The Experts below are selected from a list of 28191 Experts worldwide ranked by ideXlab platform
M Minami - One of the best experts on this subject based on the ideXlab platform.
-
Elevated frequency of sister chromatid exchanges of lymphocytes in Sarin-exposed victims of the Tokyo Sarin disaster 3 years after the event.
Toxicology, 2004Co-Authors: Yukiyo Hirata, Tomoyuki Kawada, M MinamiAbstract:We previously reported that the frequency of sister chromatid exchanges (SCEs) among victims of the Tokyo subway Sarin disaster was significantly higher than that of controls 2-3 months after the disaster. It has been reported that the victims were also exposed to the by-products generated during Sarin synthesis, i.e., diisopropyl methylphosphonate (DIMP), diethyl methylphosphonate (DEMP) and N,N-diethylaniline (DEA) during the disaster and we previously found that DIMP, DEMP and DEA induced a significant SCE increase in human lymphocytes in vitro. To monitor the genetic aftereffects of the Sarin exposure, SCEs of peripheral blood lymphocytes were measured in fire fighters and police officers involved in the disaster 3 years after the event. We found that the frequency of SCEs was still significantly higher in the exposed subjects than the controls, suggesting a risk of the genetic aftereffects of the Sarin exposure. We further found a significant positive correlation between the frequency of SCEs and the inhibition of serum cholinesterase activity in the exposed subjects, suggesting that the elevated frequency of SCEs is related to the Sarin exposure. On the other hand, there was no significant difference in natural killer activity between the exposed and the controls.
-
The by-products generated during Sarin synthesis in the Tokyo Sarin disaster induced inhibition of natural killer and cytotoxic T lymphocyte activity.
Toxicology, 2000Co-Authors: Yukiyo Hirata, S Piao, M MinamiAbstract:More than 5000 passengers on Tokyo subway trains were injured by the nerve gas, Sarin and its by-products. Analysis of phosphor-carrying metabolites of Sarin and its by-products in urine samples from the victims suggested that they were exposed not only to Sarin, but also by-products generated during Sarin synthesis, i.e. diisopropyl methylphosphonate (DIMP) and diethyl methylphosphonate (DEMP). We suspected genetic after-effects due to Sarin by-products, thus, we checked the frequency of sister chromatid exchange (SCE) and found that SCE was significantly higher in the victims than in a control group, and that DIMP and DEMP significantly induced human lymphocyte SCE in vitro. In the present study, to explore whether DIMP and DEMP, which induced a high frequency of SCE of lymphocytes, also affected the lymphocyte functions, we examined the effect of DIMP and DEMP on splenic natural killer (NK) and splenic cytotoxic T lymphocyte (CTL) activity in mice, and NK activity of human lymphocytes in vitro. We found that DIMP and DEMP significantly inhibited NK and CTL activity in a dose-dependent manner. The inhibition induced by DIMP was stronger than that by DEMP. The effect of DIMP and DEMP on the splenic NK activity of mice was stronger than on the splenic CTL activity, and the human lymphocytes is more sensitive to DIMP and DEMP than the splenocytes of mice.
-
Elevated frequency of sister chromatid exchanges in lymphocytes of victims of the Tokyo Sarin disaster and in experiments exposing lymphocytes to by-products of Sarin synthesis.
Toxicology letters, 1998Co-Authors: M Minami, J G Clement, C A BouletAbstract:More than 5000 passengers of Tokyo subway trains were injured with toxic chemicals including the nerve gas Sarin. Most of the victims examined had marked miosis and decreased serum cholinesterase activity. To monitor the genetic aftereffects of Sarin exposure, we measured sister chromatid exchanges (SCEs) of the victims using peripheral blood lymphocytes. The frequency of SCEs was significantly higher in the victims than in the control group. Analyzing results using samples of urine from the victims suggested that the victims were exposed to not only Sarin per se, but by-products of Sarin synthesis, i.e. diisopropyl methylphosphonate (DIMP), diethyl methylphosphonate (DEMP) and ethyl isopropyl methylphosphonate (EIMP). Thus, the in vitro SCE-inducing effect of DIMP, DEMP and EIMP was examined using human lymphocytes and we obtained positive results.
Madhusoodana P. Nambiar - One of the best experts on this subject based on the ideXlab platform.
-
Aerosolized scopolamine protects against microinstillation inhalation toxicity to Sarin in guinea pigs.
Toxicology Mechanisms and Methods, 2011Co-Authors: Magnus M. Che, Soma Chanda, Peter Rezk, Praveena Sabnekar, Michael W Perkins, Bhupendra P Doctor, Alfred M. Sciuto, Jian Song, Madhusoodana P. NambiarAbstract:Sarin is a volatile nerve agent that has been used in the Tokyo subway attack. Inhalation is predicted to be the major route of exposure if Sarin is used in war or terrorism. Currently available treatments are limited for effective postexposure protection against Sarin under mass casualty scenario. Nasal drug delivery is a potential treatment option for mass casualty under field conditions. We evaluated the efficacy of endotracheal administration of muscarinic antagonist scopolamine, a secretion blocker which effectively crosses the blood-brain barrier for protection against Sarin inhalation toxicity. Age and weight matched male Hartley guinea pigs were exposed to 677.4 mg/m3 or 846.5 mg/ m3 (1.2 × LCt50) Sarin by microinstillation inhalation exposure for 4 min. One minute later, the animals exposed to 846.5 mg/ m3 Sarin were treated with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 h for efficacy evaluation. The results showed that treatment with scopolamine increased...
-
Aerosolized scopolamine protects against microinstillation inhalation toxicity to Sarin in guinea pigs
Toxicology mechanisms and methods, 2011Co-Authors: Magnus M. Che, Soma Chanda, Peter Rezk, Praveena Sabnekar, Michael W Perkins, Bhupendra P Doctor, Alfred M. Sciuto, Jian Song, Madhusoodana P. NambiarAbstract:Sarin is a volatile nerve agent that has been used in the Tokyo subway attack. Inhalation is predicted to be the major route of exposure if Sarin is used in war or terrorism. Currently available treatments are limited for effective postexposure protection against Sarin under mass casualty scenario. Nasal drug delivery is a potential treatment option for mass casualty under field conditions. We evaluated the efficacy of endotracheal administration of muscarinic antagonist scopolamine, a secretion blocker which effectively crosses the blood-brain barrier for protection against Sarin inhalation toxicity. Age and weight matched male Hartley guinea pigs were exposed to 677.4 mg/m³ or 846.5 mg/ m³ (1.2 × LCt₅₀) Sarin by microinstillation inhalation exposure for 4 min. One minute later, the animals exposed to 846.5 mg/ m³ Sarin were treated with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 h for efficacy evaluation. The results showed that treatment with scopolamine increased the survival rate from 20% to 100% observed in untreated Sarin-exposed animals. Behavioral symptoms of nerve agent toxicity including, convulsions and muscular tremors were reduced in Sarin-exposed animals treated with scopolamine. Sarin-induced body weight loss, decreased blood O₂ saturation and pulse rate were returned to basal levels in scopolamine-treated animals. Increased bronchoalveolar lavage (BAL) cell death due to Sarin exposure was returned to normal levels after treatment with scopolamine. Taken together, these data indicate that postexposure treatment with aerosolized scopolamine prevents respiratory toxicity and protects against lethal inhalation exposure to Sarin in guinea pigs.
-
recombinant paraoxonase 1 protects against Sarin and soman toxicity following microinstillation inhalation exposure in guinea pigs
Toxicology Letters, 2011Co-Authors: Manojkumar Valiyaveettil, Peter Rezk, Michael W Perkins, Bhupendra P Doctor, Madhusoodana P. Nambiar, Alfred M. Sciuto, Yonas AlamnehAbstract:To explore the efficacy of paraoxonase 1 (PON1) as a catalytic bioscavenger, we evaluated human recombinant PON1 (rePON1) expressed in Trichoplusia ni larvae against Sarin and soman toxicity using microinstillation inhalation exposure in guinea pigs. Animals were pretreated intravenously with catalytically active rePON1, followed by exposure to 1.2 X LCt50 Sarin or soman. Administration of 5 units of rePON1 showed mild increase in the blood activity of the enzyme after 30 min, but protected the animals with a significant increase in survival rate along with minimal signs of nerve agent toxicity. Recombinant PON1 pretreated animals exposed to Sarin or soman prevented the reduction of blood O2 saturation and pulse rate observed after nerve agent exposure. In addition, rePON1 pretreated animals showed significantly higher blood PON1, acetylcholinesterase (AChE), and butyrylcholinesterase activity after nerve agent exposure compared to the respective controls without treatments. AChE activity in different brain regions of rePON1 pretreated animals exposed to Sarin or soman were also significantly higher than respective controls. The remaining activity of blood PON1, cholinesterases and brain AChE in PON1 pretreated animals after nerve agent exposure correlated with the survival rate. In summary, these data suggest that human rePON1 protects against Sarin and soman exposure in guinea pigs.
Nobuo Yanagisawa - One of the best experts on this subject based on the ideXlab platform.
-
Sequelae of Sarin toxicity at one and three years after exposure in Matsumoto, Japan.
Journal of epidemiology, 1999Co-Authors: Tamie Nakajima, Setsuko Ohta, Yoshimitsu Fukushima, Nobuo YanagisawaAbstract:In order to clarify the later sequelae of Sarin poisoning that occurred in Matsumoto City, Japan, on June 27, 1994, a cohort study was conducted on all persons (2052 Japanese people) inhabiting an area 1050 meters from north to south and 850 meters from east to west with the Sarin release site in the center. Respondents numbered 1237 and 836 people when surveys were conducted at one and three years after the Sarin incident, respectively. Numbers of persons with symptoms of Sarin toxicity were compared between Sarin victims and non-victims. Of the respondents, 58 and 46 people had symptoms associated with Sarin such as fatigue, asthenia, shoulder stiffness, asthenopia and blurred vision at both points of the survey, respectively. The prevalences were low; some complained of insomnia, had bad dreams, difficulty in smoking, husky voice, slight fever and palpitation. The victims who had symptoms one year after the incident had a lower erythrocyte cholinesterase activity than did those who did not have symptoms at the early stage; such persons lived in an area with a 500 meter long axis north east from the Sarin release site. The three-year cohort study clearly showed that the odds ratios of almost all of the symptoms were high in the Sarin-exposed group, suggesting a positive relationship between symptoms and grades of exposure to Sarin. These results suggest that symptoms reported by many victims of the Sarin incident are thought to be sequelae related to Sarin exposure J Epidemiol, 1999 ; 9 : 337-343
-
Urinary metabolites of Sarin in a patient of the Matsumoto Sarin incident.
Archives of toxicology, 1998Co-Authors: Tamie Nakajima, Yoshimitsu Fukushima, Hiroshi Morita, K. Sasaki, H. Ozawa, Yoshiki Sekijima, Nobuo YanagisawaAbstract:Sarin metabolites were measured in urine from a patient with Sarin poisoning. Two metabolites, methylphosphonic acid (MPA) and isopropylmethylphosphonic acid (iPMPA), were detected by gas chromatography after conversion to volatile derivatives with N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide in the urine from the victim collected on the first day of hospitalization. iPMPA was detected in the urine on the seventh day, but MPA could not be detected in the urine sample. MPA was narrowly detected in the urine collected on the third day. The concentration of iPMPA was estimated on the assumption that the sensitivity of phosphorus was the same as that of MPA. The total excretion of iPMPA and MPA in the urine was 2.1 mg and 0.45 mg, respectively. When all the Sarin inhaled was excreted within a week as these two metabolites, the subject was considered to have been exposed to 2.79 mg (0.05 mg/kg) Sarin at the incident. Thus, the measurement of Sarin metabolites in urine is a useful tool for the biological monitoring of exposure to Sarin.
-
Epidemiological Study of Sarin Poisoning in Matsumoto City, Japan
Journal of epidemiology, 1998Co-Authors: Tamie Nakajima, Setsuko Ohta, Hiroshi Morita, Youko Midorikawa, Shohei Mimura, Nobuo YanagisawaAbstract:On the night of June 27, 1994, about 12 liters of Sarin were released by terrorists in Matsumoto City, Japan. In order to investigate the epidemic, community-based questionnaire surveys were conducted. The subjects were all inhabitants (2052 people) living and staying in an area of 1050 meters from north to south and 850 meters from east to west including the Sarin release site. Participants included 1743 people who answered the questionnaire at the first survey; those with symptoms were contacted for follow-up at four months and one year after the episode. The number of Sarin victims were 471 persons. Muscarinic signs were common to all victims; nicotinic signs were only seen in severely affected victims. The geographical distribution of Sarin victims was closely related to the direction of the wind. Three weeks after the intoxication, 129 victims still had some symptoms such as dysesthesia of the extremities. At that time, many victims had begun to experience asthenopia, which was even more frequent at four months. Although victims who felt Sarin-related symptoms had decreased by a year, some still had symptoms such as asthenopia. Sarin released in a suburban area affected approximately 500 inhabitants living nearby; some still had symptoms a year after the intoxication. J Epidemiol, 1998; 8 : 33-41.
-
Sarin poisoning of a rescue team in the Matsumoto Sarin incident in Japan.
Occupational and environmental medicine, 1997Co-Authors: Tamie Nakajima, Seiji Sato, Hiroshi Morita, Nobuo YanagisawaAbstract:OBJECTIVES: A nerve agent Sarin (isopropyl methyl phosphonofluoridate) was released in Matsumoto city, Japan, on 27 June 1994. About 600 people were affected by the Sarin, including seven who died. Fifty two rescuers engaged in helping the victims and 18 were affected. The aim was to investigate how the rescuers were affected by Sarin. METHODS: Health examinations and a questionnaire survey were conducted with all rescuers. RESULTS: A rescuer who was one of the first engaged and who worked for about five hours in areas contaminated with Sarin was admitted to hospital after poisoning; the others did not consult doctors although they showed slight muscarinic symptoms. The later the rescuers started their work, the less likely they were to experience symptoms of Sarin exposure, and no one starting work 270 minutes after the original release of Sarin was affected. The symptoms of exposure included ocular pain, darkness of visual field, nausea, vomiting, headache, rhinorrhea, narrowing of visual field, sore throat, fatigue, and dyspnoea, which were similar to those reported by the citizens who were Sarin victims. There were no rescuers who had abnormal physical or neurological signs associated with Sarin at the time of the physical examination conducted three weeks after the Sarin release. A year after the Sarin incident, the symptoms of all the rescuers had resolved. CONCLUSIONS: Rescuers should protect themselves with appropriate clothing, gloves, and a mask to prevent a secondary disaster for at least 24 hours after a similar accident.
Gerald H. Stein - One of the best experts on this subject based on the ideXlab platform.
-
Prehospital management of Sarin nerve gas terrorism in urban settings: 10 years of progress after the Tokyo subway Sarin attack.
Resuscitation, 2005Co-Authors: Yasuharu Tokuda, Makiko Kikuchi, Osamu Takahashi, Gerald H. SteinAbstract:Chemical agents have been used previously in wartime on numerous occasions, from World War I to the Gulf War. In 1994 and1995, Sarin nerve gas was used first in peacetime as a weapon of terrorism in Japan. The Tokyo subway Sarin attack was the first large-scale disaster caused by nerve gas. A religious cult released Sarin gas into subway commuter trains during morning rush hour. Twelve passengers died and about 5500 people were harmed. Sarin is a highly toxic nerve agent that can be fatal within minutes to hours. It causes the clinical syndrome of cholinergic hyperstimulation by inhibition of the crucial enzyme acetylcholinesterase. Therapy of nerve agent toxicity is divided into three categories, decontamination, respiratory support, and antidotes. All of these therapies may be given simultaneously. This article reviews toxicology and management of this acute chemical emergency. To help minimize the possible catastrophic impact on the public, we make several recommendations based on analysis of the Tokyo subway Sarin attack and systematically review the current scientific literature.
Tamie Nakajima - One of the best experts on this subject based on the ideXlab platform.
-
Sequelae of Sarin toxicity at one and three years after exposure in Matsumoto, Japan.
Journal of epidemiology, 1999Co-Authors: Tamie Nakajima, Setsuko Ohta, Yoshimitsu Fukushima, Nobuo YanagisawaAbstract:In order to clarify the later sequelae of Sarin poisoning that occurred in Matsumoto City, Japan, on June 27, 1994, a cohort study was conducted on all persons (2052 Japanese people) inhabiting an area 1050 meters from north to south and 850 meters from east to west with the Sarin release site in the center. Respondents numbered 1237 and 836 people when surveys were conducted at one and three years after the Sarin incident, respectively. Numbers of persons with symptoms of Sarin toxicity were compared between Sarin victims and non-victims. Of the respondents, 58 and 46 people had symptoms associated with Sarin such as fatigue, asthenia, shoulder stiffness, asthenopia and blurred vision at both points of the survey, respectively. The prevalences were low; some complained of insomnia, had bad dreams, difficulty in smoking, husky voice, slight fever and palpitation. The victims who had symptoms one year after the incident had a lower erythrocyte cholinesterase activity than did those who did not have symptoms at the early stage; such persons lived in an area with a 500 meter long axis north east from the Sarin release site. The three-year cohort study clearly showed that the odds ratios of almost all of the symptoms were high in the Sarin-exposed group, suggesting a positive relationship between symptoms and grades of exposure to Sarin. These results suggest that symptoms reported by many victims of the Sarin incident are thought to be sequelae related to Sarin exposure J Epidemiol, 1999 ; 9 : 337-343
-
Urinary metabolites of Sarin in a patient of the Matsumoto Sarin incident.
Archives of toxicology, 1998Co-Authors: Tamie Nakajima, Yoshimitsu Fukushima, Hiroshi Morita, K. Sasaki, H. Ozawa, Yoshiki Sekijima, Nobuo YanagisawaAbstract:Sarin metabolites were measured in urine from a patient with Sarin poisoning. Two metabolites, methylphosphonic acid (MPA) and isopropylmethylphosphonic acid (iPMPA), were detected by gas chromatography after conversion to volatile derivatives with N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide in the urine from the victim collected on the first day of hospitalization. iPMPA was detected in the urine on the seventh day, but MPA could not be detected in the urine sample. MPA was narrowly detected in the urine collected on the third day. The concentration of iPMPA was estimated on the assumption that the sensitivity of phosphorus was the same as that of MPA. The total excretion of iPMPA and MPA in the urine was 2.1 mg and 0.45 mg, respectively. When all the Sarin inhaled was excreted within a week as these two metabolites, the subject was considered to have been exposed to 2.79 mg (0.05 mg/kg) Sarin at the incident. Thus, the measurement of Sarin metabolites in urine is a useful tool for the biological monitoring of exposure to Sarin.
-
Epidemiological Study of Sarin Poisoning in Matsumoto City, Japan
Journal of epidemiology, 1998Co-Authors: Tamie Nakajima, Setsuko Ohta, Hiroshi Morita, Youko Midorikawa, Shohei Mimura, Nobuo YanagisawaAbstract:On the night of June 27, 1994, about 12 liters of Sarin were released by terrorists in Matsumoto City, Japan. In order to investigate the epidemic, community-based questionnaire surveys were conducted. The subjects were all inhabitants (2052 people) living and staying in an area of 1050 meters from north to south and 850 meters from east to west including the Sarin release site. Participants included 1743 people who answered the questionnaire at the first survey; those with symptoms were contacted for follow-up at four months and one year after the episode. The number of Sarin victims were 471 persons. Muscarinic signs were common to all victims; nicotinic signs were only seen in severely affected victims. The geographical distribution of Sarin victims was closely related to the direction of the wind. Three weeks after the intoxication, 129 victims still had some symptoms such as dysesthesia of the extremities. At that time, many victims had begun to experience asthenopia, which was even more frequent at four months. Although victims who felt Sarin-related symptoms had decreased by a year, some still had symptoms such as asthenopia. Sarin released in a suburban area affected approximately 500 inhabitants living nearby; some still had symptoms a year after the intoxication. J Epidemiol, 1998; 8 : 33-41.
-
Sarin poisoning of a rescue team in the Matsumoto Sarin incident in Japan.
Occupational and environmental medicine, 1997Co-Authors: Tamie Nakajima, Seiji Sato, Hiroshi Morita, Nobuo YanagisawaAbstract:OBJECTIVES: A nerve agent Sarin (isopropyl methyl phosphonofluoridate) was released in Matsumoto city, Japan, on 27 June 1994. About 600 people were affected by the Sarin, including seven who died. Fifty two rescuers engaged in helping the victims and 18 were affected. The aim was to investigate how the rescuers were affected by Sarin. METHODS: Health examinations and a questionnaire survey were conducted with all rescuers. RESULTS: A rescuer who was one of the first engaged and who worked for about five hours in areas contaminated with Sarin was admitted to hospital after poisoning; the others did not consult doctors although they showed slight muscarinic symptoms. The later the rescuers started their work, the less likely they were to experience symptoms of Sarin exposure, and no one starting work 270 minutes after the original release of Sarin was affected. The symptoms of exposure included ocular pain, darkness of visual field, nausea, vomiting, headache, rhinorrhea, narrowing of visual field, sore throat, fatigue, and dyspnoea, which were similar to those reported by the citizens who were Sarin victims. There were no rescuers who had abnormal physical or neurological signs associated with Sarin at the time of the physical examination conducted three weeks after the Sarin release. A year after the Sarin incident, the symptoms of all the rescuers had resolved. CONCLUSIONS: Rescuers should protect themselves with appropriate clothing, gloves, and a mask to prevent a secondary disaster for at least 24 hours after a similar accident.
