997, 1998) detected the sarin metabolite IMPA in urine of humans after the terrorist attack in Tokyo in 1995. They found peak levels of IMPA or methylphosphonic acid in urine 10-18 h after exposure. The levels of IMPA in urine correlated with the clinical symptoms. They also found evidence of distribution of sarin to the human brain in four of the 12 people who died after exposure. IMPA and MPA were detected in patients from the Matsumoto sarin exposure (Nakajima et al, 1998). 

The 1995 terrorist attack in the Tokyo subway system that left 12 people dead and over 5,000 injured (Suzuki et al, 1995 Nagao et al, 1997) provided the opportunity to investigate the role of PON 1 in modulating the toxicity of sarin in humans. The prevalence of the PONIR192 genotype in the Japanese population is 0.66, compared with 0.25-0.30 in various Caucasian populations (Brophy et al, 2002 Yamasaki et al, 1997). Thus, Japanese individuals may... 

Yamada, Y., Takatori, T., Nagao, M., Iwase, H., Kurada, N., Yanagida, J., Shinozuka, T. (2001). Expression of paraoxonase isoform did not confer protection from acute sarin poisoning in the Tokyo subway terrorist attack. Int. J. Leg. Med. 115 82-4. Yamasaki, Y., Sakamoto, K., Watade, H., Kajimoto, Y., Hori, M. (1997). The Argi92 isoform of paraoxonase with low sarinhydrolyzing activity is dominant in the Japanese. Hum. Genet. 101 67-8. 

The October 2001 anthrax events revealed that terrorist attacks do not have to cause many casnalties to create mass anxiety and disruption (1,4). Other than that experience, however, we have little historic data to tell us how the public will react following a large-scale biologic, chemical or radiological attack (1). Most available information comes from studies of pubhc reactions to natural disasters, conventional terrorist events, such as the Sarin attack in Tokyo and the September 11 attack, and nuclear accidents (1,5,6). Additional information is available from stnd-ies of soldier s reactions to military campaigns involving toxic agents (1). 

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