Botulinum Toxicity

Bohnel, H., Schwagerick, B., Gessler, F. (2001). Visceral botulism-a new form of bovine Clostridium botulinum toxication. J. Vet. Med. A Physiol. Pathol. Clin. Med. 48 373-83. 

Human toxicity values have not been fully established or have not been published. However, based on available information, this material appears to have approximately half as toxic as Botulinum toxins (C16-A005). 

C. botulinum toxins cause botulism. They are among the most toxic substances known. A lethal dose for humans is 1 microgram (a millionth of a gram). In a... 

Classical bacterial exotoxins, such as diphtheria toxin, cholera toxin, clostridial neurotoxins, and the anthrax toxins are enzymes that modify their substrates within the cytosol of mammalian cells. To reach the cytosol, these toxins must first bind to different cell-surface receptors and become subsequently internalized by the cells. To this end, many bacterial exotoxins contain two functionally different domains. The binding (B-) domain binds to a cellular receptor and mediates uptake of the enzymatically active (A-) domain into the cytosol, where the A-domain modifies its specific substrate (see Figure 1). Thus, three important properties characterize the mode of action for any AB-type toxin selectivity, specificity, and potency. Because of their selectivity toward certain cell types and their specificity for cellular substrate molecules, most of the individual exotoxins are associated with a distinct disease. Because of their enzymatic nature, placement of very few A-domain molecules in the cytosol will normally cause a cytopathic effect. Therefore, bacterial AB-type exotoxins which include the potent neurotoxins from Clostridium tetani and C. botulinum are the most toxic substances known today. However, the individual AB-type toxins can greatly vary in terms of subunit composition and enzyme activity (see Table 2). 

M toxin (12S) consists of neurotoxin and non-toxic non-hemaglutynin (NTNH) components. It is produced by all types of C. botulinum, except C. botulinum type G. 

Botulinum toxin Antiserum Immunologically neutralizes toxicant... 

Botulinum toxin is the most toxic substance known. One gram of crystalline toxin adequately dispersed can kill a population of a million people, so its use in bioterrorism is a possibility. The toxin can be introduced through inhalation or ingestion but not through dermal... 

How many times more toxic is botulinum toxin than nicotine in the rat ... 

Large molecules and particles such as carrageenen and polystyrene particles of 22-p.m diameter may also be absorbed from the gut, presumably by phagocytosis. The bacterial product botulinum toxin, a large molecule (molecular weight 200,000-400,000), is sufficiently well absorbed after oral ingestion to be responsible for toxic and often fatal effects. 

Surprisingly perhaps, given its extreme toxicity, botulinum toxin was introduced into medical practice in 1983 to treat patients with squint. Since then, its use has been expanded to include other disorders of muscle control suffered by patients with cerebral palsy or after a severe stroke where the brain cannot control the muscles, which may remain permanently contracted. Tiny amounts of the toxin are injected into the affected muscle, which then becomes paralyzed and, so, relaxed. There are several forms of the toxin that are now marketed as "Botox 7 (type A toxin) and Myobloc (type B toxin). More recently, Botox has been used in "cosmetic77 medicine as a way of reducing lines and wrinkles in the face due to aging. 

Botulinum is highly toxic but can be used as a drug. Describe the therapeutic action and the mechanism. 

Brin MF (1997) Botulinum toxin chemistry, pharmacology, toxicity, and immunology. Muscle Nerve Suppl 6 S146-68... 

Hanna PA, Jankovic J, Vincent A (1999) Comparison of mouse bioassay and immunoprecipitation assay for botulinum toxin antibodies. J Neurol Neurosurg Psychiatry 66 612-16 Hanson MA, Stevens RC (2000) Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 A resolution. Nat Struct Biol 7 687-92 Harlow ML, Ress D, Stoschek A, Marshall RM, McMahan UJ (2001) The architecture of active zone material at the frog s neuromuscular junction. Nature 409 479-84 Harris JB (1997) Toxic phospholipases in snake venom an introductory review. Symp. zool. Soc. Lond. 70 235-50... 

Lacy DB, Tepp W, Cohen AC, DasGupta BR, Stevens RC (1998) Crystal structure of botulinum neurotoxin type a and implications for toxicity. Nat Struct Biol 5 898-902... 

O Sullivan G, Mohammed N, Foran P, Lawrence G, Dolly O (1999) Rescue of exocytosis in botulinum toxin A-poisoned chromaffin cells by expression of cleavage-resistant SNAP-25. Identification of the minimal essential C-terminal residues. J Biol Chem 274 36897-904 Oberg SG, Kelly RB (1976) The mechanism of beta-bungarotoxin action. I. modification of transmitter release at the neuromuscular junction. J Neurobiol 7 129 11 Ohishi I, Sugii S, Sakaguchi G (1977) Oral toxicities of Clostridium botulinum toxins in response to molecular size. Infect Immun 16 107-9... 

Botulinum toxin is produced by the bacterium Clostridium botulinum it is the most toxic protein known. The toxin consists of a heavy chain and a light chain the hght chain has protease activity, which degrades a cellular protein (SNAP-25) required for the normal release of neurotransmitters from the axon endings. The consequent lack of release of acetylcholine results in muscle paralysis. 

Botulinum toxin is both a medication and a neurotoxin, produced by the bacterium Clostridium botulinum. It is the most toxic protein known. It can be used to treat muscle spasms, and is sold commercially under various names (Botox, Dysport, Myobloc, etc.). Botox Cosmetic and Vistabel are available for cosmetic treatment. The toxin protein consists... 

Chemicals come in all shapes and sizes and derive from a variety of sources. While to many people the words chemical and indeed poison are synonymous with man-made things such as dioxin, organo-phosphates, pesticides, and nerve gas, there are many, many other chemicals that occur naturally These may be produced by plants, for example belladonna in deadly nightshade, and ricin in the castor bean, or bacteria, for example botulinum toxin. Various animals such as snakes and spiders produce toxic venoms, and some poisons occur naturally in the ground, like asbestos, cadmium, and lead. 

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