Potential Role Of Ricin As A Toxic Agent

Faculty Medicine Year: 2007
Type of Publication: Theses Pages: 188
Authors:
BibID 10341777
Keywords : ricin    
Abstract:
Summary and ConclusionThis essay gives an overview on chemical and biological terrorism agents and presents in details one of the toxic weapons which became a favorite tool of extremist individuals or groups who seek to harm others.Biological and chemical weapons:Chemical and biological warfare agents are weapons that can be used not only for military purposes, but also on civilian populations as weapons of terror because of their toxicity and rapid effect. Terrorist interest in the use of chemical and biological (CB) weapons has grown substantially since the Tokyo subway was attacked with sarin, a nerve agent, in 1995. The recent war between the United States and Iraq as well as the current threat of further US military involvement in the Gulf region has reportedly raised the prospect of the use of CB weapons both on the battlefield and in terrorist attacks on civilian populations anywhere in the world.There has always been the possibility of a chemical attack, but only since 11 September 2001 have we been especially aware of this vulnerability. In addition to the death and physical injury they cause, the use of CWAs may also give rise to fear, panic, and psychological trauma throughout the population. Fear of the use of these weapons should cause the government and the general public to expand resources to tackle this threat, including purchasing protective equipment, delivering specialised training. In many ways, medical preparedness is the best defence and is something that can be done immediately. Successful management of casualties in a toxic chemical attack depends on planning, preparation, and training. Medical care of the casualties depends on knowledge of the agent and timely intervention.Biological weapons:A report in 2000 from the CDC divided biological agents into 3 categories based on the potential terrorist threat they may represent.Category A (highest priority) agents include organisms that pose arisk to national security because they are either easy to disseminate or highly contagious, cause high mortality with a potentially major public health impact, cause public panic and social disruption, and require special action for public health preparedness. This category includes the causative agents of anthrax, smallpox, plague, tularemia, botulism, and viral hemorrhagic fevers (eg, Ebola, Marburg, Lassa, and others).Category B (second highest priority) agents include those that are moderately easy to disseminate. These agents cause lower mortality but significant morbidity and require specific enhancements of diagnostic capacity and enhanced disease surveillance. They include the following: Coxiella burnetti (Q fever), Brucella species (brucellosis), Burkholderia mallei (glanders); alpha viruses (Venezuelan encephalomyelitis and similar diseases), ricin toxin from Ricinus communis (castor beans), _ toxin of Clostridium perfringens, and Staphylococcus enterotoxin B. Also included in this category are food or waterborne pathogens such as Salmonella species, Shigella dysenteriae, Escherichia coli O157:H7, Vibrio cholerae, and Cryptosporidium parvum.Category C (third highest priority) agents could be engineered for mass dissemination in the future because of availability, ease of production and dissemination, and potential for high morbidity and mortality and major health impact. Some of these agents include Nipah virus, hantaviruses, tickborne hemorrhagic fever viruses, tickborne encephalitis viruses, yellow fever, and multidrug-resistant tuberculosis.Chemical agents:They include:Nerve agents: they are organophosphorus compounds acting as potent inhibitors of acetyl cholinesterase similar to the organophosphate insecticides.Vesicants: The major vesicants, or blistering agents, are cellular poisons and include the DNA alkylating agent, mustard, and the organic arsenical, lewisite.Pulmonary Agents: The toxic inhalants chlorine and phosgene were used as weapons in World War I, and are commonly used for industrial purposes today. Chlorine lung injury probably is mediated both by generation of hydrochloric acid and free oxygen radical cascade.Cyanide: Its efficacy as a chemical terrorism agent is considered limited by its volatility in open air and relatively low lethality compared with nerve agents.Riot Control Agents: Several compounds of the lacrimator, or “tear gas,” category could cause significant disruption and panic if released into a large crowd, especially within a closed space.Ricin:History and military significance:Stillmark discovered ricin in the late 1800s, and from this date till now many scientists performed different studies on that agent. Because of its heat stability, relatively high toxicity and extreme ease of production, ricin was considered for weaponization since the World Ware II and in the recent years it became a favorite tool of extremist individuals and groups who seek to harm other.Description of the agent:Ricin toxin, found in the bean of the castor plant, Ricinis communis, is one of the most toxic and easily produced plant toxins. It is a lectin consisting of two polypeptide chains, the A-chain and the B-chain, linked by a disulfide bond. It is one of a group of dichain ribosome-inactivating proteins, which are specific for the depurination of a single adenosine in ribosomal ribonucleic acid (RNA).Mechanism of ricin action:The B polypeptide chain of ricin is responsible for binding ricin to cell surface glycoproteins and glycolipids. After this binding, ricin is taken into the cells by endocytosis. From the endocytotic vesicles ricin is delivered to early endosome where it is either recycled to the cell surface or delivered to the lysosomes. However recent studies revealed that ricin is transported from endosome to Golgi apparatus and retrograde transport from Golgi to endoplasmic reticulum does occur.The active chain (ie, the A-chain) has the ability to modify catalytically the 28S subunit of eucaryotic ribosomes to block protein synthesis.Many studies were performed to prove that ricin induces oxidative stresses.Therapeutic uses of ricin:Ricin is a promising candidate for treatment of cancer because it can be selectively targeted to tumor cells via linkage to monoclonal antibodies.Ricin also have been tried in treatment of many immunological disorders as diabetes mellitus type I, rheumatoid arthritis, systemic lupus erythematosus, graft versus host disease with encouraging results.Clinical manifestations of toxicity:The clinical signs, symptoms, and pathological manifestations of ricin toxicity vary with the dose and the route of exposure. Experimental animal studies indicate that clinical signs and pathological changes are largely route specific; for example, inhalation results in respiratory distress and airway and pulmonary lesions; ingestion causes gastrointestinal signs and gastrointestinal hemorrhage with necrosis of liver, spleen, and kidneys; and intramuscular intoxication causes severe localized pain, muscle and regional lymph node necrosis, and moderate involvement of visceral organs.Diagnosis of ricin intoxication:Like other potential intoxications on the unconventional battlefield, epidemiological findings will likely play a central role in diagnosis. The observation of multiple cases of very severe pulmonary distress in a population of previously healthy young soldiers, linked with a history of their having been at the same place and time during climatic conditions suitable for biological warfare attack, would be suggestive. The differential diagnoses of aerosol exposure to ricin would include staphylococcal enterotoxin B, exposure to pyrolysis by-products of organofluorine polymers. Confirmation of ricin inhalational intoxication would most likely be through enzyme-linked immunosorbent assay analysis of a swab sample from the nasal mucosa. Enzyme-linked immunosorbent assays (for blood or other body fluids) or immunohistochemical techniques (for direct analysis of tissues) may be useful in confirming ricin intoxication. However, because ricin is bound very quickly regardless of route of challenge, and metabolized before excretion, identification in body fluids or tissues is difficult.Treatment of ricin intoxication:Because ricin acts rapidly and irreversibly (directly on lung parenchyma after inhalation, or is distributed quickly to vital organs after parenteral exposure), post exposure therapy is more difficult and it depends mainly on symptomatic therapies. Therefore, immunization of personnel at risk for ricin exposure is even more important than it is for some of the other potential biological warfare agents. 
   
     
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