07 - Source Answers - Botulinum toxin is among the most poisonous substances known. The toxin, which can be ingested or inhaled, and which disrupts transmission of nerve impulses to muscles, is naturally produced by the bacterium Clostridium botulinum.

Certain strains of C. baratii and C. butyricum can also be capable of producing the toxin.

Botulinum toxin has become well known in recent years for two reasons. First, the toxin has become a weapon in the arsenal of terrorists. Contamination of food is one route for infection with the toxin. The toxin can also be released into the air, which was attempted on at least three occasions between 1990 and 1995 by the Japanese cult Aum Shinrikyo. The government of Iraq admitted to United Nations inspectors following the 1991 Persian Gulf War that tens of thousands of liters of botulism toxin had been produced and loaded into weapons. The toxin was the most numerous of all the biological weapons then developed by Iraq.

Paradoxically, the other reason for the toxin's fame is the use of the toxin as a cosmetic enhancement (i.e., "botox").

There are at least seven structurally different versions of botulinum toxin. The type designated as type A is responsible for some food-borne outbreaks in the United States and elsewhere. Improperly canned foods are a particular threat.

Clostridium botulinum is a spore-forming bacterium. Like the well-known anthrax bacillus, the spores of Clostridium botulinum can persist in the environment for many years and, when conditions become more favorable (i.e., in a wound, food, and the lungs) the spore can germinate and free the toxin. Dried preparations of the spores can thus represent a terrorist weapon.

The use of botulinum toxin as a weapon began in the 1930s, with experiments conducted by the Japanese on prisoners during the occupation of Manchuria. In World War II, plans were made to vaccinate Allied troops participating in the D-day invasion of Normandy, because of concerns that Germany had weaponized the toxin. Even the United States maintained an active biological weapons program, including the use of botulism toxin, into the late 1960s.

Botulism toxin acts by preventing the transmission of nerve signals between the nerves that connect with muscle cells. Progressive functional deterioration of the affected muscles occurs. Symptoms of botulism intoxication include dizziness, blurred or double vision, nausea, vomiting, diarrhea, and weakness of muscles in various areas of the body. The muscle failure can be so severe as to lead to coma and respiratory arrest. Even in those who survive exposure to the toxin, complete recovery can take months.

Further Reading

Books

Tucker, J.B., (ed.). Toxic Terror: Assessing the Terrorist Use of Chemical and Biological Weapons. Cambridge: MIT Press, 2000.

Periodicals

Byrne, M.P., and L.A. Smith. "Development of Vaccines for Prevention of Botulism." Biochimie no. 82 (2000): 955–966.

Kahn, A.S., S. Morse, and S. Lillibridge. "Public-health Prepardness for Biological Terrorism in the USA." Lancet no. 356 (2000): 1179–1182.

Montecucco, C. (ed.). "Clostridial Neurotoxins: The Molecular Pathogenesis of Tetanus and Botulism." Current Topics in Microbiology and Immunology no. 195 (1995): 1–278.

Lacy, D.B., W. Tepp, A.C. Cohen, et al. "Crystal Structure of Botulinum Neurotoxin Type A and Implications for Toxicity." Nature Structural Biology no. 5 (1998): 898–902.

Electronic

Centers for Disease Control and Prevention. "Botulism." Public Health Emergency Preparedness and Response. February 7, 2003. <http://www.bt.cdc.gov/agent/botulism/index.asp>(April 15, 2003).

Johns Hopkins University. "Botulinum Toxin." Center for Civilian Biodefense Strategies. 2002. <http://www.hopkins-biodefense.org/pages/agents/agentbotox.html>(April 15, 2003).

07 - Botulinum toxin - Richard Robinson - Source The Gale group

Definition

Botulinum toxin is the purified form of a poison created by the bacterium Clostridium botulinum. These bacteria grow in improperly canned food and cause botulism poisoning. Minute amounts of the purified form can be injected into muscles to prevent them from contracting; it is used in this way to treat a wide variety of disorders and cosmetic conditions.

Purpose

Botulinum toxin was developed to treat strabismus (cross-eye or lazy eye), and was shortly thereafter discovered to be highly effective for many forms of dystonia. Spasticity can also be effectively treated with botulinum toxin. Injected into selected small muscles of the face, it can reduce wrinkling. Other conditions treated with botulinum toxin include:

* achalasia
* anismus
* back pain
* bruxism
* excess saliva production
* eyelid spasm
* headache
* hemifacial spasm
* hyperhidrosis
* migraine
* palatal myoclonus
* spastic bladder
* stuttering
* tics
* tremor
* uncontrollable eye blinking
* vaginismus

It is important to note that as of early 2004, the only Food and Drug Administration-approved uses for botulinum toxin are for certain forms of dystonia, hemifacial spasm, strabismus, blepharospasm (eyelid spasms), and certain types of facial wrinkles. While there is general recognition that certain other conditions can be effectively treated with botulinum toxin, other uses, including for headache or migraine, are considered experimental.

Description

A solution of botulinum toxin is injected into the overactive muscle. The toxin is taken up by nerve endings at the junction between nerve and muscle. Once inside the cell, the toxin divides a protein. The normal job of this protein is to help the nerve release a chemical, a neurotransmitter, which stimulates the muscle to contract. When botulinum toxin divides the protein, the nerve cannot release the neurotransmitter, and the muscle cannot contract as forcefully.

The effects of botulinum toxin begin to be felt several days after the injection. They reach their peak usually within two weeks, and then gradually fade over the next 2–3 months. Since the effects of the toxin disappear after several months, reinjection is necessary for continued muscle relaxation.

Recommended dosage

In the United States, purified botulinum toxin is available in two commercial forms: Botox and MyoBloc. The recommended doses of the two products are quite different, owing to the differing potencies of the two products. The size of the muscle and the degree of weakening desired also affect the dose injected. For Botox, the maximum recommended dose for adults is 400–600 units in any three-month period, while for MyoBloc it is 10,000–15,000 units. The maximum dosage may be reached in the treatment of spasticity or cervical dystonia, while much smaller amounts are used in the treatment of facial lines, strabismus, and hemifacial spasm.

Precautions

When injected by a trained physician, botulinum toxin is very safe. The toxin remains mainly in the muscle injected, spreading only slightly to surrounding muscles or beyond. Botulism poisoning, which occurs after ingesting large amounts of the toxin, is due to the effects of the poison on the breathing muscles. In medical use, far less toxin is injected, and care is taken to avoid any chance of spread to muscles needed for breathing. Injection into the shoulders or neck may weaken muscles used for swallowing, which patients need to be aware of. Some patients may need to change to a softer diet to make swallowing easier during the peak effect of their treatment.

Repeated injections of large amounts of botulinum toxin can lead to immune system resistance. While this is not a dangerous condition, it makes further treatment ineffective.

Patients with neuromuscular disease should not receive treatment with botulinum toxin without careful consultation with a neurologist familiar with its effects.

Side effects

Botulinum toxin can cause a mild flu-like syndrome for several days after injection. Injection of too much toxin causes excess weakness, which may make it difficult to carry on normal activities of daily living. In some patients, toxin injection may cause blurred vision and dry mouth. This is more common in patients receiving MyoBloc than with Botox.

Interactions

Patients taking aminoglycoside antibiotics may be cautioned against treatment with botulinum toxin. These antibiotics include gentamicin, kanamycin, and tobramycin, among others.

Resources

BOOKS

Brin, M. F., M. Hallett, and J. Jankovic, editors. Scientific and Therapeutic Aspects of Botulinum Toxin. Philadelphia: Lippincott, 2002.

WEBSITES

WE MOVE. December 4, 2003 (February 18, 2004). http://www.wemove.org

MD Virtual University. December 4, 2003 (February 18, 2004). www.mdvu.org