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.
Biological Warfare Agents ; Chemical Warfare Agents ; Civil Defense ; Nuclear Weapons ; Terrorism

Phosgene is not only a dangerous asphyxiating chemical warfare agent, but also an important chemical raw material, which is widely used in chemical production. According to statistics, there are more than 1 000 phosgene production enterprises in China, with an annual production volume of more than 3 million tons and hundreds of thousands of employees. Therefore, once the leakage accident occurs during production, storage and transportation, it often causes a large number of casualties. In the past 20 years, phosgene poisoning accidents in China have occurred from time to time, and due to the weak irritation, high density, and high concentration of phosgene at the scene of the accident, it often results in acute high-concentration inhalation of the exposed, triggering acute lung injury (ALI), and is very likely to progress to acute respiratory distress syndrome (ARDS), with a mortality rate up to 40%-50%. In view of the characteristics of sudden, mass, concealed, rapid and highly fatal phosgene, and the mechanism of its toxicity and pathogenicity is still not clear, there is no effective treatment and standardized guidance for the sudden group phosgene poisoning. In order to improve the efficiency of clinical treatment and reduce the mortality, this paper has summarized the pathophysiological mechanism of phosgene poisoning, clinical manifestations, on-site treatment, research progress, and innovative clinical therapies by combining the extensive basic research on phosgene over the years with the abundant experience in the on-site treatment of sudden mass phosgene poisoning. This consensus aims to provide guidance for the clinical rescue and treatment of patients with sudden mass phosgene poisoning, and to improve the level of treatment.
Humans ; Phosgene ; Chemical Warfare Agents ; Acute Lung Injury/drug therapy* ; Respiratory Distress Syndrome/therapy* ; Treatment Outcome

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.
Adult ; Chemical Warfare ; Chemical Warfare Agents ; pharmacology ; Humans ; Iran ; Lung ; diagnostic imaging ; Lung Injury ; chemically induced ; epidemiology ; Male ; Middle Aged ; Mustard Gas ; pharmacology ; Respiratory System ; drug effects ; Survivors ; Tomography, X-Ray Computed ; Veterans ; statistics & numerical data

OBJECTIVESulfur 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.

METHODSA 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.

RESULTSSearch 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.

CONCLUSIONSSM 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.

Alanine Transaminase ; blood ; Chemical Warfare Agents ; poisoning ; Hormones ; blood ; Humans ; Immune System ; drug effects ; Male ; Mustard Gas ; poisoning ; Myocardial Perfusion Imaging ; Spirometry ; Veterans

OBJECTIVETo observe the significance of ricin (RT) with chemical nidification to reduce the hepatotoxicity in mice and its anticancer effect.

METHODSMice were exposed to RT and RT-PDP [ricin chemically modified by N-succinimidyl 3-(2-pyridyldithio)-propionate, (SPDP)] respectively, and their serum activity of glutathione-S-transferase (GST) and liver glutathione (GSH) content were determined. The ultramicro-structure under electron microscope was also observed.

RESULTSThe GST activity increased with doses, and the increase in ricin group was higher than that in RT-PDP group; the activities of GST in RT group at 12.5, 15.0 micro g/kg [(93.65 +/- 12.30), (153.71 +/- 26.64) IU/L respectively] were higher than those in RT-PDP group [(62.97 +/- 11.22), (78.20 +/- 15.71) IU/L] (P < 0.05). The contents of GSH were decreased with doses; but the contents of GSH in RT-PDP group at 2.5, 5.0, 7.5, 10.0, 15.0 micro g/kg [(6.34 +/- 1.43), (4.14 +/- 1.82), (3.54 +/- 0.64), (2.73 +/- 1.82), (1.82 +/- 0.62) micro mol/L respectively] were still higher than those in RT group [(3.53 +/- 0.95), (2.12 +/- 0.54), (1.82 +/- 0.71), (1.52 +/- 0.34), (0.81 +/- 0.36) micro mol/L] (P < 0.01). Electron microscopic examination showed that the injury of liver cells in RT group was more severe than that in RT-PDP group.

CONCLUSIONThe hepatotoxicity of ricin in mice may be reduced by chemical modification.

Animals ; Chemical Warfare Agents ; toxicity ; Female ; Glutathione ; metabolism ; Glutathione Transferase ; metabolism ; Liver ; drug effects ; metabolism ; ultrastructure ; Male ; Mice ; Microscopy, Electron ; Ricin ; analogs & derivatives ; toxicity

OBJECTIVETo study the effect of acute phosgene inhalation on the antioxidant enzymes, nitric oxide (NO) and nitric oxide synthase (NOS) in rats.

METHODSPhosgene was produced by decomposing bis (trichdomethyl) carbonate in the presence of N,N-dimethyl formamide. SD rats were randomly divided into two groups: control and phosgene exposure groups. In a special experimental device with equipment modulating the gas flow, phosgene exposed rats inhaled phosgene quantitatively for five minutes. Two hours later, all the rats were sacrificed and the ratio of wet weight to dried weight of lung (WW/DW) was calculated. Peripheral blood, serum and liver were collected to examine the activities of antioxidant enzymes including glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), NOS, and NO level. The total content of proteins were also determined.

RESULTSThe WW/DW ratio of lung in phosgene exposure group was much higher than that in control group (P < 0.01). The activities of GST in serum and liver of phosgene exposure group increased significantly (P < 0.05). The activities of SOD, CAT, GSHPx and NOS in serum or blood and liver of phosgene exposure group were also increased significantly (P < 0.05). But the content of NO was significantly decreased (P < 0.01).

CONCLUSIONAcute phosgene inhalation may cause a dramatically changes of several antioxidant enzyme activities, and acute injury of liver to some extent in rats. The latter is related to reactive oxygen species. But the elevation of antioxidant enzyme activities suggests that antioxidative treatment for acute phosgene poisoning should not be considered first.

Animals ; Antioxidants ; metabolism ; Chemical Warfare Agents ; poisoning ; Glutathione Peroxidase ; metabolism ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Phosgene ; poisoning ; Poisoning ; enzymology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the protective efficacy of gossypin (3,3',4',5,7,8-hexahydroxyflavone 8-glucoside) by administering it intraperitoneally, for dose, time, and vehicle dependent effects against sulphur mustard (SM), administered through percutaneous route in mice.

METHODSSM (diluted in PEG-300) was administered percutaneously. The protective efficacy of gossypin was evaluated by administering it intraperitoneally (50, 100, 200, and 400 mg/kg), in various vehicles (water, PEG-300 and DMSO), and time intervals (30 min prior, simultaneous and 2 h post). The time dependent protection of gossypin (200 mg/kg in PEG-300; i.p.) was also evaluated using selected biochemical variables (GSH, GSSG, MDA, total antioxidant status, Hb, WBC count, RBC count, glutathione peroxidase, glutathione reductase, and superoxide dismutase) and liver histology. The protection of gossypin by oral route was also evaluated against percutaneously administered SM.

RESULTSThe protection against systemic toxicity of SM (LD50 8.1 mg/kg) was better when gossypin was given with PEG-300 (8.0 folds) than DMSO (5.7 folds). No protection was observed when gossypin was administered with water. Good protection (8.0 folds) was observed when gossypin was administered (200 mg/kg in PEG-300; i.p.) at 30 min prior or simultaneous to SM exposure, but no protection was observed when gossypin was administered 2 h post to SM exposure. A significant weight loss was observed 7 days after SM administration (2 LD50), with a significant increase in RBC and Hb. A significant decrease in total antioxidant status of plasma, liver GSH and GSSG levels, and in the activities of glutathione peroxidase, glutathione reductase and superoxide dismutase was also observed 7 days after SM administration. SM treated mouse liver also showed necrosis. A significant protection was observed when gossypin (200 mg/kg in PEG-300; i.p.) was administered either as a pretreatment (30 min before) or simultaneous treatment, and not as a post treatment (2 h). The protective efficacy of gossypin was better through oral route when administered with DMSO (4.8 folds) than with PEG-300 (2.4 folds). No protection was observed when gossypin was administered orally with water.

CONCLUSIONPercutaneous administration of SM induces oxidative stress and gossypin can protect it as a prophylactic agent by intraperitoneal or oral routes.

Administration, Cutaneous ; Animals ; Blood Cell Count ; Body Weight ; drug effects ; Chemical Warfare Agents ; toxicity ; Female ; Flavonoids ; administration & dosage ; pharmacology ; Hemoglobins ; metabolism ; Liver ; cytology ; drug effects ; pathology ; Mice ; Mustard Gas ; administration & dosage ; toxicity ; Oxidative Stress ; drug effects ; Time Factors

OBJECTIVETo study the apoptosis of alveolar type II cells, alterations of vascular endothelial growth factor (VEGF), VEGF receptor (Flt1) in serum and lung and expression of VEGF mRNA in lung in pulmonary edema mice induced by phosgene.

METHODSTwenty-six BALB/C mice were randomly divided into 2 groups: control group, exposed group (13 mice in each group). Mice of exposed group were intoxicated by inhalation of phosgene 11.9 mg/L for 5 minutes. Mice of control group were treated as the same way by inhalation of air. Isolation of mice alveolus type II cells 4 h after intoxication was carried out to observe their apoptosis under electron microscope. Contents of VEGF and Flt1 in lung and serum by ELISA, and expression of VEGF mRNA were determined.

RESULTSAlveolar type II cells were identified by tannic acid staining and electron microscopy. After exposed to 11.9 mg/L of phosgene for 5 minutes, the apoptotic body in alveolus type II cells was found in exposed group. The contents of VEGF in serum and lung and Flt1 in lung of exposed mice [(134.07 +/- 120.26), (477.76 +/- 98.06), (1,2818.48 +/- 2,304.15) pg/ml] were significantly lower than those of control group [(445.57 +/- 173.30), (1,026.87 +/- 474.56), (21,976.51 +/- 7,421.01) pg/ml, P < 0.05] but the content of Flt1 in serum [(2,369.56 +/- 381.70) pg/ml] was higher than that in control group [(1,898.00 +/- 453.69) pg/ml, P < 0.05]. The expression of VEGF mRNA in pulmonary edema mice was decreased.

CONCLUSIONPhosgene can induce apoptosis of alveolar type II cells, and decrease in the content of VEGF and Flt1, and expression of VEGF mRNA in lung.

Animals ; Apoptosis ; drug effects ; Cells, Cultured ; Chemical Warfare Agents ; toxicity ; Endothelial Growth Factors ; biosynthesis ; genetics ; Enzyme-Linked Immunosorbent Assay ; Male ; Mice ; Mice, Inbred BALB C ; Phosgene ; toxicity ; Pulmonary Alveoli ; drug effects ; metabolism ; pathology ; Pulmonary Edema ; chemically induced ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Vascular Endothelial Growth Factor A ; analysis ; genetics ; physiology ; Vascular Endothelial Growth Factor Receptor-1 ; analysis ; genetics

OBJECTIVETo 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).

METHODSWe 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.

RESULTSA 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).

CONCLUSIONAd.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.

Acute Lung Injury ; chemically induced ; metabolism ; Adenoviridae ; genetics ; Angiopoietin-1 ; physiology ; Animals ; Bronchoalveolar Lavage Fluid ; Chemical Warfare Agents ; toxicity ; Disease Models, Animal ; Lung ; metabolism ; Matrix Metalloproteinase 2 ; genetics ; Matrix Metalloproteinases ; metabolism ; Phosgene ; toxicity ; RNA, Messenger ; genetics ; RNA, Small Interfering ; Rats ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism

OBJECTIVETo investigate the effect of melatonin (MT) on p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with phosgene-induced lung injury.

METHODSFifty 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.

RESULTSCompared 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).

CONCLUSIONMT 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.

Animals ; Bronchoalveolar Lavage Fluid ; Chemical Warfare Agents ; toxicity ; Imidazoles ; Lung ; drug effects ; Lung Injury ; chemically induced ; Male ; Malondialdehyde ; adverse effects ; Melatonin ; physiology ; Mice ; Nitric Oxide ; adverse effects ; Nitric Oxide Synthase Type II ; metabolism ; Phosgene ; toxicity ; Pyridines ; Rats, Sprague-Dawley ; Respiratory Distress Syndrome, Adult ; metabolism ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases ; metabolism