NationMaster - Encyclopedia: Botulin toxin

Botulin toxin is a neurotoxic protein produced by the bacterium clostridium botulinum. Though it is highly toxic, it is used in minute doses as a cosmetic treatment in some parts of the world, and it is sold commercially under the brand names Botox® and Dysport® for this purpose. The terms Botox and Dysport are trade names and are not used generically to describe the neurotoxins produced by Clostridia species. Taken from Image:WMD.png by Wapcaplet File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ... Chemical warfare is warfare (and associated military operations) using the toxic properties of chemical substances to kill, injure or incapacitate an enemy. ... Weapons of mass destruction (WMD) generally include nuclear, biological, chemical and, increasingly, radiological weapons. ... A blood agent (also called a cyanogen agent) is a compound that prevents the normal transfer of oxygen from the blood to the body tissues, resulting in chemical asphyxiation. ... Cyanogen chloride, also known as CK, is a highly toxic blood agent first proposed for use in warfare by the French. ... Flash point âˆ’17. ... Blister agents are named for their ability to cause large, painful water blisters on the bodies of those affected. ... Chemical structure of Lewisite Lewisite is a chemical compound from a chemical family called arsines. ... 0. ... The nitrogen mustards are cytotoxic chemotherapy agents similar to mustard gas. ... Nerve agents (also known as nerve gases, though these chemicals are liquid at room temperature) are a class of phosphorus-containing organic chemicals (organophosphates) that disrupt the mechanism by which nerves transfer messages to organs. ... Tabun or GA (Ethyl N,N-dimethylphosphoramidocyanidate) is an extremely toxic substance that is one of the worlds most dangerous military weapons. ... Sarin or GB (O-Isopropyl methylphosphonofluoridate) is an extremely toxic substance. ... Boiling point 198 Â°C (388 Â°F) Freezing/melting point âˆ’42 Â°C (âˆ’44 Â°F) Vapor pressure 0. ... Cyclosarin or GF (Cyclohexyl methylphosphonofluoridate) is an extremely toxic substance that is one of the worlds most dangerous weapons of war. ... VE (S-(Diethylamino)ethyl O-ethyl ethylphosphonothioate) is a V-series nerve agent closely related to the better-known VX nerve gas. ... VG (also called Amiton or Tetram) is a V-series nerve agent closely related to the better-known VX nerve agent. ... VM (Phosphonothioic acid, methyl-, S-(2-(diethylamino)ethyl) O-ethyl ester) is a V-series nerve agent closely related to the better-known VX nerve agent. ... The VX nerve agent is the most well-known of the V-series of nerve agents. ... Categories: Chemical weapons | Stub ... General Name, Symbol, Number chlorine, Cl, 17 Chemical series halogens Group, Period, Block 17, 3, p Appearance yellowish green Atomic mass 35. ... Chloropicrin is a slightly oily, colorless liquid of the formula CCl3NO2. ... Phosgene (also known as carbonyl chloride, COCl2) is a highly toxic gas or refrigerated liquid that was used as a chemical weapon in World War I. It has no color, but is detectable in air by its odor, which resembles moldy hay. ... Diphosgene (ClCO2CCl3) Diphosgene (Trichloromethyl chloroformate, ClCO2CCl3) is a chemical originally developed for chemical warfare, a few months after the first use of phosgene. ... The term incapacitating agent is defined by the U.S. Department of Defense as An agent that produces temporary physiological or mental effects, or both, which will render individuals incapable of concerted effort in the performance of their assigned duties. ... Diagram of a BZ molecule 3-quinuclidinyl benzilate (QNB), empirical formula C21H23NO3, full chemical name 1-azabicyclo[2. ... KOLOKOL-1 is an opiate-derived incapacitating agent. ... A riot control agent is a type of lachrymatory agent (or lacrimatory agent). ... Pepper spray (also known as OC spray (from Oleoresin Capsicum), OC gas, or capsicum spray) is a lachrymatory agent (a chemical compound that irritates the eyes to cause tears, pain, and even temporary blindness) that is used in riot control, crowd control and personal self-defense, including defense against dogs. ... CS or 2-chlorobenzalmalononitrile (chemical formula: C10H5ClN2) is a substance that is used as a riot control agent and is usually claimed to be non-lethal by the forces who use it. ... Categories: Stub | Chemical weapons | Less-lethal weapons ... CR gas or dibenzoxazepine, chemically dibenz[b,f][1,4]oxazepine, is an incapacitating agent and a lachrymatory agent. ... It has been suggested that Neurotoxicity be merged into this article or section. ... Binomial name Clostridium botulinum van Ermengem, 1896 Clostridium botulinum is a bacterium that produces the toxin botulin, the causative agent in botulism. ...

History

The German physician and singer Justinus Kerner called botulinum toxin "sausage poison", as this bacterium often causes poisoning cases by growing in badly handled prepared meat products. He first conceived a possible therapeutic use of botulinum toxin. In 1870, Muller (another German physician) coined the name botulism, from Latin botulus = "sausage". In 1895, Emile Van Ermengem first isolated the bacterium Clostridium botulinum. In 1944, Edward Schantz cultured Clostridium botulinum and isolated the toxin, and, in 1949, Burgen's group discovered that botulinum toxin blocks neuromuscular transmission. Throughout the 1950s, the toxin was used experimentally in the medical cosmetic treatment of politicians. Then actor-turned-politician Ronald Reagan is rumoured to be one of the earliest patients of this microexpression-concealing procedure. Justinus Kerner in old age Justinus Andreas Christian Kerner (September 18, 1786 - February 21, 1862), was a German poet and medical writer. ... Freshly cooked pork sausages. ... 1870 (MDCCCLXX) was a common year starting on Saturday (see link for calendar) of the Gregorian calendar or a common year starting on Monday of the 12-day-slower Julian calendar. ... Botulism (from Latin botulus, sausage) is a rare but serious paralytic illness caused by a nerve toxin, botulin, that is produced by the bacterium Clostridium botulinum. ... Latin is an ancient Indo-European language originally spoken in the region around Rome called Latium. ... 1895 (MDCCCXCV) was a common year starting on Tuesday (see link for calendar) of the Gregorian calendar (or a common year starting on Thursday of the 12-day-slower Julian calendar). ... 1944 (MCMXLIV) was a leap year starting on Saturday (the link is to a full 1944 calendar). ... 1949 (MCMXLIX) was a common year starting on Saturday (the link is to a full 1949 calendar). ... Ronald Wilson Reagan (February 6, 1911 â€“ June 5, 2004) was the 40th President of the United States (1981â€“1989) and the 33rd Governor of California (1967â€“1975). ... A microexpression is a tiny facial expression that lasts less than a quarter of a second. ...

By 1973, Alan B Scott, MD, of Smith-Kettlewell Institute used botulinum toxin type A (BTX-A) in monkey experiments, and, in 1980, he officially used BTX-A for the first time in humans to treat strabismus. In December 1989, BTX-A (BOTOX) was approved by the US Food and Drug Administration (FDA) for the treatment of strabismus, blepharospasm, and hemifacial spasm in patients over 12 years old. The cosmetic effect of BTX-A was initially described by the Carruthers, a dermatologist/ophthalmologist husband and wife team although the effect had been observed by a number of independent groups. On April 15, 2002, the FDA announced the approval of botulinum toxin type A (BOTOX Cosmetic) to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines). BTX-A has also been approved for the treatment of excessive underarm sweating. The acceptance of BTX-A use for the treatment of spasticity and muscle pain disorders is growing, with approvals pending in many European countries and studies on headaches (including migraine), prostatic symptoms, asthma, obesity and many other possible indications are ongoing. 1973 (MCMLXXIII) was a common year starting on Monday. ... The Smith-Kettlewell Institute of Visual Sciences in San Francisco was formed in 1962 by Dr. Arthur Jampolsky as the Eye Research Institute on the former campus of the Stanford Medical School. ... 1980 (MCMLXXX) was a leap year starting on Tuesday. ... Strabismus prevents bringing the gaze of both eyes to the same point in space Strabismus, also known as heterotropia, squint, crossed eye, wandering eye, or wall eyed, is a disorder in which the eyes do not point in the same direction. ... This article or section is in need of attention from an expert on the subject. ... The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ... The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ... Spasticity is a disorder of the bodys motor system in which certain muscles are continuously contracted. ... On either side of the urethral crest is a slightly depressed fossa, the prostatic sinus, the floor of which is perforated by numerous apertures, the orifices of the prostatic ducts from the lateral lobes of the prostate. ...

Dysport is a therapeutic formulation of the type A toxin developed and manufactured in the UK and which is licenced for the treatment of focal dystonias and certain cosmetic uses in many territories world wide.

Botulinum Toxin Type B (BTX-B) received FDA approval for treatment of cervical dystonia on December 21, 2000. Trade names for BTX-B are Myobloc in the United States, and Neurobloc® in the European Union. The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ... Dystonia (literally, abnormal muscle tone) is a generic term used to describe a neurological movement disorder involving involuntary, sustained muscle contractions. ...

Medical uses

Researchers discovered in the 1950s that injecting overactive muscles with minute quantities of botulinum toxin type A decreased muscle activity by blocking the release of acetylcholine at the neuromuscular junction, thereby rendering the muscle unable to contract for a period of 4 to 6 months. Image File history File links Stop_hand. ... The skeletal structure of acetylcholine The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. ... A neuromuscular junction is the junction of the axon terminal of a motoneuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscles surface. ...

Alan Scott, a San Francisco ophthalmologist, first applied tiny doses of the toxin in a medicinal sense to treat crossed eyes and uncontrollable blinking, but needed a partner to gain regulatory approval to market his discovery as a drug. Allergan, Inc., a small pharmaceutical company that focused on prescription eye therapies and contact lens products, bought the rights to the drug in 1988 and received FDA approval in 1989. Allergan renamed the drug Botox. This page is a candidate for speedy deletion. ... Ophthalmology is the branch of medicine which deals with the diseases of the eye and their treatment. ... Strabismus prevents bringing the gaze of both eyes to the same point in space Strabismus, also known as heterotropia, squint, crossed eye, wandering eye, or wall eyed, is a disorder in which the eyes do not point in the same direction. ... Allergan, Inc. ... The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ...

Cosmetically desirable effects of Botox were quickly discovered thereafter when the frown lines between the eyebrows were observed to soften following treatment for eye muscle disorders, leading to clinical trials and subsequent FDA approval for cosmetic use in April 2002. As of 2006, botox injection is the most common cosmetic operation in the United States. The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ... 2006 is a common year starting on Sunday of the Gregorian calendar. ...

Other uses of botulinum toxin type A that are widely known but not specifically approved by FDA include: Dystonia (literally, abnormal muscle tone) is a generic term used to describe a neurological movement disorder involving involuntary, sustained muscle contractions. ... The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ...

In the Journal of Dermatologic Surgery, Eric Finzi claims to have treated clinically depressed patients with botox. On Good Morning America, he claimed that by taking away the ability to frown, he was somehow taking away the ability to feel depressed. [1] A diagram showing the CNS: 1. ... For other uses, see Stroke (disambiguation). ... Cerebral palsy or CP is the most common childhood physical disability. ... Dystonia (literally, abnormal muscle tone) is a generic term used to describe a neurological movement disorder involving involuntary, sustained muscle contractions. ... Laryngoscopic view of the vocal folds. ... The temporomandibular joint (TMJ) is a diarthrosis joint that connects the mandible (lower jaw) to the temporal bone at the side of a skull. ...

Treatment and prevention of chronic headache and chronic musculoskeletal pain are emerging uses for botulinum toxin type A. In addition, there is evidence that Botox may aid in weight loss by increasing the gastric emptying time.

A side effect in some patients is a jaw left too weak to chew solid food for about 3 months after the injection. In addition, the cosmetic treatment generally wears off after 6 months.

Chemical overview

There are seven serologically distinct toxin types, designated A through G; 3 subtypes of A have been described. The toxin is a two-chain polypeptide with a 100-kDa heavy chain joined by a disulphide bond to a 50-kDa light chain. This light chain is an enzyme (a protease) that attacks one of the fusion proteins at a neuromuscular junction, preventing vesicles from anchoring to the membrane to release acetylcholine. By inhibiting acetylcholine release, the toxin interferes with nerve impulses and causes paralysis of muscles in botulism. It is possibly the most acutely toxic substance known, with a lethal dose of about 200-300 pg/kg, meaning that somewhat over a hundred grams could kill every human on earth (for perspective, the rat poison Strychnine, often described as highly toxic, has an LD₅₀ of 1 mg/kg, or 1 billion pg/kg). It is also remarkably easy to come by: Clostridium spores are found in soil practically all over the earth. Food-borne botulism usually results from ingestion of food that has become contaminated with spores (such as a perforated can) in an anaerobic environment, allowing the spores to germinate and grow. The growing (vegetative) bacteria produce toxin; ingestion of preformed toxin causes botulism, not ingestion of the spores or vegetative organism. Infant (intestinal) and wound botulism both result from infection with spores which subsequently germinate, resulting in production of toxin and the symptoms of botulism. Peptides are the family of molecules formed from the linking, in a defined order, of various amino acids. ... The unified atomic mass unit (u), or dalton (Da), is a small unit of mass used to express atomic masses and molecular masses. ... A disulfide bond (SS-bond), also called a disulfide bridge, is a strong covalent bond between two sulfhydryl groups. ... Proteases (proteinases, peptidases or proteolytic enzymes) are enzymes that break peptide bonds between amino acids of proteins. ... A neuromuscular junction is the junction of the axon terminal of a motoneuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscles surface. ... In cell biology, a vesicle is a relatively small and enclosed compartment, separated from the cytosol by at least one lipid bilayer. ... It has been suggested that Net flux be merged into this article or section. ... The skeletal structure of acetylcholine The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. ... Botulism (from Latin botulus, sausage) is a rare but serious paralytic illness caused by a nerve toxin, botulin, that is produced by the bacterium Clostridium botulinum. ... The picogram is an SI unit of mass (symbol pg) defined as: 1 pg = 1 × 10-15 kilogram (1 × 10-12 gram) A picogram is one trillionth (1/1000000000000) of a gram. ... Strychnine (pronounced (British) or (U.S.)) is a very toxic (LD50 = 1 mg/kg), colourless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as rodents. ... An LD50 test being administered In toxicology, the LD50 or colloquially semilethal dose of a particular substance is a measure of how much constitutes a lethal dose. ... Look up Anaerobic in Wiktionary, the free dictionary. ... Botulism (from Latin botulus, sausage) is a rare but serious paralytic illness caused by a nerve toxin, botulin, that is produced by the bacterium Clostridium botulinum. ...

Chemical warfare

Botulin toxin has always been considered an inferior agent for chemical warfare since it degrades rapidly on exposure to air, and therefore an area attacked with the toxic aerosol would be safe to enter within a day or so. There are no documented cases of the toxin actually being used in warfare; however, it was probably used in the Operation Anthropoid to kill top Nazi Reinhard Heydrich ([2]) and in "Operation Mongoose", where in 1961, the CIA saturated some cigars, of Fidel Castro's favorite brand, with botulinum toxin for a possible assassination attempt. The cigars were never used, but when tested years later were found still effective. [3]. Chemical warfare is warfare (and associated military operations) using the toxic properties of chemical substances to kill, injure or incapacitate an enemy. ... http://visibleearth. ... Reinhard Heydrich During World War II, the Czech-British Operation Anthropoid was the assassination of top Nazi leader Reinhard Heydrich, the chief of Reich Main Security Office, the Protector of Bohemia and Moravia and the chief planner of the Final Solution, the Nazi term for the genocide of the Jews. ... Reinhard Heydrich as SS-GruppenfÃ¼hrer Reinhard Tristan Eugen Heydrich (March 7, 1904 â€“ June 4, 1942, Prague) was an SS-ObergruppenfÃ¼hrer, chief of the Reich Security Main Office (which included the Gestapo, security agency and criminal police) and Reich governor of Bohemia and Moravia. ... The Cuban Project (also known as Operation Mongoose) is the general name for CIA covert operations and plans initiated by President John F. Kennedy on November 30, 1961. ... The CIA Seal The Central Intelligence Agency (CIA) is an American intelligence agency, responsible for obtaining and analyzing information about foreign governments, corporations, and individuals, and reporting such information to the various branches of the U.S. Government. ... Fidel Alejandro Castro Ruz (born August 13, 1926) has been the ruler of Cuba since 1959, when he commanded the attack that overthrew Fulgencio Batista. ...

There has been concern over the use of botulin toxin as a terrorist weapon, but it appears not to be ideal for this purpose. The vials used therapeutically are considered impractical as weapons because each vial contains only an extremely small fraction of the lethal dose. Nor is home-growing very viable; the bacterium in question is anaerobic and grows poorly in the presence of oxygen. This would make it difficult for terrorists to produce the toxin in bulk. Terrorism, as defined by the United States Department of Defense, is the calculated use of unlawful violence to inculcate fear; intended to coerce or intimidate governments or societies in pursuit of goals that are generally political, religious, or ideological. ... An anaerobic organism or anaerobe is any organism that does not require oxygen for growth. ...

The toxin's properties did not escape the attention of the Aum Supreme Truth cult in Japan, who had set up a plant for bulk production of this agent, though their assassination and other attacks used the nerve agent sarin instead, because of its easy dispersal and faster-acting properties. Aum Shinrikyo (also spelled Om Shin Rikyo) was a Buddhist religious group based in Japan. ... The Sarin gas attack on the Tokyo subway, usually referred to in the Japanese media as the åœ°ä¸‹é‰„ã‚µãƒªãƒ³äº‹ä»¶ (chikatetsu sarin jiken subway sarin incident) was an act of domestic terrorism perpetrated by members of the religious group Aum Shinrikyo on March 20, 1995. ... Nerve agents (also known as nerve gases, though these chemicals are liquid at room temperature) are a class of phosphorus-containing organic chemicals (organophosphates) that disrupt the mechanism by which nerves transfer messages to organs. ... Sarin or GB (O-Isopropyl methylphosphonofluoridate) is an extremely toxic substance. ...

Chemical mechanism of toxicity

The heavy chain of the toxin is particularly important for targeting the toxin to specific types of axon terminals. The toxin must get inside the axon terminals in order to cause paralysis. Following the attachment of the toxin heavy chain to proteins on the surface of axon terminals, the toxin can be taken into neurons by endocytosis. The light chain is able to leave endocytotic vesicles and reach the cytoplasm. The light chain of the toxin has protease activity. The type A toxin proteolytically degrades the SNAP-25 protein, a type of SNARE protein. The SNAP-25 protein is required for the release of neurotransmitter substances from the axon endings [4]. Botulin toxin specifically cleave these SNAREs, and so prevent neuro-secretory vesicles from docking/fusing with the nerve synapse plasma membrane and releasing their neurotransmitters. An axon, or nerve fiber, is a long slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neurons cell body or soma. ... Endocytosis is a process whereby cells absorb material (molecules such as proteins) from outside by engulfing it with their cell membrane. ... Cytoplasm is like jelly-like material that fills cells. ... Paired sets of SNARE proteins (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors) mediate fusion of vesicles with target membranes. ... Neurotransmitters are chemicals that are used to relay, amplify and modulate electrical signals between a neuron and another cell. ...

Though it affects the nervous system, common nerve agent treatments (namely the injection of atropine and 2-pam-chloride) will increase mortality by enhancing botulin toxin's mechanism of toxicity. Attacks involving botulin toxin are distinguishable from those involving nerve agent in that NBC detection equipment (such as M-8 paper or the ICAM) will not indicate a "positive" when a sample of the agent is tested.

External links

The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ...

References

Categories: NPOV disputes | Chemical weapons | Muscle relaxants | Neurotoxins The Economist is a weekly news and international affairs publication of The Economist Newspaper Ltd edited in London, UK. It has been in continuous publication since September 1843. ... May 22 is the 142nd day of the year in the Gregorian calendar (143rd in leap years). ... 2003 (MMIII) was a common year starting on Wednesday of the Gregorian calendar. ... May 31 is the 151st day of the year in the Gregorian calendar (152nd in leap years), with 214 days remaining. ... 2006 (MMVI) is a common year starting on Sunday of the Gregorian calendar. ...