Instruct: Given a question, retrieve documents that answer the question.
Query: Who first discovered Botulinum toxin?
In 1895 (seventy-five years later), Émile van Ermengem, professor of bacteriology and a student of Robert Koch, correctly described Clostridium botulinum as the bacterial source of the toxin. Thirty-four attendees at a funeral were poisoned by eating partially salted ham, an extract of which was found to cause botulism-like paralysis in laboratory animals. Van Ermengem isolated and grew the bacterium, and described its toxin,[41] which was later purified by P Tessmer Snipe and Hermann Sommer.[42]
Foodborne botulism
"Signs and symptoms of foodborne botulism typically begin between 18 and 36 hours after the toxin gets into your body, but can range from a few hours to several days, depending on the amount of toxin ingested."Wound botulism
Most people who develop wound botulism inject drugs several times a day, so it's difficult to determine how long it takes for signs and symptoms to develop after the toxin enters the body. Most common in people who inject black tar heroin, wound botulism signs and symptoms include:Infant botulism
If infant botulism is related to food, such as honey, problems generally begin within 18 to 36 hours after the toxin enters the baby's body. Signs and symptoms include:Beneficial effects of botulinum toxin:
Purified botulinum toxin is diluted by a physician for treatment:
In the United States, botulinum toxin products are manufactured by a variety of companies, for both therapeutic and cosmetic use. A U.S. supplier reported in its company materials in 2011 that it could "supply the world's requirements for 25 indications approved by Government agencies around the world" with less than one gram of raw botulinum toxin.[67] Myobloc or Neurobloc, a botulinum toxin type B product, is produced by Solstice Neurosciences, a subsidiary of US WorldMeds. AbobotulinumtoxinA), a therapeutic formulation of the type A toxin manufactured by Galderma in the United Kingdom, is licensed for the treatment of focal dystonias and certain cosmetic uses in the U.S. and other countries.[31]
Botulinum toxin A is marketed under the brand names Botox and Xeomin. Botulinum toxin B is marketed under the brand name Myobloc.
In all cases, illness is caused by the botulinum toxin produced by the bacterium C. botulinum in anaerobic conditions and not by the bacterium itself. The pattern of damage occurs because the toxin affects nerves that fire (depolarize) at a higher frequency first.[16]
In response to the occurrence of these side effects, in 2008 the U.S. Food and Drug Administration notified the public of the potential dangers of the botulinum toxin as a therapeutic. Namely, they warned that the toxin can spread to areas distant from the site of injection and paralyze unintended muscle groups, especially when used for treating muscle spasticity in children treated for cerebral palsy.[29] In 2009, the FDA announced that boxed warnings would be added to available botulinum toxin products, warning of their ability to spread from the injection site.[30] Additionally, the FDA announced name changes to several botulinum toxin products, meant to emphasize that the products are not interchangeable and require different doses for proper use. Botox and Botox Cosmetic were renamed onabotulinumtoxinA, Myobloc was renamed rimabotulinumtoxinB, and Dysport name renamed abobotulinumtoxinA.[30] In conjunction with this, the FDA issued a communication to health care professionals reiterating the new drug names and the approved uses for each.[31] A similar warning was issued by Health Canada in 2009, warning that botulinum toxin products can spread to other parts of the body.[32]
Botulinum toxin therapy of strabismus is a medical technique used sometimes in the management of strabismus, in which botulinum toxin is injected into selected extraocular muscles in order to reduce the misalignment of the eyes. The injection of the toxin to treat strabismus, reported upon in 1981, is considered to be the first ever use of botulinum toxin for therapeutic purposes. Today, the injection of botulinum toxin into the muscles that surround the eyes is one of the available options in the management of strabismus. Other options for strabismus management are vision therapy and occlusion therapy, corrective glasses (or contact lenses) and prism glasses, and strabismus surgery.
Botulinum toxin is used to treat a number of disorders characterized by overactive muscle movement, including post-stroke spasticity, post-spinal cord injury spasticity, spasms of the head and neck,[8] eyelid,[9] vagina,[10] limbs, jaw, and vocal cords.[11] Similarly, botulinum toxin is used to relax clenching of muscles, including those of the oesophagus,[12] jaw,[13] lower urinary tract and bladder,[14] or clenching of the anus which can exacerbate anal fissure.[15] It may also be used for improper eye alignment.[16] Botulinum toxin appears to be effective for refractory overactive bladder.[17]
Botulinum toxin is considered as an alternative to surgery in certain clinical situations. A study performed in the 1980s found outcomes of surgery to be "more predictable and longer lasting" than those of botulinum toxin therapy. As stated in a review article of 2007, its use for strabismus "varies enormously in different cities and countries for no apparent reason."
Botulinum toxin is also used to treat disorders of hyperactive nerves including excessive sweating,[23] neuropathic pain,[26] and some allergy symptoms.[11] In addition to these uses, botulinum toxin is being evaluated for use in treating chronic pain.[27]
Some patients experience or develop immunoresistance to botulinum toxin type A and must use botulinum toxin type B. Approximately 4% to 17% of patients develop botulinum toxin type A antibodies. The only botulinum toxin type B accessible in the United States is Myobloc. Treatment using botulinum toxin type B is comparable to type A, with an increased frequency of the side effect dry mouth.
Botulinum toxin is the most acutely lethal toxin that is known. It is produced by the bacterium clostridium botulinum. It acts inside nerve terminals by decreasing the release of acetylcholine, blocking neuromuscular transmission and thereby causing flaccid muscular paralysis. As a result, the muscle is weakened for about 3 to 4 months.
Botulinum toxin produced by Clostridium botulinum is the cause of botulism.[9] Humans most commonly ingest the toxin from eating improperly-canned foods in which C. botulinum has grown. However, the toxin can also be introduced through an infected wound. In infants, the bacteria can sometimes grow in the intestines and produce botulinum toxin within the intestine and can cause a condition known as floppy baby syndrome.[33] In all cases, the toxin can then spread, blocking nerves and muscle function. In severe cases, the toxin can block nerves controlling the respiratory system or heart, resulting in death.[1] Botulism can be difficult to diagnose, as it may appear similar to diseases such as Guillain–Barré syndrome, myasthenia gravis, and stroke. Other tests, such as brain scan and spinal fluid examination, may help to rule out other causes. If the symptoms of botulism are diagnosed early, various treatments can be administered. In an effort to remove contaminated food which remains in the gut, enemas or induced vomiting may be used.[34] For wound infections, infected material may be removed surgically.[34] Botulinum antitoxin is available and may be used to prevent the worsening of symptoms, though it will not reverse existing nerve damage. In severe cases, mechanical respiration may be used to support patients suffering from respiratory failure.[34] The nerve damage heals over time, generally over weeks to months.[4] With proper treatment, the case fatality rate for botulinum poisoning can be greatly reduced.[34]
The effects that are due only to the toxin itself (including the side effects) generally wear off within 3 to 4 months. In contrast, improvements in alignment may be long-lasting, particularly in two circumstances. First, if the "antagonist" muscle (the muscle pulling in the opposite direction) is active, the injected muscle will be stretched, and may permanently lengthen by adding tissue during the period of toxin paresis. Second, if binocular vision has been achieved and stabilized, alignment may "lock in". There are indications that botulinum toxin therapy is as successful as strabismus surgery for patients with binocular vision and that it is less successful than surgery for those who have no binocular vision.
For patients who have had healthy vision heretofore until a small, horizontal deviation set in suddenly, the injection of botulinum toxin may allow them to maintain the binocular vision skills that had been acquired earlier.
After local or general anaesthesia has been applied, the botulinum toxin is injected directly into the selected eye muscles using a specially designed needle electrode that is connected to an electromyography (EMG) apparatus as well as to a syringe containing the botulinum toxin solution.
Botulinum toxin exerts its effect by cleaving key proteins required for nerve activation. First, the toxin binds specifically to nerves which use the neurotransmitter acetylcholine. Once bound to the nerve terminal, the neuron takes up the toxin into a vesicle. As the vesicle moves farther into the cell, it acidifies, activating a portion of the toxin which triggers it to push across the vesicle membrane and into the cell cytoplasm.[1] Once inside the cytoplasm, the toxin cleaves SNARE proteins preventing the cell from releasing vesicles of neurotransmitter. This stops nerve signaling, leading to paralysis.[1]
Botulinum toxin is used to treat a number of problems.
Botulinum toxin (BTX) is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species.[1] It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction and thus causes flaccid paralysis. Infection with the bacterium causes the disease botulism. The toxin is also used commercially in medicine, cosmetics and research.
"C. botulinum" is a diverse group of pathogenic bacteria initially grouped together by their ability to produce botulinum toxin and now known as four distinct groups, "C. botulinum" groups I-IV. "C. botulinum" groups I-IV, as well as some strains of "Clostridium butyricum" and "Clostridium baratii", are the bacteria responsible for producing botulinum toxin.
"C. botulinum" is responsible for foodborne botulism (ingestion of preformed toxin), infant botulism (intestinal infection with toxin-forming "C. botulinum"), and wound botulism (infection of a wound with "C. botulinum"). "C. botulinum" produces heat-resistant endospores that are commonly found in soil and are able to survive under adverse conditions.
Adults with CP are more likely to use medication to manage pain than active pain management methods.
Botulinum toxin injections are given into muscles that are spastic or sometimes dystonic, the aim being to reduce the muscle hypertonus that can be painful. A reduction in muscle tone can also facilitate bracing and the use of orthotics. Most often lower extremity muscles are injected. Botulinum toxin is focal treatment, meaning that a limited number of muscles can be injected at the same time. The effect of the toxin is reversible and a reinjection is needed every 4–6 months. In children it decreases spasticity and improve range of motion and thus has become commonly used. Botulin toxin has been used in CP treatment for around two decades and can be recommended for children above the age of two. A Cochrane review published in 2010 found that there is high level evidence in the use of botulinum toxin as an add on therapy to occupational therapy in order to manage spasticity in the arms of children with cerebral palsy. However, there is no strong research associated with the use of botulinum toxin in the management of spasticity in the legs or improving gait compared to casting. More evidence related to the frequency and dosage of injections as it relates to long-term outcomes is needed in order to support or refute the use of botulinum toxin in the management of lower limb spasticity in children with cerebral palsy.
Botulinum toxin therapy has been reported to be similarly successful as strabismus surgery for patients with binocular vision and less successful than surgery for those who have no binocular vision. One study found that botulinum toxin therapy had similar long-term success rates for treating infantile esotropia with botulinum toxin A before the age of 12 months as would have been expected from strabismus surgery. Another study reported similar long-term success rates for infantile esotropia treated before 24 months of age by either strabismus surgery or botulinum toxin treatment.
With regard to detection, current protocols using NBC detection equipment (such as M-8 paper or the ICAM) will not indicate a "positive" when samples containing botulinum toxin are tested. To confirm a diagnosis of botulinum toxin poisoning, therapeutically or to provide evidence in death investigations, botulinum toxin may be quantitated by immunoassay of human biological fluids; serum levels of 12–24 mouse LD50 units per milliliter have been detected in poisoned patients.[64]
In 2014, the US Food and Drug Administration (FDA) banned the import of Thai fish sauces due to lack of information about tests for botulinum toxin. The toxin can cause death if more than 0.5 microgram is consumed. The Thai Office of Food Safety and Quality then tested 48 brands of fish sauce to determine the content of botulinum toxin in the products. Of 48 brands tested, 28 were genuine fish sauce from 18 production sites in 12 provinces. Twenty samples from production sites in eight provinces were adulterated fish sauce. Tests showed that none were contaminated with botulinum toxin types A, B, E and F and were free of clostridium botulinum bacteria. In 2018, rumours again surfaced concerning banned Thai fish sauce.